Duoc-Ly-Hoc 2007 Y HN

dc l hc 2007 - i hc Y H ni
(sch dng cho sinh vin h bc s a khoa)
Bi 1: i cng v dc ng hc
Mc tiu hc tp: Sau khi hc xong bi ny, sinh vin c kh nng:

1. Phn tch c qu trnh hp thu v phn phi thuc trong c th.
2. Nu c ngha ca cc thng s dc ng hc ca cc qu trnh hp thu v phn
phi thuc.
3. Nu c ngha ca vic gn thuc vo protein huyt tng.
4. Trnh by c nhng qu trnh v ngha ca s chuyn ha thuc trong c th.
5. K ra c ngha thng s dc ng hc v h s thanh thi, t/2 v cc ng thi tr
thuc khi c th.
Dc ng hc (Pharmacokinetics) nghin cu cc qu trnh chuyn vn ca thuc t lc c

hp thu vo c th cho n khi b thi tr hon ton (H 1). Cc qu trnh l:
- S hp thu (Absorption)
- S phn phi (Distribution)
- S chuyn ha (Metabo lism)
- S thi tr (Excretion)
Mu M
Thuc - protein D tr
Hp thu
(ung, bi...) Protein
+
Thuc thuc(T) T T - Rec Tc dng
t/m
Chuyn ha
M Cht chuyn ha (M)
Thi tr
Hnh 1.1. S chuyn vn ca thuc trong c th
thc hin c nhng qu trnh ny, thuc phi vt qua cc mng t bo. V th trc khi
nghin cu 4 qu trnh ny, cn nhc li cc c ch vn chuyn thuc qua mng sinh hc v cc
c tnh l ha ca thuc v mng sinh hc c nh hng n cc qu trnh vn chuyn .
1. Cc cch vn chuyn thuc qua mng sinh hc

1.1. c tnh l ha ca thuc
- Thuc l cc phn t thng c trng lng phn t P M 600. Chng u l cc acid hoc cc
base yu.
- Kch thc phn t ca thuc c th thay i t rt nh (P M = 7 nh ion lithi) cho ti rt ln
(nh alteplase- tPA- l protein c P M = 59.050). Tuy nhin, a s c P M t 100- 1000. gn
"kht" vo 1 loi receptor, phn t thuc cn t c mt kch c duy nht vi kch thc ca
receptor c hiu thuc khng gn c vo cc receptor khc (mang tnh chn lc). Kinh
nghim cho thy P M nh nht phi t khong 100 v khng qu 1000, v ln qu th khng qua
c cc mng sinh hc ti ni tc dng.
Mt s thuc l acid yu: l phn t trung tnh c th phn ly thun nghch thnh mt anion (in
tch (-)) v mt proton (H +).
C8H7O2COOH C8H7O2COO- + H+
Aspirin trung tnh Aspirin anion Proton
Mt s thuc l base yu : l mt phn t trung tnh c th to thnh mt cation (in tch (+))
bng cch kt hp vi 1 proton:
C12H11ClN3NH3+ C12H11ClN3NH2 + H+
Pyrimethamin cation Pyrimethamin Proton
trung tnh
- Cc phn t thuc c sn xut di cc dng bo ch khc nhau :
Tan c trong nc (dch tiu ha, dch khe), do d c hp thu.
Tan c trong m thm qua c mng t bo gy ra c tc dng dc l v mng t
bo cha nhiu phospholipid .
V vy c hp thu vo t bo thun li nht, thuc cn c mt t l tan trong nc/ tan trong
m thch hp.
- Cc phn t thuc cn c c trng bi hng s phn ly pKa
pKa c suy ra t phng trnh Hend erson- HasselbACh:
dng ion ha
pH = pKa + log
dng khng ion ha
Cho 1 acid:
nng phn t
pKa = pH + log
nng ion
Cho 1 base:
nng ion
pKa = pH + log
nng phn t
K l hng s phn ly ca 1 acid; pKa = - logKa

pKa dng cho c acid v base. pKa +pKb=14
Mt acid hu c c pKa thp l 1 acid mnh v ngc li. Mt base c pKa thp l 1 base yu, v
ngc li.
Ni mt cch khc, khi mt thuc c hng s pKa bng vi pH ca mi trng th 50% thuc c
dng ion ha (khng khuch tn c qua mng) v 50% dng khng ion ha (c th khuch
tn c). V khi , nng phn t/ nng ion= 1 v log 1 = 0.
Ni chung, mt thuc phn tn tt, d c hp thu khi
C trng lng phn t thp
t b ion ha: ph thuc vo hng s phn ly (pKa) ca thuc v pH ca mi trng.
D tan trong dch tiu ha (tan trong nc)
ho tan trong lipid cao d qua mng ca t bo
1.2. Vn chuyn thuc bng cch lc
Nhng thuc c trng lng phn t thp (1 00- 200), tan c trong nc nhng khng tan c
trong m s chui qua cc ng dn (d= 4 - 40 ) ca mng sinh hc do s chnh lch p lc thu
tnh. ng dn ca mao mch c vn c ng knh l 30 , ca mao mch no l 7- 9, v th
nhiu thuc khng vo c thn kinh trung ng.
1.3. Vn chuyn bng khuch tn th ng (theo bc thang nng ).
Nhng phn t thuc tan c trong nc/ m s chuyn qua mng t ni c nng cao sang
ni c nng thp.
iu kin ca s khuch tn th ng l thuc t b ion ho v c nng cao b mt mng.
Cht ion ha s d tan trong nc, cn cht khng ion ha s tan c trong m v d hp thu
qua mng.
S khuch tn ca acid v base yu ph thuc vo hng s phn ly pKa ca thuc v pH ca mi
trng.
Th d: khi ung 1 thuc l acid yu, c pKa = 4, gian 1 d dy c pH= 1 v gian 2 l huyt
tng c pH = 7 (H.1)
Gian 2 Gian 1
pH = 7 pH = 1
pKa = 4
1000 R- COO- + H+ R- COO- + H+ 1

1 R- COOH R- COOH 1000
Hnh 1.2: S khuch tn qua mng

p dng phng trnh Henderson - Hasselbach, ta c:
gian 1 (d dy):
[ R- COOH ]
log = 4 - 1 = 3; Log ca 3 = 1000
[ R - COO- ]
gian 2 (mu):
[ R- COOH ]
log = 4 - 7 = - 3; Log ca - 3 = 1/1000
[ R - COO- ]
V ch phn khng ion ha v c nng cao mi khuch tn c qua mng cho nn acid ny s
chuyn t gian 1 (d dy) sang gian 2 (mu) v c hp thu.
Tr s pKa ca mt s thuc l acid yu v base yu c g hi bng1. Nn nh rng base c pKa
cao l base mnh v acid c pKa cao l acid yu.
Bng 1.1: Tr s pKa ca mt s thuc l acid v base yu
( nhit 25 0C)
Acid yu pKa Base yu pKa
Salicylic acid 3.00 Reserpin 6.6
Acetylsalicylic acid 3.49 Codein 7.9
Sulfadiazin 6.48 Quinin 8.4
Barbital 7.91 Procain 8.8
Boric acid 9.24 Atropin 9.65
S ion ha ca thuc cn ph thuc vo pH mi trng.
Bng 1.2: nh hng ca pH n s ion ha ca salicylic acid

c pKa = 3
pH % khng ion ha
1 99,0
2 90,9
3 50,0
4 9,09
5 0,99
6 0,10
Nh vy, salicylic acid (aspirin) uc hp thu nhiu d dy v phn trn ca ng tiu ha. Qua
bng ny cho thy khi b ng c thuc, mun ngn cn hp thu hoc thuc b hp thu ra
ngoi, ta c th thay i pH ca mi t rng.
Th d phenobarbital (Luminal, Gardenal) l mt acid yu c pKa = 7,2; nc tiu bnh thng
c pH cng bng 7,2 nn phenobarbital b ion ha 50%. Khi nng pH ca nc tiu ln 8, ion
ha ca thuc s l 86%, do thuc khng thm c vo t b o. iu ny c dng trong
iu tr nhim c phenobarbital: truyn dung dch NaHCO 3 1,4% base ha nc tiu, thuc
s b tng thi tr.
i vi mt cht kh (th d thuc m bay hi), s khuch tn t khng kh ph nang vo mu
ph thuc vo p lc ring phn ca cht kh gy m c trong khng kh th vo v ha tan
ca kh m trong mu.
1.4. Vn chuyn tch cc
Vn chuyn tch cc l s ti thuc t bn ny sang bn kia mng sinh hc nh mt "cht vn
chuyn" (carrier) c hiu c sn trong mng sinh hc.
* c im ca s vn chuyn ny l:
- C tnh bo ha: do s lng carrier c hn
- C tnh c hiu: mi carrier ch to phc vi vi cht c cu trc c hiu vi n.
- C tnh cnh tranh: cc thuc c cu trc gn ging nhau c th gn cnh tranh vi 1 carrier,
cht no c i lc mnh hn s gn c nhiu hn.
- C th b c ch: mt s thuc (nh actinomycin D) lm carrier gim kh nng gn thuc
vn chuyn.
* Hnh thc vn chuyn: c hai cch
- Vn chuyn thun li (Vn chuyn tch cc th pht) : khi km theo carrier li c c s chnh
lch bc thang nng , v vy s vn chuyn ny khng cn nng lng. Th d vn chuyn
glucose, pyramidon theo bc thang nng ca Na +
- Vn chuyn tch cc thc th (Vn chuyn tch cc nguyn pht): l vn chuyn i ngc bc
thang nng , t ni c nng thp sang ni c nng cao hn. V vy i hi phi c nng
lng c cung cp do ATP thu phn, thng c gi l cc "bm", th d s vn chuyn ca
Na+, K+, Ca++,I-, acid amin.
Hnh 1.3. Cc cch vn chuyn thuc qua mng sinh hc
2. Cc qu trnh dc ng hc
2.1. S hp thu
Hp thu l s vn chuyn thuc t ni dng thuc (ung, tim) vo mu ri i khp c th, ti
ni tc dng. Nh vy s hp thu s ph thuc vo:
- ha tan ca thuc. Thuc dng di dng dung dch nc d hp thu hn dng du, dch
treo hoc dng cng
- pH ti ch hp thu v c nh hng n ion ha v tan ca thuc.
- Nng ca thuc. Nng cng cao cng hp thu nhanh.
- Tun hon ti vng hp thu: cn g nhiu mch, cng hp thu nhanh.
- Din tch vng hp thu. Phi, nim mc rut c din tch ln, hp thu nhanh.
T nhng yu t cho thy ng a thuc vo c th s c nh hng ln n s hp thu.
Ngoi tr ng tim tnh mch, trong qu trnh hp thu vo vng tun hon, mt phn thuc s
b ph hu do cc enzym ca ng tiu ha, ca t bo rut v c bit l gan, ni c i lc
vi nhiu thuc. Phn thuc b ph hu trc khi vo vng tun hon c gi l "first pass
metabolism" (chuyn ha do hp thu hay chuyn ha qua gan ln th nht v thng l ung
thuc). Phn vo c tun hon mi pht huy tc dng dc l, c gi l sinh kh dng
(bioavailability) ca thuc (xin xem phn sau)
Sau y s im qua cc ng dng thuc thng thng v cc c im ca chng.
2.1.1. Qua ng tiu ha
u im l d dng v l ng hp thu t nhin.
Nhc im l b cc enzym tiu ha ph hu hoc thuc to phc vi thc n lm chm hp thu.
i khi thuc kch thch nim mc tiu ha, gy vim lot
2.1.1.1. Qua nim mc ming: thuc ngm di li
Do thuc vo thng vng tun hon nn khng b dch v ph hu, khng b chuyn ha qua gan
ln th nht
2.1.1.2. Thuc ung
Thuc s qua d dy v qua rut vi cc c im sau:
* d dy:
- C pH = 1- 3 nn ch hp thu cc acid yu, t b ion ha, nh aspirin, phenylbutazon, barbiturat.
- Ni chung t hp thu v nim mc t mch mu, li cha nhiu cholesterol, thi gian thuc d
dy khng lu.
- Khi i hp thu nhanh hn, nhng d b kch thch
* rut non:
L ni hp thu ch yu v c din tch hp thu rt rng (> 40 m 2), li c ti mu nhiu, pH
tng dn ti base (pH t 6 n 8).
- Thuc t b ion ha nhng nu t hoc khng tan trong lipid (sulfaguanidin, streptomycin) th t
c hp thu.
- Thuc mang amin bc 4 s b ion ha mnh kh hp thu, th d cc loi cura.
- Cc anion sulfat SO 4- - khng c hp thu: MgSO 4, Na2SO4 ch c tc dng ty.
2.1.1.3. Thuc t trc trng
Khi khng dng ng ung c (do nn, do hn m, hoc tr em) th c d ng thuc t vo
hu mn. Khng b enzym tiu ha ph hu, khong 50% thuc hp thu qua trc trng s qua
gan, chu chuyn ha ban u.
Nhc im l hp thu khng hon ton v c th gy kch ng nim mc hu mn.
2.1.2. Thuc tim
- Tim di da: do c nhiu si thn kinh cm gic nn au, t mch mu nn thuc hp thu chm
- Tim bp: khc phc c hai nhc im trn ca tim di da - mt s thuc c th gy hoi
t c nh ouabain, calci clorid th khng c tim bp.
- Tim tnh mch: thuc hp thu n hanh, hon ton, c th iu chnh liu c nhanh. Dng tim
cc dung dch nc hoc cc cht kch ng khng tim bp c v lng mch t nhy cm v
mu pha long thuc nhanh nu tim chm.
Thuc tan trong du, thuc lm kt ta cc thnh phn ca mu h ay thuc lm tan hng cu u
khng c tim mch mu.
2.1.3. Thuc dng ngoi
- Thm qua nim mc: thuc c th bi, nh git vo nim mc mi, hng, m o, bng quang
iu tr ti ch. i khi, do thuc thm nhanh, li trc tip vo mu, khng b c c enzym ph
hu trong qu trnh hp thu nn vn c tc dng ton thn: ADH dng bt xng mi; thuc t
(lidocain, cocain) bi ti ch, c th hp thu, gy c ton thn.
- Qua da: t thuc c th thm qua c da lnh. Cc thuc dng ngoi (thuc m, thu c xoa bp,
cao dn) c tc dng nng ti ch st khun, chng nm, gim au.
Tuy nhin, khi da b tn thng, vim nhim, bng... thuc c th c hp thu. Mt s cht c
d tan trong m c th thm qua da gy c ton thn (thuc tr su ln hu c, cht c cng
nghip anilin)
Gi m ni bi thuc (bng p), xoa bp, dng thuc gin mch ti ch, dng phng php ion -
di (iontophoresis) u lm tng ngm thuc qua da.
Hin c dng thuc cao dn mi, lm gii phng thuc chm v u qua da, duy tr c lng
thuc n nh trong mu: cao dn scopolamin, estrogen, nitrit
Da tr s sinh v tr nh, c lp sng mng manh, tnh thm mnh, d b kch ng cho nn cn
thn trng khi s dng, hn ch din tch bi thuc.
- Thuc nh mt: ch yu l tc dng t i ch. Khi thuc chy qua ng mi - l xung nim
mc mi, thuc c th c hp thu trc tip vo mu, gy tc dng khng mong mun.
2.1.4. Cc ng khc
- Qua phi: cc cht kh v cc thuc bay hi c th c hp thu qua cc t bo biu m ph
nang, nim mc ng h hp. V din tch rng (80 - 100 m 2) nn hp thu nhanh. y l ng
hp thu v thi tr chnh ca thuc m hi. S hp thu ph thuc vo nng thuc m trong
khng kh th vo, s thng kh h hp, ha tan ca thuc m trong mu ( hay h s phn ly
mu: kh )
Mt s thuc c th dng di dng phun sng iu tr ti ch (hen ph qun).
- Tim tu sng: thng tim vo khoang di nhn hoc ngoi mng cng gy t vng thp
(chi di, khung chu) bng dung dch c t trng cao (hyperbaric solution) hn dch no tu.
2.1.5. Thng s dc ng hc ca s hp thu: sinh kh dng (F)
2.1.5.1. nh ngha:
Sinh kh dng F (bioavailability) l t l phn trm lng thuc vo c vng tun hon dng
cn hot tnh v vn tc hp thu t huc (biu hin qua C max v Tmax) so vi liu dng. Sinh kh
dng phn nh s hp thu thuc.
2.1.5.2. ngha
- Khi thay i t dc, cch bo ch thuc s lm thay i ha tan ca thuc (hot cht) v
lm thay i F ca thuc. Nh vy, 2 dng bo ch ca cng mt sn phm c th c 2 sinh kh
dng khc nhau. Khi nim tng ng sinh hc (bioequivalence) dng so snh cc F ca
cc dng bo ch khc nhau ca 1 hot cht: F 1/F2.
- Khi thay i cu trc ha hc, c th lm F thay i:
Ampicilin c F = 50%
Amoxicilin (gn thm nhm OH) c F = 95%
- S chuyn ha thuc khi qua gan ln th nht, hay chuyn ha trc khi vo tun hon (first
pass metabolism) lm gim sinh kh dng ca thuc. Song i khi v thuc qua gan li c th
c chuyn ha thnh cht c hot tnh nn tuy sinh kh dng ca ng ung l thp nhng tc
dng dc l li khng km ng tim chch tnh mch. Th d propranolol c sinh kh dng
theo ng ung l 30% nhng gan n c chuyn ha thnh 4 - OH propranolol vn c hot
tnh nh propranolol.
- Cc yu t lm thay i F do ngi dng thuc:
. Thc n lm thay i pH hoc nhu ng ca ng tiu ha.
. Tui (tr em, ngi gi): thay i hot ng ca cc enzym.
. Tnh trng bnh l: to bn, tiu chy, suy gan.
. Tng tc thuc: hai thuc c th tranh chp ti ni hp thu hoc lm thay i tan, phn
ly ca nhau.
2.2. S phn phi
Sau khi c hp thu vo mu, mt phn thuc s gn vo protein ca huyt tng (cc protein
trong t bo cng gn thuc), phn thuc t do khng g n vo protein s qua c thnh mch
chuyn vo cc m, vo ni tc dng (cc receptor), vo m d tr, hoc b chuyn ha ri thi
tr (H1). Gia nng thuc t do (T) v phc hp protein - thuc (P- T) lun c s cn bng
ng:
T+P P-T
Qu trnh phn phi thuc ph thuc nhiu vo tun hon khu vc. Tu theo s ti mu, thng
chia c th thnh 3 gian (H 2)
Gian II Gian I Gian III
C quan c ti Huyt C quan c ti

mu nhiu: tim, thn, tng mu t hn: m m,
gan, no, phi da, c
Hnh 1.4. H phn phi thuc 3 gian

Hai loi yu t c nh hng n s phn phi thuc trong c th:
- V pha c th: tnh cht mng t bo, mng mao mch, s lng v tr gn thuc v pH ca mi
trng.
- V pha thuc: trng lng phn t, t l tan trong nc v trong lipid, tnh acid hay base,
ion ha, i lc ca thuc vi receptor.
2.2.1. S gn thuc vo protein huyt tng

2.2.1.1. V tr gn: phn ln gn vo albumin huyt tng (cc thuc l acid yu) v vo 1
glycoprotein (cc thuc l base yu) theo cch gn thun nghch .
2.2.1.2. T l gn: tu theo i lc ca tng loi thuc vi protein huyt tng(bng 1)
Bng 1.3: T l gn thuc vo protein huyt tng
T l gn thuc vi protein huyt tng
Thuc l acid yu Thuc l base yu

75-100%: 75- 100%:
Phenylbutazon, Diazepam
Warfarin Digitoxin
Phenytoin Clopromazin
Aspirin Erythromycin
25- 75%: 25- 75%:
Benzylpenicilin Cloroquin
Methotrexat Morphin
Khng gn: Khng gn:
Ethosuximid Isoniasid
Ouabain
S gn thuc vo protein huyt tng ph thuc vo 3 yu t:
- S lng v tr gn thuc trn protein huyt tng
- Nng phn t ca cc protein gn thuc
- Hng s gn thuc hoc hng s i lc gn thuc
2.2.1.3. ngha ca vic gn thuc vo protein huyt tng
- Lm d hp thu, chm thi tr v protein mu cao nn ti ni hp thu, thuc s c ko nhanh
vo mch.
- Protein huyt tng l cht m, l kho d tr thuc, sau khi gn thuc, s gii phng t t
thuc ra dng t do v ch c dng t do mi qua c cc mng sinh hc pht huy tc dng
dc l.
- Nng thuc t do trong huyt tng v ngoi dch k lun trng thi cn bng. Khi nng
thuc dch k gim, thuc huyt tng s i ra, protein gn thuc s nh thuc gi c n
bng.
- Nhiu thuc c th cng gn vo 1 v tr ca protein huyt tng, gy ra s tranh chp, ph
thuc vo i lc ca thuc. Thuc b y khi protein s tng tc dng, c th gy c. Th d
trn ngi ang dng tolbutamid iu tr i tho ng , nay v au khp, dng thm
phenylbutazon, phenylbutazon s y tolbutamid ra dng t do, gy h ng huyt t ngt.
C khi thuc y c cht ni sinh, gy tnh trng nhim c cht ni sinh: salicylat y bilirubin,
sulfamid h ng huyt y insulin ra khi v tr gn vi protein.
- Trong iu tr, lc u dng liu tn cng bo ha cc v tr gn, sau cho liu duy tr
n nh tc dng.
- Trong cc trng hp bnh l lm tng - gim lng protein huyt tng (nh suy dinh dng,
x gan, thn h, ngi gi...), cn hiu chnh liu thuc.
2.2.2. S phn phi li
Thng gp vi cc thuc tan nhiu trong m, c tc dng trn thn kinh trung ng v dng
thuc theo ng tnh mch. Th d in hnh ca hin tng ny l gy m bng thiopental, mt
thuc tan nhiu trong m. V no c ti mu nhiu, nng thuc t c ti a trong no
rt nhanh. Khi ngng tim, nng thiopental trong huyt tng gim nhanh v thuc khuch tn
vo cc m, c bit l m m. Nng thuc trong no gim theo n ng thuc trong huyt
tng. V vy khi m nhanh, nhng tc dng m khng lu. Khi cho cc liu thuc b xung
duy tr m, thuc tch ly nhiu m m. T y thuc li c gii phng li vo mu ti
no khi ngng cho thuc, lm cho tc dng c a thuc tr nn ko di.
2.2.3. Cc phn phi c bit
2.2.3.1. Vn chuyn thuc vo thn kinh trung ng
Phng thc vn chuyn: thuc phi vt qua 3 "hng ro"
- T mao mch no vo m thn kinh (hng ro mu - no): thuc tan nhiu trong lipid th d
thm, thuc tan trong nc rt kh vt qua v cc t bo thn kinh m (astrocyte - t bo hnh
sao) nm rt st nhau, ngay ti mng y, ngoi ni m mao mch.
- T m ri mng mch vo dch no tu (hng ro mu - mng no hoc mu- dch no tu):
nh hng ro trn; thuc cn tan mnh trong lipid.
- T dch no tu vo m thn kinh (hng ro dch no tu - no), thc hin bng khuch tn th
ng.
Cc yu t quyt nh tc vn chuyn thuc vo dch no tu v no th cng ging nh
nguyn tc thm qua mng sinh hc, l:
- Mc gn thuc vo protein huyt tng
- Mc ion ha ca phn thuc t do (ph thuc vo pH v pKa)
- H s phn b lipid/ nc ca phn thuc t do khng ion ha ( tan trong lipid)
Thuc ra khi dch no tu c thc hin m t phn bi c ch vn chuyn tch cc trong m
ri mng mch (mt h thng vn chuyn tch cc cho cc acid yu v mt h thng khc cho
cc base yu). T no, thuc ra theo c ch khuch tn th ng, ph thuc ch yu vo tan

trong lipid ca thuc.
Hng ro mu - no cn ph thuc vo la tui v vo trng thi bnh l: tr s sinh v tr nh,
lng myelin cn t, cu trc "hng ro" cn cha "cht ch" nn thuc d khuch tn c
vo no. Penicilin khng qua c mng no bnh thng, nhng kh i b vim, penicilin v nhiu
thuc khc c th qua c.
Hng ro mu no mang tnh cht mt hng ro lipid khng c ng dn, v vy, i vi nhng
cht tan mnh trong lipid, coi nh khng c hng ro. Mt s vng nh ca no nh cc nhn bn
ca vng di i, sn no tht 4, tuyn tng v thu sau tuyn yn cng khng c hng ro.
Kt qu ca s vn chuyn
- Cc thuc tan nhiu trong m s thm rt nhanh vo no, nhng li khng li c lu (xin
xem "s phn phi li").
Thuc b ion ha nhiu, kh tan trong m, kh thm vo thn kinh trung ng: atropin sulfat,
mang amin bc 3, t ion ha, vo c TKT; cn atropin methyl bromid, mang amin bc 4, ion
ha mnh, khng vo c TKT.
- C th thay i s phn phi thuc gia huyt tng v no bng thay i pH ca huyt tng:
trong iu tr ng c phenobarbital, truyn NaHCO 3 nng pH ca mu (7,6) vt ln trn pH
ca dch no ty (7,3), lm cho nng dng ion ha trong huyt tng ca phenobarbital tng
cao nng dng khng ion ha gim thp s ko dng khng ion ha ca thuc t dch no tu
vo mu.
2.2.3.2. Vn chuyn thuc qua rau thai
Phng thc
- Mao mch ca thai nhi nm trong nhung mao c nhng trong h mu ca m, v vy gia
mu m v thai nhi c "hng ro rau thai". Tnh thm ca m ng mao mch thai nhi tng theo tui
thai. S thm thuc cng theo quy lut chung:
- Cc thuc tan trong m s khuch tn th ng: thuc m hi, (protoxyd nit, halothan,
cyclopropan), thiopental.
- Vn chuyn tch cc: cc acid amin, cc ion Ca ++, Mg++.
- Thm bo (pinocytosis) vi cc git huyt tng ca m
Kt qu
- Tr cc thuc tan trong nc c trng lng phn t ln trn 1000 (nh dextran) v cc amin
bc 4 (galanin, neostigmin) khng qua c rau thai, rt nhiu thuc c th vo c mu thai
nhi, gy nguy him cho thai (phenobarbital, sulfamid, morphin), v vy, khng nn coi l c
"hng ro rau thai".
- Lng thuc gn vo protein - huyt tng mu m cao th nng thuc t do thp, ch c
thuc t do ny mi sang c mu con, ti y mt phn thuc ny li gn vo protein huyt
tng mu con, v vy nng thuc t do trong mu con cng thp. t c nng thuc
t do tng ng nh mu m, cn khong thi gian ti 40 pht. V d tim thiopental cho m
trong thi gian chuyn d, v sau 10 pht m c th nng thiopental trong mu con vn
cha t c mc m, iu gii thch v sao b m ng m li c th ra a con vn cn

thc.
- Ngoi ra, rau thai cn c nhiu enzym nh cholinesterase, monoamin oxydase, hydroxylase c
th chuyn ha thuc, lm gim tc dng bo v thai nhi.
2.2.4. S tch lu thuc
Mt s thuc hoc cht c c mi lin kt rt cht ch (thng l lin kt cng ha tr) vi mt
s m trong c th v c gi li rt lu, hng thng n hng chc n m sau dng thuc, c khi
ch l 1 ln: DDT gn vo m m, tetracyclin gn vo xng, mm rng, As gn vo t bo
sng...
Mt s thuc tch ly trong c vn v cc t bo ca m khc vi nng cao hn trong mu.
Nu s gn thuc l thun nghch th thuc s li c gii phng t "kho d tr" vo mu (xin
xem "s phn phi li"). Nng quinacrin trong t bo gan khi dng thuc di ngy c th cao
hn nng huyt tng vi trm ln do t bo gan c qu trnh vn chuyn tch cc ko
quinacrin vo trong t bo.
2.2.5. Thng s dc ng hc ca s phn phi: th tch phn phi (Vd)
2.2.5.1. nh ngha
Th tch phn phi biu th mt th tch biu kin (khng c thc) cha ton b lng thuc
c a vo c th c nng bng nng thuc trong huy t tng.
D
Vd = lit
Cp
D: liu lng thuc a vo c th (mg) theo ng tnh mch. Nu theo ng khc th phi tnh
n sinh kh dng : D F
Cp: nng thuc trong huyt tng o ngay sau khi phn phi v trc khi thi tr.
Vd: th tch khng c thc, tnh bng L (lt) hoc L/ kg.
Th d: mt ngi nng 60 kg, c lng nc trong c th l 36 L (60% trng lng c th),
ung 0,5 mg (500 g) digoxin c F theo ng ung l 0,7. o nng digoxin trong huyt
tng thy Cp= 0,7 ng/ mL (0,0007 mg/ mL).
Vy: 0,5 0,7
Vd = = 500L hoc 8,3 L/ kg
0,0007
Vd = 500L , ln bng gn 14 ln lng nc trong c th nn l th tch biu kin.
2.2.5.2. Nhn xt v ngha lm sng
- Vd nh nht l bng th t ch huyt tng (3L hoc 0,04L/ kg). Khng c gii hn trn cho Vd.
Vd cng ln chng t thuc cng gn nhiu vo m: iu tr nhim khun xng khp nn chn
khng sinh thch hp c Vd ln.
- Khi bit Vd ca thuc, c th tnh c liu cn dng t nn g huyt tng mong mun:
D = Vd Cp
2.3. S chuyn ha thuc
2.3.1. Mc ch ca chuyn ha thuc:

thi tr cht l (thuc) ra khi c th. Nhng nh ta bit, thuc l nhng phn t tan c
trong m, khng b ion ha, d thm qua mng t bo, gn vo prot ein huyt tng v gi li
trong c th. Mun thi tr, c th phi chuyn ha nhng thuc ny sao cho chng tr nn cc
phc hp c cc, d b ion ha, do tr nn t tan trong m, kh gn vo protein, kh thm vo
t bo, v v th, tan hn trong n c, d b thi tr (qua thn, qua phn). Nu khng c cc qu
trnh sinh chuyn ha, mt s thuc rt tan trong m (nh pentothal) c th b gi li trong c th
hn 100 nm !
2.3.2. Ni chuyn ha v cc enzym chnh xc tc cho chuyn ha:
- Nim mc rut: protease, lipase, decarboxylase
- Huyt thanh: esterase
- Phi: oxydase
- Vi khun rut: reductase, decarboxylase
- H thn kinh trung ng: monoaminoxydase, decarboxylase
- Gan: l ni chuyn ha chnh, cha hu ht cc enzym tham gia chuyn ha thuc, s trnh by
di y
2.3.3. Cc phn ng chuyn ha chnh
Mt cht A c a vo c th s i theo 1 hoc cc con ng sau:
- c hp thu v thi tr khng bin : bromid, lithi, saccharin.
- Chuyn ha thnh cht B (pha I), ri cht C (pha II) v thi tr
- Chuyn ha thnh cht D ( pha II) ri thi tr
Cht A c th c hoc khng c hot tnh, sinh ra cht B khng c hoc c hot tnh. Cht C v D
lun l cht khng c hot tnh sinh hc. Mt cht m A c th sinh ra nhiu cht chuyn ha
loi B hoc C.
Hp thu Sinh chuyn ha Thi tr
Pha I Pha II
A
B
A B Tan trong
Tan trong C C nc
m D D
Hnh 1.5. Cc phn ng chuyn ha thuc c ph n lm 2 pha

2.3.3.1. Cc phn ng pha I
Qua pha ny, thuc ang dng tan c trong m s tr nn c cc hn, d tan trong nc
hn. Nhng v mt tc dng sinh hc, thuc c th mt hot tnh, hoc ch gim hot tnh, hoc
i khi l tng hot tnh, tr nn c hot tnh.
Mt s th d:
Oxy kh
+ Prontosil Sulfanilamid
(khng hot tnh (c hot tnh)
"tin thuc")
oxy ha
+ Phenylbutazon oxyphenbutazon
(c hot tnh) (cn hot tnh)
thu phn
+ Acetylcholin Cholin + A.acetic
(c hot tnh) (mt hot tnh)
Cc phn ng chnh pha ny gm:

- Phn ng oxy ha: l phn ng rt thng gp, c xc tc bi cc enzym ca microsom gan,
c bit l hemoprotein, cytocrom P 450.
- Phn ng thu phn do cc enzym esterase, amidase, protease... Ngoi gan, huyt thanh v cc
m khc (phi, thn...) cng c cc enzym ny.
- Phn ng kh.
Phn ng oxy ha
y l phn ng ph bin nht, c xc tc bi cc enzym oxy ha (mixed - function oxydase
enzym system- mfO), thy c nhiu trong microsom gan, c bit l h enzym cytochrom P 450
(Cyt- P450), l cc protein mng c cha hem (hemoprotein) khu tr li ni bo nhn ca t
bo gan v vi m khc. Trong c th ngi hin thy c ti 17 typ v rt nhiu di typ
cytochrom P 450 tham gia chuyn ha cc cht ni sinh v ngoi sinh t mi trng, thuc. Phn
ng oxy ha loi ny i hi NADPH v O 2 theo phc sau:
C cht C cht (R- OH)

(RH) oxy ha
Cytochrom P 450
O2 H 2O
NADPH + H + NADP +
Phn ng c thc hin theo nhiu bc:

1) C cht (thuc , RH) phn ng vi dng oxy ha ca Cyt P 450 (Fe3+) to thnh phc hp RH -
P450 (Fe3+)
2) Phc hp RH- P450 (Fe3+) nhn 1 electron t NADPH, b kh thnh RH - P450 (Fe2+)
3) Sau , phc hp RH- P450 (Fe2+) phn ng vi 1 phn t oxy v 1 electron th 2 t NADPH
to thnh phc hp oxy hot ha.
4) Cui cng, 1 nguyn t oxy c gii phng, to H 2O. Cn nguyn t oxy th 2 s oxy ha
c cht (thuc): RH ROH, v Cyt.P 450 c ti to.
Qu trnh phn ng c tm tt s sau:
Hnh 1.6: S oxy ha thuc ca cytocrom P 450
Phn ng kh
Kh cc dn xut nitro, cc aldehyd, carbonyl bi cc enzym nitroreductase, azoreductase,
dehydrogenase... (bng 1.4)
Phn ng thu phn
Cc ng ni este v amid b thu phn bi cc enzym esterase, amidase c trong huyt tng,
gan, thnh rut v cc m khc (bng 1.4)
Bng 1.4: Cc phn ng chnh trong chuyn ha thuc pha I

Loi phn ng Phn ng Th d cc thuc
1. Phn ng oxy
ha
- N- mt alkyl Imipramin, diazepam,
RNHCH 3 R- NH2 + CH2O
morphin, codein,
- N- oxy ha Clorpheniramin,
R- NH2 R - NHOH dapson
OH Diazepam,
-Mt amin oxy ha
R- CHCH3 R- C- CH3 R- C- CH3 amphetamin
NH2 NH 2 O + NH 2 Tolbutamid,
ibuprofen,
Hydroxy ha mch cyclosporin,
thng R- CH2- CH3 R- CH2- CH3 midazolam
OH
2. Phn ng kh
Prontosil, tartrazin
- Azo- kh RN=NR1RNH- NHR1RNH2+R1NH2

Nitrobenzen,
chloramphenicol,
- Nitro- kh RNO2 RNO RNHOH R-NH2 clorazepam, dantrolen
Methadon, naloxon
- Carbonyl- kh R- CR' R- CHR'

O OH
3. Phn ng thy Procain,

phn succinylcholin,
aspirin, clofibrat
- Cc este
R1COOR 2 R1COOH + R 2OH
Procainamid,
lidocain,
indomethacin
RCONHR 1 RCOOH + R 1NH2
- Cc amid
2.3.3.2. Cc phn ng pha II
Cc cht i qua pha ny tr thnh cc phc hp khng cn hot tnh, tan d trong nc v b
thi tr. Tuy vy, pha ny, sulfanilamid b acetyl ha li tr nn kh tan trong nc, kt thnh
tinh th trong ng thn, gy i mu hoc v niu.
Cc phn ng pha II u l cc phn ng lin hp: mt phn t ni sinh (acid glucuronic,
glutathion, sulfat, glycin, acetyl) s ghp vi mt nhm ha hc ca thuc to thnh cc phc
hp tan mnh trong nc. Thng thng, cc phn ng pha I s to ra cc nhm chc phn cn
thit cho cc phn ng pha II, l cc nhm - OH, -COOH, -NH2, -SH...
Cc phn ng chnh: cc phn ng lin hp vi acid glucuronic, acid sulfuric, acid amin (ch yu
l glycin), phn ng acetyl ha, methyl ha. Cc phn ng ny i hi nng lng v c cht ni
sinh, l c im ca pha II.
Bng 1.5: Cc phn ng chnh tr ong chuyn ha thuc pha II
Loi phn C cht ni Enym chuyn (v Loi c cht Th d cc
ng sinh tr) thuc
- Glucuro- hp Acid UDP UDP glucuronosyl Phenol, alcol, Morphin,
glucuronic transferase acid diazepam,
(microsom) carboxylic, digitoxin,
sulfonamid acetaminophen,
sulfathiazol
Acid ethacrynic
GSH- S- bromobenzen
- Glutathion- Glutathion transferase (dch Epoxid, nhm
hp bo tng, nitro
microsom) hydroxylamin
Acid salicylic,
a.benzoic,
Glycin Acyl- CoA
a.nicotinic,
- Glycin- hp transferase (ty Dn xut acyl- a.cholic
th) CoA ca acid
carboxylic
Estron, anilin,
methyldopa, 3-
OH cumarin,
Phosphoaden Phenol, alcol, acetaminophen
osyl Sulfotransferase
- Sulfo- hp cc amin vng
phosphosulfat (dch bo tng)
thm
Dopamin,
adrenalin,
pyridin,
histamin
S- adenosyl Transmethylase
(dch bo tng)
-Methyl- ha methionin Catecholamin, Sulfonamid,
phenol amin, isoniazid,
histamin clonazepam,
dapson.
N-
Acetyl- CoA
acetyltrasferase Cc amin
- Acetyl- ha
(dch bo tng)
Ngoi ra, c mt s thuc hon ton khng b chuyn ha, l nhng hp cht c cc cao (nh
acid, base mnh), khng thm qua c lp m ca microsom. Phn ln c thi tr nhanh nh
hexamethonium, methotrexat.
Mt s hot cht khng c cc cng c th khng b chuyn ha: barbital, ether, halothan,
dieldrin.
Mt thuc c th b chuyn ha qua nhiu phn ng xy ra cng mt lc hoc tip ni nhau. Th
d paracetamol b glucuro - hp v sulfo- hp cng mt lc; chlorpromazin b chuyn ha nhn
phenothiazin qua nhiu phn ng, sau l nhnh bn cng qua mt lot phn ng cui
cng cho ti hn 30 cht chuyn ha khc nhau.
2.3.4. Cc yu t lm thay i tc chuyn ha thuc
2.3.4.1. Tui
- Tr s sinh thiu nhiu enzym chuyn ha thuc
- Ngi cao tui enzym cng b lo ho
2.3.4.2. Di truyn
- Do xut hin enzym khng in hnh khong 1: 3000 ngi c enzym cholinesterase khng
in hnh, thu phn rt chm suxamethonium nn lm ko di tc dng ca thuc n y.
- Isoniazid (INH) b mt tc dng do acetyl ha. Trong mt nghin cu, cho ung 10 mg/ kg
isoniazid, sau 6 gi thy lng isoniazid trong mu mt nhm l 3 - 6 g/ mL, nhm khc ch
l 2,5g/ mL. Nhm u l nhm acetyl ha chm, cn gim liu v d c vi TKT. V di
truyn, thuc nhm acetyl ha chm, thy 60% l ngi da trng, 40% l da en v 20% l da
vng. Nhm sau l nhm acetyl ha nhanh, cn phi tng liu, nhng sn phm chuyn ha
acetyl isoniazid li c vi gan.
- Ngi thiu glucose 6 phosphat dehydrogenase (G 6PD) s d b thiu mu tan mu khi dng
phenacetin, aspirin, quinacrin, vi loi sulfamid...
2.3.4.3. Yu t ngoi lai
- Cht gy cm ng enzym chuyn ha: c tc dng lm tng sinh cc enzym microsom gan,
lm tng hot tnh cc enzym ny.
Th d: phenobarbital, meprobamat, clorpromazin, phenylbutazon, v hng trm thuc khc: khi
dng nhng thuc ny vi cc thuc b chuyn ha qua cc enzym c cm ng s lm gim tc
dng ca thuc c phi hp, hoc ca chnh n (hin t ng quen thuc).
Tri li, vi nhng thuc phi qua chuyn ha mi tr thnh c hot tnh ("tin thuc"), khi dng
chung vi thuc gy cm ng s b tng c tnh (parathion paraoxon)
- Cht c ch enzym chuyn ha: mt s thuc khc nh cloramphenicol, d icumarol, isoniazid,
quinin, cimetidin... li c tc dng c ch, lm gim hot tnh chuyn ha thuc ca enzym, do
lm tng tc dng ca thuc phi hp.
2.3.4.4. Yu t bnh l
- Cc bnh lm tn thng chc phn gan s lm suy gim sinh chuyn ha thu c ca gan: vim
gan, gan nhim m, x gan, ung th gan... d lm tng tc dng hoc c tnh ca thuc chuyn
ha qua gan nh tolbutamid, diazepam.
- Cc bnh lm gim lu lng mu ti gan nh suy tim, hoc dng thuc chn giao cm ko
di s lm gim h s chit xut ca gan, lm ko di t/2 ca cc thuc c h s chit xut cao ti
gan nh lidocain, propranolol, verapamil, isoniazid.
2.4. Thi tr
Thuc c thi tr di dng nguyn cht hoc b chuyn ha
2.4.1. Thi tr qua thn
y l ng thi tr quan trng nht ca cc thuc tan trong nc, c trng lng phn t nh
hn 300.
2.4.1.1. Qu trnh thi tr
- Lc th ng qua cu thn: dng thuc t do, khng gn vo protein huyt tng.
- Bi tit tch cc qua ng thn: do phi c cht vn chuy n (carrier) nn ti y c s cnh tranh
thi tr. Th d dng thiazid ko di, do phi thi tr thiazid, c th gim thi acid uric, d gy
bnh gut (thiazid v a.uric c cng carrier ng thn).
Qu trnh bi tit tch cc xy ra ch yu ng ln gn, c 2 h vn chuyn khc nhau, mt h
cho cc anion (cc acid carboxylic nh penicilin, thiazid, cc cht glucuro - v sulfo- hp), v mt
h cho cc cation (cc base hu c nh morphin, thiamin).
- Khuch tn th ng qua ng thn: mt phn thuc th i tr trong nc tiu ban u li c
ti hp thu vo mu. l cc thuc tan trong lipid, khng b ion ha pH nc tiu (pH = 5 -6)
nh phenobarbital, salicylat. Cc base yu khng c ti hp thu.
Qu trnh ny xy ra ng ln gn v c ng ln xa do bc thang nng c to ra trong
qu trnh ti hp thu nc cng Na + v cc ion v c khc. Qu trnh ti hp thu th ng y
ph thuc nhiu vo pH nc tiu. Khi base ha nc tiu, th cc acid yu (acid barbituric) s b
thi tr nhanh hn v b ion ha nhiu nn ti hp thu gim. Ngc li, khi acid ha nc tiu
nhiu hn th cc base (amphetamin) s b thi tr nhiu hn. iu ny c ng dng trong iu
tr nhim c thuc.
2.4.1.2. ngha lm sng

- Lm gim thi tr tit kim thu c: penicilin v probenecid c chung h vn chuyn ti ng
thn. Thn thi probenecid (r tin, t tc dng iu tr) v gi li penicilin (t tin hn, c tc
dng iu tr).
- Lm tng thi tr iu tr nhim c: base ha nc tiu, lm tng ion ha ca
phenobarbital, tng thi tr khi b nhim c phenobarbital (xin xem"khuch tn th ng").
- Trong trng hp suy thn, cn gim liu thuc dng
2.4.2. Thi tr qua mt
- Sau khi chuyn ha gan, cc cht chuyn ha s thi tr qua mt theo p hn ra ngoi. Phn
ln sau khi b chuyn ha thm rut s c ti hp thu vo mu thi tr qua thn.
- Mt s hp cht chuyn ha glycuronid ca thuc c trng lng phn t trn 300 sau khi thi
tr qua mt xung rut c th b thu phn bi glycuronidase ri li c ti hp thu v gan
theo ng tnh mch gnh li vo vng tun hon, c gi l thuc c chu k rut - gan.
Nhng thuc ny tch lu trong c th, lm ko di tc dng (morphin, tetracyclin, digitalis tr
tim...).
2.4.3. Thi tr qua phi
- Cc cht bay hi nh ru, tinh du (eucalyptol, menthol)
- Cc cht kh: protoxyd nit, halothan
2.4.4. Thi tr qua sa
Cc cht tan mnh trong lipid (barbiturat, chng vim phi steroid, tetracyclin, cc alcaloid), c
trng lng phn t di 2 00 thng d dng thi tr qua sa.
V sa c pH hi acid hn huyt tng nn cc thuc l base yu c th c nng trong sa hi
cao hn huyt tng v cc thuc l acid yu th c nng thp hn.
2.4.5. Thi tr qua cc ng khc
Thuc c th cn c thi tr qua m hi, qua nc mt, qua t bo sng (lng, tc, mng),
tuyn nc bt. S lng khng ng k nn t c ngha v mt iu tr. Thng c th gy tc
dng khng mong mun (diphenyl hydantoin gy tng sn li khi b bi tit qua nc bt) . Hoc
dng pht hin cht c (c gi tr v mt php y): pht hin asen trong tc ca Napoleon sau 150
nm!
2.4.6. Thng s dc ng hc ca chuyn ha v thi tr thuc
Mc ch ca chuyn ha l lm cho thuc mt hot tnh, d tan trong nc v thi tr. V vy,
qu trnh chuyn ha chnh l qu trnh thi tr thuc. C 2 thng s dc ng hc l thanh
thi (CL) v thi gian bn thi (t 1/2) u nh gi qu trnh chuyn ha v thi tr thuc.
2.4.6.1. thanh thi (clearance CL)
nh ngha
thanh thi (CL) biu th kh nng ca 1 c quan (gan, thn) trong c th thi tr hon ton
mt thuc (hay mt cht) ra khi huyt tng khi mu tun hon qua c quan .
Clearance c biu th bng mL/ pht, l s mL huyt tng c thi tr thuc ho n ton trong
thi gian 1 pht khi qua c quan. Hoc c khi tnh theo kg thn trng: mL/ pht/ kg.
V
CL = (mL/ pht)
Cp
V: tc thi tr ca thuc qua c quan (mg/ pht)
Cp: nng thuc trong huyt tng (mg/ L)
Clearance cng l mt tr s o, mang tnh l thuyt v s tun hon ca mu qua c quan c
lin tc lp i lp li. Trong thc t, thuc c coi l lc sch khi huyt tng sau mt khong
thi gian l 7 t1/2.
Hai c quan chnh thamgia thi tr thuc khi c th l gan (lng thuc b chuyn ha v thi
tr nguyn cht qua mt) v thn, v vy, CL ton b c coi l CL gan + CL thn.
ngha
- Thuc c CL ln l thuc c thi tr nhanh, v th thi gian bn thi (t 1/2 ) s ngn.
- Dng CL tnh liu lng thuc c th duy t r c nng thuc n nh trong huyt tng.
Nng ny t c khi tc thi tr bng tc hp thu.
- Bit CL hiu chnh liu trong trng hp bnh l suy gan, suy thn.
2.4.6.2. Thi gian bn thi (half - life- t1/2)
nh ngha
Thi gian bn thi t1/2 c phn bit lm 2 loi :
- t1/2 hay t1/2 hp thu l thi gian cn thit 1/2 lng thuc dng hp thu c vo tun
hon. nu dng thuc theo ng tim bp th t 1/2 khng ng k.
- t1/2 hay t1/2 thi tr l thi gian cn thit nng thuc trong huyt tng gim cn 1/2.
Trong thc hnh iu tr, hay dng t 1/2 v thng ch vit l t 1/2 hoc t/2.
ngha
- T cng thc trn ta thy t 1/2 t l nghch vi clearance. Khi CL thay i theo nguyn nhn sinh
l hoc bnh l s lm t 1/2thay i, hiu qu ca iu tr b nh hng. Cn phi hiu chnh liu
lng hoc khong cch gia cc liu (xem phn Nhng bin i ca dc ng hc).
- Trong thc hnh iu tr, thng coi thi gian 5 l n t1/2 (5 ln dng thuc cch u) th nng
thuc trong mu t c trng thi n nh (Css), v sau khi ngng thuc khong 7 ln t 1/2 th
coi nh thuc b thi tr hon ton khi c th (xem bng).
Lng thuc c thi tr theo t/2
S ln t 1/2 Lng thuc c thi tr (%)

1 50
2 75
3 88
4 94
5 97
6 98
7 99
- i vi mi thuc, thi gian bn thi l ging nhau cho mi liu dng. Do c th suy ra
khong cch dng thuc:
. Khi t1/2 < 6h: nu thuc t c, cho liu cao ko di c nng hiu dng ca thuc trong
huyt tng. Nu khng th cho c liu cao (nh heparin, insulin) th truyn tnh mch lin tc
hoc sn xut dng thuc gii phng chm.
. Khi t1/2 t 6 n 24h: dng liu thuc vi khong cch ng bng t 1/2.
. Khi t1/2 > 24h: dng liu duy nht 1 ln mi ngy.
cu hi t lng gi
1. S hp thu thuc ph thuc vo nhng yu t no?
2. Phn tch, so snh cc c im ca cc ng hp thu thuc: ng tiu ha, ng
tim, ng h hp v ng qua da, nim mc.
3. Trnh by v s vn chuyn thuc vo thn kinh trung ng v qua rau thai. ngha lm
sng.
4. Sinh kh dng ca thuc l g? ngha.
5. Trnh by v th tch phn phi (Vd) v ngha lm sng?
6. S gn thuc vo protein huyt tng v ngha?
7. K tn cc phn ng chnh (khng vit cng thc) ca chuyn ha thuc pha I, kt qu
v ngha?
8. K tn cc phn ng chnh (khng vit cng t hc) ca chuyn ha thuc pha II, kt qu
v ngha?
9. Trnh by cc cch thi tr thuc qua thn, qua gan, qua sa v ngha lm sng.
10. thanh thi l g? ngha?
11. Thi gian bn thi l g? ngha?
Bi 2: i cng v Dc lc hc

1. Trnh by c c ch tc dng ca thuc qua receptor v khng qua receptor.
2. Phn bit c cc cch tc dng ca thuc.
3. Trnh by c nhng yu t thuc v bn thn thuc quyt nh tc dng ca thuc (l
ha, cu trc, dng bo ch).
4. Nu c nhng yu t chnh v pha ngi bnh c nh hng n tc d ng ca thuc
(tui, quen thuc).
5. Trnh by c 5 trng thi tc dng c bit ca thuc.
Dc lc hc nghin cu tc dng ca thuc ln c th sng, gii thch c ch ca cc tc dng

sinh ha v sinh l ca thuc. Phn tch cng y c cc tc dng, cng cung cp c
nhng c s cho vic dng thuc hp l trong iu tr. y l nhim v c bn nht v cng l
kh khn ln nht ca dc lc hc.
1. C ch tc dng ca thuc
1.1. Receptor
- Tc dng ca phn ln cc thuc l kt qu ca s tng tc gia thuc vi receptor (th th
cm). Receptor l mt thnh phn i phn t (macromolcular) tn ti vi mt l ng gii hn
trong mt s t bo ch, c th nhn bit mt cch c hiu ch mt phn t "thng tin" t nhin
(hormon, cht dn truyn thn kinh), hoc mt tc nhn ngoi lai (cht ha hc, thuc) gy
ra mt tc dng sinh hc c hiu, l kt qu ca tc dng tng h .
Thnh phn i phn t ca receptor thng l protein v ch c protein mi c cu trc phc tp
nhn bit c hiu ca mt phn t c cu trc 3 chiu.
Receptor c 2 chc phn:
1) Nhn bit cc phn t thng tin (hay cn gi l ligand) bng s gn c hiu cc phn t ny
vo receptor theo cc lin kt ha hc:
- Lin kt ion: cc cht ha hc mang in tch (nh nhm amoni bc 4 cu acetylcholin c in
tch dng), s gn vo vng mang in tch tri du ca receptor theo lin kt ny, vi lc lin
kt khong 5- 10 kcal/ mol.
- Lin kt hydro: do s phn b khng ng u electron trong phn t nn c mi lin kt gia
nguyn t hydro vi cc nguyn t c in tch m cao nh oxy, nit v fluor. Lc lin kt
khong 2- 5 kcal/ mol
- Lin kt Van- der- Waals: l lc lin kt ca mi tng h gia cc electron vi cc nhn ca
cc phn t st bn. Lc lin kt ph thuc vo khong cch gia cc phn t, lc ny tng i
yu, khong 0,5 kcal/ mol. Cc thuc c vng benzen, c mt electron phn b ng u
thng c mi lin kt ny.
Cc lc lin kt trn u l thun nghch.

- Lin kt cng ha tr: l lc lin kt gia cc nguyn t bng nhng cp in t chung. V l lc
lin kt ln 50- 150 kcal/ mol nn l lin kt khng thun nghch nhit c th, khng c cht
xc tc. Loi lin kt ny t gp. Th d lin kt gia cht alkyl ha vi t bo ung th, cc thuc
c ch enzym monoamin oxydase (MAOI), thuc tr su ln hu c vi cholinesterase.
Mt phn t thuc c th gn vo receptor theo nhiu kiu lin kt. Th d: acetylcholin gn vo
receptor M- cholinergic:
Hnh 2.1. Phc hp acetylcholin - receptor M

Acetylcholin gn vo receptor M theo ng ni sau:
- Hai O ca chc ester to lin kt hydro vi receptor
- Nhm CH 2- CH2 gn vi receptor bng lin kt phn t (lc Van - der- Waals)
- Hai gc CH 3 ca amin bc 4 gn vo cc khoang ca v tr anion cng bng lc
Van- der- Waals
2) Chuyn tc dng tng h gia ligand v receptor thnh mt tn hiu gy ra c p ng

t bo. Cc receptor nm nhn t bo c hot ha bi cc ligand gn trn cc v tr c hiu
ca ADN nm trong cc vng iu ha gen, gy ra s sao chp cc gen c hiu (receptor ca
hormon steroid, vitamin D 3...). Cc receptor nm mng t bo v xa nhn nn khng tham gia
trc tip vo cc chng trnh biu hin ca gen. Khi cc ligand tc ng ln receptor s lm sn
xut ra cc phn t trung gian - "ngi truyn tin th 2" (AMPv, GMPv, IP 3, Ca2+, diacetyl
glycerol...)- Nhng cht ny s gy ra mt lot phn ng trong t bo, dn ti mt thay i
chuyn ha trong t bo, cng vi hoc khng c s thay i v biu hin gen (receptor ca
adrenalin, ca benzodiazepin...).
Nh vy, khi thuc gn vo receptor ca t bo th gy ra c tc dng sinh l. Nhng c khi
thuc gn vo t bo m khng gy ra tc dng g, ni gn thuc c gi l ni tip nhn
(acceptor) hoc receptor cm, (silent receptor) nh thuc m gn vo t bo m, digitalis gn vo
gan, phi, thn...
Thuc gn vo receptor ph thuc vo i lc (affinity) ca thuc vi receptor. Hai thuc c cng
receptor, thuc no c i lc cao hn s y c thuc khc ra. Cn tc dng ca thuc l do
hiu lc (efficacy) ca thuc trn receptor . i lc v hiu lc khng phi lc no cng i cng
nhau: acetylcholin l cht dn truyn thn kinh ca h ph giao cm, khi gn vo receptor M, gy
hiu lc lm tng tit nc bt, co ng t, chm nhp tim...; atropin c i lc trn receptor M
mnh hn acetylcholin rt nhiu nn y c acetylcholin ra kh i receptor M, nhng bn thn
n li khng c hiu lc g. lm sng, tc dng ca atropin quan st c chnh l tc dng ca
s thiu vng acetylcholin trn receptor M: kh ming (gim tit nc bt), gin ng t, nhp
tim nhanh...
1.2. Cc c ch tc dng ca thuc
1.2.1. Tc dng ca thuc thng qua receptor
Thuc tc dng trc tip trn cc receptor ca cc cht ni sinh (hormon, cht dn truyn thn
kinh): nhiu thuc tc dng trn cc receptor sinh l v thng mang tnh c hiu. Nu tc dng
ca thuc ln receptor ging vi cht ni sinh, gi l cht ng vn hay cht ch vn (agonists),
nh pilocarpin trn receptor M - cholinergic. Nu thuc gn vo receptor, khng gy tc dng
ging cht ni sinh, tri li, ngn cn cht ni sinh gn vo receptor, gy tc dn g c ch cht
ng vn, c gi l cht i khng (antagonists), nh d- tubocurarin tranh chp vi
acetylcholin ti receptor N ca c vn.
- Mt s thuc thng qua vic gii phng cc cht ni sinh trong c th gy tc dng:
amphetamin gii phng adren alin trn thn kinh trung ng, nitrit lm gii phng NO gy gin
mch...
Xt trn nhiu mt, protein l mt nhm quan trng ca receptor - thuc. Do , ngoi receptor t
bo, cc receptor ca thuc cn l:
- Cc enzym chuyn ha hoc iu ha cc qu trn h sinh ha c th b thuc c ch hoc hot
ha:
. Thuc c ch enzym: captopril c ch enzym chuyn angiotensin I khng hot tnh thnh
angiotensin II c hot tnh dng cha cao huyt p; cc thuc chng vim phi steroid c ch
cyclooxygenase, lm gim t ng hp prostaglandin nn c tc dng h st, chng vim; thuc tr
tim digitalis c ch Na +- K+ ATPase...
. Thuc hot ha enzym: cc yu t vi lng nh Mg 2+, Cu2+, Zn2+ hot ha nhiu enzym protein
kinase, phosphokinase tc dng ln nhiu qu trnh chuy n ha ca t bo.
- Cc ion: thuc gn vo cc knh ion, lm thay i s vn chuyn ion qua mng t bo.
Novocain cn tr Na + nhp vo t bo thn kinh, ngn cn kh cc nn c tc dng gy t;
benzodiazepin lm tng nhp Cl - vo t bo, gy an thn.
1.2.2. Tc dng ca thuc khng qua receptor
Mt s thuc c tc dng khng phi do kt hp vi receptor.
- Thuc c tc dng do tnh cht l ha, khng c hiu:
Cc mui cha cc ion kh hp thu qua mng sinh hc nh MgSO 4, khi ung s "gi nc"
thnh rut vo lng rut v gi nc trong lng rut nn c tc dng ty; khi tim vo tnh mch
s ko nc t gian bo vo mu nn c dng cha ph no.
Isosorbid, mannitol dng liu tng i cao, lm tng p lc thm thu trong huyt tng. Khi
lc qua cu thn, khng b ti hp thu ng thn, lm tng p lc thm thu trong ng thn, c
tc dng li niu.
Nhng cht to chelat hay cn gi l cht "cng cua" do c cc nhm c cc nh -OH, -SH, -
NH2, d to phc vi cc ion ha tr 2, y chng ra khi c th. Cc c ht "cng cua" nh EDTA
(ethyl diamin tetra acetic acid), BAL (British anti lewisit - dimercaprol), d- penicilamin thng
c dng cha ng c kim loi nng nh Cu 2+, Pb2+, Hg2+ hoc thi tr Ca 2+ trong ng c
digital.
Than hot hp ph c cc hi, cc c t nn dng cha y hi, ng c.
Cc base yu lm trung ha dch v acid dng cha lot d dy (khng acid), nh hydroxyd
nhm, magnesi oxyd.
- Thuc c cu trc tng t nh nhng cht sinh ha bnh thng, c th thm nhp vo cc
thnh phn cu trc ca t bo, lm thay i chc phn ca t bo. Thuc ging purin, ging
pyrimidin, nhp vo acid nucleic, dng chng ung th, chng virus. Sulfamid gn ging
paraamino benzoic acid (PABA), lm vi khun dng "nhm", khng pht trin c.
2. Cc cch tc dng ca thuc
Khi vo c th, thuc c th c 4 cch tc dng sau:
2.1. Tc dng ti ch v ton thn:
- Tc dng ti ch l tc dng ngay ti ni thuc tip xc, khi thuc cha c hp thu vo mu:
thuc st khun ngoi da, thuc lm sn nim mc (tani n), thuc bc nim mc ng tiu ha
(kaolin, hydroxyd nhm).
- Tc dng ton thn l tc dng xy ra sau khi thuc c hp thu vo mu qua ng h
hp, ng tiu ha hay ng tim: thuc m, thuc tr tim, thuc li niu. Nh vy, tc dng
ton thn khng c ngha l thuc tc dng khp c th m ch l thuc vo mu "i" khp
c th.
Tc dng ti ch hoc ton thn c th gy hiu qu trc tip hoc gin tip: tim d-
tubocurarin vo tnh mch, thuc trc tip tc dng ln bn vn ng lm lit c vn v gin tip
lm ngng th do c honh v c lin sn b lit ch khng phi thuc c ch trung tm h hp.
Mt khc, tc dng gin tip cn c th thng qua phn x: khi ngt, ngi ammoniac, cc ngn
dy thn kinh trong nim mc ng h hp b kch thch, gy phn x kch thch trung tm h
hp v vn mch hnh ty, lm ngi bnh hi tnh.
2.2. Tc dng chnh v tc dng ph
- Tc dng chnh l tc dng iu tr
- Ngoi tc dng iu tr, thuc c th cn gy nhiu tc dng khc, khng c ngha trong iu
tr, c gi l tc dng khng mong mun, tc dng dng ngoi (adverse drug reactions -
ADR). Cc tc dng ngoi c th ch gy kh chu cho ngi dng (chng mt, bun nn, mt
ng), gi l tc dng ph; nhng cng c th gy ph n ng c hi (ngay vi liu iu tr) nh
xut huyt tiu ha, gim bch cu, tt huyt p th ng...
Th d: aspirin l thuc h st, gim au, chng vim (tc dng chnh), nhng gy chy mu tiu
ha (tc dng c hi). Nifedipin, thuc chn knh calci dng iu tr tng huyt p (tc dng
chnh), nhng c th gy nhc u, nhp tim nhanh (tc dng ph), ho, ph chn, tng enzym
gan, tt huyt p (tc dng c hi).
Trong iu tr, thng phi hp thuc lm tng tc dng chnh v gim tc dng khng mong
mun. Th d ung thuc chn giao cm cng vi nifedipin s lm gim c tc dng lm
tng nhp tim, nhc u ca nifedipin. Cng c th thay i ng dng thuc nh dng thuc
t hu mn trnh tc dng kh ung, gy bun nn.
2.3. Tc dng hi phc v khng hi phc
- Tc dng hi phc: sau tc dng, thuc b thi tr, chc phn ca c quan li tr v bnh
thng. Sau gy m phu thut, ngi bnh li c trng thi bnh thng, tnh to.
- Tc dng khng hi phc: thuc lm mt hon ton chc ph n ca t bo, c quan. Th d:
thuc chng ung th dit t bo ung th, bo v t bo lnh; thuc st khun bi ngoi da dit vi
khun nhng khng nh hng n da; khng sinh cloramphenicol c tai bin gy suy ty xng.
2.4. Tc dng chn lc
Tc dng chn lc l tc dng iu tr xy ra sm nht, r rt nht. Th d aspirin ung liu 1 - 2
g/ ngy c tc dng h st v gim au, ung liu 4 - 6 g/ ngy c c tc dng chng vim;
digitalis gn vo tim, no, gan, thn... nhng vi liu iu tr, ch c tc dng trn tim; albuterol
(Salbutamol- Ventolin) kch thch chn lc receptor 2 adrenergic...
Thuc c tc dng chn lc lm cho vic iu tr tr nn d dng hn, hiu qu hn, trnh c
nhiu tc dng khng mong mun.
3. Nhng yu t nh hung n tc dng ca thuc:
3.1. V thuc
3.1.1. Thay i cu trc lm thay i dc lc hc ca thuc.
Nh ta bit, thuc mun c tc dng, phi gn c vo receptor (i lc vi receptor) v sau
l hot ha c receptor (c hiu lc hay tc dng dc l). Receptor mang tnh c hiu
cho nn thuc cng phi c cu trc c hiu. Receptor c v nh kha v thuc l cha kha.
Mt s thay i nh v cu trc ha hc (hnh dng phn t ca thuc) cng c th gy ra nhng
thay i ln v tc dng.
Nh vy vic tng hp cc thuc mi thng nhm:
- Lm tng tc dng iu tr v gim tc dng khng mong mun. Khi thm F vo v tr 9 v CH 3
vo v tr 16 ca corticoid (hormon v thng thn), ta c betametason c tc dng chng vim
gp 25 ln v khng c tc dng gi Na + nh corticoid, trnh phi n nht.
- Lm thay i tc dng dc l: thay i cu trc ca isoniazid (thuc chng lao), ta c
iproniazid, c tc dng chng trm cm, do gn vo receptor hon ton khc.
Sulfanilamid PABA (para amino benzoic acid)

Khng histamin H1 c cng thc gn ging vi histamin, tranh chp vi histamin ti receptor H 1.
- Cc ng phn quang hc hoc ng phn hnh hc ca thuc cng lm thay i cng tc
dng, hoc lm thay i hon ton tc dng ca thuc.
l. isoprenalin c tc dng kch thch receptor adrenergic 500 ln mnh hn d. isoprenalin.
l. quinin l thuc cha st rt, d. quinin (quinidin) l thuc cha lon nhp tim.
- Cng ngy ngi ta cng hiu r c siu cu trc ca receptor v sn xut cc thuc rt c
hiu, gn c vo di typ ca receptor: receptor adrenergic 1, 2, 1, 2, 3, receptor
cholinergic M 1, M2, M3, receptor dopaminergic D 1, D2, ... D7.
3.1.2. Thay i cu trc thuc, lm thay i dc ng hc ca thuc
Khi cu trc ca thuc thay i, lm tnh cht l ha ca thuc thay i, nh hng n s ha
tan ca thuc trong nc hoc trong lipid, nh hng n s gn thuc vo protein, ion ha
ca thuc v tnh vng bn ca thuc. Mt s v d:
- Dopamin khng qua c hng ro mu no, nhng l. dopamin (Levo dopa), cht tin thn ca
dopamin th qua c.
- Estradiol thin nhin khng ung c v b chuyn ha mnh gan. dn xut ethinyl estradiol
(-C CH gn v tr 17) rt t b chuyn ha nn ung c.
- Tolbutamid b microsom gan oxy ha gc CH 3 v tr para, c t/2 huyt tng l 4 - 8 h. Thay
gc CH3 bng Cl (Clorpropamid) s rt kh b chuyn ha, lm t/2 ca thuc ko di ti 35 h.
- Cc thiobarbituric t b phn ly hn barbituric pH ca ng thn nn b thi tr chm hn.
Qua y ta c th nhn th y rng, khi thuc gn vo receptor gy hiu lc, khng phi ton b
phn t thuc m ch c nhng nhm chc phn gn vo receptor. Khi thay i cu trc ca
nhm hoc vng chc phn, dc lc hc ca thuc s thay i. Cn khi thay i cu trc
ngoi vng chc phn, c th thay i dc ng hc ca thuc.
3.2. Dng thuc
Dng thuc l hnh thc trnh by c bit ca dc cht a dc cht vo c th. Dng thuc
phi c bo ch sao cho tin bo qun, vn chuyn, s dng v pht huy ti a hiu lc cha
bnh ca thuc.
C th tm tt qu trnh hnh thnh v pht huy tc dng ca mt dng thuc trong c th nh
sau:
Dc cht
K thut bo ch ng dng thuc
Dng thuc
T dc
Dng thuc Gii phng dc Dc cht ti ni Hiu qu

trong c th vo mu iu tr
cht v hp thu (sinh kh dng) tc dng
Qua s , ta thy t 1 dc cht, cc nh bo ch c th a ra th trng nhiu loi bit dc
(dng thuc) khc nhau, c sinh kh dng khc nhau do c nh hng khc nhau ti hiu qu
iu tr.
3.2.1. Trng thi ca dc cht
- tn nh: thuc cng mn, din tip xc cng tng, hp thu thuc cng nhanh.
- Dng v nh hnh v dng tinh th: thuc rn dng v nh hnh d tan, d hp thu.
3.2.2. T dc
T dc khng phi ch l "cht n" bao gi thuc m cn nh hng n ha tan, khuch
tn...ca thuc. Khi thay calci sulfat (thch cao, t dc c in) bng lactose dp vin
diphenylhydantoin, gy hng lot ng c diphenylhydantoin do lng thuc c hp thu
nhiu hn (c, 1968). Nguyn nhn l t dc calci sulfat ch ng vai tr mt khung mang,
khng tiu v xp, lm dc cht c gii phng t t trong ng tiu ha. Cn lactose li lm
dc cht d tan, nn c hp thu nhanh trong thi gian ngn.
3.2.3. K thut bo ch v dng thuc
K thut bo ch l mt yu t khng km phn quan trng c tc ng trc tip n sinh kh
dng ca thuc, c th kim sot c s gii phng dc cht v v tr thuc gii phng ( gii
phng ti ch). V vy n thng c cc nh sn xut gi b mt.
Hin c rt nhiu dng thuc khc nhau c sn xut theo cc k thut khc nhau sao cho:
- Hot tnh ca thuc c vng bn
- Dc cht c gii phng vi tc n nh
- Dc cht c gii phng ti ni cn tc ng (gii phng ti ch, targetting medication)
- Thuc c sinh kh dng cao.

3.3. V ngi dng thuc
3.3.1. c im v tui (xin xem phn "dc ng hc")
3.3.1.1. Tr em:
"Tr em khng phi l ngi ln thu nh li", ngha l khng phi ch gim liu thuc ca ngi
ln th thnh liu ca tr em, m tr em cn c nhng c im ring ca s pht trin, l:
- S gn thuc vo protein huyt tng cn t, mt khc, mt phn protein huyt tng cn gn
bilirubin, d b thuc y ra, gy ng c bilirubin.
- H enzym chuyn ha thuc cha pht trin
- H thi tr thuc cha pht trin
- H thn kinh cha pht trin, myelin cn t, hng ro mu - no cha bo v nn thuc d
thm qua v t bo thn kinh cn d nhy cm (nh vi morphin)
- T bo cha nhiu nc, khng chu c thuc gy mt nc.
- Mi m v c quan ang pht trin, ht sc thn trng khi dng cc loi hormon.
Mt s tc gi a ra cc cng thc tnh liu lng cho tr em:
1. Cng thc ca Young: dng cho tr t 2- 12 tui
Tui TE
Liu ngi ln
Tui TE + 12
2. Cng thc ca Cowling: Dng cho tr em t 2 - 12 tui
Tui TE + 1
Liu ngi ln
24
Th d: liu cho ngi ln l 2,0. Liu cho tr 4 tui l

4+1
2,0 g = 0,41 g
24
3. Cng thc ca Fried: dng cho nh nhi
Tui TE (thng)
Liu ngi ln
150 (Trng lng trung bnh ca ngi ln)
4. Cng thc ca Clark

Trng lng TE (pounds)
Liu ngi ln
150
Tuy nhin tnh liu theo din tch c th th tt hn. Khi dng cng thc:
BSA (m 2) ca tr em
Liu ngi ln
1.7
BSA: Body Surface Area -Din tch c th (tra monogram)

1.7: BSA trung bnh ca ngi ln
3.3.1.2. Ngi cao tui
Ngi cao tui cng c nhng c im ring cn lu :
- Cc h enzym u km hot ng v "lo ha"
- Cc t bo t gi nc nn cng khng chu c thuc gy mt n c
- Ngi cao tui thng mc nhiu bnh (cao huyt p, x va mch, thp khp, tiu ng...)
nn phi dng nhiu thuc mt lc. Cn rt ch tng tc thuc khi k n (xin xem phn
"tng tc thuc")
3.3.2. c im v gii
Nhn chung, khng c s kh c bit v tc dng v liu lng ca thuc gia nam v n. Tuy
nhin, vi n gii, cn ch n 3 thi k:
3.3.2.1. Thi k c kinh nguyt
Khng cm hn thuc. Nu phi dng thuc di ngy, c tng t ngng thuc th nn sp xp
vo lc c kinh.
3.3.2.2. Thi k c thai
Trong 3 thng u, thuc d gy d tt bm sinh, to ra qui thai. Trong 3 thng gia thuc c th
nh hng xu n s pht trin ca bo thai, n chc phn pht trin ca cc c quan. Trong 3
thng cui, thuc c th gy xy thai, n on.
V vy, khi cn ch nh thuc cho ph n c thai, cn cn nhc tht k gia li ch cho ngi m
v mc nguy hi cho bo thai. Ni chung, trong 3 thng u, tuyt i trnh dng mi loi thuc.
i vi ngi m, khi c thai, lng nc gi li trong c th tng, th tch mu tng, hm lng
protein huyt tng c th gim, lng lipid c th tng... lm nh hng n ng hc ca
thuc.
3.3.2.3. Thi k cho con b
Rt nhiu thuc khi dng cho ngi m s thi tr qua sa v nh vy c th gy c hi c ho con.

Cc nghin cu v cc loi thuc ny ni chung cn cha c y , do tt nht l ch nn
dng nhng loi thuc tht cn thit cho m. Tuyt i khng dng nhng thuc c cha thuc
phin v dn xut ca thuc phin (thuc ho, codein, vin ra ) v thuc thi tr qua sa v trung
tm h hp ca tr rt nhy cm, c th b ngng th. Khng dng cc loi corticoid (lm suy
thng thn tr), cc khng gip trng tng hp v iod (gy ri lon tuyn gip), cloramphenicol
v thuc phi hp sulfametoxa zol + trimethoprim (Co- trimoxazol) v c th gy suy tu xng.
Cn rt thn trng khi dng cc thuc c ch thn kinh trung ng (meprobamat, diazepam),
thuc chng ng kinh, u gy m mng v li b cho tr.
4. Nhng trng thi tc dng c bit ca th uc
Trong qu trnh s dng thuc, ngoi tc dng iu tr, i khi cn gp nhng tc dng "khng
mong mun" do s phn ng khc nhau ca tng c th vi thuc.
4.1. Phn ng c hi ca thuc (Adverse drug reactions - ADR)
"Mt phn ng c hi ca thuc l mt p hn ng c hi, khng nh c trc v xut hin
liu lng thng dng cho ngi " (nh ngha ca Chng trnh gim st thuc quc t - WHO).
ADR l tn gi chung cho mi triu chng bt thng xy ra khi dng thuc ng liu. C th
ch l nhng triu chng rt nh nh nhc u, bun nn... cho n nhng triu chng rt nng
dn n t vong nh sc, phn v, suy tu xng. Tu theo nc v tu theo tc gi, ADR c th
xy ra khong 8- 30% s ngi dng thuc.
4.2. Phn ng d ng
D ng thuc cng l 1 AD R.
Do thuc l 1 protein l (insulin, thyroxin ly t sc vt), l a peptid, polysaccharid c phn t
lng cao, mang tnh khng nguyn. Tuy nhin, nhng thuc c phn t lng thp hoc chnh
sn phm chuyn ha ca n cng c th gy d ng, chng c gi l bn khng nguyn hay
"hapten". Vo c th, hapten c kh nng gn vi mt protein ni sinh theo ng ni cng ha
tr v to thnh phc hp khng nguyn.
Nhng thuc c mang nhm NH 2 v tr para, nh benzocain, procain, sulfonamid,
sulfonylurea... l nhng thuc d gy mn cm v nhm NH 2 d b oxy ha v sn phm oxy ha
s d gn vi nhm SH ca protein ni sinh thnh khng nguyn.
Phn ng min dch d ng c chia thnh 4 typ da trn c s ca c ch min dch:
- Typ I hay phn ng phn v (anaphylactic reactions) do s kt hp ca khng nguyn vi khng
th IgE, gn trn bch cu a base tun hon hoc cc dng bo. Phn ng lm gii phng nhiu
cht ha hc trung gian nh histamin, leucotrien, prostaglandin, gy gin mch, ph v vi m. Cc
c quan ch ca phn ng ny l ng tiu ha (d ng thc n), da (my ay, vim da d ng),
ng h hp (vim mi, hen) v h tim - mch (sc phn v)
Cc phn ng ny thng xy ra ngay sau khi dng thuc.
Cc thuc d gy phn ng typ I: thu c t procain, lidocain, khng sinh nhm lactam,
aminoglycosid, huyt thanh, globulin, vaccin, vitamin B 1 tim tnh mch.
- Typ II hay phn ng hu t bo (cytolytic reactions) xy ra khi c s kt hp khng nguyn vi
khng th IgG v IgM ng thi c s hot ha h b th. M ch ca phn ng ny l cc t
bo ca h tun hon. Th d: thiu mu tan mu do penicilin, thiu mu tan mu t min do

methyl dopa, ban xut huyt gim tiu cu do quinidin, gim bch cu ht do sulfamid, luput ban
h thng do procainamid.
- Typ III hay phn ng Arthus, trung gian ch yu qua IgG c s tham gia ca b th. Phn ng
gia khng nguyn v khng th to thnh phc hp min dch. Phc hp ny lng ng vo ni
mc mch, gy tn thng vim hu hoi, c gi l bnh huyt thanh. Biu hin lm sng
thng l: my ay, ban , au, vim khp, ni hch, st. Thng xy ra sau 6 - 12 ngy.
Cc thuc c th gp l sulfonamid, penicilin, mt s thuc chng co git, iod, mui Hg, huyt
thanh.
Hi chng Stevens- Johnson l biu hin nng ca typ ny.
- Typ IV hay phn ng nhy cm mun, trung gian qua t bo lympho T c mn cm v i
thc bo. Khi cc t bo mn cm tip xc vi khng nguyn, s gii phng cc lymphokin gy
ra phn ng vim. Vim da tip xc l biu hin thng gp ca typ ny.
Cc phn ng d ng thuc khng lin quan n liu lng thuc dng, s ln dng v thng c
d ng cho. V vy cn hi tin s d ng ca bnh nhn trc khi dng thuc. Vi nhng thuc
hay gy d ng (penicilin, lidocain,.. .) khi dng, phi c sn thuc v phng tin cp cu
(adrenalin). Sc phn v c th xy ra do ng dng thuc khc nhau: vitamin B 1 dng tim tnh
mch c th gy sc cht ngi, trong khi dng ung khng gy phn ng ny.
4.3. Tai bin thuc do ri lon di truyn
Thng l do thiu enzym bm sinh, mang tnh di truyn trong gia nh hay chng tc.
Ngi thiu enzym glucose - 6- phosphat deshydrogenase (G -6-PD) hoc glutathion reductase d
b thiu mu tan mu khi dng primaquin, quinin, pamaquin (xin xem bi " Thuc chng st rt"),
sulfamid, nitrofuran...
Gen kim tra vic to G- 6-PD nm trn chromosom X, v vy, tai bin thng xy ra nam.
Ngi ta c lng c khong 100 - 200 triu ngi mang gen ny v thng gp trn ngi da
en.
Ngi thiu enzym methe moglobin reductase l nhng ngi d hp t (khong 1% dn s). Khi
dng thuc st rt (pamaquin, primaquin), thuc khng sinh, st khun (cloramphenicol, sulfon,
nitrofurantoin), thuc h st (phenazol, paracetamol) rt d b methemoglobin.
Ngi thiu acetyl transferase s chm acetyl ha mt s thuc nh hydralazin, isoniazid,
phenelzin... nn d b nhim c cc thuc ny.
Hin tng c ng (idiosyncrasy) l nhy cm c nhn bm sinh vi thuc chnh l s thiu
ht di truyn 1 enzym no .
4.4. Quen thuc
Quen thuc l s p ng vi thuc yu hn hn so vi ngi bnh thng dng cng liu. Liu
iu tr tr thnh khng c tc dng, i hi ngy cng phi tng liu cao hn.
Quen thuc c th xy ra t nhin ngay t ln u dng thuc do thuc t c hp thu, hoc b
chuyn ha nhanh, hoc c th km mn cm vi thuc. Thng do nguyn nhn di truyn.
Thng gp quen thuc do mc phi sau mt thi gian dng thuc, i hi phi tng dn liu.
4.4.1. Quen thuc nhanh (tAChyphylaxis)

Thc nghim dng nhng liu ephedrin bng nhau, tim tnh mch cch nhau tng 15 pht, sau
4- 6 ln, tc dng gy tng huyt p gim dn ri mt hn. Mt s thuc khc cng c hin tng
quen thuc nhanh nh amphetamin, isoprenalin, adrenalin, histamin...
Nguyn nhn l:
- Thuc tc dng gin tip qua s gii phng cht ni sinh ca c th, lm cn kit cht ni sinh.
Ephedrin, amphetamin lm gii phng adrenalin d tr ca h giao cm.
- Kch thch gn nhau qu lm receptor "mt mi"
- To cht chuyn ha c tc dng i khng vi ch t m: isoprenalin (cng giao cm) qua
chuyn ha gan, to ra 3 - orthomethylisoprenalin c tc dng hu .
4.4.2. Quen thuc chm
Sau mt thi gian dng thuc lin tc, tc dng ca thuc gim dn, i hi phi tng liu hoc
i thuc khc. C nhiu nguyn nhn:
- Do gy cm ng enzym chuyn ha thuc, lm nhng liu thuc sau b chuyn ha nhanh, mt
tc dng nhanh. Barbiturat, diazepam, tolbutamid, ru ethylic... u l nhng thuc gy cm
ng enzym chuyn ha ca chnh n.
- Do gim s lng receptor c m ng vi thuc mng t bo (iu ha gim - down regulation):
khi dng thuc cng giao cm, ph giao cm ko di... Tri li, khi dng cc thuc phong to
ko di s lm tng s lng receptor (iu ha tng - up regulation) nh dng thuc hu giao
cm, thuc an thn c ch h dopaminergic. Khi ngng thuc d gy hin tng hi ng
(rebound)
- Do c th phn ng bng c ch ngc li dng cc thuc li niu thi Na + lu, c th mt
nhiu Na + s tng tit aldosteron gi li Na +, lm gim tc dng li niu.
trnh hin tng quen thuc, trong lm sng thng dng thuc ngt qung hoc lun phin
thay i cc nhm thuc (s trnh by trong phn thuc c th)
4.5. Nghin thuc
Nghin thuc l mt trng thi c bit lm cho ngi nghin ph thuc c v t m l v th cht
vo thuc vi cc c im sau:
- Thm thung mnh lit nn xoay s mi cch c thuc dng, k c hnh vi phm php
- C khuynh hng tng liu
- Thuc lm thay i tm l v th cht theo hng xu: ni iu, li lao ng, bn thu, thiu
o c... gy hi cho bn thn v x hi
- Khi cai thuc s b thuc " vt" hay ln cn "i thuc" : vt v, ln ln, d cm, v m hi, tiu
chy... Nu li dng thuc cn "vt" s ht ngay.
Nhng thuc gy nghin u c tc dng ln thn kinh tr ung ng gy sng khoi lng lng, o
nh, o gic ("ph" thuc) hoc trng thi hng phn mnh (thuc lc), c gi chung l "ma
ty": morphin v cc cht loi thuc phin (heroin, pethidin, methadon), cocain, cn sa (cannabis,
marijuana), metamphetamin, ectasy... Ru v thuc l hin cn c coi l ma ty "hp php".
C ch nghin cn cha c hon ton bit r, c nhiu gi thuyt gii thch: do c th khng
sn xut morphin ni sinh; lm ri lon chc phn ca nron, gy phn ng b tr ca c th; to
ra cht i khng vi ma ty nn i hi phi tng liu...
Hin nay khng c phng php cai nghin no c hiu qu, ngoi tr ch ca ngi nghin. V
vy, nghin ma tu l mt t nn x hi phi c loi tr.
Cu hi t lng gi
1. Trnh by cc c ch tc dng ca thuc.

2. Trnh by cc cch tc dng ca thuc.
3. Phn tch nhng yu t v thuc c nh hng n tc dng ca thuc.
4. Phn tch nhng yu t ca ngi dng thuc c nh hng n tc dng ca thuc.
5. Trnh by nhng tai bin khi dng thu c: phn ng c hi, phn ng d ng, ri lon do
di truyn, nghin thuc.
Bi 3: tng tc thuc

1. Trnh by c tng tc dc lc hc v dc ng hc.
2. Trnh by c hiu qu v p dng ca tng tc thuc.
1.Tng tc thuc- thuc

Nhiu thuc khi cho dng c ng mt lc s c tc dng qua li ln nhau, c gi l tng tc
thuc. Trong lm sng, thy thuc mun phi hp thuc lm tng tc dng iu tr, gim cc
tc dng khng mong mun. Song trong thc t, nhiu khi khng t c nh th. V vy, khi
k n c t 2 thuc tr ln, thy thuc rt cn hiu r s tng tc gia chng.
1.1. Tng tc dc lc hc
L tng tc ti cc receptor, mang tnh c hiu
1.1.1. Tng tc trn cng receptor: tng tc cnh tranh
Thng lm gim hoc mt tc dng ca cht ng vn (a gonist), do cht i khng (antagonist)
c i lc vi receptor hn nn ngn cn cht ng vn gn vo receptor: atropin khng
acetylcholin v pilocarpin ti receptor M; nalorphin khng morphin ti receptor ca morphin;
cimetidin khng histamin ti receptor H2.
Thuc cng nhm c cng c ch tc dng, khi dng chung tc dng khng tng bng tng liu
ca mt thuc m c tnh li tng hn: CVKS, aminosid vi dy VIII.
1.1.2. Tng tc trn cc receptor khc nhau: tng tc chc phn.
- C cng ch tc dng: do lm tng hiu qu iu tr.
Th d: trong iu tr bnh cao huyt p, phi hp thuc gin mch, an thn v li tiu; trong iu
tr lao, phi hp nhiu khng sinh (DOTS) tiu dit vi khun cc v tr v cc giai on pht
trin khc nhau.
- C ch tc dng i lp, gy ra c chc phn i lp, dng iu tr nhim c: strychnin
liu cao, kch thch ty sng gy co cng c, cura do c ch dn truyn tm vn ng, lm mm
c; histamin tc ng trn receptor H 1 gy gin mch, tt huyt p, trong khi noradrenalin tc
ng ln receptor 1 gy co mch, tng huyt p.
1.2. Tng tc dc ng hc
L cc tng tc nh hng ln nhau thng qua cc qu trnh hp thu, phn phi, chuyn ha v
thi tr v th n khng mang tnh c hiu.
1.2.1. Thay i s hp thu ca thuc
- Do thay i ion ha ca thuc:
Nh ta bit, ch nhng phn khng ion ha ca thuc mi d dng qua c mng sinh hc v
d phn tn hn trong lipid. phn ly ca thuc ph thuc vo hng s pKa ca thuc v pH
ca mi trng. Cc thuc c bn cht acid yu (nh aspirin) s hp thu tt trong mi trng acid
(d dy), nu ta trung ha acid ca dch v th s hp thu aspirin d dy s gim i.
- Vi cc thuc dng theo ng ung: khi dng vi thuc lm thay i nhu ng rut s lm
thay i thi gian lu gi thuc trong rut, thay i s hp thu ca thuc qua rut. Mt khc cc
thuc d tan trong lipid, khi dng cng vi parafin (hoc thc n c m) s lm tng hp thu.
- Vi cc thuc dng theo ng tim bp, di da: procain l thuc t , khi trn vi adrenalin l
thuc co mch th procain s chm b hp thu vo mu do thi gian gy t s c ko di.
Insulin trn vi protamin v km (protemin - zinc- insulin- PZI) s lm ko di thi gian hp thu
insulin vo mu, ko di tc dng h ng huyt ca insulin.
- Do to phc, thuc s kh c hp thu:
Tetracyclin to phc vi Ca ++ hoc cc cation kim loi khc rut, b gim hp thu.
Cholestyramin lm ta mui mt, ngn cn hp thu lipid, dng lm thuc h cholesterol mu.
- Do cn tr c hc: Sucralfat, smecta, maaloc (Al 3+) to mng bao nim mc ng tiu ha, lm
kh hp thu cc thuc khc.
trnh s to phc hoc cn tr hp thu, 2 thuc nn ung cch nhau t nht 2 gi.
1.2.2. Thay i s phn b thuc
l tng tc trong qu trnh g n thuc vo protein huyt tng. Nhiu thuc, nht l thuc
loi acid yu, gn thun nghch vi protein (albumin, globulin) s c s tranh chp, ph thuc
vo i lc v nng ca thuc trong huyt tng. Ch c thuc dng t do mi c tc dng
dc l. V vy, tng tc ny c bit c ngha vi thuc c t l gn vo protein huyt tng
cao (trn 90%) v c phm vi iu tr hp nh:
. Thuc chng ng mu loi khng vitamin K: dicumarol, warfarin
. Sulfamid h ng huyt: tolbutamid, clopropamil
. Thuc chng ung th, c bit l methotrexat
Tt c u b cc thuc chng vim phi steroid d dng y khi protein huyt tng, c th gy
nhim c.
1.2.3. Thay i chuyn ha
Nhiu thuc b chuyn ha gan do cc enzym chuyn ha thuc ca microsom ga n (xin xem
phn dc ng hc). Nhng enzym ny li c th c tng hot tnh (gy cm ng) hoc b c
ch bi cc thuc khc. Do s lm gim t/2, gim hiu lc (nu l thuc gy cm ng enzym)
hoc lm tng t/2, tng hiu lc (nu l thuc c ch enzy m) ca thucdng cng.
- Cc thuc gy cm ng (inductor) enzym gan: phenobarbital, phenytoin, carbamazepin,
griseofulvin, rifampicin...
- Cc thuc c ch (inhibitor) enzym gan: allopurinol, cloramphenicol, cimetidin, MAOI,
erythromycin, isoniazid, dicuma rol.
Cc thuc hay phi hp vi cc loi trn thng gp l cc hormon (thyroid, corticoid, estrogen),
thuc chng ng kinh, thuc h ng huyt, thuc tim mch.
Ph n ang dng thuc trnh thai ung, nu b lao dng thm rifampicin, hoc b ng kinh
dng phenytoin, c th s b "v k hoch" do estrogen trong thuc trnh thai b gim hiu qu v
b chuyn ha nhanh, hm lng tr nn thp.
1.2.4. Thay i thi tr thuc
Thi tr (elimination) thuc gm 2 qu trnh l chuyn ha thuc gan ( ni phn trn ) v
bi xut (excretion) thuc qua thn. Nu thuc bi xut qua thn dng cn hot tnh th s tng/
gim bi xut s c nh hng n tc dng ca thuc.
- Thay i pH ca nc tiu: khi mt thuc lm thay i pH ca nc tiu, s lm thay i ion
ha ca thuc dng km, lm thay i bi xut ca thuc. Th d barbital c pKa = 7,5; pH
= 7,5 th 50% thuc b ion ha; pH = 6,5 th ch c 9% b ion ha pH = 9,5 th 91% barbital b
ion ha. V vy, khi ng c cc thuc barbiturat, truyn dch NaHCO3 base ha nc tiu s
tng bi xut barbiturat.
Cc thuc l acid yu (vitamin C, amoni clorid) dng liu cao, lm acid ha nc tiu s lm tng
thi tr thuc loi alcaloid (quinin, morphin).
- Bi xut tranh chp ti ng thn: do 2 cht cng c c ch bi xut chung ti ng thn nn tranh
chp nhau, cht ny lm gim bi xut cht khc. Dng probenecid s lm chm thi tr
penicilin, thiazid lm gim thi tr acid uric nn c th gy bnh gut.
1.3. Kt qu v ngha ca tng tc thuc
1.3.1. Tc dng hip ng
Thuc A c tc dng l a, thuc B c tc dng l b. Khi kt hp thuc A vi thuc B c tc dng
c. Nu
c = a + b, ta c hip ng cng (additive effect)
c > a + b, ta c hip ng tng mc (synergysm)
Hip ng cng thng khng c dng lm s ng v nu cn th tng liu thuc ch khng
phi hp thuc.
Hip ng tng mc thng dng trong iu tr lm tng tc dng iu tr v lm gim tc
dng ph, tc dng c hi. Hai thuc c hip ng tng mc c th qua tng tc dc ng
hc (tng hp thu, gim thi tr) hoc tng tc dc lc hc (trc tip hoc gin tip qua
receptor)
1.3.2. Tc dng i khng
Nh trong nh ngha trn, nhng khi tc dng c ca thuc A + B li nh hn tc dng cng ca
tng thuc (c < a + b) ta gi l tc dng i khng. i khng c th ch mt phn (partial
antagonism) khi c < a + b, nhng cng c th i khng hon ton khi a lm mt hon ton tc
dng ca b.
Trong lm sng, thng dng tc dng i khng gii c.
- i khng c th xy ra ngoi c th, gi l t ng k (incompatibility), mt loi tng tc
thun ty l ha:
+ Acid gp base: to mui khng tan. Khng tim khng sinh loi acid (nhm lactam) vo ng
dn dch truyn c tnh base.
+ Thuc oxy ha (vitamin C, B 1, penicilin) khng trn vi thuc oxy kh (vitamin B 2)

+ Thuc c bn cht l protein (insulin, heparin) khi gp mui kim loi s d kt ta.
+ Than hot, tanin hp ph hoc lm kt ta nhiu alcaloid (quinin, atropin) v cc mui kim loi
(Zn, Pb, Hg...)
- i khng xy ra trong c th:
Khi thuc A lm gim nng ca thuc B trong mu (qua dc ng hc) hoc lm gim tc
dng ca nhau (qua dc lc hc), ta gi l i khng (antagonism)
V dc lc hc, c ch ca tc dng i khng c th l:
+ Tranh chp trc tip ti receptor: ph thuc vo i lc v nng ca thuc ti receptor. Th
d: acetylcholin v atropin ti receptor M - cholinergic; histamin v cimetidin trn receptor H 2
d dy.
+ i khng chc phn: hai cht ng vn (agonist) tc dng trn 2 receptor khc nhau nhng
chc phn li i khng trn cng mt c quan. Strychnin kch thch tu sng, gy co git; cura
c ch dn truyn tm vn ng, gy mm c, chng c co git. Histamin kch thch receptor
H1 lm co c trn kh qun, gy hen; albuterol (Ventolin), kch thch rec eptor 2 adrenergic lm
gin c trn kh qun, dng iu tr cn hen.
1.3.3. o ngc tc dng
Adrenalin va c tc dng kch tch receptor adrenergic (co mch, tng huyt p), va c tc
dng kch thch receptor adrenergic (gin mch, h huyt p). Khi dng mt mnh, do tc dng
mnh hn nn adrenelin gy tng huyt p. Khi dng phentolamin (Regitin) l thuc c ch
chn lc receptor ri mi tim adrenalin th do ch kch thch c receptor nn adrenelin
gy h huyt p, tc dng b o ngc.
ngha ca tng tc thuc
Trong lm sng, thy thuc dng thuc phi hp vi mc ch:
- Lm tng tc dng ca thuc chnh (hip ng tng mc)
- Lm gim tc dng khng mong mun ca thuc iu tr
- Gii c (thuc i khng, thuc lm tng thi tr, gim hp thu, trung ha...)
- Lm gim s quen thuc v khng thuc
Tuy nhin, nu khng hiu r tc dng phi hp, thy thuc c th lm gim tc dng iu tr
hoc tng tc dng c ca thuc. Trong cc sch hng dn dng thuc, thng c mc tng
tc ca tng thuc.
2. Tng tc thuc- thc n- ung
2.1. Tng tc thuc- thc n:
Thng hay gp l thc n lm thay i dc ng hc ca thuc.
2.1.1. Thc n lm thay i hp thu thuc:
- S hp thu ph thuc vo thi gian rng ca d dy. D dy khng phi l ni c ch c nng hp

thu ca b my tiu ha. Tuy nhin, do pH rt acid (khi i, pH 1; khi no pH 3) cho nn cn
lu :
+ Ung thuc lc i, thuc ch gi li trong d dy khong 10 - 30 pht.
+ Ung thuc vo lc no, thuc b gi li trong d dy khong 1 - 4 gi, do :
. Nhng thuc t tan s c thi gian tan, khi xung rut s c hp thu nhanh hn (penicilin
V). Tuy nhin, nhng thuc d to phc vi nhng thnh phn ca thc n s b gim hp thu
(tetracyclin to phc vi Ca ++ v mt s cation ho tr 2 khc).
. Cc thuc km bn trong mi trng acid (ampicilin, erythromycin) nu b gi lu d dy s
b ph hu nhiu.
. Vin bao tan trong rut s b v (cn ung trc ba n 0,5 - 1h hoc sau ba n 1- 2 gi)
. Nhng thuc d kch ng ng tiu ha, n n ung vo lc no.
- S hp thu cn ph thuc vo dng bo ch: aspirin vin nn ung sau khi n s gim hp thu
50%, trong khi vin si bt li c hp thu hon ton.
2.1.2. Thc n lm thay i chuyn ha v thi tr thuc
Thc n c th nh hng n enzym c huyn ha thuc ca gan, nh hng n pH ca nc
tiu, v qua nh hng n chuyn ha v bi xut thuc. Tuy nhin, nh hng khng ln.
Ngc li, thuc c th nh hng n chuyn ha mt s cht trong thc n. Thuc c ch
enzym monoamin- oxydase (MAOI) nh iproniazid - l enzym kh amin- oxy ha ca nhiu
amin ni, ngoi sinh- c th gy cn tng huyt p kch pht khi n cc thc n c nhiu tyramin
(nh khng c chuyn ha kp, lm gii phng nhiu noradrenalin ca h giao cm trong thi
gian ngn.
2.2. Tng tc thc n ung
2.2.1. Nc
- Nc l ung (dung mi) thch hp nht cho mi loi thuc v khng xy ra tng k khi
ha tan thuc.
- Nc l phng tin dn thuc (dng vin) vo d dy - rut, lm tng tan r v ha tan hot
cht, gip hp thu d dng. V vy cn ung nc (100 - 200 mL cho mi ln ung thuc)
trnh ng vin thuc ti thc qun, c th gy kch ng, lot.
- c bit cn ch :
+ Ung nhiu nc trong qu trnh dng thuc (1,5 - 2 l/ ngy) lm tng tc dng ca thu c
(cc loi thuc ty), lm tng thi tr v lm tan cc dn xut chuyn ha ca thuc (sulfamid,
cyclophosphamid).
+ Ung t nc hn bnh thng duy tr nng thuc cao trong rut khi ung thuc ty sn,
ty giun (niclosamid, mebendazol).
+ Trnh dng nc qu, nc khong base hoc cc loi nc ngt ng hp c gas v cc loi
nc ny c th lm hng thuc hoc gy hp thu qu nhanh.
2.2.2. Sa
Sa cha calci caseinat. Nhiu thuc to phc vi calci ca sa s khng c hp thu

(tetracyclin, lincomycin, mui Fe...)
Nhng thuc d tan trong lipid s tan trong lipid ca sa chm c hp thu.
Protein ca sa cng gn thuc, lm cn tr hp thu.
Sa c pH kh cao nn lm gim s kch ng d dy ca cc thuc acid.
2.2.3. C ph, ch
- Hot cht cafein trong c ph, nc ch lm tng tc dng ca thuc h st gim au aspirin,
paracetamol; nhng li lm tng tc dng ph nh nhc u, tng nhp tim, tng huyt p
nhng bnh nhn ang dng thuc loi MAOI.
- Tanin trong ch gy ta cc thuc c Fe hoc al caloid
- Cafein cng gy ta aminazin, haloperidol, lm gim hp thu; nhng li lm tng ha tan
ergotamin, lm d hp thu.
2.2.4. Ru ethylic
Ru c rt nhiu nh hng n thn kinh trung ng, h tim mch, s hp thu ca ng tiu
ha. Ngi nghin ru cn b gim protein huyt tng, suy gim chc nng gan, nhng li gy
cm ng enzym chuyn ha thuc ca gan (xin xem bo "ru"), v th ru c tng tc vi rt
nhiu thuc v cc tng tc ny u l bt li. Do khi dng thuc th khng ung ru.
Vi ngi nghin ru cn phi dng thuc, thy thuc cn kim tra chc nng gan, tnh trng
tm thn... chn thuc v dng liu lng thch hp, trong thi gian dng thuc cng phi
ngng ung ru.
3. Thi im ung thuc
Sau khi nhn r c tng tc g ia thuc- thc n- ung, vic chn thi im ung thuc hp
l t c nng cao trong mu, t c hiu qu mong mun cao v gim c tc dng
ph l rt cn thit.
Nn nh rng: ung thuc vo lc i, thuc ch b gi li d dy 10 - 30 pht, vi pH 1;
ung lc no (sau n), thuc b gi li 1 - 4 gi vi pH 3,5. Nh vy, tu theo tnh cht ca thuc,
mc ch ca iu tr, c mt s gi chn thi im ung thuc nh sau:
3.1.Thuc nn ung vo lc i (trc ba n 1/2 - 1 gi)
- Thuc "bc" d dy cha lot trc khi thc n c mt, nh sucralfat.
- Cc thuc khng nn gi li lu trong d dy nh: cc thuc km bn vng trong mi trng
acid (ampicilin, erythromycin), cc loi vin bao tan trong rut hoc cc thuc gii phng ch m.
3.2. Thuc nn ung vo lc no (trong hoc ngay sau ba n)
- Thuc kch thch bi tit dch v (ru khai v), cc enzym tiu ha (pancreatin) chng i tho
ng loi c ch gluconidase nn ung trc ba n 10 - 15 pht.
- Thuc kch thch d dy, d gy vim lot ng tiu ha: cc thuc chng vim phi steroid,
mui kali, quinin.
- Nhng thuc c thc n lm tng hp thu, hoc do thc n lm chm di chuyn thuc nn
ko di thi gian hp thu: cc vitamin, cc vin nang amoxicilin, cephalexin, cc vin nn
digoxin, sulfamid.
- Nhng thuc c hp thu qu nhanh lc i, d gy tc dng ph: levodopa, thuc khng
histamin H 1.
3.3. Thuc t b nh hng bi thc n, ung lc no cng c: prednisolon, theophylin,
augmentin, digoxin.
3.4. Thuc nn ung vo bui sng, ban ngy
- Cc thuc kch thch thn kinh trung ng, cc thuc li niu trnh nh hng n gic ng.
- Cc corticoid: thng ung 1 liu vo 8 gi sng duy tr c nng n nh trong mu.
3.5. Thuc nn ung vo bui ti, trc khi i ng.
- Cc thuc an thn, thuc ng
- Cc thuc khng acid, chng lot d dy. Dch v acid thng tit nhiu vo ban m, cho nn
ngoi vic dng thuc theo ba n, cc thuc khng acid dng cha lot d dy nn c ung
mt liu vo trc khi i ng .
Cn nh rng khng nn nm ngay sau khi ung thuc, m cn ngi 15 - 20 pht v ung nc
(100- 200 mL nc) thuc xung c d dy.
Dc l thi khc (chronopharmacology) cho thy c nhiu thuc c hiu lc hoc c tnh
thay i theo nhp ngy m. Tuy nhin, trong iu tr, vic cho thuc cn tu thuc vo thi
gian xut hin triu chng.
cu hi t lng gi
1. Trnh by tng tc dc ng hc ca thuc.

2. Trnh by tng tc dc lc hc.
3. Trnh by ngha v p dng lm sng ca tng tc th uc.
4. Trnh by tng tc thuc vi thc n v ung.
Bi 4: i cng v phn loi

1. Phn bit c v gii phu, sinh l v dc l cc h giao cm, ph giao cm,
adrenergic, cholinergic
2. Phn bit c cc tc dng sinh l ca h M - N- cholinergic
H thn kinh thc vt (cn gi l h thn kinh t ng) chuyn iu khin cc hot ng ngoi
mun, c vai tr iu ha chc phn ca nhiu c quan, h thng cho gii hn sng ca c th
gi c s n nh trong mi trng sng lun lun thay i.
H thng thn kinh thc vt hnh thnh t nhng trung tm trong no v tu sng, xut pht
nhng si thn kinh ti cc tng, mch mu v c nhn. Trc khi ti c quan thu nhn, cc si
ny u dng mt xinap ti hch, v vy c si trc hch (hay tin hch) v si sau hch (hay
hu hch). Khc vi nhng b phn do h thn kinh trung ng iu khin, cc c quan do h
thn kinh thc vt chi phi vn c th hot ng t ng khi ct t nhng si thn kinh n
chng.
H thng thn kinh thc vt c chia thnh 2 h giao cm v ph giao cm khc nhau v c gii
phu v chc phn sinh l.
1. Phn loi theo gii phu
1.1. im xut pht
- H giao cm xut pht t nhng t bo thn kinh sng bn ca tu sng t t sng ngc th
nht n t sng tht lng th 3 (T1- L3).
- H ph giao cm xut pht t no gia, hnh no v tu cng. no gia v hnh no, cc si
ph giao cm i cng vi cc dy thn kinh trung ng: dy III vo mt; dy VII vo cc tuyn
nc bt; dy IX vo c mi, cc tuyn tit nc mt, n c bt, tuyn tit nim mc mi, ming,
hu; dy X vo cc tng trong ngc v bng. tu cng, xut pht t cc t sng cng th 2
n th 4 (S2- S4) chi phi cc c quan trong h chu.
1.2. Hch
- H giao cm c 3 nhm hch:
. Chui hch cnh ct sng n m hai bn ct sng
. Nhm hch trc ct sng, gm hch tng, hch mc treo v hch h v, u nm trong bng.
. Nhm hch tn cng gm nhng hch nm cnh trc trng v bng quang.
- H ph giao cm: cc hch nm ngay cnh hoc ngay trong thnh c qua n.
1.3. Si thn kinh
- H giao cm: mt si tin hch thng tip ni vi khong 20 si hu hch cho nn khi kch
thch giao cm, nh hng thng lan rng.
- H ph giao cm: mt si tin hch thng ch tip ni vi mt si hu hch, cho nn xung tc

thn kinh thng khu tr hn so vi xung tc giao cm. Tuy nhin, i vi dy X th m ri
AuerbACh v m ri Meissner (c coi l hch) th mt si tin hch tip ni vi khong 8000
si hu hch.
V hch nm ngay cnh c quan, cho nn cc si hu hch ph giao cm rt ngn.
Hnh 4.1. Cu to gii phu ca h thn kinh thc vt

2. Chc phn sinh l
2.1. Chc phn sinh l
Chc phn sinh l ca hai h giao cm v ph giao cm trn cc c quan ni chung l i khng
nhau (bng 4.1)
Bng 4.1: p ng ca c quan vi h thn kinh thc vt
C quan Kch thch giao cm Kch thch ph giao cm

Loi receptor p ng p ng
Mt
C nan hoa 1 Co (gin ng t) ++
C co ng t Co (co ng t ) +++
Tim
Nt nh- tht 1 (2) Tng tn s ++ Gim tn s ngng tim
Tm nh 1(2) Tng bin ++ Gim bin ++
Mao ng mch
Mch vnh 1, 2, 2 Co +; gin ++ Gin +
C vn , 2 Co ++; gin ++ Gin +
Da, nim mc 1, 2 Co +++ Gin
No 1 Co nh Gin
Tng Co +++; Gin + -
1, , 2
Thn Co +++; gin + -
1, 2, 1, 2
Tnh mch 1, 2 Co ++; gin ++ -
Ph qun 2 Gin + Co ++
Rut
Nhu ng 1, 2, 2 Gim + Tng +++
C tht 1 Co + Gin +
Bi tit 2 c ch Tng +++
Thn
Tit renin 1, 1 Gim +; tng ++ -
T cung 1, 2 Cha: co (1); gin (2) Thay i theo chu k
Khng cha; gin (2) kinh...
C quan sinh 1 Phng tinh +++ Cng +++
dc nam
Bng quang
C bng quang 2 Gin + Co +++
C trn 1 Co ++ Gin ++
Gan 1, 2 Hu glycogen v tn to -
glucose +++
Ty
Acini Gim tit + Tng tit ++
T bo 1 Gim tit +++ -
2 tng tit ++ -
T bo m 2, 1 (3) Hu lipid +++ -
Ghi ch: - Cc receptor ca h ph giao cm u l cc loi receptor M
- Mc p ng t thp (+) n cao (+++)
2.2. Xinap v cht dn truyn thn kinh

Khi ta kch thch cc dy thn kinh (trung ng v thc vt) th u mt ca cc dy s tit
ra nhng cht ha hc lm trung gian cho s dn truyn gia cc dy tin hch vi hu hch,
hoc gia dy thn kinh vi cc c quan thu nhn. Cht ha hc lm trung gian cho s dn truyn
gi l cht dn truyn thn kinh.
H thng thn kinh ca ngi c hng chc t nron. S thng tin gia cc nron cng da
vo cc cht dn truyn thn kinh. Cc thuc nh hng n chc phn thn kinh thng l thng
qua cc cht dn truyn thn kinh .
Cht dn truyn thn kinh hch giao cm, ph giao cm v hu hch ph giao cm u l
acetylcholin, cn hu hch giao cm l noradrenalin, adrenalin v dopamin (gi chung l
catecholamin). Cc cht dn truyn thn kinh tc ng n mng sau xinap lm thay i tnh
thm ca mng vi ion Na +, K+ hoc Cl - do gy ra hin tng bin cc (kh cc hoc u cc
ha). Ion Ca ++ ng vai tr quan trng trong s gii phng cht dn truyn thn kinh.
2.3. Cc cht dn truyn khc

Trong nhng nm gn y, nhiu nghin cu cho thy rng phn ln cc nron trung ng v
ngoi bin c cha 2 hoc nhiu cht dn truyn, c th c gii phng ra cng mt lc xinap
khi dy thn kinh b kch thch. Nh vy, h thn kinh thc vt, ngoi acetylcholin (ACh) v
noradrenalin (NA), cn c nhng cht dn truyn thn kinh (neurotransmitters) khc cng c
gii phng v c th c vai tr nh cht cng dn truyn (cotransmitters), cht iu bin thn
kinh (neuromodulators) hoc chnh n cng l cht dn truyn (transmitters).
Ngi ta tm thy trong tu thng thn, trong cc si thn kinh, trong hch thn kinh thc vt
hoc trong cc cu trc do h thn kinh thc vt chi phi mt lot cc peptid sau: e nkephalin,
cht P, somatostatin, hormon gii phng gonadotropin, cholecystokinin, vasoactive intestinal
peptide (VIP), neuropeptid Y (NPY)... Vai tr dn truyn ca ATP, VIP v NPY trong h thn
kinh thc vt dng nh c coi l nhng cht iu bin t c dng ca NA v ACh. Nh vy,
bn cnh h thn kinh thc
vt vi s dn truyn bng ACh v NA cn tn ti mt h thng dn truyn khc c gi l dn
truyn khng adrenergic, khng cholinergic [Nonadrenergic, non cholinergic (NANC)
transmission].
Burnstock (1969, 1986) thy c cc si thn kinh purinergic chi phi c trn ng tiu ha,
ng sinh dc- tit niu v mt s mch mu. Adenosin, ATP l cht dn truyn, cc receptor
gm receptor adenosin (A hoc P 1) v receptor ATP (P 2). Cc di typ receptor u hot ng
thng qua protein G, cn receptor P 2x li thng qua knh ion (Fredholm v cs, 1994).
Methylxantin (cafein, theophylin) l cht c ch cc receptor ny.
Nitric oxyd cng l mt cht dn truyn ca h NANC c tc dng lm gin mch, gin ph
qun. Nitric oxyd c ni m thnh mch, khi c gii phng s hot ha guanylyl cyclase,
lm tng tng hp GMPv, gy gin c trn thnh mch.
Cc cht dn truyn thn kinh c tng hp ngay ti t bo thn kinh, sau c lu tr di
th phc hp trong cc ht c bit nm ngn dy thn kinh trnh b ph hu. Di tc dng
ca nhng lung xung tc thn kinh, t cc ht d tr , cht dn truyn thn kinh c gii
phng ra di dng t do, c hot tnh tc ng ti cc receptor. Sau chng c thu hi li
vo chnh cc ngn dy thn kinh va gii phng ra, hoc b ph hu rt nhanh bi cc enzym
c bit. Acetylcholin b cholinesterase thu phn, cn noradrenalin v adrenalin th b oxy ha
v kh amin bi catechol - oxy- methyl- transferase (COMT) v monoamin- oxydase (MAO).
c bit:
- Dy giao cm i ti tu thng thn khng qua mt hch no c. tu thng thn, dy ny
tit ra acetylcholin kch thch tuyn tit ra adrenelin. V vy, thng thn c coi nh mt
hch giao cm khng l.
- Cc ngn dy hu hch giao cm chi phi tuyn m hi ng l phi tit noradrenalin, nhng li
tit ra acetylcholin.
- Cc dy thn kinh vn ng i n cc c xng (thuc h thn kinh trung ng) cng gii
phng ra acetylcholin.
- Trong no, cc xung tc gia cc nron cng nh acetylcholin. Ngoi ra cn c nhng cht
trung gian ha hc khc nh serotonin, catecholamin, acid - gama- amino- butyic (GABA)...
2.4. H thng thn kinh thc vt trong no

Khng th tch ri hot ng ca h thn kinh tr ung ng vi h thn kinh thc vt. Gia 2 h
lun lun c mi lin quan cht ch vi nhau m bo tnh thng nht ca c th. Nhng mi
lin quan v ang c tm thy vng di i, h vin (systema limbicus), hi hi m
(hyppocampus), l nhng ni c cc trung tm iu ha thn nhit, chuyn ha nc, ng, m,
iu ha huyt p, ni tit, hnh vi...
Trong h thn kinh trung ng cng thy cc cht dn truyn thn kinh v cc receptor nh
ca h thng thn kinh thc vt ngoi bin.
3. Phn loi theo dc l
Nhng thuc c tc dng ging nh tc dng kch thch giao cm c gi l thuc cng giao
cm (sympathicomimetic), cn nhng thuc c tc dng ging nh kch thch ph giao cm c
gi l thuc cng ph giao cm (para - sympathicomimetic).
Thuc no c tc dng km hm tc dng ca giao cm hay ph giao cm th gi l hu giao cm
(sympathicolytic) hay hu ph giao cm (parasympathicolytic).
Nh chng ta thy, hot ng ca thn kinh l nh nhng cht trung gian ha hc, cho nn
cch phn loi v gi tn theo gii phu v sinh l khng ni ln c y v chnh xc tc
dng ca thuc. V vy, mt cch hp l hn c, ng v phng din dc l, ta chia h thn
kinh thc vt thnh 2 h: h phn ng vi acetylcholin, gi l h cholinergic (gm cc hch giao
cm, ph giao cm; hu hch ph giao cm; bn vn ng c vn; mt s vng trn thn kinh
trung ng) v h phn ng vi adrenalin, gi l h adrenergic (ch gm hu hch giao cm)
Phn loi cc thuc tc dng trn h thng thn ki nh thc vt
Cc thuc tc dng trn h thn kinh thc vt cng mang tnh c hiu, tc dng chn lc trn
cc receptor ring i vi chng.
Cc receptor ca h cholinergic cn c chia lm 2 loi:
- Loi nhn cc dy hu hch (v d tim, cc c trn v tu yn ngoi tit) cn b kch thch bi
muscarin v b ngng hm bi atropin, nn c gi l h cm th vi muscarin (hay h M).
- Loi nhn dy tin hch cn b kch thch bi nicotin, nn cn c gi l h cm th vi
nicotin (hay h N), h ny phc tp, bao gm cc hch giao cm v ph giao cm, tu thng
thn, xoang ng mch cnh (b ngng hm bi hexametoni), v bn vn ng c vn thuc h
thn kinh trung ng (b ngng hm bi d - tubocurarin).
Cng trn nhng c s tng t, cc receptor ca h adrenergic c chia lm 2 loi: alpha ( )
v beta ().
Cc thuc kch thch c th tc ng theo nhng c ch:
. Tng cng tng hp cht dn truyn thn kinh
. Phong to enzym phn hu cht dn truyn thn kinh
. Ngn cn thu hi cht dn truyn thn kin h v ngn dy thn kinh.
. Kch thch trc tip cc receptor
Dn truyn xinap thn kinh

ngoi bin
Trung gian acetylcholin Trung gian noradrenalin

(cholinergic) (adrenergic)
H muscarinic(M) H nicotinic (N)
Hu hch ph Hch thc vt C vn Hu hch giao cm

giao cm
Receptor Receptor
Cc thuc c ch c th l:
- Ngn cn tng hp cht dn truyn thn kinh
- Ngn cn gii phng cht dn truyn thn kinh
- Phong to ti receptor.
Cu hi t lng gi
1. Trnh by c im gii phu v chc phn sinh l ca h giao cm v ph giao cm.
Phn bit h cholinergic (M,N) v h adrenergic v gii phu v dc l.
Bi 5:Thuc tc dng trn h h cholinergic

1. Trnh by c tc dng v p dng iu tr ca acetylcholin, pilocarpin v atropin
2. Phn tch c c ch tc dng ca nicotin v thuc lit hc h
3. Ni r c tc dng, c ch v p dng ca 2 loi cura
4. Trnh by c c ch, triu chng v cch iu tr nhim c cc cht phong to
khng hi phc cholinesterase.
1. Thuc kch thch h muscarinic (h M)

1.1. Acetylcholin
1.1.1. Chuyn ha
Trong c th, acetylcholin (ACh) c tng hp t cholin coenzym A vi s xc tc ca cholin -
acetyltransferase.
Acetylcholin l mt base mnh, to thnh cc mui rt d tan trong nc
CH3
CH3 - CO - O - CH2 - CH2 - N CH3
CH3
OH
Sau khi tng hp, acetylc holin c lu tr trong cc nang c ng knh khong 300 - 600 A0
ngn dy cholinergic di th phc hp khng c hot tnh. Di nh hng ca xung ng thn
kinh v ca ion Ca ++, acetylcholin c gii phng ra dng t do, ng vai tr mt cht trung gian
ha hc, tc dng ln cc receptor cholinergic mng sau xinap, ri b thu phn mt hot tnh
rt nhanh di tc dng ca cholinesterase (ChE) thnh cholin (li tham gia tng hp
acetylcholin) v acid acetic.
Chol.acetyltransferase a.acetic
Cholin + Acetyl CoA ChE
ACh cholin
C hai loi cholinesterase:

- Acetylcholinesterase hay cholinesterase tht (cholinesterase c hiu), khu tr cc nron v
bn vn ng c vn lm mt tc dng ca acetylch olin trn cc receptor.
- Butyryl cholinesterase, hay cholinesterse gi (cholinesterase khng c hiu, thy nhiu trong
huyt tng, gan, t bo thn kinh m (nevroglia). Tc dng sinh l khng quan trng, cha
hon ton bit r. Khi b phong to, khng gy nhng bin i chc phn quan trng.
Qu trnh tng hp acetylcholin c th b c ch bi hemicholin. c t ca vi khun botulinus
c ch gii phng acetylcholin ra dng t do.
Hnh 5.1. Chuyn vn ca ACh ti tn cng dy ph giao cm

Cholin c nhp vo u tn cng dy ph giao cm bng cht vn chuyn ph thuc Na + (A).
Sau khi c tng hp, ACh c lu gi trong cc nang cng vi peptid (P) v ATP nh cht
vn chuyn th hai (B). Di tc ng ca Ca 2+, ACh b y ra khi nang d tr vo khe xinap.
1.1.2. Tc dng sinh l
Acetylcholin l cht dn truyn thn kinh c nhiu ni trong c th, cho nn tc dng rt phc
tp:
- Vi liu thp (10 g/ kg tim tnh mch ch), ch yu l tc dng trn hu hch ph giao cm
(h muscarinic):
. Lm chm nhp tim, gin mch, h huyt p
. Tng nhu ng rut

. Co tht ph qun, gy cn hen
. Co tht ng t
. Tng tit dch, nc bt v m hi
Atropin lm mt hon ton nhng tc dng ny.
- Vi liu cao (1mg/ kg trn ch) v trn sc vt c tim trc bng at ropin sulfat phong
to tc dng trn h M, acetylcholin gy tc dng ging nicotin: kch thch
cc hch thc vt, tu thng thn (h N), lm tng nhp tim, co mch, tng huyt p v kch
thch h hp qua phn x xoang cnh.
V c amin bc 4 nn acetyl cholin khng qua c hng ro mu - no vo thn kinh trung
ng. Trong phng th nghim, mun nghin cu tc dng trung ng, phi tim acetylcholin
trc tip vo no, nhng cng b cholinesterase c rt nhiu trong thn kinh trung ng ph hu
nhanh. Acetylcholin l mt cht dn truyn thn kinh quan trng trong h thng thn kinh trung
ng, c tng hp v chuyn ha ngay ti ch, c vai tr kch thch cc yu t cm th (nh
cc receptor nhn cm ha hc), tng phn x ty, lm gii phng cc hormo n ca tuyn yn, tc
dng trn vng di i lm h thn nhit, p trc tip vo v no gy co git...
1.1.3. Cc receptor ca h cholinergic
Receptor Cht ch Cht i T chc (m) p ng C ch phn
vn khng t
Nicotinic Phenyltrimet Tm vn ng Kh cc ti M knh
muscle (Nm) hyl tubocurarin thn kinh - c tm vn cation ti
(N- c vn) ammonium ng, co c receptor Nm
Hch thc vt Kh cc si M knh
Nicotinic Dimethylphe Trimethapha
sau hch cation ti
nron (Nn) nyl piperazin n
Tu thng thn Tit receptor Nn
(hch tk) (DMPP)
catecholam
Trung ng TK in
Cha xc
nh
Hch thc vt Kh cc Kch thch
Hu hch ph Oxotremorin Atropin
Trung ng TK chm phospholipas
giao cm M 1 Pirenzepin Cha xc e C to IP 3
nh v DAG;
tng Ca2+
trong cytosol
Tim
M2 Atropin
Xoang nh Chm kh Hot ha
(M4) AF; DX 15 cc t pht knh K +
Nt nh tht Gim dn c ch
truyn adenylcyclas
Tm tht e (tc dng
Gim lc trn protein
co bp Gi)
M3 Atropin C trn Co tht Hot ha
knh K +
Hexahydro Tuyn tit tng tit
siladifenidol c ch
adenylcyclas
e (tc dng
trn protein
Gi)
1.1.4. p dng lm sng
V acetylcholin b ph hu rt nhanh trong c th nn t c dng trong lm sng. Ch dng
lm gin mch trong bnh Ray - n (Raynaud- tm ti u chi) hoc cc biu hin hoi t.
Tc dng gin mch ca ACh ch xy ra khi ni m mch cn nguyn vn. Theo Furchgott v cs
(1984), ACh v cc thuc cng h M lm gii phng yu t gin mch ca ni m mch
(endothelium- derived relaxing factor - EDRF) m bn cht l nitric oxyd nn gy gin mch.
Nu ni m mch b tn thng, ACh khng gy c gin mch.
Tim di da hoc tim bp 0,05 - 0,1 g, mi ngy 2- 3 ln
ng 1 mL = 0,1 g acetylcholin clorid
1.2. Cc este cholin khc
Nu thay th nhm acetyl bng nhm carbamat th bo v c thuc khi tc dng ca
cholinesterase, do ko di c thi gian tc dng ca thuc. Cc thuc u c amin bc 4
nn kh thm c vo thn kinh trung ng.
1.2.1. Betanechol (Urecholin)- Dn xut tng hp
Tc dng chn lc trn ng tiu ha v tit niu. Dng iu tr chng bng, y hi v b i
sau khi m.
Chng ch nh: hen, lot d dy - t trng.

Ung 5- 30 mg. Vin 5- 10- 25- 50 mg
Tim di da: 2,5- 5 mg, 3- 4 ln mt ngy.
1.2.2. CarbAChol
Dng cha bnh tng nhn p, nh dung dch 0,5 -1%
Cn dng lm chm nhp tim trong cc cn nhp nhanh kch pht, ri lon tun hon ngoi bin
(vim ng mch, bnh Raynaul), to bn, chng bng, b i sau m.
Ung 0,5- 2,0 mg/ ngy. Tim di da 0,5 - 1 mg/ ngy.
1.3. Muscarin
C nhiu trong mt s nm c lo i Amanita muscaria, A.pantherina
- Tc dng in hnh trn h thng hu hch ph giao cm, v vy c gi l h muscarinic.
Mnh hn acetylcholin 5 - 6 ln v khng b cholinesterase ph hu.
- Khng dng cha bnh. Nhng c th gp ng c muscarin do n phi nm c: ng t co,
si bt mp, m hi lnh lng, kh th do kh o co tht, nn e, a chy, i dm, tim p
chm, huyt p h...
iu tr: atropin liu cao. C th tim tnh mch tng liu 1 mg atropin sulfat.
1.4. Pilocarpin
c, bng A
L alcaloid ca l cy Pilocarpus jaborandi, P.microphylus - Rutaceae, mc nhiu Nam M.
tng hp c. Kch thch mnh hu hch ph giao cm, tc dng lu hn acetylcholin; lm tit
nhiu nc bt, m hi v tng nhu ng rut. Khc vi muscarin l c c tc dn g kch thch
hch, lm gii phng adrenalin t tu thng thn, nn trn ng vt c tim trc bng
atropin, pilocarpin s lm tng huyt p. Trong cng thc, ch c amin bc 3 nn thm c vo
thn kinh trung ng, liu nh kch thch, liu cao c ch.
Liu trung bnh 0,01- 0,02g
Thng ch dng nh mt dung dch du pilocarpin base 0,5 - 1% hoc dung dch nc pilocarpin
nitrat hoc clohydrat 1- 2% cha tng nhn p hoc i lp vi tc dng gin ng t ca
atropin.
2. Thuc i khng h muscarinic (H M)
2.1. Atropin
c, bng A.
Atropin v ng loi l alcaloid ca l cy Belladon (Atropa belladona), c c dc (Datura
stramonium), thin tin t (Hyoscyamus niger)...
2.1.1. Tc dng
Atropin v ng loi l nhng cht i khng tranh chp vi acetylcholin r eceptor ca h
muscarinic (i lc > 0; hiu lc ni ti = 0). Ch vi liu rt cao v tim vo ng mch th mi
thy tc dng i khng ny trn hch v bn vn ng c vn.
V vy, cc tc dng thng thy l:
- Trn mt, lm gin ng t v mt kh n ng iu tit, do ch nhn c xa. Do lm c mi
gin ra nn cc ng thng dch nhn cu b p li, lm tng nhn p. V vy, khng c dng
atropin cho nhng ngi tng nhn p.
- Lm ngng tit nc bt lng, gim tit m hi, dch v, dch rut
- Lm n kh o, nht l khi n b co tht v cng ph giao cm. t c tc dng trn kh o

bnh thng. Km theo l lm gim tit dch v kch thch trung tm h hp, cho nn atropin
thng c dng ct cn hen.
- t tc dng trn nhu ng rut bnh thng, nhng lm gim khi rut tng nhu ng v co tht.
- Tc dng ca atropin trn tim th phc tp: liu thp do kch thch trung tm dy X hnh no
nn lm tim p chm; liu cao hn, c ch cc receptor muscarinic ca tim, li lm tim p
nhanh. Tim th khng chu s chi phi ca ph giao cm nn atropin khng c nh hng.
- Atropin t nh hng n huyt p v nhiu h mch khng c dy ph giao cm. Ch lm gin
mch da, nht l mi trng nng, v thuc khng lm tit m hi c, nn mch cng gin ra
chng vi xu hng tng nhit.
- Liu c, tc ng ln no gy tnh trng kch thch, thao cung, o gic, st, cui cng l hn
m v cht do lit hnh no.
iu tr nhim c bng thuc khng cholinesterase (physostignin) tim tnh mch cch 2 gi 1
ln v chng triu chng kch thch thn kinh trung ng bng benzodiazepin.
2.1.2. Chuyn ha
D hp thu qua ng tiu ha v ng tim di da. C th hp thu qua nim mc khi dng
thuc ti ch, cho nn tr c th gp tai bin ngay c khi nh mt. Khong 50% thuc b thi
tr nguyn cht qua nc tiu.
2.1.3. p dng lm sng
- Nh mt dung dch atropin sulfat 0,5 - 1% lm gin ng t ti a sau 25 pht, dng soi y mt
hoc iu tr vim mng mt, vim gic mc. Phi vi ngy sau ng t mi tr li bnh thng.
C th dng eserin salicylat (dung dch 0,2%) hay pilocarpin hydrat hoc nitrat (dung dch 1%)
rt ngn tc dng ca atropin.
- Tc dng lm gin c trn c dng ct cn hen, cn au ti mt, cn au thn, au d dy.
- Tim trc khi gy m trnh tit nhiu m di, trnh ngng tim do phn x ca dy ph v.
- Ri lon dn truyn nh tc nh tht (Stockes - Adams) hoc tim nhp chm do nh hng ca
dy X.
- iu tr ng c nm loi muscarin v ng c cc thuc phong to cholinesterase .
Chng ch nh: bnh tng nhn p, b i do ph i tuyn tin lit.
2.1.4. Ch phm v liu lng
Dng di dng base hoc sulfat. Tim tnh mch 0,1 - 0,2 mg; tim di da 0,25 - 0,50 mg (liu
ti a 1 ln: 1 mg; 24gi: 2 mg); ung 1 - 2 mg (liu ti a 1 ln: 2 mg; 24 gi: 4 mg).
Atropin sulfat ng 1 mL = 0,25 mg; vin 0,25 mg
Atropin sulfat ng 1 mL = 1 mg (c bng A), ch dng iu tr ng c cc cht phong to
cholinesterase.
2.2. Homatropin bromhydrat (homatropini hydrobromidum)
c, bng A
Tng hp. Lm gin ng t thi gian ngn hn atropin (trung bnh 1 gi). Dng soi y mt,
dung dch 0,5- 1%.
2.3. Scopolamin (scopolaminum; hyoscinum)
c, bng A
- L alcaloid ca cy Scopolia carniolica.
Tc dng gn ging atropin. Thi gian tc dng ngn hn. Trn th n kinh trung ng, atropin
kch thch cn scopolamin th c ch cho nn c dng cha bnh Parkinson, cc cn co git
ca bnh lit rung, phi hp vi thuc khng histamin chng nn khi say tu, say sng.
Ung hoc tim di da 0,25 - 0,5 mg
Liu ti a mi ln 0,5mg; 24 gi: 1,5mg
Vin Aeron c scopolamin camphonat 0,1mg v hyoscyamin camphonat 0,4mg; dng chng say
sng, say tu: ung 1 vin 30 pht trc lc khi hnh.
2.4. Thuc bn tng hp mang amoni bc 4: Ipratropium
Do gn thm nhm isopropyl vo ngu yn t N ca atropin, ipratropium mang amoni bc 4, khng
hp thu c qua ng ung v khng vo c thn kinh trung ng. Thng dng di dng
kh dung iu tr bnh phi tc nghn mn tnh v ct cn hen. Ch 1% hp thu vo mu v
khong 90% liu kh dung c nut vo ng tiu ha v thi tr theo phn. Tc dng ti a
sau 30- 90 pht v t/2 > 4 gi.
Ch phm: Ipratropium bromid (Atrovent, Berodual) dng kh dung nh liu, 20 g/ nht bp
200 liu.
Ngi ln mi ln bp 2 nht, mi ngy 3 - 4 ln.
3. Thuc kch thch h nicotinic (H N)
Cc thuc ny t c dng trong iu tr, nhng li quan trng v mt dc l v c dng
nghin cu cc thuc tc dng trn hch. Hin nay cc thuc kch thch hch c chia thnh hai
nhm: nhm u gm nicotin v cc thuc tng t, tc dng kch thch trn cc receptor
nicotinic ca hch, b hexametoni c ch; nhm sau gm muscarin, pilocarpin, oxotremorin,
thuc phong to cholinesterase... tc dng kch thch trn cc receptor muscarinic (h M 1) ca
hch, khng b hexametoni, m b atropin c ch.
Serotonin, histamin v cc a peptid kch thch hch c th l trn cc receptor c hiu ring.
Trong phn ny ch ni ti cc cht thuc loi nicotin.
3.1. Nicotin (- pyridyl- metyl pyrrolidin)
c, bng A
C trong thuc l, thuc lo di hnh thc acid hu c (0,5 -

8,0%). Khi ht thuc, nicotin c gii phng ra di dng base
t do. Trung bnh, ht 1 iu thuc l, hp thu khong 1 - 3 mg
nicotin. Liu cht khong 60mg. Trn hch thc vt, liu nh
(0,02- 1,0mg/ kg ch, tim tnh mch) kch thch; liu cao (10 - 30
mg/ kg trn ch) lm lit hch do gy bin cc v sau l tranh
chp vi acetylcholin.
Tc dng:
- Trn tim mch, gy tc dng ba pha: h huyt p tm thi, tng huyt p mnh ri cui cng l
h huyt p ko di.
- Trn h hp, kch thch lm tng bin v tn s
- Gin ng t, tng tit dch, tng nhu ng rut
Nguyn nhn ca nhng tc dng l do:
- Lc u nicotin kch thch hch ph giao cm v trung tm c ch tim hnh no nn lm ti m
p chm, h huyt p.
- Nhng ngay sau , nicotin kch thch hch giao cm, trung tm vn mch v cc c trn, lm
tim p nhanh, tng huyt p, gin ng t v tng nhu ng rut. ng thi kch thch tu
thng thn (coi nh hch giao cm khng l) l m tit adrenalin, qua cc receptor nhn cm ha
hc xoang cnh kch thch phn x ln trung tm h hp.
- Cui cng l giai on lit sau khi b kch thch qu mc nn lm h huyt p ko di.
Nicotin khng dng trong iu tr, ch dng trong cc phng th nghim hoc git su b.
Nicotin gy nghin, nhng khi cai thuc th khng gy bin chng nh cai thuc phin. Ht
thuc l c hi n tim, mch, nim mc ng h hp v khi thuc c oxyd carbon (gy
carboxyhemoglobin trong mu ngi nghin), c c c base nit, cc acid bay hi, cc phenol... l
nhng cht kch thch mnh nim mc. Ngoi ra cn c hc n (c hot cht l 3,4 - benzpyren, c
th l mt trong nhng nguyn nhn gy ung th phi).
3.2. Cc thuc khc
- Lobelin:
L alcaloid ca l cy lobelia inflata.
Tc dng km nicotin rt nhiu. Hu nh khng cn c dng trong lm sng na.
- Tetramethylamoni (TMA) v dimethyl - phenyl- piperazin (DMPP)
Tc dng ging nicotin, kch thch c hch giao cm v ph giao cm nn tc dng phc tp,
khng c dng trong iu tr. Hay c dng trong thc nghim. DMPP cn kch thch thng
thn tit nhiu adrenalin.
4. Thuc phong b h nicotinic (h N)
c chia lm 2 loi: loi phong b hch thc vt, nh hng n hot ng ca c trn, v
loi phong b trn bn vn ng ca c vn.
4.1. Loi phong b h nicotinic ca hch
Cn gi l thuc lit hch, v lm ngn cn lung xung tc thn kinh t si tin hch ti si hu
hch. C ch chung l tranh chp vi acetylcholin ti receptor mng sau ca xinap ca hch.
Nh ta bit, cc hch thn kinh thc vt cng c c hai loi receptor cholinergic l N v M 1.
Khi ni ti cc thuc lit hch l c ngha ch bao hm cc thuc c ch trn receptor N ca hch
m thi.
Tuy cc c quan thng nhn s chi phi ca c hai h giao cm v ph giao cm, song bao gi
cng c mt h chim u th. V vy, tc dng ca cc thuc lit hch trn c quan thuc vo
tnh u th y ca tng h (xem bng di):
C quan H thn kinh chim Tc dng ca thuc lit hch

u th
ng mch nh Giao cm Gin mch, h huyt p
Tnh mch Giao cm Gin: tr tun hon , gim cung lng
tim
Tim Ph giao cm p nhanh
ng t Ph giao cm Gin
Rut Ph giao cm Gim trng lc v nhu ng, to b n
B tiu tin
Bng quang Ph giao cm Gim tit, kh ming
Tuyn nc bt Ph giao cm
Trong lm sng, cc thuc lit hch thng c dng lm h huyt p trong cc cn tng
huyt p, h huyt p iu khin trong m x, v i khi iu tr ph phi cp, do chng c
nhng c im sau:
- Cng c ch giao cm gy gin mch t l vi liu dng
- Tc dng mt i nhanh sau khi ngng thuc, do d kim tra c hiu lc ca thuc
- Cc receptor adrenergic ngoi bin vn p ng c bnh thng nn cho php d dng iu tr
khi c tai bin
Nhng tai bin v tc dng ph thng gp l:
- Do phong b hch giao cm, nn:
. D gy h huyt p khi ng (phi ngi bnh nm 10 - 15 pht sau khi tim)
iu tr tai bin bng adrenalin v ephedrin.
. Ri lon tun hon mch no, mch vnh.
. Gim tit niu.
- Do phong b hch ph giao cm nn:
. Gim tit dch, gim nhu ng rut, lm kh ming v to bn.
. Gin ng t, ch nhn c xa.
. B i do gim trng lc bng quang.
Cc thuc c (tetra ethyl amoni - TEA v hexametoni) u mang amoni bc 4, kh h p thu. Hin
cn 2 thuc c s dng.
4.1.1. Trimethaphan (Arfonad)
Phong b hch trong thi gian rt ngn. Truyn tnh mch dung dch 1 mg trong 1 mL, huyt p
h nhanh. Khi ngng truyn, 5 pht sau huyt p tr v bnh thng
Dng gy h huyt p iu khin trong phu thut hoc iu tr ph phi cp.
ng 10 mL c 500 mg Arfonad, khi dng pha thnh 500 mL trong dung dch mn ng trng
c 1 mg trong 1 mL.
4.1.2. Mecamylamin (Inversin)
Mang N ha tr 2, cho nn d hp thu qua ng tiu ha, c th ung c. T c dng ko di 4-
12 gi. Dng lu tc dng s gim dn
Ung mi ln 2,5 mg, mi ngy 2 ln. Tng dn cho ti khi t c hiu qu iu tr, c th
ung ti 30 mg mi ngy.
Vin 2,5 mg v 10 mg
Liu cao c th kch thch thn kinh trung ng v phong to bn vn ng c vn.
4.2. Loi phong b h nicotinic ca c vn
Cura v cc ch phm
c, bng B
4.2.1. Tc dng
Cura tc dng u tin trn h nicotinic ca cc c xng (c vn), lm ngn cn lung xung tc
thn kinh ti c bn vn ng (Claude Bernard, 1856 ) nn lm gin c. Khi kch thch trc tip,
c vn p ng c. Di tc dng ca cura, cc c khng b lit cng mt lc, m ln lt l
cc c mi (gy sp mi), c mt, c c, c chi trn, chi di, c bng, cc c lin sn v cui
cng l c honh, lm bnh nhn ngng h hp v cht. V tc dng ngn nn nu c h hp
nhn to, chc phn cc c s c hi phc theo th t ngc li.
Ngoi ra, cura cng c tc dng c ch trc tip ln trung tm h hp hnh no v lm gin
mch h huyt p hoc co tht kh qun do gii phng histamin
Hu ht u mang amin bc 4 nn rt kh thm vo thn kinh trung ng, khng hp thu qua
thnh rut.
4.2.2. Cc loi cura v c ch tc dng. Theo c ch tc dng, chia lm hai loi:
4.2.2.1. Loi tranh chp vi acetylc holin bn vn ng, lm cho bn vn ng khng kh cc
c, gi l loi cura chng kh cc (antidpolarisant), hoc loi ging cura (curarimimetic) hay
pakicura (Bovet). Gii c bng cc thuc phong to cholinesterase (physostigmin, prostigmin
tim tnh mch tng 0,5 mg, khng vt qu 3 mg. C th tim thm atropin 1 mg ngn cn
tc dng cng h muscarinic ca thuc).
Loi ny c tc dng hip ng vi thuc m, thuc ng loi barbiturat, thuc an thn loi
benzodiazepin
- d- Tubocurarin: l alcaloid ly t cc cy loi Chondodendron tementosum v Strychnos m th

dn Nam M dng tm tn c. Tc dng ko di vi gi. Khng dng trong lm sng
- Galamin (flaxedil): tng hp. C thm tc dng ging atropin nn lm tim p chm, khng
lm gii phng histamin v km c hn d - tubocurarin 10- 20 ln. Tc dng pht trin chm trn
cc nhm c khc nhau, thi gian lm gin c bng n lit c honh kh di nn gii hn an
ton rng hn.
Ch phm: Remiolan ng 5 mL = 0,1g galamin triethyl iodid. Liu 0,5 mg/ kg
- Pancuronium (Pavulon): l steroid mang 2 amoni bc 4. Tc dng khi pht sau 4 - 6 pht v
ko di 120- 180 pht. u im chnh l t tc dng trn tun hon v khng lm gii phng
histamin.
- Pipecuronium (Arduan): khi pht tc dng sau 2 - 4 pht v ko di 80- 100 pht.
L cha bt pha tim 4 mg + 2 mL dung mi. Tim tnh mch 0,06 - 0,08 mg/ kg
4.2.2.2. Loi tc ng nh acetylcholin, lm bn vn ng kh cc qu mnh, (depolarisant) gi
l loi ging acetylcholin, (acetylcholinomimetic) ho c leptocura (Bovet). Cc thuc phong b
cholinesterase lm tng c tnh. Khng c thuc gii c, tuy d - tubocurarin c tc dng i
khng. Trc khi lm lit c, gy git c trong vi giy.
-Decametoni bromid: gy git c v au c, c th gy tai bin ngng th ko di nn c xu
hng dng succinylcholin thay th.
Succinylcholin: l thuc duy nht ca nhm cura kh cc c dng lm sng. C cu trc ha
hc nh 2 phn t ACh gn vo nhau:
Succinylcholin
Khi pht tc dng sau 1 - 1,5 pht v ko di ch khong 6- 8 pht, do b cholinesterase trong
huyt tng thu phn. Succinylcholin y K + t trong t bo ra nn c th lm tng K + mu 30-
50%, gy lon nhp tim.
Ch phm: Myo- relaxin ng 0,25g succinylcholin bromid. Tim tnh mch t 1 mg/ kg.
4.2.3. Ch nh v liu lng
- Lm mm c trong phu thut, trong chnh hnh, t ng ni kh qun.
- Trong tai mi hng, dng soi thc qun, gp d vt...
- Chng co git c trong chong in, un vn, ng c strychnin.
Khi dng phi t ng ni kh qun. Khng hp th qua nim mc tiu ha nn phi tim tnh
mch. Liu lng tu theo tng trng hp, c th tim 1 ln hoc truyn nh git vo tnh mch.
Liu mm c u tin thng l:
d- Tubocurarin 15 mg
Methyl d- tubocurarin 5 mg
Galamin (flaxedyl) 20- 100 mg
Decametoni 4 mg
Succinylcholin diiodua 30- 60 mg
Ch : mt s thuc khi dng cng vi cura loi curarimimetic (d - tubocurarin) c th c tc
dng hip ng, lm tng tc dng lit c ca cura, nn cn gim liu:
- Cc thuc m nh ether, halothan, cyclopropan.
- Cc khng sinh nh neomycin, streptomycin, polimycin B, kanamycin.
- Quinin, quinidin
5. Thuc khng cholinesterase
Cholinesterase l enzym thu phn lm mt tc dng ca acetylcholin. Mt phn t acetylcholin
s gn vo hai v tr hot ng ca enzym; v tr anion (anionic site) s gn vi cation N + ca
acetylcholin, cn v tr gn este (esteratic site) gm mt nhm base v mt nhm acid proton ( --
H) to nn mt lin kt hai ha tr vi nguyn t C ca nhm carboxyl ca este:
Physostigmin
5.1.1. Physostigmin (physotigminum; eserin)
c, bng A
L alcaloid ca ht cy Physostigma venenosum. V c amin bc 3, nn d hp th v thm c
c vo thn kinh trung ng
Dng cha tng nhn p (nh mt dung dch eserin sulfat hoc salicylat 0,25 - 0,5%) , hoc kch
thch nhu ng rut (tim di da, ng 0,1% - 1 mL, mi ngy 1- 3 ng).
Khi ng c, dng atropin liu cao.
5.1.2. Prostigmin (neostigmin, pros erin)
c, bng A
V mang amin bc 4 nn khc physostigmin l c i lc
mnh hn vi cholinesterase, v khng thm c vo
thn kinh trung ng. Tc dng nhanh, t tc dng trn
mt, tim v huyt p. Ngoi tc dng phong to
cholinesterase, prostigmin cn kch thch trc tip c Prostigmin
vn, tc dng ny khng b atropin i khng.
p dng:
- Ch nh tt trong bnh nhc c bm sinh (myasthenia gravis) v thiu ht acetylcholin bn
vn ng c vn. Cn c dng trong cc trng hp teo c, lit c .
- Lit rut, b i sau khi m
- Nh mt cha tng nhn p
- Cha ng c cura loi tranh chp vi acetylcholin
Liu lng, ch phm:
- Tim di da mi ngy 0,5 - 2,0 mg
- Ung mi ngy 30-90 mg v thuc kh thm qua d dy v d b ph hu
ng 1 mL = 0,5 mg prostigmin methyl sulfat
5.1.3. Edrophonium clorid (Tensilon)
Cht tng hp
Tc dng mnh trn bn vn ng c vn, l thuc gii c
cura loi tranh chp vi acetylcholin. Tc dng ngn hn
prostigmin.
Trong bnh nhc c, tim tnh mch 2 - 5 mg; gii c cura:
5- 20 mg
ng 1 mL = 10 mg edrophonium clorid. Tensilon
5.2. Loi c ch khng hi phc hoc rt kh hi phc
5.2.1. Cc hp cht ca phospho hu c: cc cht ny kt hp vi cholinesterase ch v tr gn
este. Enzym b phosphoryl ha rt vng bn, kh c thu phn hi phc tr li, i hi c
th phi tng hp li cholinesterase mi. V vy lm tch lu nhiu acetylcholin ton b h
cholinergic t vi ngy ti hng thng.
c ch mnh c cholinesterase tht cng nh gi. Trong lm sng, nh gi tnh trng nhim c
bng nh lng cholinesterase gi trong huyt tng.
Cc cht c ch cholinesterase loi phospho hu c c cng thc chung l:
R1 O

P

R2 X
Trong X c th l halogen, cyanid (CN), thiocyanat, alkoxy, thiol, pyrophosphat...
Ch c DFP (di- isopropyl- fluo- phosphat) c dng nh mt cha bnh tng nhn p (dung
dch 0,01- 0,05%). Cc dn xut khc c dng lm thuc tr su (TEPP, parathion,...), hoc s
dng lm hi c chin tranh (tabun, sarin, soman...).
5.2.2. Du hiu nhim c cp: cc du hiu nhim c cp phn nh s trn ngp acetylcholin
ton b h cholinergic.
- Du hiu kch thch h M: co ng t, sung huyt gic mc, chy nc mi, nc bt , dch kh
qun, co kh qun, nn, au bng, tiu chy, tim p chm, h huyt p.
- Du hiu kch thch h N: mt mi, git c, cng c, lit v nguy him hn c l lit h hp.
- Du hiu kch thch thn kinh trung ng: l ln, mt ng tc, mt phn x , nhp th Cheyne-
Stokes, co git ton thn, hn m, lit h hp, h huyt p do trung tm hnh tu b c ch.
Nguyn nhn dn ti t vong l do suy h hp v tim mch do c 3 c ch kch thch h M, N v
trung ng.
5.2.3. iu tr nhim c
5.2.3.1. Thuc hu h M: atropin sulfat liu rt cao. Tim tnh mch liu 1- 2 mg, cch 5- 10
pht mt ln cho n khi ht triu chng kch thch h M, hoc bt u c du hiu nhim c
atropin (gin ng t). Ngy u c th tim ti 200 mg.
5.2.3.2. Dng thuc hot ha cholinesterase: mt s cht a nhn (nucleophylic agents) nh
hydroxylamin (NH 2OH), acid hydroxamic (R - CO- NHOH) v oxim (R- CH = NOH) c kh
nng gii phng c enzym b phospho hu c phong ta v hot ha tr li. Cht thng dng
l pralidoxim (2- PAM) tc dng ln ChE phosphoryl ha, to oximphosphonat b thi tr v gii
phng cholinesterase.
Pralidoxim (2- PAM): l 1g km ng nc 20 mL. Mi u, tim tnh mch 1 - 2g, sau truyn
nh git tnh mch mi gi 0,5g.
5.2.3.3. iu tr h tr
Thay qun o, ra cc vng da c tip xc vi cht c, ra d dy nu ng c do ng ung.
H hp h tr, th oxy. Chng co git bng diazepam (5 - 10 mg tim tnh mch) hoc natri
thiopental (2,5% tim tnh mch). iu tr sc.
Cu hi t lng gi
1. Trnh by sinh chuyn ha, c ch tc dng v p dng iu tr ca acetylcholin.
2. Trnh by tc dng ca muscarin v iu tr ng c muscarin.
3. So snh acetylcholin v pilocarpin.
4. Trnh by c ch tc dng v p dng iu tr ca atropin
5. Phn tch c ch tc dng ca nicotin.

6. Phn tch c ch tc dng ca thuc lit hch (ngng hm h N ca hch) v p dng
lm sng.
7. Phn bit 2 loi cura v c ch tc dng, tc dng v p dng lm sng.
8. Phn tch c ch tc dng, tc dng v cch iu tr ng c th uc phong ta khng hi
phc cholinnesterase.
Bi 6: Thuc tc dng trn h adrenergic

1. Trnh by c chu trnh chuyn ha ca catecholamin ti ngn dy thn kinh giao
cm
2. Phn bit c tc dng ca adrenalin, noradrenalin v DA
3. Phn bit c tc dng ca thuc cng 1 v 2: Isoproterenol, dobutamin v
salbutamol
4. Phn tch c c ch tc dng ca cc thuc hu giao cm
5. Trnh by c tc dng v p dng iu tr ca thuc hy giao cm
6. Phn bit c c ch tc dng v p dng iu tr ca thuc hy 1
H adrenergic l h hu hch giao cm, gii phng cht trung gian ha hc gi chung l
catecholamin v u mang nhn catechol (vng benzen c hai nhm -OH v tr ortho v mt gc
amin chui bn. Cc catecholamin gm c adrenalin (c sn xut ch yu tu thn g thn)
noradrenalin ( u tn cng cc si giao cm) v dopamin ( mt s vng trn thn kinh trung
ng).
Hnh 6.1. Sinh tng hp catecholamin

1. Chuyn ha ca catecholamin
Catecholamin c sinh tng hp t tyrosin di tc dng ca mt s enzym trong t bo a
crm tu thng thn, cc nron hu hch giao cm v mt s nron ca thn kinh trung ng
theo s trn (hnh 6.2)
Hnh 6.2. Chuyn vn ca catecholamin ti tn cng dy giao cm

Tyrosin c vn chuyn vo u tn cng dy giao cm nh c ht vn chuyn ph thuc Na +
(A). Tyrosin c chuyn ha thnh dopamin (DA) ri c cht vn chuyn (B) a vo cc ti
d tr (cc ht). Cht vn chuyn ny cng vn chuyn c noradrenalin (NA) v vi amin khc.
Trong ti d tr, DA c chuyn ha thn h NA. in th hot ng lm m knh calci, Ca 2+
vo t bo, gii phng NA t ti d tr.
Sau khi c tng hp, mt phn catecholamin s kt hp vi ATP hoc vi mt dng protein ha
tan l chromogranin tr thnh dng khng c hot tnh, khng b cc e nzym ph hu, lu li
trong cc kho d tr l nhng ht c bit nm bo tng (khong 60%), cn mt phn khc
(khong 40%) vn dng t do trong bo tng, d di ng, nm ngoi ht. Gia hai dng ny
lun c s thng bng ng, khi dng t do gim i th li c b sung ngay t cc kho d tr.
Lng noradrenalin trong bo tng iu chnh hot tnh ca tyrosin hydroxylase theo c ch
iu ha ngc chiu: khi noradrenalin tng th hot tnh ca enzym gim, v ngc li. Mt
khc, cc cht cng re ceptor 2 lm gim gii phng noradrenalin ra khe xinap v do tr
lng ca noradrenalin trong bo tng s tng ln.
Theo gi thit ca Burn v Rand (1959 - 1962) di nh hng ca xung tc thn kinh, ngn dy
giao cm lc u tit ra acetylcholin, l m thay i tnh thm ca mng t bo, do Ca ++ t
ngoi t bo thm nhp c vo trong t bo, ng vai tr nh mt enzym lm v lin kt ATP -
catecholamin, gii phng catecholamin ra dng t do.
Sau khi c gii phng, mt phn noradrenalin s tc n g ln cc receptor (sau v trc xinap),
mt phn chuyn vo mu tun hon tc dng xa hn ri b ging ha, cn phn ln (trn
80%) s c thu hi li, phn nh khc b mt hot tnh ngay trong bo tng.
Hnh 6.3. S phn ca noradrenalin khi c gii phng

1. Tc dng trn receptor sau (1a) v trc (1b) xinap
2. Thu hi
3. Vo tun hon v b chuyn ha bi COMT
4. Chuyn ha trong bo tng bi MAO
Catecholamin b mt hot tnh bi qu trnh oxy ha kh amin do hai enzym MAO (mono - amin
oxydase) v COMT (catechol - oxy- transferase) cui cng thnh acid 3 - methoxy- 4
hydroxy mandelic (hay vanyl mandelic acid - VMA) thi tr qua nc tiu.
MAO c nhiu trong ti th (mitochondria), v vy n ng vai tr ging ha catecholamin trong
t bo hn l tun hon. Phong to MAO th lm tng
catecholamin trong m nhng khng nh hng n tc dng ca catecholamin ngoi lai.
COMT l enzym ging ha catecholamin ngoi t bo, c mng xinap v nhiu ni nhng
m cao hn c l gan v thn. Phong to COMT th ko di c thi gian tc dng ca
catecholamin ngoi lai.
Receptor: Adrenalin v noradrenalin sau khi c gii phng ra s tc dng ln cc receptor ca
h adrenergic. Ahlquist (1948) chia cc receptor thnh hai loi v do chng c tc dng
khc nhau trn cc c quan (bng sau).
Ta thy rng tc dng cng c tnh cht kch thch, lm co tht cc c trn, ch c c trn
thnh rut l gin. Ngc li, tc dng cng c tnh cht c ch, lm gin c, tr c tim li
lm p nhanh v p mnh.
Land, Arnold v Mc Auliff (1966) cn chia cc receptor thnh hai nhm 1 (tc dng trn tim
v chuyn ha m) v nhm 2 (lm gin mch, gin kh o v chuyn ha ng). 2 trc
xinap kch thch lm tng gii phng NA, c vai tr iu ha ngc vi 2.
Theo xut ca Langer (1974), cc receptor c chia thnh hai loi: loi 1 l receptor sau
xinap, lm co mch tng huyt p, loi 2 l receptor trc xinap, c tc dng iu ha, khi kch
thch s lm gim gii phng norad renalin ra khe xinap, ng thi lm gim tit renin, gy h
huyt p. Cc receptor 2 c nhiu h giao cm trung ng. Hin cng thy c receptor 2
sau xinap ca mch mu v t bo c trn (lm co), m m v cc t bo biu m xut tit (rut,
thn, tuyn ni tit)
Dopamin ch yu tc dng thn kinh trung ng, thn v cc tng, trn cc receptor c hiu
i vi n gi l cc receptor dopaminergic (receptor delta - )
Bng 6.1: Cc receptor adrenergic
Recepto Cht ch Chti M p ng C ch phn t
r vn khng
1 Adr NA Prazosin - C trn Co tht Kch thch
>>Iso thnh mch Co tht phospholipase C
Phenylephrin - C trn Hu glycogen to IP3 v
sinh dc Tn to ng DAG; tng Ca ++
tit niu u cc ha v cytosol
- Gan gin - Hot ha knh
- C trn Tng co bp, lon K+ ph thuc vo
rut nhp Ca++
- Tim - c ch dng K +
2 AdrNA >> Yohimbi - T bo Gim tit insulin - c ch
Iso n ca ty adenylcyclase
Clonidin - Tiu cu Ngng kt (Gi) - Hot ha
- Tn cng Gim tit NA knh K +
si TK - c ch knh Ca ++
- C trn Co -Tng lung Ca,
thnh mch tng Ca ++ trong
cytosol
1 Iso>Adr =NA Metoprol - Tim Tng tn s, bin Hot ha
Dobutamin ol v tc dn adenylcyclase v
truyn A-V knh Ca

- T bo Tng tit renin
gn cu
thn
2 Iso>Adr >> ICI - C trn - Gin Hot ha
NA 118551 (mch kh - Hu glycogen adenylcyclase
Terbutalin qun, gn K+
rut...) - Hy glycogen
- C vn - Tn to ng
- Gan
3 Iso=NA>Adr ICI Hu lipid Hot ha
BRL 37344 118551 adenylcyclase
CGP
20712A
Iso*: Isoproterenol Adr: adrenalin NA: noradrenalin
Ghi ch ca bng 3:
- Mi receptor u kch thch adenylcyclase thng qua protein G S v lm tng AMPv, ngoi ra
cn lm knh calci cm ng vi in th ca c vn v c tim.
- Receptor 2, tri li, c ch adenylcyclase thng qua protein G i, ng thi hot ha knh kali,
c ch knh calci.
- Receptor 1 kch thch lm tng calci ni bo thng qua 2 cht trung gian Diacylglycerol
(DAG) v Inositol triphosphat (IP 3).
2. Thuc cng h adrenergic
L nhng thuc c tc dng ging adrenalin v noradrenalin , kch thch hu hch giao cm nn
cn gi l thuc cng giao cm. Theo c ch tc dng c th chia cc thuc ny lm hai loi:
- Loi tc dng trc tip trn cc receptor adrenergic sau xinap nh adrenalin, noradrenalin,
isoproterenol, phenylephrin
- Loi tc dng gin tip do kch thch cc receptor trc xinap, lm gii phng catecholamin ni
sinh nh tyramin (khng dng trong iu tr), ephedrin, amphetamin v phenyl - ethyl- amin. Khi
dng reserpin lm cn d tr catecholamin th tc dng ca cc thuc s gim i. Trong nhm
ny, mt s thuc c tc dng kch thch thn kinh trung ng theo c ch cha hon ton bit r
(nh ephedrin, amphetamin), reserpin khng nh hng n tc dng ny; ho c c ch mono-
amin- oxydase (MAOI), lm vng bn catecholamin.
2.1.Thuc cng receptor alpha v beta
2.1.1.Adrenalin
c, bng A
L hormon ca tu thng thn, ly ng vt hoc tng hp. Cht t nhin l ng phn t
tuyn c tc dng mnh nht.
2.1.1.1.Tc dng
Adrenalin tc dng c trn v receptor.

- Trn tim mch:
Adrenalin lm tim p nhanh, mnh (tc dng ) nn lm tng huyt p ti a, tng p lc t
ngt cung ng mch ch v xoang ng mch cnh, t pht sinh cc phn x gim p qua
dy thn kinh Cyon v Hering lm cng trung tm dy X, v vy lm tim p chm dn v huyt
p gim. Trn ng vt th nghim, nu ct dy X hoc tim atropin (hoc methylatropin) trc
ct phn x ny th adrenalin ch lm tim p nhanh mnh v hu yt p tng rt r.
Mt khc, adrenalin gy co mch mt s vng (mch da, mch tng - receptor ) nhng li gy
gin mch mt s vng khc (mch c vn, mch phi - receptor ...) do huyt p ti thiu
khng thay i hoc c khi gim nh, huyt p tru ng bnh khng tng hoc ch tng nh trong
thi gian ngn. V l adrenalin khng c dng lm thuc tng huyt p.
Tc dng lm gin v tng lu lng mch vnh ca adrenalin cng khng c dng trong iu
tr co tht mch vnh v tc dng ny li km theo lm tng cng nng v chuyn ha ca c tim.
Di tc dng ca adrenalin, mch mu mt s vng co li s y mu ra nhng khu vc t chu
nh hng hn, gy gin mch th ng nhng ni (nh mch no, mch phi) do d gy
cc bin chng t mch no, hoc ph phi cp.
- Trn ph qun:
t tc dng trn ngi bnh thng. Trn ngi b co tht ph qun do hen th adrenalin lm gin
rt mnh, km theo l co mch nim mc ph qun, lm gim ph cho nn nh hng rt tt ti
tnh trng bnh. Song adrenalin b mt tc dng rt nhanh vi nhng ln dng sau, v vy khng
nn dng ct cn hen.
- Trn chuyn ha:
Adrenalin lm tng hu glycogen gan, lm tng glucose mu, lm tng acid bo t do trong mu,
tng chuyn ha c bn, tng s dng oxy c a m.
Cc c ch tc dng ca adrenalin hay catecholamin ni chung l lm tng tng hp adenosin 3' -
5'- monophosphat (AMP- vng) t ATP do hot ha adenylcyclase (xem s )
S tc ng ca catecholamin ln chuyn ha ng v m
Catecholamin Cafein
Diazoxid
(-)
Adenylcyclase Phosphodiesterase
ATP 3', 5'- AMP AMP
(AMP vng)
Triglycerid Triglycerid
lipase
Glycogen (-)
Glycogen
Phospho- Glucose- 1- phosphat synthetase Diglycerid Acid bo
rylase
Glucose- 6- phosphat Monoglycerid Acid bo
Glucose mu Nng lng

Acid lactic Glycerol Acid bo
2.1.1.2. p dng iu tr:
- Chng chy mu bn ngoi (p ti ch dung dch adrenalin hydroclorid 1% lm co mch).
- Tng thi gian gy t ca thuc t v adrenalin lm co mch ti ch nn lm chm hp thu thuc
t.
- Khi tim b ngng t ngt, tim adrenalin trc tip vo tim hoc truyn mu c adrenalin vo
ng mch hi tnh.
- Sc ngt: dng adrenalin tng huyt p tm thi bng cch tim tnh mch theo phng php
trng bm tim.
Liu trung bnh: tim di da 0,1- 0,5 mL dung dch 0,1% adrenalin hydroclorid.
Liu ti a: mi ln 1 mL; 24 gi : 5 mL
ng 1 mL = 0,001g adrenalin hydroclorid
2.1.2. Noradrenalin (arterenol)
c, bng A
L cht dn truyn thn kinh ca cc si hu hch giao cm. Tc dng mn h trn cc receptor ,
rt yu trn , cho nn:
- Rt t nh hng n nhp tim, v vy khng gy phn x cng dy ph v.
- Lm co mch mnh nn lm tng huyt p ti thiu v huyt p trung bnh (mnh hn adrenalin
1,5 ln)
- Tc dng trn ph qun rt yu, v c trn ph qun c nhiu receptor 2.
- Tc dng trn dinh dng v chuyn ho u km adrenalin. Trn nhiu c quan, tc dng ca
NA trn receptor km hn adrenalin mt cht. Nhng do t l cng tc dng gia v
khc nhau nn tc dng c hung khc nhau r rt.
Trn thn kinh trung ng, noradrenalin c nhiu vng di i. Vai tr sinh l cha hon ton
bit r. Cc cht lm gim d tr catecholamin no nh reserpin, methyldopa u
gy tc dng an thn. Tri li, nhng thuc c ch MAO, lm tng catecholamin th u c tc

dng kch thn.
iu ha thn nhit ph thuc vo s cn bng gia NA, serotonin v acetylcholin phn trc
ca vng di i.
C th cn tham gia vo c ch gim au: thuc lm gim lng catechola min tim vo no tht
c ch c tc dng gim au ca morphin.
Ch nh: nng huyt p trong mt s tnh trng sc: sc nhim c, nhim khun, sc do d
ng...
Ch truyn nh git tnh mch t 1 - 4 mg pha long trong 250 - 500 mL dung dch glucose ng
trng. Khng c tim bp hoc di da v lm co mch ko di, d gy hoi t ti ni tim.
ng 1 mL = 0,001g
2.1.3. Dopamin
Dopamin l cht tin thn ca noradrenalin v l cht trung gian ha hc ca h dopaminergic.
C rt t ngn dy giao cm. Trong no, tp trung cc nhn xm trung ng v b en vn.
Trn h tim mch, tc dng ph thuc vo liu:
- Liu thp 1- 2 g/ kg/ pht c gi l "liu thn", tc dng ch yu trn receptor dopaminergic
D1, lm gin mch thn, mch tng v mch vnh. Ch nh tt trong sc do suy tim hoc do gim
th tch mu (cn phc hi th tch mu km theo).
- Ti thn, "liu thn" ca dopamin lm tng nc tiu, tng thi Na +, K+, Cl-, Ca++, tng sn xut
prostaglandin E 2 nn lm gin mch thn gip thn chu ng c thiu oxy.
- Liu trung bnh > 2- 10 g/ kg/ pht, tc dng trn receptor 1, lm tng bin v tn s tim.
Sc cn ngoi bin ni chung khng thay i.
- Liu cao trn 10g/ kg/ pht tc dng trn receptor 1, gy co mch tng huyt p.
Trong lm sng, tu thuc vo tng loi sc m chn liu.
Dopamin khng qua c hng ro mu no
Ch nh: cc loi sc, km theo v niu
ng 200 mg trong 5 mL. Truyn chm tnh mch 2 - 5 g/ kg/ pht. Tng gim s git theo hiu
qu mong mun.
Chng ch nh: cc bnh mch vnh
2.2. Thuc cng receptor
2.2.1. Metaraminol (Aramin)
Tc dng u tin trn receptor 1. Lm co mch mnh v lu hn adrenalin, c th cn do kch
thch gii phng noradrenalin, khng gy gin mch th pht. Lm tng lc co bp ca c tim, t
lm thay i nhp tim. Khng kch thch thn kinh trung ng, khng nh hng n chuyn ha.
V mt gc phenol trn vng benzen nn vng bn hn adrenalin.
Dng nng huyt p trong cc trng hp h huyt p t ngt (chn thng, nhim khun, sc).
Tim tnh mch 0,5- 5,0 mg trong trng hp cp cu. Truyn chm tnh mch dung dch 10 mg
trong 1 mL. C th tim di da hoc tim bp. ng 1 mL= 0,01g metaraminol bitartrat.
2.2.2. Phenylephrin (neosynephrin)
Tc dng u tin trn receptor 1. Tc dng co mch tng huyt p ko di, nhng khng mnh
bng NA. Khng nh hng n nhp tim, khng kch thch thn kinh trung ng, khng lm
tng glucose huyt.
Ch nh: nh noradrenalin
Tim bp 5- 10 mg
Truyn chm vo tnh mch 10 - 15 mg trong 1000 mL dung dch glucose ng trng
Cn dng chng xung huyt v gin ng t trong mt s ch phm chuyn khoa.
2.2.3. Clonidin (Catapressan)
Clonidin (dicloro- 2, 6 phenyl- amino- imidazolin) c tc dng cng receptor 2 trc xinap
trung ng v thuc qua c h ng ro mu- no. Tc dng cng 2 sau xinap ngoi bin ch
thong qua nn gy tng huyt p ngn. Sau , do tc dng cng 2 trung ng chim u th,
clonidin lm gim gii phng NA t cc nron giao cm hnh no, gy gim nhp tim, gim
trng lc giao cm, gim lu lng mu no, tng, thn v mch vnh, a n h huyt p.
Clonidin lm cn bi tit nc bt, dch v, m hi, lm gim hot tnh ca renin huyt tng,
gim li niu. ng thi c tc dng an thn, gim au v gy mt mi. Mt s t c gi cho rng
clonidin gn vo receptor imidazolin thn kinh trung ng, l loi receptor mi ang c
nghin cu.
Tc dng khng mong mun: ng g, kh ming
Ch nh: tng huyt p th va v nng (xin xem bi "Thuc cha tng huyt p")
Chng ch nh: trng thi trm cm.
Khng dng cng vi guanetidin hoc thuc lit hch v c th gy cn tng huyt p.
Liu lng: vin 0,15 mg. Ung liu tng dn ti 6 vin mt ngy, tc dng xut hin chm.
Dng cng vi thuc li niu, tc dng h huyt p s t ng.
2.3. Thuc cng receptor
C 4 tc dng dc l chnh
- Tc dng gin ph qun, dng cha hen: loi cng 2.
- Tc dng gin mch: loi cng 2
- Tc dng kch thch 1 lm tng tn s, tng lc co bp ca c tim, tng tc dn truyn trong
c tim, tng ti mu cho c tim.
- Trn t cung c cha, thuc cng 2 lm gim co bp c dng chng da xy thai.
2.3.1. Isoproterenol (Isoprenalin, Isuprel, Aleudrin, Novodrin, Isopropyl noradrenalin)
Tc dng u tin trn receptor (1 v 2). Lm tng nhp tim, tng sc co bp ca c tim v
cung lng tim, gy gin mch, h huyt p, lm gin kh qun nhanh v mnh (gp 10 ln
adrenalin), ng thi lm gim tit dch nim mc nn ct cn hen rt tt.
Dng trong cc trng hp nhp tim chm thng xuyn , nghn nh tht hon ton, lon nhp do
nhi mu c tim: truyn tnh mch 0,5mg trong 250 - 500 ml dung dch glucose 5%. Tc dng
tng ng huyt km adrenalin v cn trc tip kch thch t bo ty tit insulin.
Trong hen ph qun v trn kh ph mc mn tnh, t di li vin 10 mg, 2 - 3 ln/ ngy.
Khng ung v b chuyn ha nhanh.
ng Novodrin 1 mL= 0,5 mg isoprenalin clohydrat
Vin 10- 20 mg isoprenalin sulfat
Phun dch 1 phn nghn
2.3.2. Dobutamin (Dobutrex)
Cng thc gn ging dopamin: tc dng u tin trn 1 receptor. Tc dng phc tp do
dobutamin raxemic c 2 ng phn; ng phn ( -) dobutamin c tc dng cng 1 mnh, gy
tng huyt p; trong khi ng phn (+) dobutamin li c tc dng i lp hy 1. C hai ng
phn u c tc dng cng , nhng ng phn (+) 10 ln mnh hn ng phn ( -). Tc dng
ca dobutamin raxemic l tng hp ca c hai ng phn.
Trn tim, do dobutamin lm tng co bp mnh v t lm tng nhp , v vy khng lm tng nhu
cu s dng oxy ca c tim. Tc dng km isopr oterenol. t tc dng trn mch nhng lm gin
mch vnh. Tc dng li niu ch yu l do tng lu lng tim.
Ch nh: suy tim cp sau m tim, nhi mu c tim
V thi gian bn thi ch khong 2 pht nn ch dng bng ng truyn chm tnh mch.
Ch phm: Dobutamin hydroclorid (Dobutrex) l 20 mL cha 250 mg dobutamin. Khi dng, ha
long trong 50 mL dung dch dextrose 5%, truyn tnh mch vi liu 2,5 - 10 g/ kg/ pht. Nu
nhp tim tng nhanh, gim tc truyn.
2.3.3. Thuc cng u tin (chn lc) rece ptor 2
L thuc thng c dng iu tr ct cn hen. Tuy nhin, liu cao cng vn kch thch c 1,
lm tng nhp tim. V vy hng nghin cu ti vn l tm cch thay i cu trc c cc thuc
tc dng ngy cng chn lc trn 1 hn v c sinh kh dng cao hn. ng thi dng thuc di
dng kh dung trnh hp thu nhiu thuc vo ng ton thn, d gy tc dng ph (tim p
nhanh, run tay)
Cc thuc cng 2 dng di dng kh dung, ngoi tc dng lm gin ph qun cn c th c
ch gii phng leucotrien v histamin khi dng bo phi (xem thm bi "Thuc iu chnh
ri lon h hp")
Chng ch nh: bnh mch vnh, lon nhp tim, cao huyt p nng, i tho ng, cng gip.
Dng ko di lin tc, tc dng c th gim dn do s lng recept or 2 mng t bo sau xinap
gim ("down regulation")
2.3.3.1. Terbutalin
Do c vng resorcinol trong cu trc nn khng b COMT metyl ha. Sau kh dung, tc dng ko
di c 3- 6 gi.
2.3.3.2. Albuterol (Salbutamol - Ventolin)
Tnh cht dc l v ch nh iu tr nh terbutalin. Dng ng ung hoc kh dung. Sau kh
dung, tc dng ti a vo pht th 15 v duy tr c 3 - 4 gi.
- Vin gii phng chm (Volmax): 4 - 8 mg 2 ln/ ngy
- Kh dung nh liu (Ventolin): 100 g/ nht bp 2 nht/ ln 3- 4ln/ ngy cch nhau 4
ting.
2.3.2.3. Ritodrin
Dng lm gin t cung, chng non (xem bi " Thuc tc dng trn t cung"). Hp thu nhanh
qua ng ung nhng sinh kh dng ch c 30%. Thi tr qua nc tiu 90% di dng lin
hp. Tim tnh mch, 50% thi tr di dng nguyn cht.
2.4. Thuc cng giao cm gin tip
2.4.1. Ephedrin (ephedrinum)
c, bng B
Ephedrin l alcaloid ca cy ma hong (Ephedra equisetina v Ephedra vulgaris). Hin nay
tng hp c. Trong y hc, dng loi t tuyn v raxemic.
L thuc va c tc dng gin tip lm gii phng catecholamin ra khi ni d tr, va c tc
dng trc tip trn receptor.
Trn tim mch, so vi noradrenalin, tc dng chm v yu hn 100 ln, nhng ko di hn ti 10
ln. Lm tng huyt p do co mch v kch th ch trc tip trn tim. Dng nhiu ln lin nhau, tc
dng tng p s gim dn (hin tng quen thuc nhanh: tAChyphylaxis)
Thng dng chng h huyt p v kch thch h hp trong khi gy t tu sng, trong nhim
c ru, morphin, barbiturat.
Kch thch trung tm h hp hnh no v lm gin ph qun nn dng ct cn hen, tc dng
tt trn tr em.
Trn thn kinh trung ng, vi liu cao, kch thch lm mt ng, bn chn, run, tng h hp.
Ephedrin d dng hp thu theo mi ng. Vng bn vi MAO. C huyn ha gan, khong 40%
thi tr nguyn cht qua nc tiu.
Dng di th mui clohydrat hoc sulfat d ha tan.
Ung 10- 60 mg / ngy. Liu ti a 24h l 150 mg
Tim di da, bp tht hoc tnh mch 10 - 20 mg/ ngy
Nh nim mc (mt, mi) dung dch 0, 5- 3%
ng 1 mL= 0,01g ephedrin clohydrat
Vin 0,01g ephedrin clohydrat
Pseudoephedrin l ng phn lp th ca ephedrin, t gy tim nhanh, tng huyt p v kch thch

thn kinh trung ng hn ephedrin. Thng c dng trong cc ch phm nh mi chng xun g
huyt nim mc.
2.4.2. Amphetamin
L thuc tng hp phenylisopropanolamin. Tc dng dc l theo kiu ephedrin, gin tip lm
gii phng noradrenalin (v c th cn c dopamin v serotonin) ra khi ni d tr. Khc
ephedrin l thm vo thn kinh trung ng nhan h, tc dng kch thch mnh tm trng v s
nhanh nhn do tc ng ln v no v h lin vng hot ha (v vy, c xp vo loi doping,
cm dng trong thi u th thao). Cn c tc dng gy chn n, dng chng bo ph.
Mt s dn xut ca amphetamin ( methamphetamin, dimethoxyamphetamin...) kch thch thn
trung ng rt mnh, gy lon thn, u xp vo cht ma tu.
2.4.3. Phenylpropanolamin
t tc dng trung ng hn. ngoi bin, tc dng co mch thng c dng chng ngt
mi, l thuc phi hp trong v in thuc chng cm cm (Atussin, Decolgen). Tuy nhin, gn y
thy nhiu tc dng ph trn tim mch nn c xu hng khng dng na.
3. Thuc hu h adrenergic
L nhng thuc lm mt tc dng ca adrenalin v noradrenalin. Cc thuc ny thng c
dng iu tr chng tng huyt p, bnh Raynaud, lon nhp tim, hi chng cng tuyn gip
(tim nhp nhanh, li mt, gin ng t, tng h hp; chnh l nhng du hiu cng giao cm).
Cc thuc c chia thnh hai nhm:
- Thuc hy giao cm (sympatholytic): l nhng thuc phong to nron adrenergic trc xinap,
lm gim gii phng catecholamin, khng c tc dng trn receptor sau xinap, khi ct cc dy
hu hch giao cm th thuc mt tc dng. Do thiu cht dn truyn thn kinh ni sinh, tnh cm
th ca cc receptor sau xinap vi catecholamin ngoi lai s tng ln.
- Thuc hu adrenalin (adrenolytic) l nhng thuc phong to ngay chnh cc receptor adrenergic
sau xinap, cho nn khi ct t cc si hu hch giao cm, tc dng ca thuc khng thay i.
Catecholamin c ni sinh ngoi lai u b mt tc dng.
1.1. Thuc hu giao cm
Cc thuc c th c tc dng nhng khu sau:
1.1.1. c ch tng hp catecholamin
Thuc hay c dng l methyl dopa (Aldomet) phong ta dopa decarboxylase, lm dopa
khng chuyn thnh dopamin v 5 - hydroxytryptophan khng chuyn thnh 5 -
hydroxytryptamin (5 HT - serotonin). Do s lng catecholamin v serotonin c ngoi bin
v thn kinh trung ng u gim. Mt khc cn ngn cn kh nng gn catecholamin vo cc
ht lu tr.
Ngoi ra, trong c th methyldopa cn c th chuyn thnh methyl noradrenalin, tc dng
nh mt cht trung gian ha hc gi chim ch ca noradrenalin (xem bi "Thuc cha tng
huyt p")
Tc dng ph: m mng, c ch tm thn, chng mt, nhc u, kh ming, ph.
Khng dng khi c ri lon tun hon no v mch vnh, cc trng thi trm cm, ri lon gan,
thn.
Liu lng: ung vin 250 mg. C th dng ti 8 vin/ ngy.
Ch phm: Dopegyt vin 0,25 g methyl dopa.
Carbidopa v bemerazid, c ch dopa decarboxylase ngo i bin. c dng phi hp vi l -
dopa iu tr bnh Parkinson.
1.1.2. Lm gim d tr catecholamin trong cc ht
* Reserpin:
Lm gii phng t t catecholamin t cc ht lu tr ra ngoi bo tng MAO ph hu, do
lng catecholamin gim c trn thn kinh trung ng (gy an thn), c ngoi bin (lm h
huyt p). Reserpin cn cn tr qu trnh gn catecholamin (c ni sinh ln ngoi sinh) vo cc
ht lu tr.
* Guanetidin (Ismelin)
Chim ch noradrenalin trong cc ht lu tr v tr thnh cht trung gian ha hc gi. Khc
reserpin l lc u guanetidin gy tng nh huyt p do lm gii phng nhanh noradrenalin ra
dng t do, mt khc guanetidin khng thm c vo thn kinh trung ng nn khng c tc
dng an thn.
Tc dng ti a xut hin sau 2 - 3 ngy v mt i 6- 10 ngy sau khi ngng thuc.
Khng dng cho ngi bnh c lot d dy, suy mch vnh, suy thn. Khng dng cng vi
clonidin.
Liu lng: lc u ung 10 mg/ ngy, sau tng dn ti 50 - 75mg/ ngy
Ch phm: vin 10 v 20 mg
1.1.3. Ngn cn gii phng catecholamin
Bretylium (Darentin)
C ch cha tht r. c ch gii phng catecholamin, nhng khng nh hng n tc dng ca
adrenalin v noradrenalin ngoi lai. C th l bretylium lm cho mng cc ht lu tr gim
tnh thm vi ion Ca ++ m lm cho catecholamin khng c gii phng ra.
C tc dng gy t ti ch.
V c nhiu tc dng ph (nh xung huyt nim mc mi, kh th, a lng, h huyt p, nhc
c) cho nn cn t c s dng lm sng.
1.1.4. Thay th catecholamin bng cc cht trung gian ho hc gi
Mt s cht khng c tc dng dc l, nhng chim ch ca catecholamin v cng c gii
phng ra di xc tc kch thch dy giao cm nh mt cht trung gian ha hc, c gi l cht
trung gian ha hc gi:
- methyldopa to thnh methyl noradrenalin
- Thuc c ch MAO: tyramin chuyn thnh octopamin
- Guanetidin
1.2. Thuc hu adrenalin

Cc thuc phong ta tc dng trn receptor tng i c hiu hn thuc kch thch, ngha l
nhiu thuc kch thch c tc dng c trn hai loi receptor v , cn thuc phong to thng
ch tc dng trn mt loi receptor m thi. Do thuc loi ny c chia thnh hai nhm:
thuc hu v thuc hu adrenergic.
1.2.1. Thuc hu - adrenergic
V phong to cc receptor nn lm gim tc dng tng huyt p ca nor adrenalin, lm o
ngc tc dng tng p ca adrenalin. Khng c ch tc dng gin mch v tng nhp tim ca cc
thuc cng giao cm v u l tc dng trn cc receptor . Hin tng o ngc tc dng tng
p ca adrenalin c gii thch l cc mao m ch c c hai loi receptor v , adrenalin tc
dng trn c hai loi receptor , nhng bnh thng, tc dng chim u th nn adrenalin lm
tng huyt p. Khi dng thuc phong to , adrenalin ch cn gy c tc dng kch thch trn
cc receptor nn lm gin mch, h huyt p.
Nhm thuc ny c ch nh trong cc cn tng huyt p, chn on u tu thng thn, iu tr
bnh Raynaud. Hin ang nghin cu thuc hu 1A iu tr ph i lnh tnh tuyn tin lit.
Nhc im chung l d gy h huy t p khi ng, nhp tim nhanh, xung huyt nim mc mi,
co ng t, bun nn, nn v tiu chy do tng nhu ng d dy - rut.
Cc thuc ch khc nhau v cng tiu chy v thi gian tc dng.
1.2.1.1. Nhm haloalkylamin:
C phenoxybenzamin (dibenzylin) v diben amin.
V ha hc, c cng thc gn ging nh m tc nit (nitrogen mustard). Khi vo c th, amin
bc 3 c chuyn thnh etylen amoni, cht ny gn cht vo cc receptor theo lin kt cng
ha tr (ch yu l receptor 1), gy c ch rt mnh v ko d i (ti 24 gi cho mt ln dng
thuc) theo kiu c ch mt chiu.
Liu lng: phenoxybenzamin, vin nang 10 mg, ung 2 - 10 vin/ ngy
1.2.1.2. Dn xut imidazolin
C tolazolin (Priscol, Divascon) v phentolamin (Regitin)
c ch tranh chp vi noradrenalin recepto r 1 v 2 nn tc dng yu v ngn hn
phenoxybenzamin nhiu.
Liu lng: Priscol ung hoc tim bp 25 - 50 mg/ ngy. Regitin ung 20 - 40 mg/ ngy
Cn dng chn on u tu thng thn: nghim php c coi l dng tnh nu ngi bnh
ngh ngi, hon ton yn tnh, tim bp hoc tim tnh mch 5 mg phentolamin, sau vi pht lm
huyt p ti a v ti thiu h khong 4 - 5 cmHg, duy tr c 7 pht ri tr li huyt p ban u
trong 10- 15 pht.
3.2.1.3. Prazosin (Minipress): cht in hnh phong to 1. Dng iu tr tng huyt p, ung 1 -
20 mg mt ngy. (xin xem bi "Thuc cha tng huyt p")
3.2.1.4. Alcaloid nhn indol:
Cc alcaloid ca nm ca g (ergot de seigle; Secale cornutum; Claviceps purpurea), c chia

thnh hai nhm: loi hu giao cm v lm co bp t cung (gm ergotamin, ergotoxin) v loi lm
co bp t cung n thun (ergometrin).
Vi liu thp, ergotamin c tc dng cng giao cm nh v ngn cn thu hi noradrenalin
ngn dy giao cm. Liu cao, tri li c tc dng phong to recepto r . Ngoi ra cn c tc dng
trc tip lm co c trn, nn c th lm co mch tng huyt p, hoc hoi t u chi v vch mi
trong trng hp nhim c mn tnh do n la mch m mc, lm co tht rut, ph qun v t
cung.
Ch nh: ct cn migren, ri l on thi k mn kinh, chy mu t cung sau s rau
Dn xut hydro ha ca cc ergot (nh dihydroergotamin, hydroergotoxin) c tc dng phong to
tng ln trong khi tc dng co c trn gim xung. Ngoi tc dng phong to receptor , tc
dng h huyt p ca ergotamin cn c gii thch l lm gim trng lc trung tm vn mch
v kch thch trung tm ph giao cm. Do c dng lm thuc gin mch, h huyt p: ung
4- 6 mg/ ngy, hoc tim di da 0,1 - 0,5 mg/ ngy.
Chng ch nh: c thai, ri lon m ch vnh
- Yohimbin: l alcaloid ca Corynantheyo himbe c nhiu Chu Phi. Cu trc ha hc gn
ging reserpin, tranh chp vi NA ti receptor 2. D vo thn kinh trung ng. Tc dng yu v
ngn, nn t c dng trong iu tr.
Trong lm sng cn dng lm thuc cng dng, v ngoi tc dng gin mch cn kch thch
phn x tu.
Liu lng: Yohimbin clorhydrat 5 - 15 mg/ ngy
1.2.2. Thuc hu adrenergic
Cn gi l thuc "phong to " (" blocking agent") c tc dng c ch tranh chp vi
isoproterenol cc receptor. Cht u tin c tm ra l dicloisoproterenol (Powell v Slater,
1958). c dng nhiu trong lm sng.
1.2.2.1. Tc dng dc l: c 4 tc dng dc l chnh vi mc khc nhau gia cc thuc:
* Kh nng hu giao cm : l tnh cht chung duy nht ca tt c cc thuc hu :
- Trn tim: lm gim nhp tim (20 - 30%), gim lc co bp ca c tim, gim lu lng tim, gim
cng nng v gim s dng oxy ca c tim, gim tc dn truyn ca t chc nt. Ch yu l
do hu 1.
- Trn kh qun: lm co, d gy h en. Ch yu l do hu 2, gy tc dng khng mong mun.
- Trn thn: lm gim tit renin, h huyt p trn ngi c HA cao
- Trn chuyn ha: c ch hu glycogen v hu lipid
+Tc dng lm n nh mng: ging quinidin, lm gim tnh thm ca mng t bo v i s trao
i ion nn c tc dng chng lon nhp tim.
+ C hot tnh ni ti kch thch receptor : mt s thuc phong to khi gn vo cc receptor
li c tc dng kch thch mt phn. Hiu qu thc t t quan trng, nhng c th hn ch tc
dng lm gim nhp tim, gim co bp c tim, gim co kh qun ca chnh n.
+ Tnh chn lc: nhiu thuc phong to i lp vi tt c cc tc dng cng giao cm ca

(1: tim v 2: mch, kh qun). Nhng mt s thuc li ch phong to c mt trong hai loi
receptor (1hoc 2), v th phn bit thnh cc loi phong to chn lc trn giao cm :
- Loi tc dng chn lc trn 1 hay loi chn lc trn tim ("cardioselectifs"), nh practolol,
acebutalol, atenolol. Thng dng metoprolol (Lopressor) v atenolol (T enormin)
Li ch ca loi thuc ny l:
- Do rt km tc dng trn 2 ca kh qun nn hn ch c tai bin co tht kh qun.
- Km tc dng trn 2 ca thnh mch s c li cho iu tr cao huyt p (gim co mch ngoi
bin)
- Do rt km tc dng trn 2 ca thnh mch vnh nn khng bc l tc dng cng -
adrenergic (tc dng co mch vnh ca CA tun hon trong mu). Bnh thng, do c tc dng
th tc dng ca b lu m. Khi b phong to th tc dng ca s c bc l ra.
- Do khng nh hng n cc receptor trong hu glycogen nn khng lm nng thm tnh trng
h ng huyt.
- Loi c tc dng chn lc trn 2, ng u l Butoxamin, t c ngha trong lm sng.
1.2.2.2. Ch nh chnh
- Cn au tht ngc, ch yu do lm gim s dng oxy ca c tim . Trong nhi mu c tim, tim
tnh mch ngay t gi u s lm gim lan rng nhi mu v ci thin c tin lng bnh.
- Lon nhp tim: nhp nhanh xoang, nhp nhanh trn tht, tim cng gip, cung ng nh do
nhim c digital.
- Tng huyt p: do lm gim lu lng tim, gim sc cn ngoi bin, gim tit renin v gim
gii phng noradrenalin (xin xem thm bi "Thuc cha tng huyt p")
- Mt s ch nh khc; cng gip, migren, glocom gc m (do lm gim sn xut thu dch),
run tay khng r nguyn nhn.
1.2.2.3. Chng ch nh:
- Suy tim l chng ch nh chnh v n c ch c ch b tr ca tim.
- Bloc nh- tht v thuc c tc dng lm gim dn truyn ni ti trong c tim.
- Hen ph qun. Loi c tc dng chn lc trn receptor 1 dng cho ngi hen t ng uy him hn,
nhng vi liu cao, trong iu tr tng huyt p th cng b mt tnh chn lc.
- Khng dng cng vi insulin v cc sulfamid h ng huyt v c th gy h ng huyt t
ngt.
- C thai: khng chng ch nh tuyt i, nhng gp tr mi b chm nhp tim, h ng
huyt, suy h hp, thai chm pht trin.
1.2.2.4. Cc tc dng khng mong mun
c chia lm hai loi:
* Loi tai bin l hu qu ca s phong to receptor
- Tim: suy tim do lm yu co bp ca c tim, chm nhp tim, nh tht phn ly .

- Mch: hi chng Raynaud, tm lnh u chi, i khp khing, (thng gp vi propranolol, do
b phong to th s cng). Cc thuc chn lc trn 1 v c hot tnh kch thch ni ti th t tai
bin ny hn
- Phi: cc thuc c tc dng hu 2 > 1 s gy co kh qun, kh th. Khng dng cho ngi
hen.
- Thn kinh trung ng: mt mi, mt ng, hay ng m, o nh, trm cm, thng gp hn vi
cc thuc d tan trong m v d thm vo t bo thn kinh (propranolol, metoprolol), loi t tan
trong m (atenolol, nadolol) t tai bin hn.
- Chuyn ho: lm h ng huyt (cn thn trng vi ngi b i tho ng), tng triglycerid
trong mu.
* Loi tai bin khng lin quan n tc dng phong to
- Hi chng mt- da- tai: xut hin ring hoc phi hp vi cc tn thng ca mt (vim gic
mc, vim cng mc), da (sn nga lng bn tay, bn chn, dy da), tai (ic v vim tai nng).
gp vi practolol, iu tr trong 1 - 2 nm
- Vim phc mc x cng: au cng bng phc mc c nhng mng dy do t chc x . Sau khi
ngng thuc hoc iu tr bng corticoid s khi. Gp sau khi iu tr ko di trn 30 thng.
- Trn thc nghim, gp ung th tuyn c, ung th v, lymphosarcom. Do cn theo di trn
ngi khi dng liu cao ko di.
1.2.2.5. Tng tc thuc
- Cc thuc gy cm ng cc enzym chuyn ha gan nh phenytoin, rifampin, phenobarbital,
ht thuc l, s lm tng chuyn ha, gim tc dng ca thuc hu .
- Cc mui nhm, cholestyramin lm gim hp thu
- Cc thuc hu c tc dng hip ng vi thuc chn knh calci, cc thuc h huyt p
- Indomethacin v cc thuc chng vim phi steroid lm gim tc dng h huyt p ca cc thuc
hu .
1.2.2.6. Phn loi
Khng c tc dng "chn lc C tc dng "chn lc trn tim"
trn tim"
n nh mng Khng n n nh mng Khng n nh
nh mng mng
Khng cng Propranolol Sotalol Esmolol
ni ti Timolol Atenolol
C cng ni Alprenolol Pindolol Acebutolol
ti Oxprenolol Metoprolol
Practolol
S phn loi ny gip cho chn thuc trong iu tr. Th d bnh nhn c r i lon co tht ph
qun th nn dng loi c tc dng "chn lc trn tim"; bnh nhn c nhp tim chm th dng loi
"c cng ni ti "
1.2.2.7. Mt s thuc chnh
* Propranolol (Inderal, Avlocardyl)
L isopropyl aminonaphtyl oxypropranolol. C tc dng phong t o nh nhau trn c 1 v 2,
khng c hot tnh ni ti kch thch.
Tc dng:
- Trn tim:lm gim tn s, gim lc co bp, gim lu lng tim ti 30%. c ch tim l do tc
dng ring ca propranolol ngn cn calci nhp vo t bo c tim, gim nng cal ci trong ti
li ni bo.
- Trn mch vnh: lm gim lu lng 10 - 30% do c ch gin mch. Lm gim tiu th oxy ca
c tim.
- Trn huyt p: lm h huyt p r sau 48 gi dng thuc. Huyt p ti thiu gim nhiu.
- Ngoi ra cn c tc dng chng lon n hp tim, gy t (do tc dng n nh mng) v an thn
Ch nh:
- Tng huyt p, lon nhp tim, nhp nhanh xoang, cung ng nh, nhp nhanh trn tht, bnh
cng gip, suy mch vnh. Ung liu hng ngy 120 - 160 mg
Vin 40 v 160 mg
- Dng trong cp cu lon nhp tim do nhim c digital hay do thng tim, do t ng ni kh
qun.
Tim tnh mch 5- 10 mg. ng 5 mg
Chng ch nh: ngoi chng ch nh chung, propranolol khng c dng cho ngi c thai
hoc lot d dy ang tin trin.
Thuc c d dng h p thu qua ng tiu ha do tan nhiu trong m. Gn vo protein huyt
tng ti 90- 95%, m ti a trong mu t c sau khi ung t 1 - 2 gi. Chuyn ha thnh
hydroxy- 4- propranolol v acid naphtoxyl acetic rt nhanh ti gan nn ch khong 25% liu ung
vo c vng tun hon, t/2: 3 - 5 gi.
Vin 40 mg. Ung trung bnh 2 - 4 vin / ngy, chia lm nhiu ln
ng 1 mL= 1 mg. Dng cp cu, tim tnh mch rt chm, t 1 - 5 mg/ ngy
* Pindolol (Visken);
C tc dng cng ni ti v khng nh hng n v n chuyn ca ion Ca ++ nn lm tng lc
co bp v tn s ca tim. Thng dng trong cc trng hp c lon nhp chm vi liu ung 5 -
30 mg/ ngy. Tan va trong m, sinh kh dng 75% v t/2 = 3 - 4 gi.
* Oxprenolol (Trasicor):
Dng iu tr cao huyt p, c n au tht ngc, lon nhp tim. Ung 160 - 240 mg/ ngy.
* Atenolol (Tenormin): Tc dng chn lc trn 1- rt tan trong nc nn t thm vo thn kinh
trung ng, sinh kh dng 50%, t/2 = 5 - 8 gi. Ung 50- 100 mg/ ngy.
* Metoprolol (Lopressor). C tc dng chn lc trn tim (1) nn gy cn hen ph qun ( 2).
Ung 50- 150 mg/ ngy. Hp thu nhanh qua ng ung, sinh kh dng 40% v t/2 = 3 - 4 gi.
cu hi t lng gi
1. Trnh by sinh chuyn ha ca catecholamin ti ngn dy giao cm.

2. Trnh by s phn loi cc receptor ca h giao cm: v tr, p ng v cht ch vn.
3. Phn tch, so snh tc dng v p dng iu tr ca adrenalin, noradrenalin v
dopamin.
4. Phn bit tc dng ca thuc cng 1 v 2 giao cm.
5. Trnh by c ch tc dng, tc dng v p dng lm sng ca isoproterenol,
dobutamin v albuterol (Salbutamol, Ventolin).
6. Phn tch c ch ca cc thuc hu giao cm.
7. Trnh by c im tc dng v p dng iu tr ca thuc hu giao cm, nu 2
thuc th d.
8. Trnh by tc dng dc l v p dng lm sng ca thuc hu .
Trnh by cc tc dng khng mong mun ca thuc hu .
(sch dng cho sinh vi n h bc s a khoa)
Bi 7: Thuc t

1. Trnh by c c ch tc dng v tc dng ca thuc t
2. Phn tch c nhng tc dng khng mong mun v c tnh ca thuc t
3. Phn bit c c im tc dng ca cocain, procain lidocain, bupivacain v
ethylclorid.
1. Tnh cht chung ca thuc t

1.1. nh ngha
Thuc t lm mt cm gic (au, nhit ) ca mt vng c th, ti ch dng thuc, trong khi
chc phn vn ng khng b nh hng.
Carl Koller (1884) dng dung dch cocain gy t gic mc, m u thi k ca cc thuc t.
Ngy nay, v tnh cht c v gy nghin ca thuc, cocain dn dn b b. Vi vic tm ra
procain (novocaine), Einhorn (1904) m u thi k th hai, rt quan trng v dng tim
gy t.
1.2. c im ca thuc t tt
Nhiu thuc c tc dng gy t, nhng mt thuc t tt cn t c cc tiu chun sau:
- Ngn cn hon ton v c hiu s dn truyn cm gic.
- Sau tc dng ca thuc, chc phn thn kinh c hi phc hon ton.
- Thi gian khi t ngn, thi gian tc dng thch hp (thng l khong 60 pht).
- Khng c, khng kch thch m v khng gy d ng.
- Tan trong nc, vng bn di dng dung dch, kh khun xong vn cn hot tnh.
1.3. Lin quan gia cu trc v tc dng
Cc thuc t u c cu trc gn ging nhau, tng t lidocain, gm ba phn chnh: cc a m,
cc a nc v chui trung gian:
Cc a m Chui trung gian Cc a nc

- Cc a m l nhn thm, c nh hng n s khuch tn v hiu lc ca tc dng gy t. Tnh

a m lm tng i lc ca thuc vi receptor nn lm tng cng t; ng thi lm chm thu
phn ca cc esterase nn lm ko di thi gian t. Tuy nhin, c tnh ca thuc li tng.
- Cc a nc l nhm amin bc 3 ( N ) hoc bc 2 ( NH ) quy nh tnh tan trong nc
v s ion ha ca thuc. Nhm amin l cht nhn H + theo phn ng:
R NH2 + H2O R NH3 + OH
- Chui trung gian: c 4-6 nguyn t (di 6-9nm) nh hng n c tnh ca thuc, chuyn ha
v thi gian tc dng ca thuc. Ngoi gii hn , tc dng s km dn. Trong chui ny c th
c :
. Nhm mang ng ni ester ( COO, nh procain) b thu phn nhanh gan v mu do cc
esterase, nn c thi gian tc dng ngn.
. Nhm mang ng ni amid ( NHCO, nh lidocain), kh b thu phn, tc dng di.
1.4. C ch tc dng
Cc thuc t tng hp lm gim tnh thm ca mng t bo vi Na + do gn vo receptor ca knh
Na+ mt trong ca mng, khc vi cc c t thin nhin nh ttrodotoxin gn mt ngoi ca
knh. Nh vy, thuc t c tc dng lm n nh mng, ngn cn Na + i vo t bo, lm t bo
khng kh cc c.
Ngoi ra, thuc t cn lm gim tn s phng xung tc ca cc si cm gic.
Hu ht cc thuc t u c pKa l 8,0 - 9,0, v vy, pH ca dch c th u phn ln dng
cation, l dng c hot tnh gn vo c receptor, nhng li khng qua c mng t bo nn
khng c tc dng, v receptor ca thuc t nm mt trong mng t bo.
Qu trnh thm nhp qua mng t bo ti c receptor din bin nh s :
R1 R1
H thng m ca m
R2 - N + - HCl- + NaHCO 3 R2 - N + NaCl + H 2CO3

R3 R3
Trong ng tim, thuc di dng mui Chuyn thnh dng base t
do,
hydroclorid, tan, l ion, khng qua c qua c mng
mng t bo
Mng t bo
R1 R1

R2 - N - + HOH R2 - NH+ + OH-

R3 R3
B ion ha thnh amoni bc 4, mang in (+), gn
c vo receptor.
Hnh 7.1. Qu trnh thm nhp ca thuc t qua mng t bo gn vo receptor

Thuc t t c hiu qu m nhim khun v pH thp nn ch c t l rt thp thuc t qua
c mng.
Mun lm t nhanh th cn tng nng ca thuc. Nhng khi s c hi cho m v d dn ti
nhim c ton thn, cho n n trong thc hnh, cn chn nng ti u.
1.5. Tc dng dc l
1.5.1. Tc dng ti ch:
Thuc t tc dng trn tt c cc si thn kinh trung ng (cm gic, vn ng) v thn kinh thc
vt, ln lt t si b n si to tu theo nng ca thuc. Th t mt cm gic l au, lnh,
nng, xc gic nng, ri n xc gic su. Khi ht thuc, tc dng hi phc theo chiu ngc li.
Tu theo mc ch lm sng m s dng cc ng a thuc khc nhau:
- Gy t b mt: bi hoc thm thuc ti ch (0,4 -4%).
- Gy t thm nhim = tim di da thuc ngm c vo tn cng thn kinh (dung dch 0,1 -
1%).
- Gy t dn truyn: tim thuc vo cnh ng dn truyn ca thn kinh (gy t thn thn kinh,
phong ta hch, gy t ngoi mng cng, gy t tu sng (xem s ).
1.5.2. Tc dng ton thn

Ch xut hin khi thuc t thm c vo vng tun hon vi nng hiu dng:
- Tc dng c ch thn kinh trung ng xut hin sm nht vi trung tm c ch nn gy cc du
hi kch thch: bn chn, lo u, run c, cn co g it (iu tr bng diazepam), mt nh hng.
- c ch dn truyn thn kinh - c gy nhc c, lit h hp.
- Lm gin c trn do tc dng lit hch v tc dng trc tip trn c trn.
- Trn tim - mch: do tc dng lm n nh mng, thuc t lm gim tn h kch thch, gim dn
truyn v gim lc co bp ca c tim. C th gy lon nhp, thm ch rung tm tht.
Trn mch, hu ht gy gin mch, h huyt p (tr cocain).
- Trn mu: liu cao (trn 10 mg/ kg) prilocain tch t cht chuyn ha O - toluidin gy oxy ha,
bin Hb thnh metHb.
1.6. Tc dng khng mong mun v c tnh
1.6.1. Loi tc dng do thuc ngm vo vng tun hon vi nng cao, gy nhng biu hin
thn kinh (bun nn, nn, mt nh hng, ng tc git rung, lit h hp), hoc tim mch (ri
lon dn truyn, bloc nh tht...).
1.6.2. Loi tc dng c hiu, lin quan n k thut gy t: h huyt p, ngng h hp do gy
t tu sng, tn thng thn kinh do kim tim m phi hoc do thuc chn p.
1.6.3. Loi phn ng qu mn hay d ng ph th uc vo tng c th. Thng gp vi cc dn
xut c thay th v tr para ca nhn thm (ester ca acid para aminobenzoic), loi ng ni
ester (procain). Rt t gp vi loi c ng ni amid (lidocain).
1.7. Dc ng hc
Cc thuc t u l base yu, t tan trong nc, nhng khi kt hp vi acid (nh HCl) s cho cc
mui rt tan v hon ton n nh (dung dch c pH acid).
Khng thm qua da lnh. Cc thuc t tng hp kh thm qua nim mc. Ging ha v thi tr
ph thuc ch yu vo cu trc. Cc thu c t c chc amid (nh lidocain) hoc chc ether ( O),
(nh quinisocain) ch b chuyn ho rt t gan bi cyt P 450, phn ln thi tr nguyn cht qua
thn. Tc chuyn ho t nhanh n chm l prilocain
>etidocain>lidocain>mepivacain>bupivacain. ngi bnh thng, t/2 ca lidocain l 1,8 gi;
ngi suy gan nng c th ti >6gi. Cc thuc t c chc ester (procain) b thu phn bi cc
esterase ca c gan v huyt tng, nn ging ho v mt tc dng nhanh, t/2 vi procain ch
khong 1 pht.
Loi ester b chuyn ho thnh para amino benzoic acid (PABA) nn d gy d ng. Cn loi
amid khng b chuyn thnh PABA nn rt him gy d ng.
1.8. Tng tc thuc
- khc phc tc dng gy gin mch ca thuc t (tr cocain gy co mch), thng phi hp
vi adrenalin, nht l khi gy t thm nhim. Adrenalin lm co mch, c tc dng ngn cn s
ngm thuc t vo tun hon chung v ko di c thi gian gy t.
- Cc thuc lm tng tc dng ca thuc t: cc thuc gim au loi morphin, cc thuc an thn
kinh (clopromazin).
- Cc thuc d lm tng c tnh ca thuc t: quinidin, thuc phong to adrenergic (lm ri
lon dn truyn c tim).
- Thuc t hip ng vi tc dng ca cura. Sulfamid i khng 2 chiu vi cc thuc t dn xut
t acid para amino benzoic (nh procain).
1.9. p dng lm sng
1.9.1. Ch nh
- Gy t b mt: Vim ming, vim hng, chun b ni soi, s dng trong nhn khoa.
- Gy t dn truyn: Mt s chng au, phu thut chi trn, trong sn ph khoa (gy t ngoi
mng cng).
- Cc ch nh khc: Lon nhp tim (xem bi thuc cha lon nhp tim).
1.9.2. Chng ch nh
- Ri lon dn truyn c tim
- C d ng (tm nhm thuc khc).
1.9.3. Thn trng khi dng thuc
- Dng ng tng liu v chn ng nng ti u. Khng dng thuc qu lo ng v khng vt
qu 1% nu tim tu sng.
- Tim ng vng cn gy t. Khng tim vo mch hoc trc tip vo thn kinh.
- Ngng ngay thuc nu c bt k mt biu hin bt thng no.
2. Cc loi thuc t thng dng
2.1. Cocain
Bng A-nghin. V vy ngy cng t dng.
L thuc t duy nht c ngun gc thc vt (l cy Erythroxylon coca) c nhiu Nam M.
2.1.1. Tc dng
- Gy t: thm qua c nim mc, dng trong tai mi hng (dung dch 10 -20%) hoc khoa mt
(dung dch 1-2%).
- Trn thn kinh trung n g: gy kch thch, sng khoi, o gic, gim mt mi (d gy nghin).
Liu cao gy run chi v co git.
- Trn thn kinh thc vt: cng giao cm gin tip do ngn cn ti thu hi noradrenalin ngn
dy giao cm, lm tim p nhanh, co mch, tng huyt p.
2.1.2. c tnh
- Cp: co mch mnh (tm ti, hi hp, lo s, d b ngt), kch thch thn kinh trung ng (o
gic, co git).
- Mn: d gy quen thuc v nghin, mt nht nht, ng t gin, hoi t vch mi.
2.2. Procain (novocaine)
Bng B. Tng hp (1905)
- L thuc t mang ng ni este, tan trong nc.
- Tc dng gy t km cocain 4 ln, t c hn 3 ln.
- Khng thm qua nim mc, khng lm co mch, ngc li, do c tc dng phong ta hch li
lm gin mch, h huyt p. Khi gy t nn phi hp vi a drenalin lm co mch, tng thi
gian gy t.
- Dng lm thuc gy t dn truyn, dung dch 1% -2% khng qu 3mg/kg cn nng.
- c tnh: d ng, co git ri c ch thn kinh trung ng.
- Hin c nhiu thuc tt hn nn ngy cng t dng.
2.3. Lidocain (xylocain): Tng hp (1948). Hin dng rt rng ri.
- L thuc t mang ng ni amid, tan trong nc.
- L thuc gy t b mt v gy t dn truyn tt. Tc dng mnh hn procain 3 ln, nhng c
hn hai ln.
- Tc dng nhanh v ko di do b chuyn ha c hm. Hai cht chuyn ha trung gian l
monoethylglycin xylidid v glycin xylidid vn cn tc dng gy t. V khng gy co mch nn
nu dng cng vi adrenalin, thi gian tc dng s lu m c tnh li gim.
- c tnh:
+ Trn thn kinh trung ng: lo u, vt v, bun nn, nhc u, run, co git v trm cm, c
ch thn kinh trung ng.
+ Trn h hp: th nhanh, ri kh th, ngng h hp.
+ Trn tim mch: tim p nhanh, tng huyt p, tip theo l cc du hiu c ch: tim p
chm, h huyt p, do tc dng c ch trung ng.
2.4. Bupivacain (Marcain)
L nhm thuc t c ng ni amid nh lidocain. Dng t 1963.
- c im gy t: thi gian khi t chm, tc dng gy t lu, cng mnh gp 16 ln
procain, nng cao phong ta cn ng kinh vn ng.
- Dng gy t tng vng, gy t thn thn kinh, m ri thn kinh v gy t tu sng. Dung
dch gy t ty sng c t trng 1,020 37 0 (ng 4ml = 20mg bupivacain clohydrat): tim tu
sng 3ml t th ngi, tc dng t v mm c (c bng, c chi di ko di 2-2,5 gi).
- D tan trong m, gn vo protein huyt tng 95%, hon ton chuyn ha gan do Cyt.P 450 v
thi tr qua thn.
- c tnh: c tnh trn tim mnh hn lidocain: gy lon nhp tht nng v c ch c tim, do
bupivacain gn mnh vo knh Na + ca c tim v c ch c trn trung tm vn mch.
- Gy t tng vng, tu thuc mc ch, tu thuc tui ca ngi bnh, dng dung dch 0,25 -
0,50% (c th km theo adrenalin gy co mch), tim t vi ml ti 20 ml. Tng liu cho 1 ln
gy t khng vt qu 150mg.
2.5. Ethyl clorid (Klne) C 2H5Cl
L dung dch khng mu, si nhit 12 0C. C tc dng gy m nhng c ch mnh h hp,
tun hon nn khng dng. Do bc hi nhit thp, nn c tc dng lm lnh rt nhanh vng
da c phun thuc, gy tc dng t mnh, nhng rt ngn.
- Ch nh: trch p xe, mn nht, chn thng th thao.
- Thuc ng trong l thy tinh, c van kim loi, tin s dng khi phun vo ni cn gy t.
cu hi t lng gi
1. Trnh by c ch tc dng v tc dng dc l ca th uc t.

2. Trnh by dc ng hc v tc dng khng mong mun ca thuc t.
Phn bit c im tc dng v p dng lm sng ca cocain, procain, lidocain, bupivacain v
ethyl clorid.
Dc l hc 2007 - i hc Y H ni
(sch dng cho sinh vin h b c s a khoa)
Bi 8: thuc ng v Ru

1. Nu c mi lin quan gia cu trc ha hc v tc dng ca barbiturat.
2. Trnh by c cc tc dng dc l ca barbiturat.
3. Nu c triu chng ng c cp v c ch x l ng c ca thuc ng barbiturat
(phenobarbital).
4. Trnh by c tc dng, ng c cp v mn, iu tr ng c ru ethylic.
1. i cng
Gic ng l nhu cu rt cn thit cho c th. nhng ng vt bc cao, cho qu trnh sng c
th din ra bnh thng phi c s lun phin ca hai trng thi thc v ng.
Do c ch thn kinh trung ng, thuc ng to mt gic ng gn gic ng sinh l. Khi dng liu
thp, thuc gy tc dng an thn, vi liu cao c th gy m. Thuc c th gy ng c v ch t
khi dng liu rt cao.
chng mt ng, lm gim trng thi cng thng thn kinh... trc y thng dng barbiturat
v mt s thuc ng khc nh dn xut piperidindion, carbamat, ru, paraldehyd, dn xut
benzodiazepin. Ngy nay, hay dng thuc an t hn- gy ng loi benzodiazepin v t gy quen
thuc v t tc dng khng mong mun.
2. Barbiturat
Cc barbiturat u l thuc c bng B, hin nay t dng.
2.1. Cu trc
Acid barbituric (2, 4, 6 - trioxohexahydropyrimidin) c to thnh t acid malonic v ure.
NH2 HOOC NH - OC H
1 6
O=C + CH2 O =C2 5C
3 4
NH2 HOOC NH - OC H
Ur acid malonic acid barbituric

V l acid mnh, d b phn ly nn acid barbituric cha khuch tn c qua mng sinh hc v
cha c tc dng. Khi thay H C 5 bng cc gc R 1 v R2, c cc barbiturat (l acid yu, t
phn ly) c tc dng c ch thn kinh trung ng.
Khi thay i cu trc, s nh hng n ion ha v kh nng tan trong lipid ca thuc, do
mc khuch tn ca thuc vo no v i lc ca thuc i vi lipid ca c th cng b thay
i, nn cng tc dng cng thay i.
Tc dng s rt yu khi ch thay th mt H C 5.
Nu thay hai H C 5 bng cc chui R 1 v R2 s tng tc dng gy ng.
Tc dng c ch thn kinh trung ng s mnh hn khi R 1 v R2 l chui nhnh hoc gc carbua
hydro vng hoc cha no.
Khi mt H C 5 c thay bng mt gc phenyl, s c phenobarbital c tc dng chng co
git.
Thay O C 2 bng S, c thiobarbiturat (thiopental) gy m nhanh v ngn.
Khi thay H N 1 hoc N3 bng gc methyl ta c barbiturat c ch thn kinh trung ng mnh v
ngn (hexobarbital).
2.3. Tc dng dc l
2.3.1. Trn thn kinh
Barbiturat c ch thn kinh trung ng. Tu vo liu dng, cch dng, tu trng thi ngi bnh
v tu loi barbiturat m c tc dng an thn, gy ng hoc gy m.
Barbiturat to ra gic ng gn ging gic ng sinh l, lm cho gic ng n nhanh, gim lng
ton th ca gic ng nghch thng (pha ng nhanh, in no c sng nhanh, ng rt say
nhng c hin tng vn ng nhn cu nhanh nn pha ny cn c gi l pha ng c vn ng
nhn cu nhanh), gim t l ca gic ng nghch thng so vi gic ng sinh l.
Vi liu gy m, barbiturat c ch ty sng, lm gim phn x a synap v c th lm gim p
lc dch no tu khi dng liu cao.
Barbiturat (v d phenobarbital) cn chng c co git, chng ng kinh, do lm gim tnh b
kch thch ca v no. Barbiturat i lp vi cn co git do strychnin, picrotoxin, cardiazol, c
t un vn...
C ch tc dng:
Gia hnh no v c no sinh t c h li ca no gia gm phn trc (phn i ln) hot ha v
phn sau (phn i xung) c tnh c ch. Barbiturat tc ng bng cch c ch chc phn ca h
li m vai tr l dn dt, chn lc nhng thng tin t ngoi bin vo v no. Thuc c th ngn
cn xung tc thn kinh qua cc trc h li - v no, ngoi bin- i no- v no, h li- c
nga, v no- i no...
Barbiturat tc dng gin tip thng qua GABA, lm tng thi lng m knh Cl -. Vi liu cao,
barbiturat tc dng trc tip trn knh Cl -, gip m knh, Cl - tin o t vo trong t bo thn
kinh, gy u cc ha. Picrotoxin i lp vi barbiturat knh Cl -, c ch vn chuyn Cl -, gy co
git.
Barbiturat c kh nng tng cng hoc bt chc tc dng c ch synap ca GABA, tuy nhin
tnh chn lc km cc benzodiazepin.
2.3.2. Trn h thng h hp
Do c ch trc tip trung tm h hp hnh no nn barbiturat lm gim bin v tn s cc

nhp th. Liu cao, thuc hu hoi trung tm h hp, lm gi m p ng vi CO 2, c th gy nhp
th Cheyne- Stockes.
Ho, ht hi, nc v co tht thanh qun l nhng du hiu c th gp, khi dng barbiturat gy m.
Cc barbiturat lm gim s dng oxy no trong lc gy m (do c ch hot ng ca neuron).
2.3.3. Trn h thng tun hon
Vi liu gy ng barbiturat t nh hng n tun hon. Liu gy m, thuc lm gim lu lng
tim v h huyt p. Barbiturat c ch tim liu c.
2.4. c tnh
Trong bi ny chng ti ch cp n c tnh ca phenobarbital, mt b arbiturat cn c dng
nhiu trn lm sng.
2.4.1. Tc dng khng mong mun
Khi dng phenobarbital, t l ngi gp cc phn ng c hi chim khong 1%.
- Ton thn: bun ng
- Mu: c hng cu khng l trong mu ngoi vi.
- Thn kinh: rung git nhn cu, mt iu ha ng tc, b kch thch, lo s, l ln (hay gp
ngi bnh cao tui).
- Da: ni mn do d ng (hay gp ngi bnh tr tui). Him gp hi chng au khp, ri lon
chuyn ha porphyrin do phenobarbital.
2.4.2. Ng c cp
Ng c cp phenobarbital phn ln do ngi bnh ung thuc vi mc ch t t. Vi liu gp
5- 10 ln liu ng, thuc c th gy nguy him n tnh mng. T vong thng xy ra khi nng
phenobarbital trong mu cao hn 80 microgam / ml.
2.4.2.1. Triu chng nhim c
- Ngi bnh bun ng, mt dn phn x. Nu ng c nng c th mt ht phn x gn xng,
k c phn x gic mc.
- ng t gin, nhng vn cn phn x vi nh sng (ch mt nu ngi bnh ngt th do tt li
hoc suy h hp).
- Gin mch da v c th h t hn nhit (v thuc lm gim chuyn ha chung nn gy gim sinh
nhit).
- Ri lon h hp, nhp th chm v nng, gim lu lng h hp, gim thng kh ph nang.
- Ri lon tun hon: gim huyt p, try tim mch. Cui cng, ngi bnh b hn m v cht do
lit h hp, ph no, suy thn cp.
2.4.2.2. X tr
X tr cp cu ph thuc vo mc nng khi bnh nhn vo vin: loi b cht c trc hay hi
sc trc.
- m bo thng kh: t ng ni kh qun, ht m, h hp nhn to, m kh qun nu c ph

thit hu, thanh mn.
- Hn ch ng c:
. Ra d dy bng dung dch NaCl 0,9% hoc KMnO 4 0,1%, ngay c khi ng c t lu v khi
ng c barbiturat, nhu ng d dy b gim nn thuc li lu trong d dy.
Ly dch ra d dy ln u xt nghim c c ht.
. Ung than hot tng o thi thuc v rt ngn thi gian hn m hoc thuc ty sorbitol 1 - 2
g/kg.
- Tng o thi:
. Gy bi niu cng bc: truyn dung dch mn ng trng hoc dung dch glucose 5% (4 - 6
lt/ ngy)
Dng thuc li niu thm th u (truyn tnh mch chm dung dch manitol 100 g/ lt) tng thi
barbiturat.
. Base ho huyt tng: truyn tnh mch dung dch base natribicarbonat 0,14% (0,5 - 1 lt)
. Lc ngoi thn: l bin php thi tr cht c rt c hiu qu nhng khng phi t uyn no
cng c th lm c, gi thnh cao.
. Khi bnh nhn ng c nng, nng barbiturat trong mu cao nn chy thn nhn to (phi
m bo huyt p bng truyn dch, dopamin hay noradrenalin).
. nhng bnh nhn c tt huyt p, suy vnh hoc suy t im, lc mng bng s c hiu qu hn
thn nhn to.
- m bo tun hon.
. Hi phc nc in gii, thng bng acid base.
. Nu try mch: chng sc, truyn noradrenalin, plasma, mu.
- Chng bi nhim, ch ti cng tc h l v chm sc c bit trong t rng hp bnh nhn b
hn m.
2.4.3. Ng c mn tnh
Ng c mn tnh barbiturat thng gp cc bnh nhn lm dng thuc dn n nghin thuc.
Biu hin ca ng c gm cc triu chng: co git, hong lon tinh thn, m sng...
2.5. Tng tc thuc
- Barbiturat gy cm ng mnh microsom gan, do s lm gim tc dng ca nhng thuc c
chuyn ha qua microsom gan khi dng phi hp, v d nh dng phenobarbital cng vi
sulfamid chng i tho ng, thuc chng th thai, estrogen, griseofulvin, cort ison, corticoid
tng hp, diphenylhydantoin, dn xut cumarin, aminazin, diazepam, doxycyclin, lidocain,
vitamin D, digitalin...
- C mt s thuc c th lm thay i tc dng ca barbiturat nh ru ethylic, reserpin,
aminazin, haloperidol, thuc chng i tho ng, thuc c ch microsom gan (cimetidin,
cloramphenicol...) lm tng gic ng barbiturat.
3. Dn xut benzodiazepin
c tng hp t 1956, ngy nay c dng nhiu hn barbiturat v t c, t tng tc vi thuc
khc. Benzodiazepin c tc dng an thn, gii lo, lm d ng, gin c v chng co git. Thng
dng cha mt ng hoc kh i vo gic ng do u t lo lng (xem bi"Thuc bnh thn").
4. Ru
4.1. Ru ethylic (ethanol)
4.1.1. Tc dng
- Thn kinh trung ng: ru c ch thn kinh trun g ng. Tc dng ca ru trn thn kinh
trung ng ph thuc vo nng ru trong mu: nng thp ru c tc dng an thn, lm
gim lo u, nng cao hn ru gy ri lon tm thn, mt iu ha, khng t ch c hnh
ng v c th b hn m, c ch h hp, nguy him n tnh mng khi nng ru trong mu
qu cao.
C ch tc dng: Trc y ngi ta cho rng tc dng c ch thn kinh trung ng l do ru
lm tan r lp lipid ca mng, nn nh hng n hot ng ca cc knh ion v cc prote in tc
ng trn cc knh.
Nhng nghin cu gn y cho thy ru lm tng kh nng gn ca GABA trn receptor
GABAA. Ru cn tc ng trn receptor NMDA glutamat (N - methyl- D- aspartat), c ch kh
nng m knh Ca ++ ca glutamat.
- Ti ch: khi bi ngoi da ru c tc dng st khun, tt nht l ru 70 0. Ru 90 0 lm ng
protein da, lm hp cc l tit m hi, do ru khng thm su vo trong da c.
- Tim mch: ru nh t nh hng n tim mch. Dng ru mnh trong thi gian di c th gy
gin c tim, ph i tm tht v x ha.
- Tiu ha: ru nh (di 10 0) lm tng tit dch v, dch v c nhiu acid v t pepsin, tng nhu
ng rut, tng kh nng hp thu thc n nim mc rut. V vy, dng ru nh c iu s
lm tng th trng.
Ngc li, ru 20 0 c ch s bi tit dch v. Ru mnh (40 0) gy vim nim mc d dy (do
nh hng ti lp cht nhy d dy), nn, co tht vng h v, lm gim s hp thu ca mt s
thuc qua rut.
- C trn: do c ch trung tm vn mch nn ru gy g in mch. Tc dng gin mch ca ru
cn do kh nng lm gin c trn ca acetaldehyd (cht chuyn ha ca ru). Do , ngi ng
c ru d b h thn nhit v khi gp lnh d b cht cng.
Ru cn lm gin c t cung.
4.1.2. Dc ng hc
Ru hp thu nhanh qua ng tiu ha. Sau khi ung 30 pht, ru t nng ti a trong
mu. Thc n lm gim hp thu ru.
Sau khi hp thu, ru c phn phi nhanh vo cc t chc v dch ca c th (qua c rau
thai). Nng ru trong t chc tng ng v i nng trong mu.
Trn 90% ru c oxy ha gan, phn cn li c thi tr nguyn vn qua phi v thn. C 2
con ng chuyn ha ru thnh acetaldehyd.
- Chuyn ha qua alcool dehydrogenase (ADH): (l con ng chnh). ADH l mt enzym cha
km, c nhiu gan. Ngi ta cn tm thy ADH no v d dy. ADH chuyn ru thnh
acetaldehyd vi s tham gia ca NAD + (nicotinamid adenin dinucleotid).
- Chuyn ha qua h microsomal ethanol oxidizing system (MEOS) khi nng ru trong mu
trn 100 mg/ dL (22 mmol/ L), ru c chuyn ha qua h MEOS. nhng ngi nghin
ru, hot tnh ca cc enzym tng ln, lm tng chuyn ha ca chnh ru v mt s thuc
c chuyn ha qua h ny nh phenobarbital, meprobamat, carbamazepin,
diphenylhydantoin...
4.1.3. ng dng ca ru
- Ngoi da: dng st khun
- Gim au: c th tim ru vo dy thn kinh b vim gim au.
4.1.4. Ng c mn
nhng ngi dng ru lu di, mt s c quan nh gan, thn kinh, d dy, tim mch... s b
tn thng.
- Gan d b vim, nhim m gan, x gan. Ph n d nhy cm vi c tnh ca ru hn nam
gii.
- Ru lm tng s bi tit dch v, dch ty, nh hng ti lp cht nhy nim mc dn ti
vim d dy.
Ngi nghin ru hay b tiu chy (ru gy thng tn ru t non), chn n, gy yu v thiu
mu.
- Vim dy thn kinh, ri lon tm thn, co git, gim kh nng lm vic tr c, m sng... thng
gp ngi nghin ru nng.
- Ung ru mnh v ko di, c tim d b tn thng v x ha. 5% ngi nghin ru b tng
huyt p.
- Ru c nh hng ti h thng min dch (thay i s ha ng ng bch cu, s lng t bo
limpho T, hot tnh ca NK (natural killer cell) do ngi nghin ru d mc cc bnh nhim
khun nh vim phi, lao...
Kh nng b ung th mi ng, thc qun, thanh qun v gan ngi nghin ru thng cao hn
ngi bnh thng.
4.1.5. iu tr ng c
4.1.5.1. Ng c cp
- Ra d dy nu bnh nhn mi b ng c
- m bo thng kh trnh suy h hp
- Gii quyt tnh trng h ng mu, tn g ceton mu bng truyn glucose.
- Bnh nhn nn nhiu, c th dng thm kali (nu chc phn thn bnh thng)
- Vitamin B 1 v mt s vitamin khc nh acid folic, vitamin B 6 c th lm gim bt cc thng
tn thn kinh do ru gy ra.
4.1.5.2. Ng c mn tnh
Dng disulfiram cha nghin ru
Disulfiram (tetraethylthiuram) c ch aldehyd dehydrogenase, lm tng nng acetaldehyd
(gp 5 n 10 ln) nn gy c.
Sau khi ung, khong 80% disulfiram c hp thu nhanh qua ng tiu ha nhng nng
thuc trong mu thp v disulfiram b chuyn ha thnh diethyldithiocarbamate (cht chuyn ha
cn tc dng).
Liu thng dng: 250 mg/ ngy (ti a 500 mg/ ngy) trong 1 - 2 tun, sau chuyn sang liu
duy tr 125 mg/ ngy (tu thuc vo mc nhy cm ca b nh nhn).
Sau khi dng disulfiram 1 gi, ngi nghin ung ru s b bng mt, nhc u d di, bun
nn, nn, v m hi, tt huyt p v bi ri. Cc du hiu ny c th ko di t 30 pht n vi
gi, sau bnh nhn ng thip i.
Mt s thuc nh metronidazol, cephalosporin, sulfamid chng i tho ng, khi phi hp vi
ru ethylic cng gy nhng phn ng nh disulfiram.
Cc nghin cu gn y cho thy c th phi hp Naltrexon (cht i khng trn receptor opioid)
vi disulfiram cha nghi n ru. S phi hp ny s lm gim c c tnh ca thuc i vi
gan. Naltrexon c dng 50 mg/ ln/ ngy.
4.1.6. Tng tc thuc
- Cc thuc an thn, thuc ng, chng co git, thuc c ch tm thn, thuc gim au loi opioid
lm tng tc dng ca r u trn thn kinh trung ng.
- Ru lm tng tc dng ph trn ng tiu ha nh vim, lot, chy mu ca cc thuc chng
vim phi steroid (aspirin...), ung ru cng vi paracetamol lm tng nguy c vim gan.
- Khi ung ko di, ru gy cm ng mt s enzym chuyn ha thuc microsom gan, lm tng
chuyn ha v gim hiu qu iu tr ca mt s thuc: sulfamid h ng huyt, thuc chng
ng mu loi cumarin, meprobamat, diphenylhydantoin, carbamazepin...
- Do tc dng gin mch ngoi vi ca ru, nu ung ng thi vi cc thuc chng tng huyt
p, c th c nguy c gy tt huyt p t ngt qu mc cn thit.
- Cc thuc h ng huyt nhm biguanid c th gy tng acid lactic mu nu ung nhiu ru
trong thi gian iu tr.
4.2. Methanol (ru methylic)
Loi ru ny dng trong cng nghip, khng dng trong y t v c. Trong c th, di s xc
tc ca alcool dehydrogenase, methanol c oxy ha thnh formaldehyd rt c (gy au u,
bun nn, nn, da lnh, hemoglobin niu v c th dn n m n u khng c iu tr kp thi).
Alcool -
CH3OH H2CO HCOO - CO 2+ H2O
methanol dehydrogenase formaldehyd format
4.3. Ethylen glycol (CH 2OHCH 2OH)
c s dng nhiu trong cng nghip, trong my iu kh ca xe t... Khng dng trong y t.
Khi ng c, ethylenglycol c th gy acid chuyn ha v suy thn (do lng ng cc tinh th
oxalat ng thn).
Cu hi t lng gi
1. Phn tch cu trc ha hc v cc c tnh l ha ca cc barbiturat.
2. Phn tch mi lin quan gia cu trc ha hc v tc dng dc l ca barbiturat.
3. Trnh by cc tc dng dc l ca thuc ng barbiturat.
4. Trnh by cc tc dng khng mong mun ca phenobarbital.
5. Trnh by triu chng ng c cp v cch x tr ng c phenobarbital.
6. Trnh by cc tc dng dc l ca ru ethylic.
7. Trnh by triu chng ng c v cch x tr ng c ru ethylic.
8. Trnh by cc tng tc ca ru ethylic vi cc thuc khc.
Bi 9: thuc gim au loi morphin

1. Nu c mi lin quan gia cu trc v tc dng ca morphin.
2. Phn tch c cc tc dng ca morphin, t nu c p dng iu tr ca
morphin.
3. Trnh by c triu chng v cch iu tr ng c cp v mn ca morphin.
4. Nu c c im tc dng ca mt s opioid tng hp: pethidin, pentazoxin,
methadon, fentanyl.
1. i cng
au l mt c ch bo v c th. au l do cc ngn dy thn kinh cm gic b kch thch qu
bi tc nhn vt l hay ha hc (nhit, c, in, cc acid hay base...). Di nh hng ca cc
kch thch au, c th gii phng ra mt hoc nhiu cht gy au nh histamin, cht P, cc cht
chuyn ha acid, cc kinin huyt tng (brady kinin, kallidin...).
Thuc gim au c chia lm 3 loi:
- Thuc gim au loi morphin.
- Thuc gim au khng phi loi morphin: paracetamol v thuc chng vim khng steroid.
- Thuc gim au h tr: l nhng thuc c tc dng lm tng hiu qu gim au hoc gim nh
tc dng khng mong mun ca cc thuc trn.
2. thuc gim au loi morphin
Thuc gim au loi morphin c chung mt c tnh l gy nghin, v vy u thuc "bng A,
gy nghin", khng k n qu 7 ngy.
Nhm thuc ny bao gm:
- Opiat: l cc dn xut ca thuc phin (opium), c tnh cht ging nh morphin.
- Opioid: l cc cht tng hp, bn tng hp, c tc dng ging morphin hoc gn c vo cc
receptor ca morphin.
Nha kh ca qu cy thuc phin c cha khong 25 alcaloid, trong morphin chim 10%,
codein gn 0,5%, papaverin 0,8%...
Da vo cu trc ha hc, cc alcaloid ca thuc phin c chia lm 2 loi:
- Nhn piperidin- phenanthren: morphin, codein..., tc dng u tin trn thn kinh trung ng.
- Nhn benzyl- isoquinolein: papaverin
Papaverin khng gy ng, tc dng ch yu l lm gin c trn (mch vnh, tiu ng mch ca
tim, phi, no, si c trn ca ph qun, rut, ng mt v niu qun).
2.1. Morphin
Trong lm sng dng mui morphin clohydrat d tan trong nc, cha 75% mo rphin.
2.1.1. Tc dng
Morphin c tc dng chn lc vi t bo thn kinh trung ng, c bit l v no. Mt s trung
tm b c ch (trung tm au, trung tm h hp, trung tm ho), trong khi c trung tm li b kch
thch gy co ng t, nn, chm nhp tim . Tc dng ca thuc thay i theo loi, gy hng phn
mo, chut nht, loi nhai li, c... nhng c ch r ngi, ch, th, chut lang.
2.1.1.1. Receptor ca morphin (v cc opioid)
Receptor c hiu ca morphin c tm thy t cui 1973, c 3 loi chnh v mi loi li c cc
phn loi nh. Gn y, mt receptor mi c pht hin, c tn l N/ OFQ receptor. Cc
receptor ny c rt nhiu sng sau tu sng ca ng vt c xng sng, nhiu vng trong
thn kinh trung ng: i th, cht xm quanh cu no, no gia. Cc receptor ca morphin cn
tm thy trong vng chi phi hnh vi (hnh nhn, hi hi m, nhn lc, v no), vng iu ha
h thn kinh thc vt (hnh no) v chc phn ni tit (li gia). ngoi bin, cc receptor c
tu thng thn, tuyn ngoi tit d dy, m ri thn kinh tng. V mt iu tr, mi receptor
c coi nh c chc phn ring.
Tc dng ca cc receptor
Tc dng Loi receptor Tc dng ca cht Tc dng ca cht

ng vn i khng
Gim au
Trn ty sng 1, 3, 1, 2 Gim au Khng
Ty sng 2, 2, 2 Gim au Khng
H hp 2 Gim Khng
Nhu ng rut 2, Gim Khng
Tm thn Tng hot ng Khng

2.1.1.2. Tc dng trn thn kinh trung ng
* Tc dng gim au
Morphin l thuc gim au mnh do lm tng ngng nhn cm gic au, thuc cn lm gim
cc p ng phn x vi au. Tc dng gim au ca morphin l do thuc kch thch trn receptor
muy v kappa.
Morphin c ch tt c cc im cht trn ng dn truyn cm gic au ca h thn kinh trung
ng nh tu sng, hnh tu, i th v v no. Nh vy, v tr tc dng ca morphin v cc
opioid ch yu nm trong h thn kinh trung ng. Khi dng morphin, cc trung tm v no
vn hot ng bnh thng, nhng cm gic au mt, chng t tc dng gi m au ca morphin
l chn lc. Khc vi thuc ng, khi tt c cc trung tm v no b c ch, bnh nhn mi ht
au.
Tc dng gim au ca morphin c tng cng khi dng cng thuc an thn kinh. Morphin
lm tng tc dng ca thuc t.
* Gy ng
Morphin lm gim hot ng tinh thn v gy ng. Vi liu cao c th gy m v lm mt tri
gic.
* Gy sng khoi
Cng vi tc dng gim au, morphin lm mt mi lo lng, bn chn, cng thng do au gy ra
nn ngi bnh cm thy thanh thn, th gin v d dn t i sng khoi.
Morphin lm thay i t th, lm tng tr tng tng, ngi bnh lun trng thi lc quan v
mt cm gic i.
* Trn h hp
Morphin tc dng trn receptor 2 v nh hng trc tip n trung tm h hp. Morphin c ch
trung tm h hp hnh tu, lm trung tm ny gim nhy cm vi CO 2 nn c tn s v bin
h hp u gim. Khi nhim c, nu ch cho th O 2 nng cao, c th gy ngng th.
tr mi v tr cn b, trung tm h hp rt nhy cm vi morphin v cc dn xut ca
morphin. Morphin qua c hng ro rau thai, hng ro mu - no. V vy, cm dng morphin v
cc opioid cho ngi c thai hoc tr em.
Morphin cn c ch trung tm ho nhng tc dng ny khng mnh bng codein, pholcodin,
dextromethorphan...
* Tc dng trn vng di i
Morphin lm mt thng bng c ch iu nhit lm thn nhit gim nh. Tuy nhin, khi dng liu
cao ko di, thuc c th gy tng nhit c th.
* Tc dng ni tit
Morphin tc ng ngay ti vng di i, c ch gii phng GnRH (Go nadotrop in- releasing
hormone) v CRF (corticotropin - releasing factor) do lm gim LH, FSH, ACTH, TSH v beta
endorphin.
Cc opioid kch thch receptor muy, lm tng tit ADH (hormon khng niu), trong khi cht ch
vn ca receptor kappa li lm gim tit ADH, gy li niu.
* Co ng t
Do kch thch cc receptor muy v kappa trn trung tm thn kinh III, morphin v opioid c tc
dng gy co ng t. Khi ng c morphin, ng t co rt mnh, ch cn nh nh u anh
ghim.
* Tc dng gy bun nn v nn
Morphin kch thch trc tip trung tm nn sn no tht IV, gy cm gic bun nn v nn. Khi
dng liu cao thuc c th c ch trung tm ny.
2.1.1.3. Tc dng ngoi bin
* Trn tim mch: liu iu tr morphin t tc dng trn tim mch. Liu cao lm h huyt p do
c ch trung tm vn mch.
* Trn c trn:
- C trn ca rut: trn thnh rut v m ri thn kinh c nhiu receptor vi morphin ni sinh.
Morphin lm gim nhu ng rut, lm gim tit mt, dch ty, dch rut v lm tng hp thu
nc, in gii qua thnh rut, do gy to bn. Lm co c vng (mn v, hu mn....) co tht
c oddi ch ni rut t- ng mt ch
- Trn cc c trn khc: morphin lm tng trng lc, tng co bp nn c th gy b i (do co
tht c vng bng quang), lm xut hin cn hen trn ngi c tin s b hen (do co kh qun).
* Trn da: vi liu iu tr morphin gy gin mch da v nga, mt, c, na thn trn ngi bnh
b .
* Trn chuyn ha: lm gim oxy ha, gim d tr base, gy tch lu acid trong mu. V vy,
ngi nghin mt b ph, mng tay v mi thm tm.
2.1.2. Lin quan gia cu trc v tc dng
Hai nhm nh hng nhiu n tc dng ca morphin l:
- Nhm phenol v tr 3: tc dng gim au gy nghin s gim i khi alkyl ha nhm ny, v d
codein (methyl morphin). N gc li, tc dng ca morphin s c tng cng nu nhm phenol
v tr 3 b ha ester, nh acetyl morphin (acetyl ha).
Cng thc:
- Nhm ru v tr 6: tc dng gim au v c tnh s tng ln nhng thi gian tc dng li

gim i khi nhm ny b kh H cho nhm ceton (hydro morphin) hay b ha ester, ha ether.
Tc dng gim au v gy nghin s tng mnh khi c 2 nhm phenol v ru u b acetyl ha,
v d heroin (diacetyl morphin).
2.1.3.Dc ng hc
2.1.3.1. Hp thu
Morphin d hp thu qua ng t iu ha, ch yu t trng, hp thu qua nim mc trc trng song
v phi qua chuyn ha ban u gan nn sinh kh dng ca morphin dng ng ung thp hn
ng tim (ch khong 25%). Morphin hp thu nhanh sau khi tim di da hoc tim bp v c
th thm nhp tt vo tu sng sau khi tim ngoi mng cng hoc trong mng cng (trong ng
sng).
2.1.3.2. Phn phi
Trong huyt tng, khong 1/3 morphin gn vi protein. Morphin khng lu trong cc m. Mc
d v tr tc dng ch yu ca morphin l h thn kinh tr ung ng, nhng ch c mt lng nh
qua c hng ro mu- no v morphin t tan trong m hn cc opioid khc, nh codein, heroin
v methadon.
2.1.3.3. Chuyn ha
Con ng chnh chuyn ha morphin l lin hp vi acid glucuronic v tr gn OH (3 v 6),
cho morphin - 3- glucuronid khng c tc dng dc l v morphin - 6- glucuronid (cht chuyn
ha chnh ca morphin) c tc dng gim au mnh hn morphin. Khi dng lu, morphin - 6-
glucuronid cng c tch lu.
Thi gian bn thi ca morphin khong 2 - 3 gi; morphin - 6- glucuronic c thi gian bn thi
di hn.
2.1.3.4. Thi tr
Morphin thi tr di dng nguyn cht rt t. Trn 90% liu dng c thi tr qua thn trong
24 gi u di dng morphin - 3- glucuronid. Morphin c chu k gan - rut, v th nhiu ngy
sau vn cn thy cht chuyn ha trong phn v nc tiu.
Khi dng morphin c th gp mt s tc dng khng mong mun:
* Thng gp: bun nn v nn (khong 20%), to bn, c ch thn kinh, co ng t, b i...
* t gp: c ch h hp, nga, tot m hi, l ln, c mng, o gic, co tht ti mt, co tht ph
qun...
Morphin tim ngoi mng cng t gy bun nn, nn, co tht ng mt hoc ng niu hn khi
dng qua cc ng khc.
2.1.5. p dng iu tr
2.1.5.1. Ch nh
- Gim au: dng trong nhng cn au d di cp tnh hoc au khng p ng vi cc thuc
gim au khc (au sau chn thng, au sau phu thut, au thi k cui ca bnh, au do
ung th...). gim au nhng bnh khng cha khi c (nh ung th thi k cui), c th
dng morphin qu 7 ngy.
- Phi hp khi gy m v tin m
2.1.5.2. Chng ch nh
- Tr em di 30 thng tui
- Triu chng au bng cp khng r nguyn nhn
- Suy h hp
- Suy gan nng
- Chn thng no hoc tng p lc ni s
- Hen ph qun (morphin gy c o tht c trn ph qun)
- Ng c ru cp
- ang dng cc cht c ch monoaminoxidase

2.1.5.3. Thn trng
Cn ch khi dng morphin ngi cao tui, suy gan, suy thn, thiu nng tuyn gip, suy
thng thn, ngi c ri lon tit niu - tin lit (nguy c b i), bnh nhc c.
- Thuc lm gim s tnh to, v vy khng nn li xe hoc vn hnh my khi dng morphin.
- Khng nn dng morphin trong thi k mang thai v cho con b.
2.1.6. Tng tc thuc
- Cm phi hp vi thuc c ch monoaminoxidase v c th gy try tim mch, tng thn nhit,
hn m v t vong. Morphin ch c dng sau khi ngng thuc MAOI t nht 15 ngy.
- Cc cht va ch vn va i khng morphin nh buprenorphin, nalbuphin, pentazocin lm
gim tc dng gim au ca morphin (do c ch cnh tr anh trn receptor)
- Cc thuc chng trm cm loi 3 vng, khng histamin H 1 loi c in, cc barbiturat,
benzodiazepin, ru, clonidin lm tng tc dng c ch thn kinh trung ng ca morphin.
2.1.7. c tnh
2.1.7.1. c tnh cp
* Triu chng ng c:
Cc biu hin ca ng c cp morphin xut hin rt nhanh: ngi bnh thy nng u, chng
mt, ming kh, mch nhanh v mnh, nn. Sau ng ngy cng su, ng t co nh nh u
anh ghim v khng phn ng vi nh sng. Th chm (2 - 4 nhp/ pht), nhp th Cheyne -
Stokes, c th cht nhanh trong vi pht sau tim hoc 1 - 4 gi sau ung trong trng thi ngng
th, mt tm xanh, thn nhit h, ng t gin v try mch.
Nu hn m ko di c th cht v vim phi.
Hn m, ng t co nh nh u anh ghim v suy gim h hp l 3 triu chng thng gp khi
ng c cc opioid.
* X tr
Cp cu bnh nhn ng c cp morphin phi da vo tnh trng bnh nhn lc c a vo
bnh vin. u tin phi m bo thng kh cho bnh nhn bng th oxy, h hp nhn to...
Truyn dch gi vng huyt p, nu bnh nhn hn m phi cho th my.
Gii c bng naloxon (thuc i khng vi morphin). Tim tnh mch naloxon 1 mL = 0,4
mg cho c ngi ln v tr em, c th cho liu ban u 2 mg nu ng c nng. Hai - ba pht sau
bnh nhn khng tnh, dng thm 0,4 mg (c th ti 4 liu), sau dng naloxon qua ng tim
bp. Tng liu naloxon c th ti 10 - 20 mg/ 24 gi.
Trong x tr ng c cp morphin nn dng naloxon qua ng truyn tnh mch lin tc d
phng suy h hp tr li v naloxon c thi gian bn thi ngn.
2.1.7.2. c tnh mn
* Quen thuc
Quen thuc ph thuc vo liu dng v s dng lp li. Ngi quen thuc c th dng morphin
vi liu gp 10- 20 ln liu ban u v cao hn nhiu so vi ngi bnh thng.
T khi tm ra morphin ni sinh, ngi ta ct ngha c hin tng quen thuc: cht ch vn
ni sinh ca receptor morphinic l enkephalin b ging ha qu nhanh, nn khng gy quen
thuc. Enkephalin (v c morphin) kch thch receptor, c ch gii phng mt s cht trung gian
ho hc, c ch adenylcyclase, lm gim sn xut AMP vng. Khi dng thuc lp i lp li, c
th phn ng bng tng tng hp AMP vng, v vy liu morphin sau i hi phi cao hn liu
trc receptor p ng mnh nh c, l hin tng que n thuc.
* Nghin thuc
Mt s tc gi cho rng khi dng morphin ngoi sinh lu s dn ti 2 hu qu:
- Receptor gim p ng vi morphin
- C th gim sn xut morphin ni sinh
S thiu ht morphin ni sinh lm ngi dng phi l thuc vo morphin ngoi lai, l nghin
thuc.
Ngi nghin morphin thng c ri lon v tm l, ni iu, li bing, t ch v sinh thn
th. Hay b to bn, co ng t, mt ng, chn n nn st cn, thiu mu, run... Kh nng
khng km, v vy h d b cht v cc bn h truyn nhim.
Ngi nghin lun "i morphin", khi thi thuc t ngt, morphin ni sinh khng , cc
receptor morphinic ang trong tnh trng chng li s tc ng thng xuyn ca morphin b ri
vo trng thi "mt thng bng" ; t l GMPv/ AMPv b o ngc, dn n mt s ri lon lm
sng: vt v, au c, au qun bng, v m hi, nn, a lng, chy nc mi, run, sn gai c, d
cm, tng nhp tim, tng huyt p, tng thn nhit, gin ng t, mt nc, st cn. Ngoi ra, cn
gp mt s du hiu v thn kinh nh: thao thc, bn chn, chn n, ngp vt, u su. Cc biu
hin ny nng nht l 36 - 72 gi sau khi dng liu thuc cui cng v mt dn sau 2 - 5 tun.
* Cai nghin morphin
Ngi nghin cn c cch ly, kt hp gia lao ng chn tay vi tm l liu php v dng
thuc. Trong thc t, d cai c cng d b nghin li.
- Dng thuc loi morphin
Phng php c in cai nghin morphin l dng methadon, mt opioid c tc dng ko di.
Methadon c tc dng lm nh cn i ma ty, phong ta tc dng gy khoi cm ca cc cht
dng thuc phin do lm cc triu chng ca hi chng cai xy ra m m hn, nh nhng
hn v khng thi thc tm ma ty cp bch ngi nghin.
Vic iu tr bng methadon c chia lm 2 giai on:
iu tr tn cng: liu thng dng t 10 - 40 mg/ngy (khng qu 120 mg/ngy), ko di 3 - 5
ngy, sau bt u gim liu tng t, mi t gim 5 mg.
iu tr duy tr: ko di t 9 - 12 thng, sau gim dn liu ri ngng hn.
Hin nay, ang dng th levomethadyl aceta t (L - - acetylmethadon) trong cai nghin heroin v
thuc c thi gian tc dng rt di, 3 ngy mi cn ung 1 ln.
- Khng dng thuc loi morphin
. iu tr triu chng: chng bn chn, vt v bng benzodiazepin hay thuc an thn kinh. Chng
au bng cc thuc gim au phi steroid (aspirin, paracetamol). Dng loperamid (l opioid t tc
dng trn thn kinh trung ng) chng tiu chy. Chng nn, chng mt ng...
. iu tr bng clonidin: ti vng nhn lc (locus ceruleus) c nhiu nron ca noradrena lin, cc
nron ny bnh thng b cc opioid tc ng trn cc receptor muy c ch. Khi cai thuc, cc
nron noradrenalin c thot c ch, gy nn cc triu chng cng giao cm, v th s rt hiu
qu nu dng clonidin, thuc cng 2 adrenergic trc synap, c tc dng lm gim tit
noradrenalin. Clonidin thng c dng 0,1 mg/ ln, mi ngy 2 ln (ti a 0,4 mg/ngy), trong
3- 4 tun.
Ngoi ra c th dng cc thuc i khng vi morphin nh naloxon, naltrexon.
2.2. Dn xut ca morphin
Mt s dn xut ca morphin nh thebain, dionin, dicodid, eucodal... c tc dng gim au, gy
sng khoi, gy nghin nh morphin. Ngi nghin morphin c th dng nhng dn xut ny
thay th. c bit c heroin gy nghin mnh hn hn nhng dn xut khc nn khng dng l m
thuc. Khng cai heroin c.
2.3. Cc opioid thng dng
2.3.1. Pethidin (meperidin, dolosal, dolargan)
2.3.1.1. Tc dng
- Sau khi ung 15 pht, pethidin c tc dng gim au mc d khng mnh bng morphin
(km 7- 10ln). t gy nn, khng gy to bn. Khng gim ho, pethidin cng gy an thn, lm
du, c ch h hp nh morphin.
- Pethidin lm gim huyt p, nht l t th ng, do lm gim sc cn ngoi vi v lm gim
hot ng ca h giao cm.
Khi dng qua ng tnh mch, pethidin lm tng lu lng tim, lm tim p nhanh, do c th
nguy him cho ngi b bnh tim.
- ng mt, thuc lm co tht c oddi, v vy khi au ng mt phi dng thm atropin.
2.3.1.2. Dc ng hc
Hp thu d qua cc ng dng. Sau khi ung, khong 50% pethidin phi q ua chuyn ha ban
u gan. Thi gian bn thi l 3 gi.
Gn vi protein huyt tng khong 60%
Pethidin t tan trong lipid, nn c i lc vi thn kinh trung ng yu hn morphin.
2.3.1.3. Tc dng khng mong mun
Pethidin t c hn morphin
Thng gp: Bun nn, nn, kh ming.
Him gp cc tc dng khng mong mun trn thn kinh trung ng nh bun ng, suy gim h
hp, ngt.
2.3.1.4. p dng iu tr
- Ch nh: gim au, tin m

- Chng ch nh nh morphin
- Liu lng: ung hoc t hu mn 0,05g m i ln, ngy dng 2- 3 ln
Tim bp 1 mL dung dch 1%, liu ti a: 0,05 g mi ln, 0,15g trong 24 gi.
- Dng pethidin cng MAOI gy nguy him: c ch mnh h hp, hn m, st cao, h huyt p,
co git ....
- Clopromazin lm tng tc dng c ch h hp ca pethidin
- Scopolamin, barbiturat v ru lm tng c tnh ca pethidin, do phi gim liu pethidin khi
dng ng thi.
2.3.2. Methadon (dolophin, amidone, phenadon)
L thuc tng hp, tc dng ch yu trn receptor muy
2.3.2.1.Tc dng
Methadon c tc dng tng t morphin nhng nhanh hn v ko di hn, t gy to bn. Gy
gim au mnh hn pethidin. D gy bun nn v nn.
2.3.2.2.Dc ng hc
Hp thu tt qua ng tiu ha, 90% gn vi protein huyt tng. Nh c nhm c eton v amin
trong cu trc nn methadon c lin kt ng ha tr bn vi protein no. Thuc c th tch lu
nu dng lin tip. Chuyn ha qua gan vi phn ng N - kh methyl. Thi tr qua nc tiu v
mt. Thi gian bn thi khong 15 - 40 gi.
2.3.2.3.Tc dng khng mong mun
Tc dng khng mong mun v c tnh ging nh morphin. Khi dng ko di, methadon c th
lm ra nhiu m hi, tng bch cu lympho, tng nng prolactin, albumin v globulin trong
mu.
2.3.2.4.p dng iu tr
Trn lm sng, methadon c dng gim au v cai nghin morphin, heroin
Liu lng: ung mi ln 2,5 mg, ngy 2 - 3 ln, tu thuc mc au v phn ng ca bnh
nhn.
2.3.3.Fentanyl (Submimaze, Fentanest, leptanal)
Thuc tng hp, tc dng ch yu trn receptor muy
2.3.3.1.Tc dng
Fentanyl gim au mnh gp 100 ln morphin, tc dng nhanh (khong 3 - 5 pht sau khi tim
tnh mch) v ko di 1 - 2 gi.
2.3.3.2.Dc ng hc
Thuc ch dng tim bp hoc tnh mch. 80% fentanyl gn vi protein huyt tng; phn b
mt phn trong dch no tu, rau thai v sa.
Fentanyl b chuyn ha gan v mt hot tnh. Thi tr qua nc tiu (khong10% di dng
cha chuyn ha).
2.3.3.3.Tc dng khng mong mun
Khong 45% trng hp iu tr vi fentanyl c th xut hin tc dng khng m ong mun.
- Ton thn: chng mt, ng l m, l ln, o gic, ra m hi, bng mt, sng khoi.
- Tiu ha: bun nn, nn, to bn, co tht ti mt, kh ming.
- Tun hon: chm nhp tim, h huyt p thong qua, nh trng ngc, lon nhp .
- H hp: th nhanh, suy h hp, ngt th
- C xng: co cng c bao gm c lng ngc, git rung
- Mt: co ng t
2.3.3.4.p dng iu tr
* Ch nh
- Gim au trong phu thut.
- Phi hp vi droperidol gim au, an thn
- Phi hp trong gy m.
* Chng ch nh
- Cc trng hp au nh (c th dng cc thuc gim au khc nh acetaminophen)
- Nhc c
- Thn trng trong cc trng hp: bnh phi mn tnh, chn thng s no v tng p lc s no,
bnh tim, trm cm, ph n c thai.
Fentanyl c ch nh i v i ph n cho con b, mc d thuc c mt trong sa m nhng
vi liu iu tr fentanyl khng nh hng n tr ang b.
* Liu lng
- Dng cho tin m: 50- 100 g, c th tim bp 30- 60 pht trc khi gy m.
- Gim au trong phu thut: 0,07 - 1,4 g/ kg th trng, c th nhc li trong 1 - 2 gi nu cn.
2.3.3.5.Tng tc thuc
- Cc thuc c ch thn kinh trung ng nh ru, thuc ng, thuc m, phenothiazin... lm tng
tc dng gim au ca fentanyl.
- Fentanyl lm gim hp thu ca mt s thuc nh metoclopamid, mexiletin... khi dng phi hp.
- Huyt p gim mnh khi phi hp fentanyl vi thuc c ch - adrenergic v thuc chn knh
calci.
Sulfentanyl (Sufenta)
- Tc dng v ch nh tng t fentanyl. Mnh hn fentanyl 10 ln, cng gy cng c.
- Gn vi protein huyt tng trn 90%, thi gian bn thi 2 - 3 gi.
- Thng tim tnh mch 8 g/ kg

Alfentanil (Alfenta)
Tc dng nhanh v ngn hn sufentanyl nn cn dng theo ng truyn tnh mch. Thng
c dng khi m v gim au, phi hp vi thuc m loi barbiturat, nitoxyd.
2.3.4.Propoxyphen
2.3.4.1.Tc dng
Propoxyphen c cng thc gn ging methadon, tc ng ch yu trn receptor muy. Tc dng
gim au km, ch bng 1/2 n 2/3 codein: 90 - 120 mg propoxyphen hydroclorid theo ng
ung, c tc dng gim au tng t 60 mg codein hoc 60 mg aspirin.
2.3.4.2.Dc ng hc
Sau khi ung 1- 2 gi, thuc t c nng ti a trong mu. Chuyn ha ch yu qua gan,
nh phn ng N- kh methyl. Thi gian bn thi t 6 - 12 gi. Cht chuyn ha l
norpropoxyphen c thi gian bn thi di hn (khong 30 gi).
Propoxyphen c th gy c ch h hp, co git, hoang tng, o gic, c vi tim... khi dng.
Dng gim au nh v trung bnh. Propoxyphen thng c phi hp vi aspirin hoc
acetaminophen.
2.3.5.Cc opioid c tc dng hn hp : va hip ng- va i lp, hoc hip ng mt phn
(Agonist- antagonist; partial agonist)
C nhiu thuc gn trn receptor muy, tranh chp vi morphin v cc opioid khc nhng khng
gy tc dng g, c gi l thuc i lp tranh chp, v d naloxon, cyclazocin... Ngc li, mt
s thuc sau khi tranh chp c receptor cn c th gy ra mt s tc dng dc l, hoc trn
receptor muy, hoc trn cc recept or khc nh delta v kappa. Cc thuc c gi l thuc c
tc dng hn hp hoc hip ng mt phn, v d: pentazocin, nalbuphin...
2.3.5.1. Pentazocin
Pentazocin l mt dn xut benzomorphan, cu trc c nhiu im ging morphin.
* Tc dng
Thuc c tc dng i khng ti receptor muy nhng li c tc dng hip ng ti receptor kappa
1, gy an thn , gim au v c ch h hp
Tc dng gim au nh morphin nhng khng gy sng khoi.

Khi dng liu cao, pentazocin lm tng huyt p v nhp tim.
* Dc ng hc
Hp thu d qua ng tiu ha. Sau khi ung 1 - 3 gi, thuc t c nng ti a trong mu.
Thi gian bn thi khong 4 - 5 gi. V phi qua chuyn ha ln u gan nn ch 20%
pentazocin vo c vng tun hon. Thuc qua c hng ro rau th ai.
* Tc dng khng mong mun
Pentazocin c th gy ra mt s tc dng khng mong mun: an thn, v m hi, chng mt,

bun nn v nn... Thuc c ch h hp khi dng liu cao.
* p dng iu tr
Thuc c ch nh trong nhng cn au nng, mn tnh h oc khi ngi bnh khng dng c
cc thuc gim au khc.
Thng dng dung dch pentazocin lactat cha 30 mg pentazocin base/ 1 mL. Tim tnh mch
hoc di da 30 mg mi ln, sau 4 gi c th tim li.
Hin nay c nhng ch phm phi hp gia pentazocin vi aspirin hay acetaminophen.
2.3.5.2. Buprenorphin
L thuc tng hp, dn xut ca thebain. Buprenorphin hip ng 1 phn trn receptor muy, c
tc dng gim au mnh hn morphin t 25 - 50 ln.
Hp thu d qua cc ng dng: ung, di li, tim bp... Gn vi protein huyt tng khong
96%, thi gian bn thi 3 gi.
c dng gim au trn lm sng. Thng tim bp hoc tnh mch 0,3 mg mi ln, ngy
dng 3- 4 ln.
2.4. Thuc i khng vi opioid
Thay i cng thc ha hc ca morphin, c bit v tr 17 mang nhm N- methyl, nhm c
hiu kch thch receptor muy, s c cc cht i khng. V d:
Morphin nalorphin
Levorphanol levallorphan
Oxymorphon naloxon, naltrexon
Cc cht ny i lp c cc tc dng do morphin gy ra, ch yu l nhng du hiu c ch nh
gim au, c ch h hp, an thn, sng khoi. Thi gian tc dng ni chung ngn hn morphin.
Nalorphin khng c dng trn lm sng v c ch h hp, lm chm nhp tim, co ng t, sng
khoi.
2.4.1. Naloxon (nalonee, narcan, narcanti)
2.4.1.1.Tc dng
Khc vi levallorphan hoc nalorphin, naloxon t hoc khng c hot tnh ch vn. ngi
dng liu ln opioid, naloxon i khng phn ln nhng tc dng khng mong mun ca opioid
nh c ch h hp, an thn, gy ng...
Khi dng, naloxon c th gy ra hi chng thiu thuc sm ngi nghin opioid, tuy vy dng
liu cao s ngn chn c triu chng suy h hp trong hi chng ny.
2.4.1.2. Dc ng hc
Mc d c hp thu d qua ng tiu ha nhng naloxon b chuyn ha gan trc khi vo
vng tun hon nn liu ung phi ln hn nhiu so vi liu tim. Thuc c tc dng nhanh (1 - 2
pht sau khi tim tnh mch) thi gian tc dng ph thuc vo liu v ng dng.
Sau khi tim, naloxon phn b nhanh vo cc m v dch c th. Thi gian bn thi l 60 - 90
pht.
- Tim mch: tng huyt p (c khi gim huyt p), nhp tim nhanh, lon nhp tht.
- Thn kinh trung ng: mt ng, kch thch, lo u
- Tiu ha: bun nn, nn
- Nhn m, ban ngoi da.
Naloxon c dng iu tr ng c cp cc opiat v opioid, cai nghin opioid
Phi ht sc thn trng khi dng naloxon cho ngi c bnh tim mch, ph n c thai v cho con
b.
Liu lng; ngi ln: 0,4 - 2 mg, tim tnh mch, 2 -3 pht tim nhc li nu cn. Tng liu 10
mg.
V thi gian tc dng ca naloxon rt ngn (60 - 90 pht) nn cn truyn lin tc naloxon khi
bnh nhn ng c opium nng.
2.4.2. Naltrexon
i khng vi opioid mnh hn naloxon, thng dng ng ung. Nng ti a trong mu t
c sau 1- 2 gi. Thi gian bn thi l 3 gi.
Naltrexon c chuyn ha thnh 6 - naltrexon (c hot tnh sinh hc yu hn nhng thi gian
bn thi di hn, khong 13 gi).
Naltrexon c dng cai nghin opioid (ung 100 mg / ngy), cai nghin ru (phi hp vi
disulfiram).
2.5. Morphin ni sinh
Hai nm sau khi tm ra receptor ca opiat, mt s cng trnh nghin cu cho thy receptor ca
morphin cn c i lc rt mnh vi mt s peptid c hiu sn c trong c th ng vt, nhng
peptid ny gy ra nhng tc dng ging morphin.
Cc morphin ni c chia thnh 3 h:
- Enkephalins (Met- enkephalin v leu- enkephalin)
- Endorphins
- Dynorphins
Mi loi c tin thn khc nhau v phn b nhng v tr khc nhau trn thn kinh tru ng ng.
Cc morphin ni sinh hot ng nh mt cht dn truyn thn kinh, hoc cht iu bin ca dn
truyn hoc l hormon thn kinh. V th, chng tham gia vo cc c ch gim au, cc cm gic
thm mun (n ung, tnh dc), cc qu trnh cm xc, tm t hn, tr nh.
tu sng, morphin ni sinh c ch gii phng cht P, l mt decapeptid (10 acid amin) c
gii phng ti ngn dy cm gic sng sau tu sng. Cht P c vai tr kim tra ng cm gic
truyn vo v kch thch cc nron vn ng ca sng trc gy phn x t v.
Cc enkephalin l pentapeptid c tc dng gim au rt ngn v b ging ha nhanh trong c th
nh cc enzym: dipeptidyl amino peptidase, aminopeptidase v enkephalinase. Cc endorphin c
4 loi, nhng ch c beta endorphin c t c dng gim au mnh v lu (3 - 4 gi) v tng i
vng bn.
3. Thuc gim au khng phi loi morphin : (xin xem bi thuc h st - gim
au- chng vim).
4. Thuc gim au h tr
Thuc gim au h tr c tc dng hip ng, lm tng tc dng gim au ca cc opioid v
thuc gim au chng vim khng steroid. Cc thuc ny c bit hiu qu i vi au do
nguyn nhn thn kinh.
4.1. Thuc chng trm cm:
Tc dng gim au khng ph thuc vo tc dng chng trm cm. Thng dng trong cc
trng hp au ko di, c lin quan n bnh l thn kinh.
Nhm thuc c tc dng tt nht l thuc chng trm cm loi ba vng (xin xem thm bi thuc
chng trm cm).
4.2. Thuc chng ng kinh
gim au trong bnh thn kinh do i tho ng, au sau zona, au dy t hn kinh, d phng
cn au na u (migraine) c th dng cc thuc: phenytoin, carbamazepin v valproat (xin xem
thm bi thuc cha ng kinh).
5. Nguyn tc s dng thuc gim au
5.1. Chn thuc
Thuc gim au ch iu tr triu chng, thuc c th che lp cc du hiu ca bnh trong khi
bnh vn tin trin nn phi ht sc cn nhc khi s dng thuc gim au. Khi la chn thuc
cn ch n cng v bn cht ca au. T chc Y t Th gii khuyn co nn ung thuc
theo bc thang gim au:
- Bc 1 (au nh): dng thuc gim au khng phi opioid nh paracetamol, thuc chng vim
khng phi steroid.
- Bc 2 (au va): phi hp thuc loi opioid yu (codein, oxycodon) vi paracetamol, thuc
vim khng steroid hoc thuc gim au h tr.
- Bc 3 (au nng): dng thuc gim au loi opioid mnh : morphin, hydromorphon,
methadon... phi hp vi thuc chng vim khng steroid.
5.2. ng dng thuc
Thng thng nn dng ng ung. Tuy nhin, trong cc cn au nng, cp tnh hoc sau phu
thut ln... phi dng ngay cc thuc gim au mnh loi opioid qua ng tim trnh sc v
nh hng xu ca au n tin trin ca bnh .
Cu hi t lng gi
1. Trnh by cc tc dng ca morphin trn thn kinh trung ng.
2. Trnh by cc tc dng ngoi bin ca morphin .
3. Phn tch mi lin quan gia cu trc ha hc v tc dng dc l ca morphin.
4. Trnh by cc ch nh v chng ch nh khi s dng morphin.
5. Trnh by cc tc dng khng mong mun v thn trng khi dng morphin.
6. Trnh by triu chng v cch x tr ng c cp morphin.
7. Trnh by triu chng ng c mn v cch cai nghin morphin.
8. Trnh by tc dng, tc dng khng mong mun v p dng iu tr ca pethidin.
9. Trnh by tc dng v p dng iu tr ca loperamid.
10. Trnh by tc dng, tc dng khng mong mun v p dng iu tr ca methadon.
11. Trnh by tc dng, tc dng khng mong mun v p dng iu tr ca pentazoxin.
12. Trnh by tc dng, tc dng khng mong mun v p dng iu tr ca fentanyl.
Bi 10: Thuc h st - gim au - chng vim

1. Phn tch c nhng tc dng chnh v c ch tc dng ca thuc chng vim phi
steroid (CVKS)
2. Trnh by c c im tc dng v p dng iu tr ca cc thuc: aspirin,
indomethacin, diclofenac.
3. Trnh by c c im tc dng v p dng iu tr ca cc thuc: dn xut Oxicam,
dn xut acid propionic, paracetamol v thuc c ch COX - 2
4. Nu c 7 nguyn tc khi s dng thuc CVKS.
Cc thuc trong nhm ny rt khc nhau v cu trc ha hc, gm cc dn xut ca salicylat,

pyrazolon, anilin, indol v mt s thuc khc. Tt c cc thuc, mc khc nhau, u c tc
dng h st, gim au, v - tr dn xut anilin - cn c tc dng chng vim , chng thp khp,
chng ng vn tiu cu. V vy cn c gi chung l thuc chng vim khng (mang nhn)
steroid (CVKS) phn bit vi cc glucocorticoid, mang nhn sterol, c gi l thuc chng
vim steroid.
1. Tc dng chnh v c ch
C ch chung ca thuc CVKS: c ch sinh tng hp prostagladin
Vane 1971 cho rng c ch tc dng chnh ca cc thuc CVKS l c ch enzym
cyclooxygenase, lm gim tng hp cc prostaglandin l nhng cht trung gian ha hc c vai tr
quan trng trong vic lm tng v ko di p ng vim m sau tn thng.
Khi tn thng, mng t bo gii phng phospholipid mng. Di tc dng ca phospholipase A 2
(l enzym b corticoid c ch), cht ny chuyn thnh acid arAChidonic. Sau , mt mt, di
tc dng ca lipooxygenas e (LOX), acid arAChidonic cho cc leucotrien c tc dng co kh
qun; mt khc, di tc dng ca cyclooxygenase, acid arAChidonic cho PGE 2 (gy vim, au),
prostacyclin (PGI 2) v thromboxan A 2 (TXA2) tc ng n s lng ng tiu cu. Cc CVKS c
ch COX nn c ch c cc phn ng vim (s )
corticoid
Phospholipid mng
(t bo tn thng)
Lipocortin
(+) (-)
Phospholipase A 2
Acid arachidonic ( -) CVKS

LOX COX
Cc leucotrien
(co kh qun) PGE 2 PGI2 TXA 2
(vim au) (lng ng tiu cu...)
Hnh 10.1: V tr tc dng ca CVKS v corticoid trong tng hp PG
Tuy nhin, c ch trn cha gii thch c y nhng nhn xt lm sng trong qu trnh s
dng CVKS, nh:
- Hiu qu v tnh an ton ca cc thu c CVKS khng ging nhau.
- Hiu qu c ch tng hp PG v TX ca cc thuc rt thay i. Nhiu thuc c ch mnh tng
hp PG hn TX v ngc li. Aspirin c ch mnh v khng hi phc s kt t tiu cu vi liu
thp, nhng phi liu rt cao mi c tc d ng chng vim.
T mi nm gn y, cc nghin cu cho thy c 2 loi COX, c gi l COX - 1 v COX-
2 c chc phn khc nhau v cc thuc chng vim tc dng vi mc khc nhau trn COX - 1
v COX-2 (s )
- COX-1: hay PGG/ H synthetase - 1 c tc dng duy tr cc hot ng sinh l bnh thng ca t
bo l mt "enzym cu to". Enzym c mt hu ht cc m, thn, d dy, ni mc mch, tiu
cu, t cung, tinh hon ... Tham gia trong qu trnh sn xut cc PG c tc dng bo v, do
cn gi l "enzym gi nh" ("house keeping enzyme") :
. Thromboxan A 2 ca tiu cu
. Prostacyclin (PGI2) trong ni mc mch, nim mc d dy
. Prostaglandin E 2 ti d dy bo v nim mc
. Prostaglandin E 2 ti thn, m bo chc phn sinh l.
- COX- 2: hay PGG/ H synthetase 2 c chc phn thc y qu trnh vim. Thy hu ht cc
m vi nng rt thp, cc t bo tham gia vo phn ng vim (bch cu 1 nhn, i thc bo,
bao hot dch khp, t bo sn). Trong cc m vim, nng COX - 2 c th tng cao ti 80 ln
do cc kch thch vim gy cm ng v hot ha mnh COX - 2. V vy COX- 2 cn c gi l
"enzym cm ng"
Nh vy, thuc c thch
Kch ch COX - 1 nhiu s gy nhiu tc dng khng mong mun, thuc c ch
Kch thch
COX- 2 mnh ssinh
c tc
l dng chng vim mnh m t gy tc dng ph.
gy vim
Gii phng acid

arAChidonic
mng t bo
CVKS (-) (-) CVKS
COX- 1 COX- 2
(enzym cu to) (enzym cm ng) Tc dng
Cc tc chng vim
dng ph
TXA2 PGI1 PGE2 Cc PG (bch

(tiu cu) (ni mc (thn) cu 1 nhn i
nim mc thc bo, t bo
d dy sn)
Chc phn bo v t bo Thc y

v "gi nh" qu trnh vim
Hnh 10.2: Vai tr sinh l ca COX - 1 v COX- 2
Ngoi tc dng c ch tng hp PG, cc CVKS cn c th c nhiu c ch khc. Cc CVKS l

cc phn t a m, d thm nhp vo mng t bo hoc mng ti th, nht l vo cc bch cu a
nhn, nn :
. c ch tit cc enzym ca cc th tiu bo
. c ch sn xut cc gc t do.
. c ch lng ng v kt dnh cc bch cu a nhn trung tnh.
. c ch cc chc phn mng ca i thc bo nh c ch NADPH, oxydase, phospholipasse C,
protein G v s vn chuyn ca cc anion qua mng.
1.1. Tc dng chng vim
Cc CVKS c tc dng trn hu ht cc loi vim khng k n nguyn nhn, theo cc c ch
sau:
- c ch sinh tng hp prostaglandin (PG) do c ch c hi phc cyclooxygenase (COX), lm
gim PG E 2 v F1 l nhng trung gian ha hc ca phn ng vim (Vane v cs. 1971).
- Lm vng bn mng lysosom (th tiu bo): vim, trong qu trnh thc bo, cc i thc bo
lm gii phng cc enzym ca lysosom (hydrolase, aldolase, phosphatase acid, colagenase,
elastase...), lm tng thm qu trnh vim. Do lm vng bn mng lysosom, cc CVKS lm ngn
cn gii phng cc enzym phn gii, c ch qu trnh vim.
- Ngoi ra c th cn c thm mt s c ch khc nh i khng vi cc cht trung gian ho hc
ca vim do tranh chp vi c cht ca enzym, c ch di chuyn bch cu, c ch phn ng
khng nguyn- khng th.
Tuy cc CVKS u c tc dng gim au - chng vim, song li khc nhau gia t l l iu chng
vim/ liu gim au. T l y ln hn hoc bng 2 vi hu ht cc CVKS, k c aspirin (ngha l
liu c tc dng chng vim cn phi gp i liu c tc dng gim au) nhng li ch gn bng
1 vi indometacin, phenylbutazon v piroxicam.
1.2. Tc dng gim au
Ch c tc dng vi cc chng au nh, khu tr. Tc dng tt vi cc chng au do vim (au

khp, vim c, vim dy thn kinh, au rng, au sau m). Khc vi morphin, cc thuc ny
khng c tc dng vi au ni tng, khng gy ng, khng g y khoan khoi v khng gy
nghin. Theo Moncada v Vane (1978), do lm gim tng hp PG F 2 nn cc CVKS lm gim
tnh cm th ca cc ngn dy cm gic vi cc cht gy au ca phn ng vim nh bradykinin,
histamin, serotinin.
i vi mt s chng au s au m, CVKS c th c tc dng gim au mnh hn c morphin v
m gy ra vim.
Trong au do chn p c hc hoc tc dng trc tip ca cc tc nhn ha hc, k c tim trc
tip prostaglandin, cc CVKS c tc dng gim au km hn, cng chng t c ch quan trng
ca gim au do CVKS l do c ch tng hp PG. Ngoi ra c th cn nhng c ch khc.
1.3. Tc dng h st
Vi liu iu tr, CVKS ch lm h nhit trn nhng ngi st do bt k nguyn nhn g, khng
c tc dng trn ngi thng. Khi vi khun , c t, nm... (gi chung l cc cht gy st ngoi
lai) xm nhp vo c th s kch thch bch cu sn xut cc cht gy st ni ti (cc cytokin,
interferon, TNF ...). Cht ny hot ha prostaglandin synthetase, lm tng tng hp PG (c bit
l PG E 1, E2) t acid arAChidonic ca vng di i, gy st do lm tng qu trnh to nhit
(rung c, tng h hp, tng chuyn ha) v gim qu trnh mt nhit (co mch da). Thuc CVKS
do c ch prostaglandin synthetase, lm gim tng hp PG, c tc dng h st d o lm tng qu
trnh thi nhit (gin mch ngoi bin, ra m hi), lp li thng bng cho trung tm iu nhit
vng di i. Cc CVKS khng c ch c st do tim trc tip PG vo vng di i. V
khng c tc dng n nguyn nhn gy st nn thuc h st ch c tc dng cha triu chng,
sau khi thuc b thi tr, st s tr li.
Thuc h st
(-) Vng di i
- rung c
Cht gy st Bch cu TKT - tng h hp
ngoi lai PG (E 1- E2)
(+) st
Cht gy st PG
ni ti synthetase TKTV - co mch
acid - tng chuyn ha
arAChidonic
Hnh 10.3. C ch gy st v tc dng ca thuc h st

1.4. Tc dng chng ngng kt tiu cu
Trong mng tiu cu c cha nhiu thromboxan synthetase l enzym chuyn endoperoxyd ca
PG G2/ H2 thnh thromboxan A 2 (ch tn ti 1 pht) c tc dng lm ng vn tiu cu. Nhng
ni mc mch cng rt giu prostacyclin synthetase, l enzym tng hp PG I 2 c tc dng i lp

vi thromboxan A 2. V vy tiu cu chy trong mch bnh thng khng b ng vn. Khi ni
mch b tn thng, PGI 2 gim; mt khc, khi tiu cu tip xc vi thnh mch b tn thng,
ngoi vic gii phng ra thromboxan A 2 cn phng ra cc "gi tc" lm dnh cc tiu cu vi
nhau v vi thnh mch, dn ti hin tng ngng kt tiu cu. Cc CVKS c ch thr omboxan
synthetase, lm gim tng hp thromboxan A 2 ca tiu cu nn c tc dng chng ngng kt tiu
cu (hnh 3.4)
Tiu cu khng c kh nng tng hp protein nn khng ti to c cyclooxyganase. V th,
mt liu nh ca aspirin (40 - 100 mg/ ngy) c th c ch khng hi phc cyclooxyganase
sut cuc sng ca tiu cu (8 - 11 ngy)
Cyclooxygenase
(-)
Aspirin Thr. synth Thromboxan A 2
Tiu cu (lm vn tiu cu)

Acid arAChodonic PGG 2/ H2 Tc dng
i khng
Prost. Synth Prostacyclin

ni mc (PG I 2)
Hnh 10.4. C ch c ch ng vn tiu cu

2. Cc dn xut
Phn loi ha hc cc thuc CVKS
Loi c ch COX khng chn l c

Nhm acid salicylic
. Aspirin
Nhm pirazolon
. Phenylbutazon
Nhm indol
. Indometacin, sulindac
. Etodolac (ring thuc ny li c ch chn lc COX - 2)
Nhm acid enolic
. Oxicam (piroxicam, meloxicam)
Nhm acid propionic

. Ibuprofen, naproxen, ketoprofen, fenoprofen
Nhm dn xut acid phenylacetic
. Diclofenac
Nhm dn xut acid heteroarylacetic
. Tolmetin, ketorolac
Loi c ch chn lc COX - 2
Nhm furanon c nhm th diaryl
. Rofecoxib
Nhm pyrazol c nhm th diaryl
. Celecoxib
Nhm acid indol acetic
. Etodolac
Nhm sulfonanilid
. Nimesulid
2.1. Dn xut acid salicylic
2.1.1. Acid salicylic (acidum salicylicum):
Tinh th hnh kim, khng mu, n h, ng nh,
khng mi, v chua v hi ngt, kh tan trong
nc. Do kch ng mnh nim mc nn khng
dng ung. Dng ngoi da, dung dch 10%
cha chai chn, ht cm, nm da...
2.1.2. Acid acetylsalicylic (aspirin):
Kt tinh hnh kim trng, hi chu a, kh tan trong
nc, d tan hn trong ru v cc dung dch
base. L sn phm acetyl ha ca acid salicylic
gim tnh kch ng nn ung c.
2.1.2.1. c im tc dng:
- Tc dng h st v gim au trong vng 1 - 4 gi vi liu 500 mg/ln. Khng g y h thn nhit.
- Tc dng chng vim: ch c tc dng khi dng liu cao, trn 3g/ngy. Liu thp ch yu l h
st v gim au.
- Tc dng thi tr acid uric: liu thp (1 -2g/ngy) lm gim thi tr acid uric qua nc tiu do
lm gim bi xut cht ny ng ln xa. Liu cao (2 -5g/ngy) lm i nhiu urat do c ch ti
hp thu acid uric ng ln gn.
- Tc dng trn tiu cu v ng mu:

Aspirin vi liu thp (40 -325mg/ngy) c ch mnh cyclooxygenase ca tiu cu, lm gim
tng hp thromboxan A 2 (cht lm ng vn tiu cu) nn lm gim ng vn tiu cu. Liu cao
hn, c ch cyclooxygenase ca thnh mch, lm gim tng hp PG I 2 (prostacyclin) l cht
chng kt dnh v lng ng tiu cu, gy tc dng ngc li. Nhng tc dng trn tiu cu mnh
hn nhiu.
Liu cao aspirin cng lm gim tng hp prothrombin, c th l do i khng vi vitamin K. V
vy, aspirin c tc dng chng ng mu.
- Tc dng trn ng tiu ha:
Nim mc d dy - rut sn xut ra PG, c bit l PG E 2, c tc dng lm tng to cht nhy v
c th l c kch thch phn bo thay th cc t bo b ph hu. Nh vy, vai tr ca PGE l
bo v nim mc ng tiu ha. Aspirin v cc thuc chng vim phi steroid ni chung, vi mc
khc nhau, c ch cyclooxygenase, lm gim PG , to iu kin cho HCl v pepsin ca dch v
gy tn thng cho nim mc sau khi hng ro bo v b suy yu. V vy, khng c dng
thuc cho nhng ngi c tin s lot d dy v phi ung thuc sau ba n.
2.1.2.2. Dc ng hc
pH ca d dy, cc dn xut salicylic t b ion ha cho nn d khuch tn qua mng, c hp
th tng i nhanh vo mu ri b thu phn thnh acid salicylic, khong 50 - 80% gn vi
protein huyt tng, b chuyn ha gan, thi gian bn thi khong 6 gi. Thi tr qua nc tiu
50% trong 24 gi di dng t do, glycuro - hp, acid salicylic v acid gentisic. Nu pH ca nc
tiu base, thi tr salicylic tng.
2.1.2.3. c tnh:
- Mc du cc dn xut salicylic u t c, d ung, nhng dng lu c th gy hi chng
salicyle (salicylisme): bun nn, tai, ic, nhc u, l ln.
- c ng: ph, m ay, mn, ph Quincke, hen.
- Xut huyt d dy th n (c hng cu trong phn) hoc th nng (lot, nn ra mu).
- Nhim c vi liu trn 10g. Do aspirin kch thch trung tm h hp, lm th nhanh v su (nn
gy nhim alcali h hp), sau v p lc ring phn ca CO 2 gim, m gii phng nhiu acid
lactic, a n hu qu nhim acid do chuyn ha (hay gp tr em v c ch iu ha cha n
nh).
Liu cht i vi ngi ln khong 20g.
2.1.2.4. Liu lng v ch phm:
- Ung 1-6g/ngy, chia lm nhiu ln. Dng h st, gim au v chng vim (thp khp cp,
thp khp mn, vim a khp, vim thn kinh...)
Vin nn aspirin 0,5g (bit dc: Acesal, Aspro, Polopyrin).
- Lysin acetyl salicylat (Aspgic): l dng mui ha tan, mi l tng ng vi 0,5g aspirin.
Tim tnh mch hoc tim bp 1 -4 l/ngy.
- Aspirin pH8: vin nn cha 0,5 g aspirin, c bao bng cht khng vi dch v, nhng tan trong
dch rut, on 2 ca t t rng, t thuc c hp thu vo mu v b thu phn thnh acid
salicylic. Nng ti a trong mu t c sau 7 gi, thi gian bn thi di hn aspirin bnh
thng, do gim c s ln ung thuc trong ngy, rt tin li cho cc trng hp iu tr
ko di.
2.1.3. Methyl salicylat
Dung dch khng mu, mi hc lu, ch dng xoa bp
gim au ti ch. Ngm qua da cho nn khi xoa bp,
thy metyl salicylat trong nc tiu.
2.2. Dn xut pyrazolon

Hin ch cn dng mt cch hn ch phenylbutazon. Cc dn xut khc nh phenazon
(antipyrin), aminophenazon (pyramidon), metamizol (analgin), khng cn dng na v c nhiu
c tnh vi mu (gim bch cu, suy tu), vi thn (i albumin, vim ng thn cp, v niu).
Ch dng phenylbutazon cho vim cng khp v vim a khp mn tnh tin trin khi cc thuc
CVKS khc khng cn tc dng v phi theo di cht ch cc tc dng khng mong mun ca
thuc.
Liu lng v ch phm:
Ngy u ung 200mg chia lm 2 ln ung trong hoc sau ba n, tng dn liu ti 600 mg /ngy.
Tu theo tnh trng bnh v sc chu ng ca ngi bnh, c th gi liu trong 4 - 5 ngy,
sau gim xung liu duy tr 100 - 200 mg. Ni chung, mt t thuc khng qu 15 ngy, sau
ngh 4 - 5 ngy mi dng.
Phenylbutazon vin 50 v 100 mg.
Oxyphenbutazon (Tandery) vin 100 mg.
Chngta s b thuc ny trong tng lai gn
2.3. Dn xut indol:
2.3.1. Indometacin
2.3.1.1. c im tc dng
- Tc dng gim vim mnh hn phenylbutazon 20 - 80 ln v mnh hn hydrocortioson 2 - 4
ln. i khng r vi PG. Tc dng c trn giai on u v giai on mun (mn tnh) ca vim.
- Tc dng gim au lin quan mt thit vi tc dng chng vim (liu chng vim/liu gim au
= 1).
- C tc dng h st, nhng khng dng cha st n thun v c nhiu c tnh v c
thuc h st khc thay th (paracetamol, aspirin).
- Sinh kh dng gn bng 100%. Gn protein huyt tng 99%, thm c vo dch khp (bng
khong 20% nng huyt tng).
2.3.1.2. c tnh: Xy ra cho khong 20 -50% ngi dng thuc.
- C th gy chng mt, nhc u (v cng thc ca indomatacin tng t nh serotonin), ri
lon tiu ha, lot d dy. V th khng c dng cho ngi c tin s d dy.
2.3.1.3. Ch nh:
- Vim xng khp, h khp, thp khp ct sng, vim nhi u khp mn tnh tin trin, au lng,
vim dy thn kinh...
- Ch phm v liu lng:
Indometacin (Indocid; Indocin): vin nn hoc vin nang 25mg. Thuc n 50 - 100mg. Mi
ngy ung 50 - 150 mg chia lm nhiu ln.
2.3.2. Sulindac
Sulindac l tin cht (prodrug): bn thn n khng c hot tnh, vo c th c chuyn ha
thnh dn cht sulfat c hot tnh sinh hc mnh, c ch cyclooxygenase 500 ln mnh hn
sulindac. V cu trc ha hc, sulindac l indometacin c thay methoxy bng fluor v thay
Cl bng gc methylsulfinyl (CH 3SO).
- Trong thc nghim, tc dng dc l ca sulindac bng 1/2 indometacin; trong thc t lm
sng, tc dng chng vim v gim au ca sulindac tng t aspirin.
- T l v mc c tnh km indometacin.
- Ch phm: Arthrocin, Artribid, Clinoril vin 150 v 200 mg; mi ngy ung 1 -2 vin, liu ti a
400mg/ngy, l liu tng ng vi 4g aspirin hoc 125 mg indometacin.
2.3.3. Etodolac
L thuc c tc dng c ch u tin COX - 2, hp thu nhanh qua tiu ha, 99% gn vo prot ein
huyt tng, c chu k gan - rut. Thi gian bn thi l 7 gi.
Liu ung 200- 400 mg
2.4. Dn xut enolic acid: oxicam (piroxicam, meloxicam v tenoxicam)
L nhm thuc gim vim mi, c nhiu u im:
- Tc dng chng vim mnh v ngoi tc dng c c h COX cn c ch proteoglycanase v
collagenase ca m sn, liu iu tr ch bng 1/6 so vi cc thuc th h trc. Tc dng gim
au xut hin nhanh, na gi sau khi ung.
- Thi gian bn thi di (2 -3 ngy) cho php dng liu duy nht trong 24 gi. G n vo protein
huyt tng ti 99%. V t/2 qu di, d c nguy c tch lu thuc.
- t tan trong m so vi cc CVKS khc, cho nn d thm vo t chc bao khp b vim, t thm
vo cc m khc v vo thn kinh, gim c nhiu tai bin.
- Cc tai bin thng nh v t l thp hn so vi cc CVKS khc, ngay c khi dng thuc ko
di ti 6 thng.
- Thng ch nh trong cc vim mn v tc dng di.
- Ch phm v liu lng:
+ Piroxicam (Feldene) 10 -40 mg/ngy. Vin nang 10 mg,20 mg;ng tim 20 mg/ ml
T 2002 do thy tai bin trn tiu ha cao nn nhiu nc b.
+ Tenoxicam (Tilcotil) 20mg/ngy.Vin nn 20 mg, ng tim 20 mg/ ml.
+ Meloxicam (Mobic). Vin nn 7,5 mg v 15 mg. Liu bnh thng 7,5 mg/ ngy, ti a 15
mg/ ngy; t/2= 20 gi. Lc u, da vo k tqu th in vitro, meloxicam c coi nh thuc c
ch chn lc COX- 2 (1999), nhng trn lm sng, in vivo, tc dng c ch COX - 2 ch mnh
hn COX- 1 c 10 ln nn khng cn c xp vo nhm thuc ny na.
2.5. Dn xut acid propionic
- Liu thp c tc dng gim au; liu cao hn, chng vim.
- So vi aspirin, indometacin v pyrazolon c t tc dng ph hn, nht l trn tiu ha, v vy
c dng nhiu trong cc vim khp mn .
- Ch phm v liu lng:
Ibuprofen:
- Tc dng chng vim v gim au tn g t aspirin, nhng tc dng ph trn tiu ha th thp
hn nhiu, d c dung np hn.
- c hp thu nhanh qua ng tiu ha, nng ti a t c trong huyt tng sau 1 - 2 gi.
Thuc b chuyn ha nhanh v thi tr qua thn, thi gian bn thi l 1,8- 2 gi.
- Ch nh chnh trong vim khp dng thp, vim cng khp, iu tr cc chng au nh v va
(nhc u, au rng, au do kinh nguyt).
- Tc dng khng mong mun: ngoi cc tc dng khng mong mun chung ca nhm thuc
CVKS, cn thy nhn m, gim th lc, thay i nhn cm mu sc. Cn ngng dng thuc v
khm chuyn khoa mt.
- Liu lng v cch dng:
. Vin nn 100, 150, 200, 300 v 400 mg
. Vin nang 200 mg
. n trc trng 500 mg
Vim khp: thng dng 1,2 - 1,8g/ ngy, chia lm 4 ln. C th tng liu nhng khng vt qu
3,2g/ ngy. Sau 1- 2 tun cn gim xung liu thp nht c tc dng (0,6 - 1,2g/ ngy).
Gim au: ung 400 mg/ ln, cch 4 - 6 gi/ ln.
Naproxen
Vin 250mg. Ung 250mg x 2 ln/ngy. Thi gian bn thi l 14 gi.

D dung np nn thng c dng nh ibuprofen
2.6. Nhm dn xut ca acid phenylacetic
i din duy nht l diclofenac (Voltaren)
- Tc dng c ch COX mnh hn indometain, naproxen v nhiu thuc khc. Ngoi ra c th
cn lm gim nng acid arAChidonic t do trong bch cu do ngn cn gii phng hoc thu
hi acid bo.
- Hp thu nhanh v hon ton qua ng tiu ha, nhng ch 50% vo c tun hon v b
chuyn ha trong qu trnh hp thu. T 1/2 = 1- 2 h, nhng tch lu dch bao khp nn tc dng
vn gi c lu.
- Ch nh trong vim khp mn. Cn dng gim au trong vim c, au sau m v au do kinh
nguyt.
- Tc dng ph t, ch khong 20%, c th lm tng aminotransferase gan gp 3 ln, nhng hi
phc c.
- Ch phm v liu lng: vin 50 - 100 mg ung 100- 150 mg/ ngy.
2.7.Nhm dn xut acid heteroarylacetic
- Tolmetin:
. Tc dng chng vim, gim au v h st tng t aspirin nhng d dung np hn. Thuc c
gi li trong bao hot dch ti 8 gi sau 1 liu duy nht.
. Tc dng ph: 25- 40%.
. Tc dng chng vim, gim au liu 0,8 - 1,6g/ ngy, tng ng vi aspirin 4 - 4,5g/
ngy hoc indometacin 100 - 150 mg/ ngy. Liu ti a l 2g/ ngy chia lm 3 - 4 ln.
- Ketorolac:
. L thuc c tc dng gim au mnh hn chng vim. Khc opioid , tc dng gim au ca
ketorolac khng gy quen thuc v du hiu cai thuc, khng c ch trung tm h hp. C tc
dng chng vim ti ch, dng nh mt.
. L mt trong s t thuc CVKS c th dng ng tim.
. Tc dng ph gp 2 ln placebo, thng l n g g, chng mt, nhc u, chm tiu, nn, au
ch tim.
Thng dng cho gim au sau m, au cp tnh.
Liu ung 5- 30 mg/ ngy; tim bp 30 - 60 mg/ ngy;
Tim tnh mch 150 30 mg/ ngy, khng dng qu 5 ngy.
. Ch nh gim au ngn hn, di 5 ng y nh au sau m: tim bp 30 - 60 mg; tim tnh
mch 15- 30 mg v ung 5- 30 mg.
. Khng dng cho au trong sn khoa. Khng dng cho au nh v au mn tnh.
2.8. Thuc CVKS loi c ch chn lc COX - 2
Cc thuc loi ny, c nhng c im sau:

- c ch chn lc trn COX -2 nn tc dng chng vim mnh, v c ch COX - 1 yu nn cc tc
dng ph v tiu ha, mu, thn, cn hen... gim i rt r rt, ch cn t 0,1 - 1%.
- Thi gian bn thi di, khong 20 gi cho nn ch cn ung mi ngy 1 ln.
- Hp thu d dng qua ng tiu ha, d thm vo cc m v dch bao khp nn c nng cao
trong m vim, ch nh tt cho vim xng khp v vim khp dng thp
V kt t tiu cu ph thuc duy nht vo COX - 1, nn cc thuc nhm ny khng dng d
phng c nhi mu c tim. Vn cn dng Aspirin.
Qua thc t s dng, vn thy c tc dng ph do c ch COX - 1 cho nn nhiu tc gi ngh
khng dng t c ch "chn lc" m nn thay bng t c ch " u tin" COX- 2 th ng hn.
Rofecoxib (Vioxx)
c ch COX- 2 mnh hn COX- 1 ti 800 ln. c dng t 1999. Qua nhiu th nghim lm
sng dng lin tc trn 18 thng iu tr polip i trng, ung th tuyn tin lit, bnh
Alzheimer, thy tai bin tim mch ca Vioxx cao hn placebo nn thng 10/ 2004 Hng sn xut
(Merck) t nguyn xin rt khi th trng.
Celecoxib (Celebrex)
Thuc c ch COX- 2 mnh hn COX- 1 t 100 n 400 ln, c dng t 1998.
- Hp thu qua tiu ha, t nng ti a trong huyt tng sau 2 - 4 gi. Gn mnh vi protein
huyt tng. Phn ln b chuyn ha gan. Thi gian bn thi l 11 gi.
- Liu thng dng 100 mg 2 ln/ ngy. trong thp khp c th tng liu ti 200 mg 2
ln/ ngy.
Etodolac: (xem 2.3.3)
Cc thuc c ch chn lc COX - 2 c khng nh l lm gim r rt t ai bin chy mu tiu
ha, nhng sau 5 nm s dng thy nguy c tim mch tng v thuc gy mt thng bng
gia PGI 2 v TXA 2, lm gim mnh PGI 2, yu t bo v ni mc mch. Hin nay (2005) thuc
vn c gim st cht ch khi dng ko di.
2.9. Dn xut para aminophenol : Acetaminophen, paracetamol
2.9.1 c im tc dng
Paracetamol c cng v thi gian tc dng tng t nh aspirin v gim au v h st.
Khng c tc dng chng vim nn nhiu tc gi khng xp vo nhm thuc CVKS. Thc ra,
trn m hnh thc nghim, paracetamol vn tc dng chng vim, nhng phi dng liu cao hn
liu gim au, v trong vim c nng cao cc peroxid, lm mt tc dng c ch COX ca
paracetamol (Marshall v cng s 1987) v mt khc, paracetamol khng c ch s hot ha
bch cu trung tnh nh cc CVKS khc (Abramson v cng s, 1989).
Trong thc hnh, paracetamol c dng h st, gim au. Ch nh tt cho nhng ngi
khng dng c aspirin (lot tiu ha, ri lon ng mu).
2.9.2. Dc ng hc
Hp thu nhanh qua tiu ha, sinh kh dng l 80 - 90%, t/2 = 2 gi, hu nh khng gn vo
protein huyt tng. Chuyn ha phn ln gan v mt phn nh thn, cho cc dn xut
glucuro v sulfo-hp, thi tr qua thn.
2.9.3. c tnh
Vi liu iu tr thng th ng, hu nh khng c tc dng ph, khng gy tn thng ng tiu
ha, khng gy mt thng bng base -acid, khng gy ri lon ng mu.
Tuy nhin, khi dng liu cao (> 10g), sau thi gian tim tng 24 gi, xut hin hoi t t bo gan
c th tin trin ti cht sau 5 - 6 ngy. Nguyn nhn l paracetamol b oxy ha gan cho N -
acetyl parabenzoquinon-imin. Bnh thng, cht chuyn ha ny b kh c ngay bng lin hp
vi glutathion ca gan. Nhng khi dng liu cao, N -acetyl parabenzoquinon-imin qu tha s gn
vo protein ca t bo gan v gy ra hoi t t bo. Biu hin bng au h sn phi, gan to, vng
da, hn m gan (do tng amoniac), acid mu. V sinh ha, AST, ALT, LDH u tng. Bnh nhn
thng cht sau 6-7 ngy. Nu iu tr sm bng N -acetyl-cystein (NAC, Mucomyst, Mucosol),
l cht tin thn ca glutathion, bnh nhn c th qua khi. Sau 36 gi, gan b tn thng, kt
qu s km. Sau ng c di 10 gi, dng NAC c hiu qu hn: ung dung dch 5% -
140mg/kg, sau , cch tng 4 gi, ung 70 mg/kg 17 liu. NAC cng c tc dng ph: ban ,
my ay, nn, tiu chy, nhng khng cn ngng thuc.
- Paracetamol (Efferalgan; Dafalgan): vin 0,5g; gi bt 0,08g; vin n 80, 150, 300 mg.
. Ngi ln: 0,5-1,0g 1-3 ln/ngy. Khng c dng qu 4 g/ngy.
. Tr em 13-15 tui: 0,5g 1-3 ln/ngy.
. Tr em 7-13 tui: 0,25g 1-3 ln/ngy.
- Propacetamol clohydrat (Pro - Dafalgan) (th h 1)
V paracetamol kh tan trong nc nn tng hp tin cht ca paracetamol tan c trong
nc, vo c th di tc dng ca esterase huyt tng s gii phng paracetamol:
esterase
Propacetamol Diethylglycin + PARACETAMOL
(2g) huyt tng (1g)
Trnh by: l thuc bt + dung mi. Pha ngay trc khi dng, khn g qu 30 pht. Tim bp
su hay tim tnh mch chm trong vng 2 pht. C th truyn tnh mch trong vng 15 pht (pha
trong 100 mL NaCl 0,9% hoc glucose 5%). Liu dng 1 -2g/ ln, cch 4- 6 gi. Khng
dng qu 8g/ ngy. Khng dng cho tr em d i 15 tui v ngi suy thn.
- Perfalgan (th h 2)
L paracetamol c lm tan hon ton trong nc (1g/ 100 mL). Perfalgan 1g c tng ng
sinh hc vi propacetamol 2g v c tc dng gim au tng ng vi diclofenac 75 mg tim
bp, hoc morphin 10 mg tim bp.
- Rt nhiu ch phm khc c cha paracetamol kt hp vi cafein, ephedrin, codein,
phenylpropanolamin (PPA)...
3. nhng vn chung
3.1. Dc ng hc chung
- Mi CVKS ang dng u l cc acid yu, c pKa t 2 n 5.
- Hp thu d qua tiu ha d o t b ion ha d dy.
- Gn rt mnh vo protein huyt tng, ch yu l albumin, c thuc ti 99,7% (nhm oxicam,
diclofenac), do d y cc thuc khc ra dng t do, lm tng c tnh ca thuc (sulfamid
h ng huyt, thuc khng vitamin K... ).
Cc thuc CVKS d dng thm nhp vo cc m vim. Nng thuc trong bao hot dch bng
khong 30- 80% nng huyt tng. Khi dng lu, s vt qu nng huyt tng. Do tc
dng vim khp c duy tr.
- B ging ha gan (tr acid salicylic), thi qua thn di dng cn hot tnh khi dng vi liu
chng vim v liu c.
- Cc thuc khc nhau v thi tr, t 1/2 huyt tng thay i t 1 - 2 gi (aspirin, nhm
propionic) n vi ngy (pyrazol, oxicam).
- Nhm salicylic dng cho au nh (rng) hoc cc vim cp. Cc CVKS c t 1/2 di c dng
cho vim mn vi liu 1 ln/ ngy.
Da theo thi gian bn thi ca thuc, c th chia cc CVKS lm 3 nhm (bng 3.3):
- Cc thuc c thi gian bn thi ngn, di 10 gi, cn ung 3 ln/ ngy, bnh nhn kh tun
th. Tuy nhin, c li l khi ngng thuc, tc dng s ht nhanh, nht l khi xy ra tc dng
khng mong mun. An ton hn cho ngi cao tui v bnh nhn suy thn.
- Cc thuc c thi gian bn thi di, trn 30 gi, ch cn dng 1 ln/ ngy, ngi b nh khng
qun. Tuy nhin, d gy tch lu thuc, nht l vi ngi c tui v suy thn, d gy tai bin
nng, khi ngng thuc tc dng c hi cn ko di. Phi 7 ln t/2 th thuc mi thi tr ht, nh
vy, vi piroxicam c t/2 = 40 gi, phi ch 12 ngy .
- Cc thuc c thi gian bn thi trung gian: tng i d dng v t tc dng ph hn.
Bng 10.1: Phn loi thuc theo thi gian bn thi (t/2)
Loi thuc Tn thuc t/2 (h) S ln dng/ ngy

Aspirin 0.25 3- 4
Diclofenac 1.1 2- 4
Ketoprofen 1.8 2- 4
t/2 ngn Salicylat 2.0- 15 3- 4
Ibuprofen 2.1 3- 4
Indomethacin 4.6 3- 4
Naproxen 14 2
t/2 trung bnh Sulindac 14 2
Meloxicam 20 1
Tenidap 20- 30 1
Piroxicam 40- 45 1
t/2 di Tenoxicam 60- 75 1
Phenylbutazon 68 1
3.2. Cc tc dng khng mong mun

Thng lin quan n tc dng c ch tng hp PG.
- Lot d dy - rut: nim mc d dy rut sn xut PG, c bit l PG E 2 c tc dng lm tng
cht nhy v c th l c kch thch phn bo thng xuyn thay th cc t bo nim mc b
ph hu. Thuc CVKS c ch tng hp PG, to iu kin cho HCl ca dch v gy tn thng cho
nim mc sau khi hng ro bo v b suy yu.
- Lm ko di thi gian chy mu do c ch ngng kt tiu cu.
- Vi thn, PG c vai tr quan trng trong tun hon thn. c ch tng hp PG gy hoi t gan v
sau l vim thn k mn, gim chc phn cu thn, d dn n tng huyt p.
- Vi ph n c thai:
+ Trong 3 thng u, CVKS d gy qui thai
+ Trong 3 thng cui, CVKS d gy cc ri lon phi, lin quan n vic ng ng ng
mch ca bo thai trong t cung. Mt khc, do lm gim PG E v F, CVKS c th ko di thi
gian mang thai, lm chm chuyn d v PG E, PG F lm tng co gp t cung, trc khi vi gi,
s tng hp cc PG ny tng rt mnh.
- Mi CVKS u c kh nng gy cn hen gi (pseudo asthma) v t l nhng ngi hen khng
chu thuc l cao v c th l CVKS c ch cyclooxygenase nn lm tng cc cht chuyn ha
theo ng lipooxygenase (tng leucotrien).
3.3. Tng tc thuc
Khng dng CVKS vi:
- Thuc chng ng mu, nht l vi loi khng vitamin K.
- Thuc li niu v h huyt p, v CVKS c ch tng hp c cc PG gy gin mch.
- Lithium: CVKS lm gim thi tr lithi qua thn, gy tch lu.
- CVKS lm tng tc dng ca phenytoin v sulfamid h ng huyt d o y chng ra khi
protein huyt tng, lm tng nng thuc t do trong mu.
3.4. Ch nh
3.4.1. Gim au v h st thng thng: aspirin, paracetamol
Gim au sau m: cho thuc trc khi rch dao, loi c t/2 trung bnh hoc di.
3.4.2. Cc bnh thp cp v mn
- V t l c tnh tiu ha/hiu qu chng vim ging nhau cho mi loi CVKS, cho nn tiu
chun chn thuc cn da trn:
+ p ng ca tng ngi bnh

+ S thun tin trong s dng
+ Tc dng nhanh.
- Th d:
+ Vim a khp dng thp: dn x ut propionic, diclofenac (Voltaren).
+ Vim khp mn ca ngi tr: aspirin
+ Vim cng khp: indometacin
+ Thoi ha khp: loi c tc dng gim au vi liu thp v khi tng liu s t c tc
dng chng vim: aspirin, dn xut propionic. Hoc mt thu c gim au n thun paracetamol.
3.4.3. Cc ch nh khc
Cc thuc c ch chn lc COX - 2 ang c th dng d phng v iu tr bnh Alzheimer,
polip i trng, ung th rut kt - trc trng, tuyn tin lit. Tuy nhin, do phi dng di ( 18
thng), thy nguy c tim mch tng.
3.5. Nguyn tc chung khi s dng CVKS
- Vic chn thuc tu thuc vo c th. C ngi chu ng c thuc ny nhng khng chu
ng c thuc khc.
- Ung trong hoc sau ba n trnh kch ng d dy.
- Khng ch nh cho bnh nhn c tin s lot d dy. Trong trng hp tht cn thit, phi dng
cng vi cc cht bo v nim mc d dy. Song, nhng tai bin tiu ha khng phi ch do tc
dng kch thch trc tip ca thuc ln nim mc m cn do tc dng chung ca th uc.
CVKS gy lot d dy do c ch tng hp PG E 2 , PG I2 nim mc d dy. Cc PG ny c vai
tr c ch bi tit HCl, v kch thch bi tit dch nhy cng bicarbonat d dy, v th c tc
dng bo v nim mc d dy. Hin tng hp c mt loi t ng t PG E 1 l Misoprostol
(Cytotec), tc 15- deoxy- 16 hydroxy- 16 metyl- PG E1 c tc dng chng lot d dy tng t
thuc khng H 2. c bit c dng trong nhng ngi phi iu tr ko di bng CVKS.
Tc dng ph: tiu chy (30%), au qun bng, x y thai.
Liu lng: Vin 200 g x 4 ln/ ngy.
ang nghin cu tng hp thuc tng t PGE 2 (Arboprostol, Enprostil, Trimoprostil).
- Ch nh thn trng i vi bnh nhn vim thn, suy gan, c c a d ng, cao huyt p.
- Khi iu tr ko di, cn ki m tra c nh k (2 tun mt ln) cng thc mu, chc phn thn.
- Nu dng liu cao tn cng, ch nn ko di 5 - 7 ngy.
Nhanh chng tm c liu thp nht c tc dng iu tr trnh c tai bin.
- Ch khi dng phi hp thuc:
+ Khng dng phi hp vi cc CVKS vi nhau v lm tng c tnh ca nhau.
+ Khng dng CVKS cng vi thuc chng ng mu loi khng vitamin K (dicumarol,
warfarin), sulfamid h ng huyt, diphenylhydantoin, v CVKS s y cc thuc ny ra khi
ni d tr (protein huyt tng), lm tng c. Nu vn cn phi hp th gim liu cc thuc .
+ Cc CVKS c th lm gim tc dng mt s thuc do lm tng ging ha hoc i khng ti
ni tc dng, nh meprobamat, androgen, li niu furosemid.
Cu hi t lng gi
1. Trnh by c ch tc dng chung ca thuc CVKS - Phn bit thuc c ch COX - 1 v c
ch COX- 2.
2. Trnh by c ch tc dng chng vim ca thuc CVKS.
3. Trnh by c ch tc dng gim au ca thuc CVKS.
4. Trnh by c ch tc dng h st ca thuc CVKS.
5. Trnh by c ch chng ngng kt tiu cu ca aspirin.
6. Phn tch so snh c im tc dng v p dng iu tr ca aspirin, dn xut indol
(indometacin), dn xut phenylacetic (diclofenac, voltaren).
7. Trnh by c im tc dng v p dng iu tr ca cc thuc CVKS loi c ch chn
lc COX- 2.
8. Trnh by tc dng, c ch tc dng, c tnh, v p dng iu tr ca paracetamol.
Trnh by cc tc dng khng mong mun v nguyn tc chung khi s dng thuc CVKS.
Bi 11: Thuc cha gt

Trnh by c c ch tc dng, ch nh cc thuc colchicin, probenecid, allopurinol.
Gt l mt bnh do tng acid uric -mu, trong dch bao khp c nhiu tinh th urat l sn phm
chuyn ha cui cng ca purin. Bnh c th nguyn pht do ri lon chuyn ha acid uric di
truyn, hoc th pht do bnh thn, do dng cc thuc phong ta thi tr urat hoc do sn xut
qu nhiu urat (metabolic overproduction).
Acid uric-mu bnh thng l 2-5mg/100ml, trong bnh gt c th tng ti 8,8mg/100ml.
iu tr gt nhm gii quyt cn cp tnh v ngn nga s ti nhim, da trn sinh bnh hc ca
bnh ny. Cc tinh th urat lc u b thc bo bi cc t bo mng hot dch (syno vioucytes).
Trong qu trnh thc bo, cc t bo ny gii phng ra cc prostaglandin, cc enzym tiu th v
interlenkin-1. Cc cht trung gian ha hc ny li gi cc bch cu ht ti khp v lm nng
thm qu trnh vim: s lng bch cu ht, i th c bo tng, lng cht ha hc trung gian gy
vim tng.
Cc thuc iu tr cn gt cp tnh s c ch cc giai on hot ha bch cu. c hiu nht l
colchicin. Ngoi ra cn dng thuc CVKS phenylbutazon, indometacin, loi c ch COX -2, hoc
corticoid.
iu tr gt mn tnh, dng thuc lm gim acid uric trong c th bng cc thuc lm i ra acid
uric nh probenecid, sunfinpyrazol v allopurinol.
1. Colchicin
Colchicin l alcaloid ca cy colchicum antumnal. Bt v nh hnh, vng nht, khng mi. c
dng t th k 18.
Tc dng iu tr c hiu cn gt cp tnh, lm gim au v gim vim trong vng 12 - 24 gi
u dng thuc, v th cn c dng lm test chn on. Colchicin khng c tc dng gim au
v chng vim khp khc.
1.1. C ch tc dng
Trong bnh gt, colchicin khng nh hng n bi xut acid uric thn v khng lm gim acid
uric mu. Colchicin gn vo protein ca tiu qun (protein tubulin) trong t bo bnh cu v cc
t bo di chuyn khc, v th, ngn cn s trng hp ca nhng pro tein ny trong vi tiu qun
(microtubulin), dn n c ch s di chuyn ca bch cu v gim hot tnh thc bo ca bch
cu ht, lm gim gii phng acid lactic v cc enzym gy vim trong qu trnh thc bo. Trong
qu trnh tiu ha cc tinh th urat, bch cu ht sn xut glycoprotein, cht ny c th l
nguyn nhn gy ra cn gt cp tnh. Colchicin ngn cn sn xut glycoprotein ca bch cu ht
nn chng c cn gt.
Colchicin cn ngn cn s phn bo ca cc t bo ng -thc vt giai on trung k v do lm
gim s hnh thnh cc thoi phn bo.
1.2. c tnh
Phn ln lin quan n tc dng c ch s trng hp ca tubulin v c ch phn bo: bun nn,
nn, tiu chy, au bng (tn thng t bo biu m nim mc tiu ha), c ch tu xng, rng
tc, vim thn kinh, c vi thn...
1.3. Dc ng hc
Hp thu nhanh qua ng ung, t nng ti a trong huyt tng sau 0,5 -2 gi. Chuyn ha
gan, phn ln thi tr qua phn (c chu k rut - gan), ch 10 - 20% thi qua thn.
1.4. Ch nh
- iu tr cn gt cp tnh: tim tnh mch 2 mg ha trong 10 - 20 ml dung dch NaCl 0,9%.
Tng liu khng vt qu 4mg. Khng tim nhc li trong vng 7 ngy. Nu khng chu c
thuc, c th thay bng indometacin.
- D phng: ung 0,5mg mi tun 2 - 4 ln.
Vin 0,5 mg, 1 mg.
ng tim 2ml = 1mg
2. Probenecid (Bennemid)
Probenecid l dn xut ca acid benzoic, tan nhiu trong lipid. Bt tinh th trng, khng mi.
Acid uric c lc qua cu thn v bi xut qua ng thn, song phn ln li c ti hp thu
on gia ca ng ln gn. Probenecid vi liu thp do cnh tranh vi qu trnh thi tr acid
uric nn lm lu acid uric trong c th (Demartini v cng s, 1962), nhng vi liu cao li c
ch ti hp thu acid uric ng thn nn lm tng thi tr acid q ua nc tiu.
Probenecid cn c ch c tranh chp qu trnh thi tr ch ng ti ng ln gn ca mt s acid
yu nh penicilin, para aminosalicylat, salicylat, clorothiazid, indometacin, sunfinpyrazon, v.v...
Probenecid khng c tc dng gim au. Khi c n gim au, c th dng cng vi paracetamol.
Khng dng cng vi salicylat, v probenecid s mt tc dng.
Dng thuc li niu loi thiazid ko di nh trong iu tr cao huyt p thng lm urat v
nhng thuc ny c ch bi xut urat ng thn. Probe necid i khng c tc dng ny m
khng nh hng n tc dng li niu ca thuc. Tuy nhin, li c ch tc dng i natri ca
furosemid.
Probenecid c hp thu nhanh qua rut, vo mu, hn 70% kt hp vi albumin huyt tng,
thi tr qua thn phn ln di dng glucuro-hp. Thi gian na thi tr khong 6 -12 gi.
Tc dng ph rt t (2-8%): bun nn, nn, mng da, st. Khi lm i nhiu acid uric, c th
gy cn si urat vi cn qun thn (khi cn base ho nc tiu).
Liu lng: vin 0,5g. Tun u ung 250mg 2ln/ngy. Tng dn tng tun. Ti a 2g/ngy,
ung 4 ln. Ung nhiu nc trnh si acid uric thn.
Dng hng nm. C th dng vi allopurinol, sunfinpyrazon.
3. Sunfinpyrazon (Anturant)
Cng thc gn ging phenylbutazon. Gy i ra acid uric mnh do ngn cn ti hp thu ng

thn, ging c ch ca probenecid. Hp thu nhanh v hon ton qua ng tiu ho. Gy tai bin
mu nh phenylbutazon, ri lon tiu ho khong 10%.
Salicylat lm mt tc dng ca sunfinpyrazon do tranh chp vi sunfinpyrazon khi vn chuyn
qua ng thn v c khi gn vo protein huyt tng.
Liu lng: vin 50mg 4ln/ngy, tng dn ti 400mg hoc 800mg mt ngy. Chia lm 2 -4
ln, ung vo ba n trnh kch ng d dy. Ung nhiu nc trong ngy.
4. Allopurinol (Zyloprim)
Allopurinol l cht ng phn ca hypoxanthin.
4.1. C ch tc dng
Acid uric l sn phm chuyn ho ca purin. Cc purin c chuyn thnh hypoxanthin v
xanthin ri b oxyho nh xc tc ca xanthin oxydase thnh acid uric. Allopu rinol l cht c ch
mnh xanthin oxydase nn lm gim sinh tng hp acid uric, gim nng acid uric mu v
nc tiu, lm tng nng trong mu v nc tiu cc cht tin thn hypoxanthin v xanthin d
tan hn. Nh vy, allopurinol cn ngn nga c s to si acid uric trong thn.
Nh vy, allopurinol cn ngn nga c s to si acid uric trong thn.
4.2. c tnh
t c. Phn ng qu mn khong 3% (mn da, st, gim bch cu, gan to, au c).
Trong nhng thng u iu tr, c th c cc cn gt c p tnh do s huy ng acid uric t cc
m d tr. Khi , cn phi hp iu tr bng colchicin.
4.3. Dc ng hc
Hp thu qua ng ung khong 80%, t nng ti a trong mu sau 30 -60 pht. Allopurinol
cng b chuyn ho bi xanthin oxydase thnh alox anthin, vn cn hot tnh, v th tc dng ko
di, ch cn ung thuc mi ngy 1 ln.
4.4. Ch nh, liu lng
- Gt mn tnh, si urat thn.
- Tng acid uric mu th pht do ung th, do iu tr bng cc thuc chng ung th, thuc li tiu
loi thiazid...
- Tng acid uric mu m khng th dng c probenecid hoc sunfinpyrazon do c phn ng

khng chu thuc.
Mc tiu ca iu tr l lm gim nng acid uric mu xung 6mg/dl (360 micro M).
Liu lng: Allopurinol (Zyloprim) vin 100 - 300 mg. Liu u 100mg, tng dn ti
300mg/ngy tu theo nng acid uric mu.
Cu hi t lng gi
Phn tch so snh c ch tc dng v ch nh iu tr ca colchicin, probenecid v
allopurinol.
Bi 12: Thuc an thn kinh v thuc bnh thn

1. Trnh by c 3 c im c bn ca thuc an thn kinh v 6 c im ca thuc bnh
thn.
2. Trnh by c c ch tc dng v tc dng dc l, tc dng khng mong mun, p dng
lm sng ca thuc an thn kinh: clopromazin, haloperidol.
3. Phn tch c c ch tc dng, tc dng v p dng lm sng ca benzodiazepin.
1. Thuc an thn kinh (thuc an thn ch yu)

Cc thuc loi ny c 3 c im c bn :
- Gy trng thi th , lnh m, ci thin c cc triu chng ca bnh tm thn phn lit.
- C thm tc dng c ch thn kinh thc vt, gy h huyt p, gim thn nhit.
- C th gy ra hi chng ngoi b thp (hi chng Parkinson).
Khc vi thuc ng, cc thuc loi ny d dng vi liu cao cng khng gy ng, ch c tc dng
gy m mng, lm d ng.
1.1. Dn xut phenothiazin v thioxanthen: clopromazin
Clorpromazin (Largactil, plegomazin, Aminazin): thuc c bng B.
Bt trng xm, rt tan tro ng nc, ru, cloroform.
c tm ra t nm 1952 trong khi nghin cu cc thuc khng histamin tng hp dn xut ca
vng phenothiazin. L thuc m u cho lnh vc dc l tm thn.
1.1.1. Tc dng dc l
1.1.1.1. Trn h thn kinh trung ng
- Clopromazin gy trng thi c bit th v tm thn vn ng: thuc khng c tc dng gy
ng, tr vi liu gn c, nhng n lm gim cc hot ng vn ng v cc s bn tm, u t
m vn gi c tng i cc hot ng v tr tu v s cnh gic. Liu rt ca o cng khng gy
hn m.
Ngi dng thuc t ra khng quan tm n mi trng xung quanh, khng biu l xc cm,
trong khi phn x tu v phn x khng iu kin vi kch thch au vn gi c.
- Thuc lm gim c o gic, thao cung, vt v.
Do , thuc c tc dng vi bnh tm thn phn lit.
- Cloprozamin gy hi chng ngoi b thp, ging bnh Parkinson biu hin bng ng tc cng
, tng trng lc.
- H thn nhit do c ch trung tm iu nhit h khu no.
- Chng nn do c ch trung tm nn sn no tht 4.
- c ch trung tm trng lc giao cm iu ha vn mch.

- Trn vn ng, liu cao gy trng thi gi nguyn th (catalepsia).
1.1.1.2. Trn h thng thn kinh thc vt
Va c tc dng hu ph giao cm va c tc dng phong ta receptor 1 adrenergic ngoi bin.
Tc dng hu ph giao cm th hin bng nhn m (ng t gin), to bn, gim tit dch v,
gim tit nc bt, m hi. Tc dng ny rt t xy ra vi cc dn xut c nhn piperazin.
Tc dng hu 1 - adrenergic tng i c ngh a, c th phong ta tc dng tng p ca
noradrenalin. V loi piperazin c tc dng an tm thn vi liu thp nn tc dng hu giao cm
rt yu.
1.1.1.3. Trn h ni tit
- Lm tng tit prolactin, gy chy sa v chng v to n ng.
- Lm gim tit FSH v LH, c th gy c ch phng non v mt kinh.
1.1.1.4. C tc dng khng histamin H 1, nhng yu.
1.1.2. Tng tc thuc
- Clopromazin lm tng tc dng ca thuc ng, thuc m, thuc t, thuc gim au loi
morphin, thuc h huyt p (nht l guaneth idin, thuc c ch enzym chuyn angiotensin), ru.
- Clopromazin i khng tc dng vi cc thuc kch thch thn kinh tm thn, c bit vi
amphetamin v cc cht gy o gic.
- Gia cc thuc an thn kinh, khng c tc dng hip ng tng mc, nhng v mt iu tr cc
triu chng ca bnh tm thn, c th dng phi hp trong thi gian ngn.
1.1.3. C ch tc dng
Sinh l hc ca hot ng thn kinh trung ng v sinh bnh hc ca ri lon tm thn (bnh tm
thn phn lit) cn cha c bit r. Tuy nh in, ngi ta nhn thy rng s cn bng gia h
dopaminergic trung ng v h serotoninergic trung ng c vai tr quyt nh n cc triu
chng ca bnh tm thn phn lit.
H dopaminergic (DA) trung ng
Cc thuc cng h DA (amphetamin, cocain, DOPA) u lm tng triu chng bnh.
Cc thuc hu h DA, c bit l cc receptor thuc nhm D 2 (gm D 2, D3, D4) nh thuc an thn
kinh u lm gim cc biu hin ca bnh tm thn.
H serotoninergic (5HT) trung ng
C ti 15 loi receptor 5HT, nhng vi bnh tm thn th receptor 5HT 2 (c bit l 5 HT 2A) c
vai tr quan trng hn c. Trong no, nhn tng hp 5HT nhiu nht (c th l duy nht) l cc
nhn Raphe (Raphe nuclei). Cc nhn ny kim sot s tng hp DA c thn t bo v s gii
phng DA trc xinap ca cc nron h DA. Nhn chung, 5HT c ch gii phng DA.
Gi thuyt sinh ha v bnh tm thn phn lit cho rng cc triu chng dng tnh (hoang tng,
o gic, kch ng, a nghi, tng t cao) l do tng hot h DA h vin v mt c ch iu
ha ngc trung ng. Cn cc triu chc m tnh (cm xc cn mn, quan h km, v cm, t
duy tru tng kh khn) l do ri lon chc phn vng trn trc, gim hot h DA no gia -
v no do tng hot h 5HT 2.
Cc thuc an thn kinh c in (clorpr omazin, haloperidol) c ch mnh D 2 hn 5HT nhiu nn
tc dng trn triu chng dng tnh mnh, t tc dng trn triu trng m tnh, mt khc, gy tc
dng ph ngoi b thp.
Cc thuc an thn mi (c nghin cu nhiu t thp k 80 ca th k 20 tr l i y) u c c
hai tc dng phong ta D 2 v 5HT2A v c ch 5HT 2A mnh hn D 2 (risperidon) do ci thin
c c triu chng m tnh v t gy triu chng ngoi b thp, cn vi triu chng dng tnh
th tc dng nh thuc c in. Hin c olanzapin, risperidon...
1.1.4. Dc ng hc
- Hp thu tt qua ng tiu ho. Nng cao hn 400mg/ml mu thng l c.
- Thuc rt a m, gn nhiu vo protein huyt tng, tp trung no v t chc m, qua nhau
thai d dng. Thi gian bn thi 20 -40gi. Hiu lc sinh hc ca liu mt ln thng tn ti t
nht l 24gi nn ch cn dng liu 1 ln mi ngy.
- Chuyn ho ch yu gan qua qu trnh oxy ho, to cc cht chuyn ho hon ton mt hoc
ch cn mt phn hot tnh.
- Thi tr: ch yu qua nc tiu (dng tan trong nc, khng c hot tnh), phn khc qua mt
(c chu k gan- rut) v ra phn. Thuc tn ti lu trong c th, sau khi ngng thuc 6 -12 thng
vn cn tm thy vt trong cht thi.
1.1.5.1. Loi thng gp, li n quan n tnh cht dc l ca thuc:
- Ri lon tm l: chng mt mi, suy ngh chm chp, trng thi trm cm, l ln (nht l ngi
c tui).
- Tt huyt p khi ng v nhp tim nhanh, nht l khi tim.
- Kh ming, nut kh, b i, ri lon iu ti t th lc, cn tng nhn p cp, to bn... l nhng
du hiu hu ph giao cm.
- Ri lon iu tit v sinh dc: c ch phng non, v kinh, chy sa, gim tnh dc, tng cn.
- Hi chng ngoi b thp: thay i tu thuc vo thi gian iu tr, vo liu lng, vo thuc
phi hp, vo tui, gii...
1.1.5.2. Loi khng ph thuc vo tc dng dc l.
- Gim bch cu.
- Vng da tc mt, xut hin gia tun th 2 n th 4. Gim dn khi ngng thuc. C th do ph
n cc ng dn mt do phn ng qu mn v khng ph thuc vo liu.
- Phn ng ngoi da: d ng, mn cm vi nh nng, ng sc t trong tin phng ca mt.
- Lon nhp tim: nhp nhanh xoang (iu tr bng propranolol), nh tht phn ly.
- Hi chng st cao c tnh: st cao, da ti nht, m hi nh nhi, trng thi sc. Phi lm hi sc
cp cu: gi thng bng nc v in gii.
- Tai bin cht t ngt, thng xut hin sau khi tim. Cha r nguyn nhn.C th lin quan
n huyt khi, vim tc mch.
1.1.6. p dng lm sng

Do c nhiu tc dng a dng, clopromazin c dng nhiu khoa:
- Khoa tm thn: lon thn kinh, tm thn phn lp, thao cung, hoang tng, o gic.
- Khoa sn: sn git (ch thuc qua c rau thai)
- Khoa gy m: tin m, gy m h th nhit, h huyt p.
- Khoa ni: chng nn, chng au, an thn, chng rung tim.
- Khoa da liu: chng nga.
- Ung 10- 25 mg/ ln 2- 4 ln/ ngy. Tim bp 25 - 50 mg/ ln 2- 3 ln/ ngy.
1.2. Dn xut butyrophenon: Haloperidol
Haloperidol (Haldol) l tiu biu cho nhm an thn kinh a nn g (polyvalent neuroleptics) hay an
thn kinh chng triu chng dng tnh (antiproductive), chng thao cung.
V cu trc ho hc, haloperidol gn ging vi acid gamma -amin- butyric (GABA) l cht trung
gian ho hc ca cc qu trnh c ch trong thn kinh trung ng. Tc dng an tm thn mnh l
do c ch receptor dopaminergic trung ng v cng v vy tc dng khng mong mun, hi
chng Parkinson cng r.
1.2.1. Ch nh
- Cc trng thi thao cung, hoang tng
- Cc trng thi hong lon tm thn cp v mn, tm thn phn lp, paranoid (hoang tng c h
thng).
- Chng nn. Nn do dng thuc chng ung th, sau chiu x.
1.2.2. Cn thn trng
- Khng dng chung vi thuc cng h dopaminergic (levodopa) v cc receptor ca h
dopaminergic b halope ridol phong ta. Nu khi ang iu tr bng haloperidol m c du
hiu ngoi b thp th dng thuc hu ph giao cm trung ng.
- Dng cng vi thuc h huyt p c th gy tt huyt p khi ng.
- Thn trng vi ngi li xe, ng my, v lc u iu t r c th gy ng g.
Ging nh vi clopromazin, hay gp ng g, hi chng ngoi b thp, ri lon ni tit.
1.2.4. Liu lng
ng 5mg/ml x 1-4 ng/ngy. Tim bp; Vin 5mg x 1 -8 vin/ngy.
1.3. Dn xut benzamid: Sulpirid (Dogmatil)
1.3.1. Tc dng
Sulpirid l i din cho nhm benzamid, l thuc an tm thn c tc dng lng cc (bipolar):
- Liu 600mg c tc dng gii c ch chng triu chng m tnh, kch thch receptor sau xinap
ca h dopaminergic trung ng.
- Liu > 600mg c tc dng chng triu chng dng tnh (antiproductive), chng hoang tng v
thuc kch thch receptor trc xinap ca h dopaminergic, lm gim gii phng dopamin.
V vy, liu thp l cng v liu cao l hu h dopaminergic (trn cc receptor D4 trung ng).
1.3.2. Ch nh
- Liu thp (di 600mg): tnh trng mt ngh lc, lon thn.
- Liu cao (liu trn 600mg): cc ri lon tm thn cp tnh: tm thn phn lp, thao cung, o
gic.
- Ri lon ni tit v chuy n ha: tng tit sa, tng cn.
- Thn kinh:
+ Lon vn ng: vo c, cng hm, xoay mt (oculogyre).
+ Hi chng ngoi b thp.
+ Ng g.
- Tim mch: tt huyt p khi ng.
Dogmatil vin 200mg, ng 2ml = 100mg
- Chng suy sp, triu chng m tnh: 1 -3 vin/ngy.
- Chng triu chng dng tnh: 4 -8 vin/ngy.
- Trong lon thn cp v mn tnh, tim bp 200 - 800mg mt ngy, trong 2 tun lin.
1.4. Nhm benzisoxasol: Risperidon
c im tc dng:
i khng vi 5 HT 2 vng trn trc ca v no nn c hiu qu iu tr cc triu chng m
tnh ca tm thn phn lp. ng thi c tc dng i khng D 2 vng no gia - h vin nn c
hiu qu iu tr cc triu chng dng tnh. Risperidon gn vo 5HT 2A khong 20 ln mnh hn
vo D2.
Vi liu iu tr (4-6 mg/ngy) rt t gy triu chng ngoi b thp.
2. Thuc bnh thn (thuc an thn th yu)
C nhiu tn gi: minor tranquillizers, anxiolytics, sedatives... hoc thuc an thn th yu, thuc
bnh thn.
Nhm thuc quan trng hn g u l benzodiazepin.
c im chung l c ch c bit trn h thng li hot ha i th h vin v cc nron kt
hp ca tu sng. Do :
- C tc dng an du (sedative), lm gim cnh gic, lm chm cc hot ng vn ng v lm
du s bn chn.
- C tc dng an thn gii lo (anxiolytic effects): lm gim cc phn ng xc cm thi qu v
gim cng thng tm thn.
- Ch c tc dng gy ng khi mt ng c lin quan n s lo u, bn chn.

- t nh hng n h thn kinh thc vt nh nhm thuc an thn ch yu (loi clopromazin).
- Chng co git.
- Gin c lm gim trng lc c do tc dng trung ng.
Benzodiazepin (BZD): l thuc i din cho nhm ny v rt thng dng.
2.1. Tc dng dc l
2.1.1. Trn thn kinh trung ng c 4 tc dng chnh
- An thn, gii lo, gim hung hn.
- Lm d ng: gim thi gian tim tng v tng thi gian gic ng nghch thng. Khc vi
barbiturat l phn ln BZD khng c tc dng gy m khi dng liu cao.
- Chng co git: clonazepam, nitrazepam, lorazepam, diazepam: do t nh cm th khc nhau ca
cc vng, cc cu trc thn kinh v s cm th khc nhau ca cc loi vi cc dn xut m tc
dng c khc nhau: c dn xut cn lm tng vn ng chut nht, chut cng, kh. Ring
flurazepam li gy co git, nhng ch trn mo.
- Lm gin c vn.
Ngoi ra cn:
. Lm suy yu k c c (retrograde amnesia) v lm tr ngi k c mi (anterograde amnesia).
. Gy m: mt s t BZD c tc dng gy m nh diazepam, midazolam (tim tnh mch)
. Liu cao, c ch trung tm h hp v vn m ch.
2.1.2. Tc dng ngoi bin
- Gin mch vnh khi tim tnh mch
- Vi liu cao, phong ta thn kinh - c.
2.2. C ch tc dng
BZD gn trn cc receptor c hiu vi n trn thn kinh trung ng. Bnh thng, khi khng c
BZD, cc receptor ca BZD b m t protein ni sinh chim gi, lm cho GABA (trung gian ha
hc c tc dng c ch trn thn kinh trung ng) khng gn vo c receptor ca h GABA -
ergic, lm cho knh Cl ca nron khp li. Khi c mt BZD, do c i lc mnh hn protein ni
sinh, BZD y protein ni sinh v chim li receptor, do GABA mi gn c vo receptor
ca n v lm m knh Cl -, Cl- i t ngoi vo trong t bo gy hin tng u cc ha (hnh
12.1).
Cc receptor ca BZD c lin quan v gii phu v chc phn vi receptor ca GA BA.
Hnh 12.1: C ch tc dng ca Benzodiazepin (BZD)
Cc receptor ca BZD c nhiu trn thn kinh trung ng: v no, vng c nga, th vn, h
khu no, hnh no, nhng c bit l h thng li, h vin v c tu sng.
BZD tc dng gin tip l lm tng hiu qu ca GABA, tng tn s m knh Cl
2.3. Cc tc dng khng mong mun
Khi nng trong mu cao hn liu an thn, t ti liu gy ng, c th gp: u oi, ng tc
khng chnh xc, l ln, ming kh ng, gim tr nh.
c tnh trn thn kinh tng theo tui.
V tm thn, i khi gy tc dng ngc: c mng, bn chn, lo lng, nhp tim nhanh, v m hi,
sng khoi, o gic, hoang tng, mun t t. Quen thuc c th l do c ch tng chuyn ha
hoc iu ha gim s lng cc receptor ca BZD trong no.
t gy ph thuc v lm dng thuc, nhng sau mt t dng BZD ko di, c th gy mt ng
tr li, lo lng, bn chn hoc co git. Mc du vy BZD vn l mt thuc an thn tng i an
ton v ang c xu hng thay th dn thuc ng loi b arbiturat. Thuc c t/2 cng ngn
(triazolam t/2 = 3 gi), cng d gy nghin.
2.4. Dc ng hc
Hp thu hu nh hon ton qua tiu ha, t nng ti a trong mu sau 30 pht n 8 gi. Gn
vo protein huyt tng t 70% (alprazolam) n 99% (diazepam) . Nng trong dch no tu
gn tng ng nng dng t do trong mu. Thuc qua c rau thai v sa.
c chuyn ho bi nhiu h enzym trong gan, thnh cc cht chuyn ho vn cn tc dng ri
li b chuyn ho tip, nhng tc chm hn cho nn t c dng t lin quan n thi gian bn
thi. Th d flurazepam c t/2 trong huyt tng l 2 -3gi, nhng cht chuyn ho cn tc dng
l N-desalkyl flurazepam cn tn ti trn 50 gi.
Da theo t/2, cc Bzd c chia lm 4 loi:
- Loi tc dng cc ngn, t/ 2 <3 gi c midazolam,triazolam.
- Loi tc dng ngn, t/2 t 3 -6 gi c, zolpidem (non-benzodiazepin) v zopiclon.
- Loi tc dng trung bnh, t/2 t 6 -24 gi c estazolam v temazepam.
- Loi tc dng di, t/2 >24 gi c flurazepam, quazepam, diazepam.
2.5. p dng
2.5.1. An thn: liu trung bnh 24gi:
Diazepam (Valium): 0,005 -0,01g. Ung

2.5.2. Chng co git
Diazepam (Valium): 0,010 -0,020g. Tim bp, tnh mch
Clorazepam (Tranxene): 0,010 -0,020g. Ung
2.5.3. Gy ng, tin m
Triazolam (Halcion): 0,125 -0,250g. Ung: Mt ng u gic. Ung
Midazolam (Versed): 0,025 - 0,050. Tim bp, tnh mch - tin m.
2.5.4. Gin c, gim au do co tht: thp khp, ri lon tiu ho
Diazepam (Valium): 0,010 -0,020g. Ung, tim bp, tim tnh mch.
Tetrazepam (Myolastan): 0,050-0,150g. Ung, tim bp, tim tnh mch.
* Nguyn tc chung khi dng thuc:
- Liu lng tu thuc tng ngi.
- Chia liu trong ngy cho ph hp.
- Dng gii hn tng thi gian ngn (1tun -3 thng) trnh ph thuc vo thuc.
- Trnh dng cng vi cc thuc c ch thn kinh trung ng, ru, thuc ng, khng histamin.
2.6. Chng ch nh
- Suy h hp, nhc c: do tc dng c ch thn kinh v gin c.
- Suy gan: do thuc chuyn ho to cc cht c tc dng ko di, c th tng c tnh hoc gy
c cho gan b suy.
- Nhng ngi li t, lm vic trn cao, ng my chuyn ng.
2.7. Nhm thuc mi
Do BZD cn mt s tc dng ph nn ang nghin cu mt nhm thuc an thn mi khng tc
dng qua h GABA: buspirone, zolpidem (nhm imidazopiridin).
Buspiron
i din cho mt nhm thuc an thn mi:
- c im dc l:
. Lm mt lo u nhng khng gy an du, ng g hoc mt tr nh.
. Khng i khng hoc hip ng vi cc thuc an thn hoc barbiturat khc.
. Dng liu cao cng khng gy c ch thn kinh trung ng r.
. Tc dng mnh trn cc triu chng tm l nh lo u, km tp trung t tng. Cn diazepam li
c tc dng lm gin c v chng mt ng tt hn.
. Nhc im: khi pht tc dng chm, km tc dng trn cn hong s.
- C ch tc dng
L cht ng vn vi receptor 5 - HT 1A c nhiu h vin, hi hi m, no gia, i th, hnh -

cu no, th vn, h khu no v tiu no. C ch cn ang nghin cu, nhng khng tc dng
trn knh Cl - qua GABA nh BZD.
- Tc dng khng mong mun:
Chng mt, mt ng, bun nn, nhc u, au ngc, tai, lo u. Cn iu chnh liu. V l thuc
mi, cn theo di thm.
- ng hc
Hp thu nhanh qua ng ung nhng c chuyn ha qua gan ln th nht do hydroxy ha v
mt alkyl, tuy nhin li to ra nhiu cht ch uyn ha cn hot tnh vo c thn kinh trung
ng, c cht c tc dng phong ta c receptor 2. Thi gian bn thi l 2- 4 gi.
Liu lng: vin 5- 10 mg (Buspar), dng t liu thp, 3 ln/ ngy.
Cu hi t lng gi
1. Phn tch 3 c im c bn ca th uc an thn kinh (thuc an thn ch yu).
2. Phn tch c ch tc dng ca clorpromazin.
3. Trnh by cc p dng lm sng v tc dng khng mong mun ca clopromazin.
4. Trnh by tc dng v c ch tc dng ca benzodiazepin.
sch dng cho sinh vin h bc s a khoa
Bi 13: Thuc cha ng kinh

1. Phn loi c thuc iu tr ng kinh theo cn v cc cch tc dng ca thuc cha
ng kinh.
2. Trnh by c c ch tc dng, tc dng dc l v p dng i u tr ca cc thuc
diphenylhydantoin, phenobarbital, carbamazepin v acid valproic.
3. Trnh by c nguyn tc dng thuc cha ng kinh.
1. i cng
Thuc cha ng kinh l nhng thuc c kh nng loi tr hoc lm gim tn s, mc trm
trng ca cc cn ng kinh, hoc cc triu chng tm thn km theo bnh ng kinh, m khng
gy ng. Thuc m v thuc ng cng c tc dng chng co git, nhng tc dng ny ch xut
hin sau khi ngi bnh ng.
Thuc chng ng kinh cng khng cng ngha vi thuc chng co git.
1.1. Phn loi cn ng kinh
Cc cn ng kinh lun xut pht t v no v c phn loi thnh:
- Cn ng kinh cc b: bt u t 1 trn v no v tu theo vng chc phn m th hin ra
triu chng. Th d, v tr tn thng vng v n o vn ng, s c triu chng git rung phn
c th do vng v no y kim tra. Trong loi ny cn phn ra:
. Cn cc b n gin, bnh nhn vn cn thc ko di khong 30 -60 giy.
. Cn cc b phc hp, c km theo mt thc, ko di khong 30 giy n 2 pht.
- Cn ng kinh ton th: ngy t u lan rng ton b 2 bn cu i no. C th gp:
. Khng c cn co git: bt cht mt thc khong 30 giy trong lc ang lm vic (ng kinh
cn nh - petit mal).
. Cn git rung c: co tht bt ng, ng n (khong 30 giy) c th gii hn mt chi, mt vng,
hoc ton th.
. Cn co cng - git rung ton c th (ng kinh cn ln - grand mal).
1.2. Phn loi thuc iu tr theo cn
Loi ng kinh Thuc thng thng Thuc mi
ng kinh cc b
. Cc b n gin Carbamazepin, phenytoin, phenobarbital, Gabapentin
primidon, valproat Lamotrigin
. Cc b phc hp Carbamazepin, phenytoin, phenobarbital, Gabapentin
primidon, valproat Lamotrigin
ng kinh ton th
. Khng cn co git Clonazepam, ethosuximid, valproat Lamotrigin
. Cn git rung valproat Lamotrigin
. Cn co cng- git Carbamazepin, phenobarbital, phenytoin, Lamotrigin
rung primidon, valproat
1.3. Cch tc dng ca thuc cha ng kinh

Cc thuc cha ng kinh c th tc ng theo mt trong ba c ch sau:
- Lm tng dn truyn c ch ca h GABA - ergic
- Lm gim dn truyn kch thch, thng l h glutamatergic.
- Lm thay i s dn truyn ion qua mng nron do tc ng trn knh Na + ph thuc in th,
hoc knh Ca ++ typ T.
V c ch bnh sinh ca ng kinh cha c hon ton bit r cho nn cc thuc cha ng
kinh ch c ch c cc triu chng ca bnh ch khng d phng v iu tr c bnh. Thuc
phi c s dng lu di, d c nhiu tc dng khng mong mun. Do cn c g im st
nghim ngt.
2. Cc thuc chnh
Sau y ch trnh by nhng thuc c trong danh mc thuc thit yu Vit Nam ln th 5 (2005)
2.1. Dn xut hydantoin: Diphenylhydantoin (Phenytoin, Dilantin)
Diphenylhydantoin l mt trong nhng thuc c tc dng t t cha mi th ng kinh, tr ng
kinh th khng c cn co git.
2.1.1. Tc dng v c ch
Phenytoin c tc dng chng cn ng kinh nhng khng gy c ch ton b h thn kinh trung
ng. Liu c cn gy kch thch. Tc dng trn cn co git ng kinh cng ging
phenobarbital, nhng khng gy an thn v ng.
Phenytoin c tc dng n nh mng t bo thn kinh v c tim, lm gim lung Na + trong hiu
th hot ng trong kh cc do cc cht ha hc (c ch knh Na + cm ng vi in th).
2.1.2. Dc ng hc
Phenytoin l acid yu, c pKa = 8,3 tan trong nc km.
Hp thu qua ng tiu ha chm v i khi khng hon ton. Nng ti a trong mu khi
ung l t 3 - 12 gi. Gn vo protein huyt tng 90%. Nng trong thn kinh trung ng
tng ng nng trong huyt tng. Phn ln chuyn ha gan v thi tr qua thn di
dng lin hp, ch 5% di dng khng chuyn ha. Thi gian bn thi t 6 -24 gi.
- Da v nim mc: vim li qu sn, mn da, lupus ban .
- Mu: thiu mu hng cu to do thiu acid folic (do thuc phong ta s hp thu acid folic ti
rut), gim bch cu...
- Tiu ha: nn, cn au bng cp.
- Thn kinh-tm thn: lin quan n nng thuc trong mu:
20 g/ml c tc dng iu tr.
= 30 g/ml lm rung git nhn cu.
= 40 g/ml gy mt phi hp ng tc.
> 40 g/ml gy ri lon tm thn.
- Xng: ci xng hoc mm xng, c th l do ri lon chuyn ha vitamin D, nht l khi
phi hp vi phenobarbital.
2.1.4. Tng tc thuc
Cloramphenicol, dicumaro l, isoniazid, cimetidin c th lm tng nng ca phenytoin trong
huyt tng do lm gim chuyn ha. Tri li, carbamazepin lm tng chuyn ha nn lm gim
nng phenytoin trong huyt tng.
Salicylat, tolbutamid, sulfisoxazol tranh chp vi phenytoi n v tr gn vo protein huyt tng.
2.1.5. p dng iu tr
Phenytoin (Dihydan, Dilantin): vin nn 30 -100mg; ng tim 50mg/ml. Liu u 3-5mg/kg
(300mg/ngy). Theo di nng thuc trong mu, khi t c nng c tc dng, ngh 1
tun. Liu cao 300mg/ngy th khong cch gia cc t iu tr l 2 tun. C th dng liu 1
ln/ngy.
Phenytoin tim tnh mch khng vt qu 50mg/pht, pha long trong NaCl 0,9% v thuc c pH
base, kch thch. Khng tim bp, gy tn thng t chc.
2.2. Phenobarbital (Gardenal, Luminal)
Phenobarbital thuc nhm barbiturat (xem bi thuc ng), l thuc u tin dng iu tr ng
kinh (1912). Khc vi barbiturat khc, phenobarbital c tc dng chng cc cn co git ca ng
kinh ngay c vi nhng liu cha gy an thn hoc ng. Thuc gii hn c s lan truyn ca
cn co git v nng c ngng kch thch gy co git.
Phenobarbital v c pentobarbital tc dng trn receptor GABA -A lm tng qu trnh c ch.
Ngoi ra cn chn knh Ca ++ trc xinap nn lm gim gii ph ng cc cht dn truyn thn kinh,
c bit l glutamat nn lm gim mnh cc qu trnh kch thch trn thn kinh trung ng.
V t c v gi r nn tng i c dng rng ri, nhng c nhc im l gy an thn, ng g
v c xu hng lm ri lon hnh vi ca tr em nn cn thn trng.
Liu lng: ung 0,1 - 0,3 g/ngy (1 - 5 mg/kg). Khng ngng thuc t ngt trnh trng thi
ng kinh lin tc.
2.3. Dn xut Iminostilben: Carbamazepin
Tuy trn ng vt thc nghim v ngi, carbamazepin c nhiu im ging nh phenytoin,

nhng:
- Tc dng chng cn co git gy ra bi pentylentretazol li mnh hn.
- C tc dng iu tr bnh nhn b hng trm cm, k c nhng trng hp lithium khng cn
tc dng.
- C tc dng chng bi ni u do lm gim nng ADH huyt tng.
Cc c ch ny u cha r. Cc dn xut iminostilben cng c ch knh Na + nh phenytoin.
2.3.2. Dc ng hc
Carbamazepin c hp thu chm qua ng tiu ha, nng ti a trong mu t c sau 4 -8
gi v gi c ti 24 gi. Gn vo protein huyt tng 75% v phn phi vo mi m. Nng
trong dch no tu tng ng vi dng t do trong huyt tng.
B chuyn ha gan, cho 10 - 11 epoxid vn cn hot tnh. Di 3% thi qua thn di dng
khng i. Thi gian bn thi t 10 n 20 gi. Dng cng vi phenobarbital hoc phenytoin,
thi gian bn thi gim cn 9 -10 gi.
- Thng gp: ng g, chng mt, nhn la, mt ng tc, bun nn, nn.
- Ngoi ra, c th gp: ri lon to mu, t n thng nng ngoi da, vim gan mt, suy thn cp,
suy tim. V vy, trong qu trnh iu tr cn kim tra cc chc phn trn.
- Phn ng d ng.
2.3.4. p dng lm sng
- Ch nh:
. Cn ng kinh th tm thn vn ng.
. Cn co git cng hoc git run g cc b hoc ton thn.
. Tc dng gim au c hiu trong vim dy thn kinh tam thoa.
- Ch phm:
Carbamazepin (Tegretol) vin nn 100 -200mg.
Liu u 200mg x2 ln/ngy. Tng dn liu ti 600 -1200mg. Tr em 20-30mg/kg. Nn chia liu
hng ngy lm 3 4 ln gi c nng hng nh trong mu.
2.4. Acid valproic
2.4.1. Tc dng dc l v c ch
- Tc dng trn mi loi ng kinh.
- Rt t tc dng an thn v tc dng ph.
- Cc gi thit hin nay u cho rng valproat c ch knh Na + nhy cm vi in th
(MacDonald, 1988) v lm tng tch lu GABA (L scher, 1985). Nhng tc dng ging vi
tc dng ca phenytoin v carbamazepin. Ngoi ra cn lm gim dng Ca ++ qua knh.
2.4.2. Dc ng hc
Hp thu nhanh v hon ton qua tiu ha. Nng ti a trong huyt tng t c sau 1 -4 gi.
Gn vo protein huyt tng 90%. Nng trong dch no tu tng ng trong huyt tng.
Hu nh hon ton b chuyn ha gan, trong c mt cht chuyn ha 2 -propyl-2-pentanoic
acid vn cn hot tnh nh cht m. Thi gian bn thi l 15 gi.
- Khong 16% c cc triu chng chn n, bun nn, nn, au vng thng v.
- Khi dng liu cao 7-30 mg/kg c th gp vim gan cp, vim tu, an thn, run, hi, gim
prothrombin.
2.4.4. p dng lm sng
- Ch nh: ng kinh cc loi, c bit l th khng c cn co git.
- Ch phm:
Acid valproic (Depakin): vin bc ng 250mg; sir 5ml c 250mg hot cht. Liu u
15mg/kg, tng dn hng tun 5 - 10mg/kg cho ti 60mg/kg. Nng iu tr trong mu t 30 n
100g/ml.
3. Nhng vn trong s dng thuc
3.1. Nguyn tc dng thuc
- Ch dng thuc khi c chn on lm sng chc chn.
- Lc u ch dng mt thuc.
- Cho liu t thp tng dn, thch ng vi cc cn.
- Khng ngng thuc t ngt.
- Phi m bo cho bnh nhn ung u hng ngy, khng qun.
- Cm ung ru trong qu trnh dng thuc.
- Ch i thi hn nh gi hiu qu ca iu tr:
. Vi ngy vi ethosuximid, benzodiazepin
. Hai ba tun vi phenobarbital, phenytoin
. Vi tun vi valproic acid.
- Hiu r cc tc dng ph, tc dng khng mong mun ca tng thuc theo di kp thi.
- Nu c th, kim tra nng ca thuc trong mu khi cn.
3.2. iu tr ng kinh v thai nghn
T l thai nhi c d dng hoc t vong ngi m c ng kinh c iu tr cao hn ngi bnh
thng 2 - 3 ln. Cc cn ng kinh cng thng tng ln khi c thai, c th do nng thuc
trong huyt tng gim.
Khi c thai vn khng c ngng thuc, tuy nhin, tu theo tng trng hp, c th gim liu,
nht l trong 3 thng u.
Tr mi nhng ngi m iu tr bng phenobarbital, primidon hoc phenytoin c th gp tai

bin chy mu do thiu vitamin K, cn b sung d phng trc bng vitamin K.
cu hi t lng gi
1. Phn loi cc thuc iu tr ng kinh theo cn v trnh by cc cch tc dng ca
thuc cha ng kinh ni chung.
2. Trnh by tc dng v p dng iu tr ca dn xut hydantoin (Phenytoin) v
phenobarbital trong iu tr ng kinh.
3. Phn tch tc dng iu tr v tc dng khng mong mun ca carbamazepin v acid
valproic.
Bi 14: thuc khng sinh khng khun

1. Pht biu c nh ngha khng sinh, tc dng km khun v dit khun
2. Trnh by c c ch tc dng, p dng iu tr v phn loi ca nhm lactam
3. Nu c c ch tc dng, p dng iu tr v c tnh ca nhm aminoglycosid
4. Trnh by c c ch tc dng, c tnh v p dng iu tr ca khng sinh nhm
cloramphenicol, tetracyclin, lincosamid & macrolid, quinolon - 5- nitroimidazol,
dn xut nitrofuran v sulfamid.
5. Trnh by c nhng nguyn tc s dng khng sinh an ton v hp l
6. Phn tch c nhng nguyn nhn gy tht bi trong vic dng khng sinh v cch
khc phc
1. i cng
1.1. nh ngha
K nguyn hin i ca ha tr liu khng khun c bt u t vic tm ra sulfonamid
(Domagk, 1936), "Thi k vng son" ca khng sinh bt u t khi sn xut penicilin dng
trong lm sng (1941). Khi , "khng sinh c coi l nhng cht do vi sinh vt tit ra (vi
khun, vi nm), c kh n ng km hm s pht trin ca vi sinh vt khc".
V sau, vi s pht trin ca khoa hc, ngi ta
- C th tng hp, bn tng hp cc khng sinh t nhin (cloramphenicol)
- Tng hp nhn to cc cht c tnh khng sinh: sulfamid, quinolon
- Chit xut t vi sinh vt nhng cht dit c t bo ung th (actinomycin)
V th nh ngha khng sinh c thay i: "Khng sinh l nhng cht do vi sinh vt tit ra
hoc nhng cht ha hc bn tng hp, tng hp, vi nng rt thp, c kh nng c hiu km
hm s pht trin hoc dit c vi khun"
1.2. C ch tc dng ca khng sinh
S di y ch r v tr v c ch tc dng chnh ca cc khng sinh trn vi khun:
Hnh 14.2. Cc khng sinh c ch qu trnh tng hp protei
1. c ch to cu peptid (Cloramphenicol)
2. Ngn cn chuyn ng chuyn on ca ribosom theo ARN m (Erythromycin)
3. Ngn cn s gn kt ca ARN t vo phc hp ribosom ARN m (Tetracyclin)
4. Lm thay i hnh dng 30S m ha trn ARN m nn c nhm (Streptomycin)
Hnh 14.3. V tr tc dng c a khng sinh c ch tng hp protein
1.3. Ph khng khun

Do khng sinh c tc dng theo c ch c hiu nn mi khng sinh ch c tc dng trn mt s
chng vi khun nht nh, gi l ph khng khun ca khng sinh
1.4. Tc dng trn vi khun
Khng sinh c ch s pht trin ca vi khun, gi l khng sinh km khun; khng sinh hu hoi
vnh vin c vi khun gi l khng sinh dit khun. Tc dng km khun v dit khun thng
ph thuc vo nng
Nng dit khun ti thiu (MBC)

T l
Nng km khun ti thiu (MIC)

Khi t l > 4, khng sinh c tc dng km khun. Kh t l gn bng1, khng sinh c
xp vo loi dit khun.
1.5. Phn loi
Cc khng sinh c phn loi theo cu trc ha hc, t chng c chung mt c ch t c dng
v ph khng khun tng t. Mt khc, trong cng mt h khng sinh, tnh cht dc ng hc
v s dung np thng khc nhau, v c im v ph khng khun cng khng hon ton ging
nhau, v vy cng cn phn bit cc khng sinh trong cng mt h
Mt s h (hoc nhm) khng sinh chnh:

- Nhm lactam (cc penicilin v cc cephalosporin)
- Nhm aminosid hay aminoglycosid
- Nhm cloramphenicol
- Nhm tetracyclin
- Nhm macrolid v lincosamid
- Nhm quinolon
- Nhm 5- nitroimidazol
- Nhm sulfonamid
2. Cc khng sinh chnh
2.1. Nhm lactam
V cu trc u c vng lactam (H )
V c ch u gn vi transpeptidase (hay PBP: Penicilin Binding Protein), enzym xc tc cho s
ni peptidoglycan to vch vi khun. Vch vi khun l b phn rt qua n trng m bo s
tn ti v pht trin. Thnh phn m bo cho tnh bn vng c hc ca vch l mng li
peptidoglycan, gm cc chui glycan ni cho vi nhau bng chui peptid. Khong 30 enzym
ca vi khun tham gia tng hp peptidoglycan, trong c transpeptidase (hay PBP). Cc
lactam v khng sinh loi glycopeptid (nh vancomycin) to phc bn vng vi transpeptidase,
c ch to vch vi khun, lm ly gii hoc bin dng vi khun. Vch vi khun gram (+) c mng
li peptidoglycan dy t 50 - 100 phn t, li ngay b mt t bo nn d b tn cng. Cn vi
khun gram (-) vch ch dy 1- 2 phn t nhng li c che ph lp ngoi cng mt v bc
lipopolysaccharid nh 1 hng ro khng thm khng sinh, mun c tc dng, khng sinh phi
khuch tn c qua ng dn (pores) ca mng ngoi nh amoxicilin, mt s cephalosporin.
Do vch t bo ca ng vt a bo c cu trc khc vch vi khun nn khng chu tc ng ca
lactam (thuc hu nh khng c). Tuy nhin vng lactam rt d gy d ng.
Cc khng sinh lactam c chia thnh 4 nhm da theo cu trc ha hc

- Cc penam: vng A c 5 cnh bo ha, gm cc penicilin v cc cht phong ta lactamase.
- Cc cephem: vng A c 6 cnh khng bo ha, gm cc cephalosporin.
- Cc penem: vng A c 5 c nh khng bo ha, gm cc imipenem, ertapenem.
- Cc monobactam: khng c vng A, l khng sinh c th tng hp nh aztreonam.
Penam Cephem
(vng A c 5 cnh (Vng A c 6 cnh,
bo ha) khng bo ha)
2.1.1.1. Penicilin G
L nhm thuc tiu biu, c tm ra u tin.
* Ngun gc v c tnh l ha
Trong sn xut cng nghip, ly t Penicillium notatum, 1 mL mi trng nui cy cho 300 UI; 1
n v quc t (UI)= 0,6 g Na benzylpenicilin hay 1.000.000 UI = 0,6g. Penicilin G l dn g bt
trng, vng bn nhit thng, nhng dung dch nc, phi bo qun lnh v ch vng bn
pH 6- 6,5, mt tc dng nhanh pH < 5 v > 7,5
* Ph khng khun
- Cu khun Gr (+); lin cu (nht l loi tan huyt), ph cu v t cu khng sn xu t
penicilinase.
- Cu khun Gr (-): lu cu, mng no cu
- Trc khun Gr (+) i kh (than, subtilis, bch cu) v ym kh (clostridium hoi th sinh hi)
- Xon khun, c bit l xon khun giang mai (treponema pallidum)
* Dc ng hc
- Hp thu: b dch v ph hu nn khng ung c. Tim bp, nng ti a t c sau 15 - 30
pht, nhng gim nhanh (cn tim 4h/ ln). Tim bp 500.000 UI, pic huyt thanh 10 UI/ mL.
- Phn phi: gn vo protein huyt tng 40 - 60%. Kh thm vo xng v no. Khi mng no
vim, nng trong dch no tu bng 1/ 10 huyt tng. Trn ngi bnh thng, t/2 l khong
30 - 60 pht.
- Thi tr: ch yu qua thn di dng khng hot tnh 60 - 70%, phn cn li vn cn hot tnh.
Trong gi u, 60- 90% thi tr qua nc tiu, trong 90% qua bi xut ng thn (mt s
acid hu c nh probenecid c ch qu trnh ny, lm chm thi tr penicilin)
* c tnh
Penicilin rt t c, nhng so vi thuc khc, t l gy d ng kh cao (1 - 10%), t phn ng rt
nh n t vong do chong phn v. C d ng cho vi mi lactam v cephalosporin.
* Ch phm, liu lng
- Penicilin G l bt, pha ra dng ngay. Liu lng tu theo tnh trng nhim khun, t 1 triu n
50 triu UI/ 24h chia 4 ln, tim bp hoc truyn tnh mch (pH dch t ruyn 6- 7). Tr em trung
bnh cho 100.000 UI/ kg/ 24 h
- Penicilin c ph G, tc dng ko di: kt hp vi cc mui t tan v chm hp thu s ko di
c tc dng ca penicilin G:
. Bipenicilin (natri benzylpenicilinat + procain benzylpenicilinat): mi n gy tim 1 ln, khng
dng cho tr em.
. Extencilin (benzathin penicilin): tim bp 1 ln, tc dng ko di 3 - 4 tun. Dng iu tr lu,
giang mai v d phng thp khp cp ti nhim - l 600.000, 1.000.000 v 2.400.000 UI
- Penicilin c ph G, ung c
Penicilin V (Oracilin, Ospen): khng b dch v ph hy, hp thu t trng, nhng phi dng liu
gp i penicilin G mi t c nng huyt thanh tng t. Cch 6h/ ln.
2.1.1.2. Penicilin khng penicilinase: Methicilin
L penicilin bn tng hp
Ph khng khun v thi gian tc dng tng t penicilin G, nhng cng tc dng th yu
hn. Tim bp hoc tnh mch 2 - 8 g/ 24h chia lm 4 ln. Khng ung dc
Mt s thuc khc vng bn vi dch v, ung c: oxacilin (Bristopen), cloxacilin (Orbenin):
ung 2- 8g mt ngy chia lm 4 ln
Ch nh tt trong nhim t cu sn xut penicilinase (t cu vng)
C th gp vim thn k, c ch ty xng liu cao
2.1.1.3. Penicilin c ph rng
Ampicilin, amoxicilin
L penicilin bn tng hp, amino - benzyl penicilin c mt s c im:
- Trn cc khun Gr (+) tc dng nh penicilin G, nhng c thm tc dng trn mt s khun
gram (-): E. coli, salmonella, Shigella, proteus, hemophilus influenzae
- B penicilinase ph hu
- Khng b dch v ph hy, ung c nhng hp thu khng hon ton (khong 40%). Hin c
nhiu thuc trong nhm ny c t l hp thu qua ng ung cao (nh amoxicilin ti 90%) nn
nhiu nc khng cn dng ampicilin na
- Liu lng: Amoxicilin (clamoxyl, Oramox)
Ung: 2- 4 g/ ngy. Tr em 50 mg/ kg/ ngy. Chia 4 ln
- Ch nh chnh: vim mng no m, thng hn, nhim khun ng mt, tit niu, nhim
khun s sinh.
2.1.1.4. Cc penicilin khng trc khun m xanh: Carboxypenicilin v ureidopenicilin.
L nhm khng sinh quan trng c dng iu tr cc nhim khun nng do trc khun gram ( -
) nh trc khun m xanh, Proteus, Enterobacter, vi khun khng penicilin v ampicilin. Thng
l nhim khun mc phi ti bnh vin, nhim khun sau bng, nhim khun tit niu, vim phi.
Cc khng sinh ny u l bn tng hp v vn b penicilinase ph hu.
- Carbenicilin, ticarcilin: ung 2 - 20g/ ngy.
- Ureidopenicilin:
. Mezlocilin: 5- 15g/ ngy. Tim bp, truyn tnh mch.
. Piperacilin: 4- 18g/ ngy. Tim bp, truyn tnh mch.
2.1.2. Cc cephalosporin
c chit xut t nm cephalosporin hoc bn tng hp, u l dn xut ca acid amino - 7-
cephalosporanic, c mang vng lactam. Tu theo tc dng khng khun, chia thnh 4 "th h"
2.1.2.1. Cephalosporin th h 1:
C ph khng khun gn vi metici lin v penicilin A. Tc dng tt trn cu khun v trc khun
gram (+), khng c penicilinase ca t cu.
C tc dng trn mt s trc khun gram ( -), trong c cc trc khun ng rut nh
Salmonella, Shigella.
B cephalosporinase ( lactamase) ph hu.
Ch nh chnh: sc nhim khun, nhim khun huyt do t cu, nhim khun khng penicilin.
Cc ch phm dng theo ng tim (bp hoc tnh mch) c: cefalotin (Kezlin), cefazolin
(Kefzol), liu 2- 8g/ ngy
Theo ng ung c cefalexin (Keforal), cefaclor (Alfatil), liu 2g/ngy.
khc phc 2 nhc im: t tc dng trn vi khun gram ( -) v vn cn b cephalosporinase
ph, cc th h cephalosporin tip theo v ang c nghin cu sn xut.
2.1.2.2. Cephalosporin th h 2:
Hot tnh khng khun tr n gram (-) tng, nhng cn km th h 3. Khng c
cephalosporinase. S dung np thuc cng tt hn.
Ch phm tim: cefamandole (Kefandol), cefuroxim (Curoxim) liu 3 - 6 g/ ngy.
Ch phm ung: cefuroxim acetyl (Zinnat) 250 mg 2 ln/ ngy.
2.1.2.3. Cephalosporin th h 3
Tc dng trn cu khun gram (+) km th h 1, nhng tc dng trn cc khun gram ( -), nht l
trc khun ng rut, k c chng tit lactamase th mnh hn nhiu.
Cho ti nay, cc thuc nhm ny hu ht u l dng tim:
Cefotaxim (Claforan), ceftizoxim (Cefizox), ceftriaxon (Rocephin), liu t 1 n 6g/ngy, chia 3 -
4 ln tim.
2.1.2.4. Cephalosporin th h 4.
Ph khng khun rng v vng bn vi lactamase hn th h 3, c bit dng ch nh trong
nhim trc khun gram (-) hiu kh khng vi th h 3.
Ch phm: cefepim, tim t/ m 2g 2 ln/ ngy.
2.1.3. Cc cht c ch lactamase (cu trc Penam)
L nhng cht c tc dng khng sinh yu, nhng gn khng hi phc vi lactamase v c i
lc vi lactam, cho nn khi phi hp vi khng sinh nhm lactam s lm vng bn v tng
cng hot tnh khng khun ca khng sinh ny. Hin c cc ch phm sau:
Cht (-) lactamase Khng sinh phi hp Bit dc

Acid clavulinic Amoxicilin - Augmentin: vin nn 250, 50 0
mg, l 500 mg, 1g tim tnh mch
- Timentin
Ticarcilin
Sulbactam Ampicilin Unasyn: vin nn 220 mg
ng tim 500- 1000 mg
Tazobactam Piperacilin Zosyn
2.1.4. Cc penem
Imipenem
Thuc nhm carbapenem, trong cng thc vng A thay S bng C.
Ph khng khun rt rng , gm cc khun i kh v k kh: lin cu, t cu (k c chng tit
penicilinase), cu khun rut (enterococci), pseudomonas.
c dng trong nhim khun sinh dc - tit niu, ng h hp di, m mm, xng - khp,
nhim khun bnh vin.
Khng hp thu qua ng ung. Ch tim tnh mch liu 1 - 2g/ ngy.
Ertapenem
Ph khng khun nh imipenem, nhng mnh hn trn gram ( -). Tim bp hoc truyn tnh mch
1g/ ngy.
2.1.5. Monobactam Aztreonam
Km tc dng trn khun gram (+) v k kh. Tri li, tc dng mnh trn khun gram (-), tng
t cephalosporin th h 3 hoc aminoglycosid. Khng lactamase.
Khng tc dng theo ng ung. Dung np tt, c th dng cho bnh nhn d ng vi penicilin
hoc cephalosporin.
Tim bp 1- 4 g/ ngy. Trng hp nng, tim tnh mch 2g, cch 6- 8 gi/ ln.
2.1.6. Thuc khc cng c ch tng hp vch vi khun: Vancomycin
Khng sinh c ngun gc t Streptococcus orientalis.
C ch tc dng: c ch transglycosylase nn ngn cn ko di v to li peptidoglycan. Vi
khun khng to c vch nn b ly gii. Vancomycin l khng sinh dit khun.
Tc dng: ch dit khun gram (+): phn ln cc t cu gy bnh, k c t cu tit lactamase v
khng methicilin. Hip ng vi gentamycin v streptomycin trn enterococcus.
ng hc: c hp thu rt t qua ng tiu ha nn ch c dng iu tr vim rut kt gi
mc cng vi tetracyclin, clindamycin. Tim truyn tnh mch, gn vi protein huyt tng
khong 55%, thm vo dch no tu 7 - 30% nu c vim mng no, trn 90% thi qua lc cu
thn (khi c vim thn phi gim liu). Thi gian bn thi khong 6 h.
Ch nh chnh: vim mng trong tim do t cu khng methicilin, cho bnh nhn c d ng
penicilin. Liu lng 1g 2 ln/ ngy.
Tc dng khng mong mun: ch khong 10% v nh. Thng gp l kch ng vim tnh mch ti
ch tim truyn, rt run, st, c vi dy VIII. Nng truyn nn gi t 5 - 15 g/ mL (di 60
g/ mL) th trnh c tc dng ph.
Ch phm: Vancomycin (Vancocin, Vancoled): l bt ng kh pha dch tim truyn 500 mg
v 1,0g.
2.2. Nhm aminosid hay aminoglycosid
u ly t nm, cu trc ha hc u mang ng (ose) v c chc amin nn c tn aminosid.
Mt s l bn tng hp.
C 4 c tnh chung cho c nhm:
- Hu nh khng hp thu qua ng tiu ha v c P M cao.
- Cng mt c ch tc dng
- Ph khng khun rng. Dng ch yu chng khun hiu kh gram ( -).
- c tnh chn lc vi dy thn kinh VIII v vi thn (tng creatinin mu, protein - niu. Thng
phc hi)
Thuc tiu biu trong nhm ny l streptomycin. Ngoi ra cn: Neomycin, kanamycin, amikacin,
gentamycin, tobramycin.
2.2.1. Streptomycin
2.2.1.1. Ngun gc v c tnh
Ly t nm streptomyces griseus (1944). Thng dng di dng mui d tan, vng bn nhit
di 25 0C v pH = 3- 7.
2.2.1.2. C ch tc dng v ph khng khun
Sau khi nhp vo vi khun, streptomycin gn vo tiu phn 30 s ca ribosom, lm vi khun c
sai m thng tin ARN m, tng hp protein b gin on. C tc dng dit khun trn cc vi khun
phn chia nhanh, ngoi t bo hn l trn vi khun phn chia chm. pH ti u l 7,8 (cho nn
cn alcali (kim) ha nc tiu nu iu tr nhim khun tit niu)
Ph khng khun rng, gm:
- Khun gram (+): t cu, ph cu, lin cu (c tc dng hip ng vi khng sinh nhm
lactam)
- Khun gram (-): Salmonella, Shigella, Haemophilus, Brucella.
- Xon khun giang mai
- L khng sinh hng u chng trc khun lao (BK)
Vi khun khng streptomycin: khun k kh, trc khun m xanh v mt s nm bnh.
2.2.1.3. Dc ng hc
- Hp thu: ung, b thi t r hon ton theo phn. Tim bp, hp thu chm hn penicilin, nhng
gi c lu hn nn ch cn tim mi ngy 1 ln. Gn vo protein huyt tng 30 - 40%.
- Phn phi: do tan nhiu trong nc v b ion ha pH huyt tng, streptomycin kh thm ra
ngoi mch. Gn nhiu hn vo thn, c, phi, gan. Nng trong mu thai nhi bng 1/2 nng
huyt tng. t thm vo trong t bo (khng dit c BK trong i thc bo nh isoniazid).
Khng qua c hng ro mu no.
- Thi tr: khong 85- 90% liu tim b thi tr qua lc cu thn trong 24h.
2.2.1.4. c tnh
- Dy VIII rt d b tn thng, nht l khi iu tr ko di v c suy thn. c tnh on tin
nh thng nh v ngng thuc s khi, cn c on c tai c th gy ic vnh vin k c
ngng thuc. Dihydrostreptomycin c t l c cho c tai cao hn nn khng cn c dng na.
- c vi thn v phn ng qu mn t gp. C th thy vim da do tip xc y t (ngi tim
thuc).
- C tc dng mm c kiu cura nn c th gy ngng h hp do lit c h hp v dng
streptomycin sau phu thut c gy m.
Khng dng cho ngi nhc c v ph n c thai.
2.2.1.5. Cch dng:
Do c tnh nn ch gii hn ginh cho cc nhim khun sau:
- Lao: phi hp vi 1 hoc 2 khng sinh khc (xem bi " thuc chng lao")
- Mt s nhim khun tit niu, dch hch, brucellose: phi hp vi tetracyclin
- Nhim khun huyt nng do lin cu: phi hp vi penicilin G.
L sulfat streptomycin 1g. Liu thng thng tim bp 1g/ ngy. Trong iu tr lao, tng liu
khng qu 80- 100g.
2.2.2. Cc aminosid khc
- Kanamycin:
Tc dng, dc ng hc v c tnh tng t nh streptomycin. Thng dng phi hp (thuc
hng 2) trong iu tr lao. Liu 1g/ ngy (xem bi" thuc chng lao")
- Gentamycin:
Ph khng khun rt rng. L thuc c chn la cho nhim khun bnh vin do Enterococcus
v Pseudomonas aeruginosa. Dng phi hp vi penicilin trong st gim bch cu v nhim trc
khun gram (-) nh vim ni tm mc, nhim khun huyt, vim tai ngoi c tnh.
Gentamycin sulfat ng trong n g 160, 80, 40 v 10 mg. Liu hng ngy l 3 - 5 mg/ kg, chia 2- 3
ln/ ngy, tim bp.
- Amikacin:
L thuc c ph khng khun rng nht trong nhm v khng c cc enzym lm mt hot
aminoglycosid nn c vai tr c bit trong nhim khun bnh vin gram ( -) khng vi
gentamycin v tobramycin.
Liu lng mt ngy 15 mg/ kg tim bp hoc tnh mch 1 ln, hoc chia lm 2 ln. ng 500 mg.
- Neomycin:
Thng dng di dng thuc bi iu tr nhim khun da - nim mc trong bng, vt thng,
vt lot v cc bnh ngoi da bi nhim. Dng neomycin n c hoc phi hp vi polymyxin,
bacitracin, khng sinh khc hoc corticoid.
2.3. Cloramphenicol v dn xut
2.3.1. Ngun gc v tnh cht l ha
Phn lp t nm Streptomyces venezualae (1947) v ngay sau t ng hp c . L bt trng,
rt ng, t tan trong nc, vng bn nhit thng v pH t 2 - 9, v th c th ung c.
2.3.2. C ch tc dng v ph khng khun
Cloramphenicol c tc dng km khun, gn vo tiu phn 50s ca ribosom nn ngn cn ARN m
gn vo ribosom, ng thi c ch transferase nn acid amin c m ha khng gn c vo
polypeptid.
Cloramphenicol cng c ch tng hp protein ca ty th t bo ng vt c v (v ribosom ca
ty th cng l loi 70s nh vi khun), hng cu ng vt c v c bit nhy cm vi
cloramphenicol.
Ph khng khun rt rng: phn ln cc vi khun Gram (+) v Gram ( -), xon khun, tc dng
c hiu trn thng hn v ph thng hn.
2.3.3. Dc ng hc
- Hp thu: sau khi ung, nng ti a trong mu t c sau 2 gi, t/ 2 t 1,5 - 3 gi, khong
60% gn vo protein huyt tng.
- Phn phi: thm d dng vo cc m, nht l cc hch mc treo, nng t c cao hn
trong mu (rt tt cho iu tr thng hn). Thm tt vo dch no tu nht l khi mng n o b
vim, c th bng nng trong mu. Qua c rau thai.
- Chuyn ha: phn ln b mt hot tnh do qu trnh glycuro - hp gan hoc qu trnh kh.
- Thi tr: ch yu qua thn, 90% di dng chuyn ha.
2.3.4. c tnh
Hai c tnh rt nguy him:
- Suy ty:
. Loi ph thuc vo liu: khi liu cao qu 25 g/ mL c th thy sau 5 - 7 ngy xut hin thiu
mu nng, gim mnh hng cu li, bch cu, hng cu non. Liu ung 0,5g s c pic huyt
thanh 6- 10 g/ mL
. Loi khng ph thuc liu, thng do c ng: gim huyt cu ton th do suy tu thc s, t l
t vong t 50- 80% v tn xut mc t 1: 150.000 n 1: 6.000
- Hi chng xm (grey baby syndrome) gp nh nhi sau khi dng liu cao theo ng tim:
nn, au bng, tm ti, mt nc, ngi mm nh n, try tim mch v cht. l do gan cha
trng thnh, thuc khng c kh c bng qu trnh glycuro - hp v thn khng thi tr kp
cloramphenicol.
- Ngoi ra, bnh nhn thng hn nng, dng ngay liu cao cloramphenicol, vi khun cht gii
phng qu nhiu ni c t c th gy try tim mch v t vong. V vy, duy nht trong trng
hp thng hn nng phi dng t liu thp.
2.3.5. Tng tc thuc
Cloramphenicol c ch cc enzym chuyn ha thuc gan nn ko di t/2 v lm tng nng
huyt tng ca phenytoin, tolbutamid, warfarin...
2.3.6. Ch phm v cch dng
V c c tnh nng nn phi cn nhc trc khi dng cloramphenicol. Ch dng cloramphenicol
khi khng c thuc tc dng tng ng, km c hn thay th.
- Thng hn v nhim salmonel la ton thn trc y l ch nh tt ca cloramphenicol. Nay
khng dng na v c thay bng cephalosporin th h 3 (ceftriaxon) hoc fluoroquinolon.
- Vim mng no do trc khun gram ( -) (H. influenzae) l ch nh tt v cloramphenicol d
thm qua mng no. Cng c th thay bng cephalosporin th h 3.
- Bnh do xon khun Rickettsia: Tetracyclin l ch nh tt nht. Nhng khi tetracyclin c chng
ch nh th thay bng cloramphenicol.
Liu lng: ung t 25- 50 mg/ kg/ 24h. Chia lm 4 - 6 ln. Khng dng cho ngi suy gan nng.
- Thiophenicol (thiamphenicol): ch phm tng hp, nhm NO 2 trong cloramphenicol c thay
bng CH 3 - SO2 - . c tnh t hn, d dung np, nhng tc dng cng km hn, v vy liu dng
gp 2 ln cloramphenicol. Khng dng cho ngi suy thn nng.
2.4. Nhm tetracyclin
u l khng sinh c 4 vng 6 cnh, ly t Streptomyces aureofaciens (clotetracyclin, 1947),
hoc bn tng hp. L bt vng, t tan trong nc, tan trong base hoc acid.
Cc tetracyclin u l khng sinh km khun, c ph khng khun rng nht trong cc khng sinh
hin c. Cc tetracyclin u c ph tng t, tr minocyclin: mt s chng khng vi
tetracyclin khc c th vn cn nhy cm vi minocyclin.
Tc dng km khun l do gn trn tiu phn 30s ca ribosom vi khun, ngn cn RNA t chuyn
acid amin vo v tr A trn phc hp ARNm - riboxom to chui polypeptid. Tc dng trn:
. Cu khun gram (+) v gram ( -): nhng km penicilin
. Trc khun gram (+) i kh v ym kh
. Trc khun gram (-), nhng proteus v trc khun m xanh rt t nhy cm
. Xon khun (km penicilin), rickettsia, amip, trichomonas...
2.4.3. Ch nh
Do ph khng khun rng, tetracyclin c dng ba bi, d g y khng thuc. V vy ch nn
dng cho cc bnh gy ra do vi khun trong t bo v tetracyclin rt d thm vo i thc bo.
- Nhim rickettsia
- Nhim mycoplasma pneumoniae

- Nhim chlamidia: bnh Nicolas - Favre, vim phi, ph qun, vim xoang, psittacos is, bnh mt
ht.
- Bnh ly truyn qua ng tnh dc
- Nhim trc khun: brucella, tularemia, bnh t, l, E.coli.
- Trng c: do tc dng trn vi khun propionibacteria khu tr trong nang tuyn b v chuyn ha
lipid thnh acid bo t do gy kch ng vi m. Dng liu thp 250 2ln/ ngy.
2.4.4. Dc ng hc
- Cc tetracyclin khc nhau v tnh cht dc ng hc, cc dn xut mi c c im hp thu tt
hn, thi tr chm hn v do c th gim c liu dng hoc ung t ln hn.
- Hp thu qua tiu ha 60 - 70%. D to phc vi st, calci, magnesi v casein trong thc n v
gim hp thu. Nng ti a trong mu t c sau 2 - 4 gi.
- Phn phi: gn vo protein huyt tng t 30% (oxytetracyclin) n 50% (tetracyclin) hoc trn
90% (doxycyclin). Thm c vo dch no tu, rau thai, sa nhng t. c bit l thm c vo
trong t bo nn c tc dng tt trong iu tr cc bnh do brucella. Gn mnh vo h li ni m
ca gan, lch, xng, rng. Nng rut cao gp 5 - 10 ln nng trong mu.
- Thi tr: qua gan (c chu k gan - rut) v thn, phn ln di dng cn hot tnh. Thi gian
bn thi l t 8h (tetracyclin) n 20h (doxycyclin)
Bng 14.1. Cc tetracyclin thng dng
Tn thuc Hp thu theo thanh thi t/2 Phn loi tc

ng ung ca thn (mL/ dng
(%) pht)
Chlortetracycli 30 35 6- 8h Tc dng
n ngn
60- 70 90 -
Oxytetracyclin -
- 65 -
Tetracyclin
Demeclocyclin - 35 12h Tc dng
Methacyclin - 31 - Trung bnh
Doxycyclin 90- 100 16 16- 18h Tc dng di
Minocyclin - 10 -
2.4.5. c tnh
- Ri lon tiu ha: bun nn, nn, tiu chy, do thuc kch ng nim mc, nhng thng l do
lon khun
- Vng rng tr em: tetracyclin lng ng vo rng trong thi k u ca s vi ha (trong t

cung nu ngi m dng thuc s au 5 thng c thai hoc tr em di 8 tui)
- c vi gan thn: khi dng liu cao, nht l trn ngi c suy gan, thn, ph n c thai c th
gp vng da gy thoi ha m, ur mu cao dn n t vong.
- Cc ri lon t gp hn: d ng, xut huyt gim tiu cu, tng p lc ni s tr ang b, nhc
u, ph gai mt...
V vy, phi thn trng theo di khi s dng v trnh dng:
. Cho ph n c mang
. Cho tr em di 8 tui
2.4.6. Ch phm, cch dng
D sao, tetracyclin vn l khng sinh c ph rng, t g y d ng, t c, c bit l thm c vo
trong t bo nn c dnh cho iu tr bnh do brucella, nhim khun ng mt, mi - hng,
phi.
Mt s dn xut chnh:
- Tetracyclin: ung 1- 2 g/ ngy, chia 3- 4 ln. Vin 250- 500 mg; dch treo 125 mg/ 5mL
- Clotetracyclin (Aureomycin): ung, tim t/m 1 - 2 g.
- Oxytetracyclin (Terramycin): ung 1- 2 g; tim bp, t/m 200 mg - 1g.
- Minocyclin (Mynocin): ung 100 mg 2 ln; tim bp hoc t/m 100 mg. Vin 50 - 100 mg; dch
treo 50 mg/ 5 mL
- Doxycyclin (Vibramycin): ung liu duy nht 100 - 200 mg. Vin 50- 100 mg; dch treo 25- 50
mg/ mL
2.5. Nhm macrolid v lincosamid
Hai nhm ny tuy cng thc khc nhau nhng c nhiu im chung v c ch tc dng, ph
khng khun v c im s dng lm sng.
2.5.1. Ngun gc v tnh cht
Nhm macrolid phn ln u ly t streptomyces, cng thc rt cng knh, i din l
erythromycin (1952), ngoi ra cn clarithromycin v azithromycin.
Cc lincosamid cng ly t streptomyces, cng thc n gin hn nhiu, i din l lincomycin
(1962), clindamycin.
Hai nhm ny c c tnh:
- Tc dng trn cc chng khng penicilin v tetracyclin, c bit l staphylococus.
- Gia chng c khng cho do c ch tng t
- Thi tr ch yu qua ng mt
- t c v dung np tt
2.5.2. C ch tc dngv ph khng khun
Gn vo tiu phn 50s ca ribosom vi khun, cn tr to chui a peptid (ngn cn chuyn v ca

ARNt) ca vi khun.
Ph tc dng tng t penicilin G: cu khun v rickettsia. Hon ton khng tc dng trn trc
khun ng rut v pseudomonas.
Tc dng km khun mnh, c tc dng dit khun, nhng yu.
2.5.3. Dc ng hc
B dch v ph hu mt phn, nu dng dng bo ch thch hp, c th ung c tt. Nng ti
a t c trong mu sau 1 - 4h v gi khng qu 6 ting nn phi ung 4 ln mi ngy. Gn vo
protein huyt tng khong 70% (lincomycin) n 90% (erythromycin), t/2 t 1h 30 n 3 h.
Thm mnh vo cc m, c bit l phi, gan, lch, xng, tuyn tin lit. Nng trong i
thc bo v bch cu a nhn gp 10 - 25 ln trong huyt tng do c vn chuyn tch cc. Rt t
thm qua mng no.
Thi tr ch yu qua mt di dng cn hot tnh (nng trong mt gp 5 ln trong huyt
tng).
2.5.4. Ch nh
L thuc c chn la ch nh cho nhim corynebacteria (bch hu, nh im nm
corynebacterium minutissimum - erythrasma); nhim clamidia ng h hp, sinh dc, mt, vim
phi mc phi cng ng; thay th penicilin cho bnh nhn b d ng vi penicilin khi nhim t
cu, lin cu hoc ph cu; d phng vim ni tm mc trong phu thut rng ming cho nhng
bnh nhn c bnh van tim.
2.5.5. c tnh
Ni chung t c v dung np tt ch gp cc ri lon tiu ha nh (bun nn, nn, tiu chy) v
d ng ngoi da.
Tuy nhin, lincomycin v clindamycin c th gy vim rut kt mc gi, i khi nng, dn n t
vong; erythromycin v Tri Acetyl Oleandomycin (TAO) c th gy vim da mt, vng da.
2.5.6.1. Nhm macrolid
- Erythromycin (Erythromycin, Erythrocin): ung 1 - 2g/ ngy, chia lm 4 ln
- Spiramycin (Rovamycin): ung 1- 3g/ ngy, truyn chm t/m 1,5 triu UI 3 ln/ ngy
- Azithromycin: thm rt nhiu vo m (tr dch no tu), t nng cao hn huyt tng ti
10- 100 ln, sau c gii phng ra t t nn t/2 khong 3 ngy. V th cho php dng l iu 1
ln/ ngy v thi gian iu tr ngn. Th d vi vim phi cng ng, ngy u cho 500 mg ung
1 ln; 3 ngy sau ung 250 mg/ ln/ ngy ch dng trong 4 ngy.
Vin nang 250 mg
2.5.6.2. Nhm lincosamid
- Lincomycin (Lincocin): ung 2g/ ngy. Chia lm 4 ln. Vin nang 500 mg.
tim bp, t/m: 0,6 - 1,8g/ ngy
- Clindamycin (Dalacin): ung 0,6- 1,2g/ ngy, chia lm 4 ln (0,15 - 0,3g/ ln)
Khng sinh 2 nhm ny thng dng cho nhim cu khun gram (+), nht l trong tai mi hng,
vim phi, nhim khun ng h hp.
Nhm lincosamid do thm mnh c vo xng nn cn c ch nh tt cho cc vim xng
ty.
2.6. Nhm Quinolon
L khng sinh hon ton tng hp. Loi kinh in c acid nalidixic (1963) l tiu biu. Loi mi,
do gn thm fluor vo v tr 6, gi l 6 - fluoroquinolon (pefloxacin 1985) c ph khng khun
rng hn, ung c. Tt c u l cc acid yu, cn trnh nh sng
Cc quinolon u c ch ADN gyrase, l enzym m vng xon ADN, gip cho s sao chp v
phin m, v vy ngn cn s tng hp ADN ca vi khun. Ngoi ra cn tc dng c trn ARN m
nn c ch tng hp protein vi khun. Cc quinolon u l thuc dit khun.
Acid nalidixic (cn gi l quinolon th h 1) ch c ch ADN gyrase nn ch c tc dng dit
khun gram (-) ng tit niu v ng tiu ha. Khng tc dng trn trc khun m xanh
(Pseudomonas aeruginosa).
Cc fluoroquinolon c tc dng ln 2 enzym ch l ADN gyr ase v topoisomerase IV ca vi
khun (Drlica, 1997) nn ph khng khun rng hn, hot tnh khng khun cng mnh hn t
10- 30 ln. Cc fluoroquinolon th h u, cn gi l quinolon th h 2 (pefloxacin, norfloxacin,
ofloxacin, ciprofloxacin... 1987 - 1997) c khc nhau tng i v tc ng trn gyrase v
topoisomerase IV: trn vi khun gram ( -), hiu lc khng gyrase mnh hn; cn trn vi khun
gram (+), li c hiu lc khng topoisomerrase IV mnh hn. Cc fluoroquinolon th h mi cn
gi l quinolon th h 3 (levofloxacin, trovafloxacin, t 1999) c tc ng cn bng trn c 2
enzym v vy ph khng m rng trn gram (+), nht l cc nhim khun ng h hp, v vi
khun kh khng thuc hn v phi t bin 2 ln trn 2 enzym ch.
Ph khng khun ca fluoroquinolon gm: E.coli, Salmonella, Shigella, Enterobacter, Neisseria,
P.aeruginosa, Enterococci, ph cu, t cu (k c loi khng methicilin). Cc vi khun trong t
bo cng b c ch vi nng fluoroquinolon huyt tng nh chlamidia, mycoplasma,
brucella, mycobacterium...
2.6.3.Dc ng hc
Acid nalidixic d hp thu qua tiu ha v thi tr nhanh qua thn, v vy c dng lm khng
sinh ng tit niu, nhng phn ln b chuyn ho gan, ch 1/4 qua thn di dng cn hot
tnh.
Cc fluorquinolon c sinh kh dng cao, ti 90% (pefloxacin), hoc trn 95% (gatifloxacin v
nhiu thuc khc), t gn vo protein huyt tng (10% vi ofloxacin, 30% vi pefloxacin). Rt
d thm vo m v vo trong t bo, k c dch no tu. B chuyn ho gan ch m t phn.
Pefloxacin b chuyn ha thnh norfloxacin vn cn hot tnh v chnh n b thi tr qua thn
70%. Thi gian bn thi t 4h (Ciprofloxacin) n 12h (pefloxacin). Nng thuc trong tuyn
tin lit, thn, i thc bo, bch cu ht cao hn trong hu yt tng.
2.6.4. Ch nh
- Nhim khun ng tit niu v vim tuyn tin lit, acid nalixilic, norfloxacin, ciprofloxacin,
ofloxacin, tc dng ging nhau, tng t nh trimethoprim - sulfamethoxazol
- Bnh ly theo ng tnh dc:
.Bnh lu: ung liu duy nht ofloxacin hoc ciprofloxacin
. Nhuyn h cam: 3 ngy ciprofloxacin
. Cc vim nhim vng chu hng: ofloxacin phi hp vi khng sinh chng vi khun k kh
(clindamycin, metronidazol)
- Nhim khun ng tiu ha: do E. coli, S.typhi, vim phc mc trn bnh nhn phi lm thm
phn nhiu ln.
- Vim ng h hp trn v di, vim phi mc phi ti cng ng, vim xoang: cc
fluoroquinolon mi nh levofloxacin, trovafloxacin, gatifloxacin.
- Nhim khun xng- khp v m mm: thng do trc khun gra m (-) v t cu vng, liu
lng phi cao hn cho nhim khun tit niu (500 - 750 mg 2 ln/ ngy) v thng phi ko
di (7- 14 ngy, c khi phi ti 4 - 6 tun)
2.6.5. c tnh
Khong 10%, t nh n nng: bun nn, nn, tiu chy, d ng ngoi da, tng p lc ni s
(chng mt, nhc u, l ln, co git, o gic). Trn tr nh, c acid chuyn ha, au v sng
khp, au c.
Thc nghim trn sc vt cn non thy m sn b hu hoi cho nn khng dng cho tr em di
18 tui, ph n c mang v ang nui con b. Khng dng cho ngi thiu G 6PD.
2.6.6.1. Loi quinolon kinh in , acid nalidixic (Negram): nhim khun tit niu do trc khun
gram (-), tr pseudomonas aeruginosa. Ung 2g/ ngy, chia 2 ln. ng tim t/m ch c dng
trong bnh vin khi tht cn thit.
2.6.6.2. Loi fluorquinolon: dng cho cc nhim khun bnh vin do cc chng a khng khng
sinh nh vim phi, nhim khun huyt, vim mng no, mng tim, nhim khun xng cn iu
tr ko di.
Mt s ch phm ang dng :
Pefloxacin (Peflacin) : ung 800 mg/ 24h chia 2 ln
Norfloxacin (Noroxin): ung 800 mg/ 24h chia 2 ln
Ofloxacin (Oflocet) : ung 400- 800 mg/ 24h chia 2 ln
Ciprofloxacin (Ciflox) : ung 0,5- 1,5g/ 24 h chia 2 ln
Levofloxacin (Levaquin): ung 500 mg
Gatifloxacin (Tequin): ung liu duy nht 400 mg/ 24h
Hin nay fluoroquinolon l thuc khng sinh c dng rng ri v:
- Ph rng
- Hp thu qua tiu ha tt, t nng huyt tng gn vi truyn tnh mch.
- Phn phi rng, c cc m ngoi mch
- t/2 di, khng cn dng nhiu ln
- D dng nn c th iu tr ngoi tr
- R hn so vi iu tr bng khng sinh tim truyn khc.
- Tng i t tc dng khng mong mun
V vy sinh ra lm dng thuc. Nn trnh dng cho cc nhim khun thng thng. H y ginh
cho cc nhim khun nng, kh tr nh: Pseudomonas aeruginosa, t cu vng khng methicilin,
E. coli v khun gram ( -) khng trimethoprim- sulfamethoxazol.
2.7. Nhm 5- nitroimidazol
L dn xut tng hp, t tan tro ng nc, khng ion ha pH sinh l, khuch tn nhanh qua mng
sinh hc. Lc u (1960) dng chng n bo (trichomonas, amip) (xem bi "thuc cha amip"),
sau (1970) thy c tc dng khng khun k kh.
Nitroimidazol c c tnh chn lc trn cc vi khun k kh v c cc t bo trong tnh trng
thiu oxy. Trong cc vi khun ny, nhm nitro ca thuc b kh bi cc protein vn chuyn
electron c bit ca vi khun, to ra cc sn phm c, dit c vi khun, l m thay i cu trc
ca ADN.
Ph khng khun: mi cu khun k kh, trc khun k kh gram ( -), trc khun k kh gram (+)
to c bo t. Loi trc khun k kh gram (+) khng to c bo t thng khng c
thuc (propionibacterium).
2.7.3. Dc ng hc
Hp thu nhanh qua tiu ha, t gn vo protein huyt tng, thm c vo mi m, k c mng
no, t/2 t 9h (metronidazol) n 14h (ornidazol). Thi tr qua nc tiu phn ln di dng cn
hot tnh, lm nc tiu c th b xm mu.
2.7.4. c tnh
Bun nn, sn da, ri lon thn kinh, gim bch cu, h huyt p.
Thng c dng trong vim mng trong tim, apxe no, d phng nhim khun sau phu thut
vng bng- h chu...
C tc dng hip ng vi khng sinh nhm lactam v aminosid.
Metronidazol (Flagyl), ornidazol (Tiberal): ung 1,5g hoc 30 - 40 mg/ kg/ 24h.
(Xin xem thm bi "thuc chng amp")
2.8. Sulfamid
Nm 1935 Domagk pht hin ra tnh khng khun ca mt phm nhum l

sulfamidochrysoidin (Prontosil), t m r a k nguyn ca cc thuc chng nhim khun trc
khi c penicilin.
Sulfamid u l cc cht tng hp, dn xut ca Sulfanilamid do thay th nhm - NH2 hoc
nhm - SO2NH2. L bt trng, rt t tan trong nc, d tan hn tron g huyt thanh v mt.
PABA (para amino benzoic acid) l ngun nguyn liu cn thit cho vi khun tng hp acid folic
pht trin. Do c cu trc ha hc gn ging vi PABA nn sulfamid tranh chp vi PABA
ngn cn qu trnh tng hp acid folic ca vi khun.
Ngoi ra, sulfamid cn c ch dihydrofolat synthetase, mt enzym tham gia tng hp acid folic
(xem s mc 2.9). V vy sulfamid l cht km khun. T bo ng vt c v v vi khun no
c th s dng trc tip acid folic t mi trng th u khng chu nh hng ca sulfamid.
V mt l thuyt, ph khng khun ca sulfamid rt rng, gm hu ht cc cu khun, trc khun
gram (+) v (-). Nhng hin nay, t l khng thuc v khng cho gia cc sulfamid ang rt cao
nn hn ch vic s dng sulfamid rt nhiu. Vi khun khng thuc bng cch tng tng hp
PABA hoc gim tnh thm vi sulfamid.
2.8.3. Dc ng hc
- Cc sulfamid c hp thu nhanh qua d dy v rut (tr loi sulfaguanidin), 70 - 80% liu ung
vo c mu, gn vi protein huyt tng 40 - 80%, nng ti a t c sau 2 - 4h.
- T mu, sulfamid khuch tn rt d dng vo cc m, vo dch no tu (bng 1/2 hoc tng
ng vi nng trong mu), qua rau thai, gy c.
- Cc qu trnh chuyn ha ch yu gan ca sulfamid gm:
. Acetyl ha, t 10- 50% tu loi. Cc sn phm acetyl ha rt t tan, d gy tai bin khi thi tr
qua thn. Cc sulfamid mi c t l acetyl ha thp (6 -16%) v sn phm acetyl ha li d tan.
. Hp vi acid glucuronic (sulfadimethoxin), rt d tan
. Oxy ha
Thi tr: ch yu qua thn (lc qua cu thn v bi xut qua ng thn). Dn xut acetyl ha (25 -
60% trong nc tiu) khng tan, to tinh th c th gy i mu hoc v niu. V vy, cn ung
nhiu nc (1g/ 0,5 lt).
* Phn loi sulfamid: V tc dng ca sulfamid u ging nhau, vic iu tr da vo dc ng
hc ca thuc cho nn ngi ta chia cc sulfamid lm 4 loi:
- Loi hp thu nhanh, thi tr nhanh: nng ti a trong mu sau ung l 2 - 4h. t/2=6-8h,
thi tr 95% trong 24h. Gm sulfadiazin, sulfisoxazol (Gantrisin), sulfamethoxazol (Gantazol).
Dng iu tr nhim khun theo ng mu.
- Loi hp thu rt t: dng cha vim rut, vim lot i trng. Gm sufaguanidin (Ganidan),
salazosulfapyridin (Salazopyrin).
- Loi thi tr chm: duy tr c nng iu tr trong mu lu, t/2 c th ti 7 - 9 ngy nn ch
cn ung 1 ln ngy. Hin dng sulfadoxin (Fanasil), phi hp vi pyrimethamin trong Fansidar
d phng v iu tr st rt khng cloroquin .
- Loi dng ti ch: t hoc kh tan trong nc. Dng iu tr cc vt thng ti ch (mt, vt
bng) di dng dung dch hoc kem. C sulfacetamid, silver sulfadiazin, mafenid.
2.8.4. c tnh
- Tiu ha: bun nn, nn, tiu chy.
- Thn: do sulfamid t tan v cc dn xut acetyl ha kt ta trong ng thn gy cn au bng
thn, i mu, v niu (iu tr, d phng bng ung nhiu nc v base ha nc tiu). Vim
ng k thn do d ng.
- Ngoi da: cc biu hin d ng t nh n rt nng nh hi chn g Stevens- Johnson, hi chng
Lyell. Thng gp vi loi sulfamid chm.
- Mu: thiu mu tan mu (do thiu G 6PD), gim bch cu, gim tiu cu, mt bch cu ht, suy
ty.
- Gan: tranh chp vi bilirubin gn vo protein huyt tng, d gy vng da, c. Khng dng
cho ph n c thai v tr em mi .
Khng dng cho ngi suy gan, suy thn, thiu G 6PD, a tng d ng.
2.8.5. Ch phm cch dng
Do c nhiu c tnh v c khng sinh thay th, sulfamid ngy cng t dng mt mnh.
Thng phi hp sulfameth oxazol vi trimethoprim (xin xem phn sau). Hin cn c ch nh
trong cc trng hp sau:
- Vim ng tit niu:
. Sulfadiazin: vin nn 0,5g
. Sulfamethoxazol (Gantanol): vin nn 0,5g
Ngy u ung 2g 4 ln; nhng ngy sau 1g 4 ln. Ung t 5- 10 ngy
- Nhim khun tiu ha:
. Sulfaguanidin (Ganidan): vin nn 0,5g ung 3 - 4g/ ngy
. Sulfasalazin (Azalin): vin nn 0,5g ung 3 - 4 g/ ngy

- Dng bi ti ch:
. Bc sulfadiazin (Silvaden): 10mg/ g kem bi
2.9. Phi hp sulfamid v trimethoprim
S di y cho thy v tr tc dng ca sulfamid v trimethoprim trong qu trnh tng hp
acid folic. Hai thuc c ch tranh chp vi 2 enzym ca vi khun 2 khu ca qu trnh tng hp
nn c tc dng hip ng mnh hn 20- 100 ln so vi dng sulfamid mt mnh.
Dihydrofolat Dihydrofolat
synthetase reductase
(-) (-)
SUL TMP
ADN
Tng hp
PABA+ Acid Acid purin v
dihydropteridin dihydrofolic tetrahydrofolic pyrimidin
ARN
Hnh 14.5. V tr tc dng ca sulfamid v trimethoprim trong qu trnh
tng hp acid folic
Trimethoprim l mt cht ha hc tng hp c tc dng c ch dihydrofolat reductase ca vi

khun 50.000- 100.000 ln mnh hn trn ngi, v c ch trn enzym ca k sinh trng st rt
2000 ln mnh hn ngi.
Ph khng khun rng v chng khng li t hn so vi sulfamid. C tc dng dit khun trn
mt s chng. Khng tc dng trn Pseudomonas, S.perfringens, xon khun.
2.9.2. Dc ng hc
T l l tng cho hip ng tc dng ca nng thuc trong mu ca sulfamethoxazol (SMZ):
trimethoprim (TMP) l 20: 1. V TMP hp thu nhanh hn SMZ (pic huyt thanh l 2 v 4h) v t/ 2
10h, cho nn nu t l SMZ: TMP trong vin thuc l 5: 1 (800 mg sulfameth oxazol + 160 mg
trimethoprim), sau khi ung, nng trong mu s t c t l 20: 1(40 g/ mL huyt tng
sulfamethoxazol v 2 g/ mL trimethoprim).
C 2 thuc c hp thu qua ng ung, phn phi tt vo cc m (dch no tu, mt, tuyn tin
lit). Thi tr ch yu qua nc tiu vi nng cn hot tnh.
2.9.3. c tnh v chng ch nh
Thuc phi hp ny c tt c cc c tnh ca sulfamid. Ngoi ra, trn nhng ngi thiu folat,
TMP c th gy thiu mu nguyn hng cu khng l, t l b ban cng cao hn.
Khng dng cho ph n c thai v tr em mi (nht l non)
Thuc kt hp c ch nh chnh trong nhim khun tit niu, tai - mi- hng, ng h hp,
ng tiu ha (thng hn, t), bnh hoa liu (clamydia)
- Phi hp trimethoprim + sulfamethoxazol:
. Vin Bactrim, Cotrimoxazol, gm trimethoprim (80 hoc 160 mg) v sulfamethoxazol (400
hoc 800 mg). Liu thng dng l 4- 6 vin (loi 80 mg TMP + 400 mg SMZ), ung trong 10
ngy
. Dch treo: trong 5 mL c 400 mg TMP + 200 mg SMZ. Dng cho tr em.
. Dch tim truyn: TMP 80 mg + SMZ 400 mg trong ng 5 mL. Ho trong 125 mL dextrose 5%
truyn tnh mch trong 60 - 90 pht.
3. mt s vn v s dng khng sinh
3.1. Nguyn tc dng khng sinh
1. Ch dng khng sinh cho nhim khun. Khng dng cho nhim virus (c loi ring). Dng
cng sm cng tt.
2. Ch nh theo ph tc dng. Nu nhim khun xc nh, dng khng sinh ph hp.
3. Dng liu t c nng v n nh. Khng dng liu tng dn.
4. Dng thi gian: trn c th nhim khun, vi khun nhiu giai on khc nhau vi
khng sinh. Nu sau 2 ngy dng khng sinh, st khng gim, cn thay hoc phi hp
khng sinh. Khi iu tr ht st, vn cn cho thm khng sinh 2 - 3 ngy na.
Ni chung, cc nhim khun cp, cho khng sinh 5- 7 ngy. Cc nhim khun c bit, dng lu
hn, nh: vim ni tm mc Osler, nhim khun tit niu (vim b thn): 2 - 4 tun; vim tuyn
nhip h: 2 thng; nhim khun khp hng: 3 - 6 thng; nhim lao: 9 thng...
5. Chn thuc theo dc ng hc (hp thu, phn phi, chuyn ha, thi tr) ph thuc vo
ni nhim khun v tnh trng bnh nhn.
6. Cn phi hp vi bin php iu tr khc: khi nhim khun c m, hoi t m, vt l
(si) th cho khng sinh phi km theo thng m, phu thut.
3.2. Nhng nguyn nhn tht bi trong vic dng khng sinh
1. Chn khng sinh khng ng ph tc dng
2. Khng sinh khng t c ti ngng tc dng ti nhim khun, do liu lng khng
hp l, do dc ng hc khng thch hp, do tng tc thuc lm gim tc dng ca
khng sinh
3. Do vi khun khng thuc. Cn thay khng sinh khc hoc phi hp khng sinh.
3.3. Vi khun khng khng sinh
3.3.1. Khng t nhin: vi khun c tnh khng t trc khi tip xc vi khng sinh, nh sn
xut lactamase, cu trc ca thnh vi khun khng thm vi khng sinh.
3.3.2. Khng mc phi: vi khun ang nhy cm vi khng sinh, sau mt thi gian tip xc, tr
thnh khng nhy cm na, do:
* t bin hoc khng qua nhim sc th.
Mi vi khun u c "protein ch" gn vi kh ng sinh c th ti ribosom, DNA gyrase, RNA
polymerase... Do t bin, cc "protein ch" thay i, khng gn khng sinh na.
*Khng qua plasmid: c nhiu dng. Thng l sn xut cc enzym lm bt hot khng sinh,
hoc gim i lc ca khng sinh vi " protein ch", hoc thay i ng chuyn ha.
Vi khun khng khng sinh c th pht trin s khng cho vi khng sinh trong cng h. Qua
plasmid c th khng nhiu loi khng sinh mt lc. Ngi ln u nu nhim vi khun khng
khng sinh, mc du ch a dng khng sinh bao gi c khng khng sinh ngay.
Loi khng mc phi thng l do dng khng sinh khng ng liu hoc lm dng thuc, ang
gy mt tr ngi rt ln cho vic iu tr.
3.4. Phi hp khng sinh
3.4.1. Ch nh phi hp khng sinh
1. Nhim 2 hoc nhiu vi khun mt lc
2. Nhim khun nng m nguyn nhn cha r
3. S dng tc dng hip ng lm tng hot tnh khng sinh trong mt s nhim khun c
bit:
. Vim ni tm mc: penicilin + streptomycin
. Trimethoprim + sulfamethoxazol
. Khng sinh lactam + cht c ch lactamase
4. Phng nga xut hin vi khun khng khng sinh.
Ch phi hp khng sinh cho mt s t cc trng hp nhim khun trong bnh vin nh cu
khun rut, mt s trc khun gram ( -) (trc khun m xanh, trc khun mt loi Serratia,
Enterobacter, Citrobacter ).
3.4.2. Nhc im ca phi hp khng sinh
Khi thy thuc khng hiu r v phi hp khng ng s:
. D gy khng do s chn la ca vi khun
. Tng c tnh ca khng sinh
. Hip ng i khng
. Gi thnh iu tr cao
Ni chung, nn hn ch phi hp v c khng sinh ph rng
3.4.3. Mt s nhim khun thng gp v cch chn khng sinh.
Bng gii thiu mt s cch la chn khng sinh.

Bng 14.2.La chn khng sinh trong iu tr nhim khun
Vi khun Bnh Thuc c chn

Th nht Th hai Th ba
Cu khun p xe Oxacillin Cephalospori Clindamycin
Gr(+) Nhim khun Nafcillin nI Erythromycin
T cu vng huyt Vancomycin Trim+
Vim ni tm sulfamethoxazol
mc Ciprofloxacin +
Vim phi rifampin
Vim xng-
tu
Lin cu sinh Vim hng Penicilin Cephalospori Erythromycin
m (nhm A) Vim tai gia, Amoxicilin nI Clindamycin
xoang Vancomycin
Vim phi
Nhim khun
huyt
Streptococcus Vim ni tm Penicilin G Ceptriaxon Vancomycin
viridans mc Gentamycin (III)
Nhim khun
huyt
Ph cu Vim phi Penicilin Cephalospori Chloramphenicol
Vim khp Amoxicilin nI macrolid
Vim xoang TMP- SMZ Clindamycin
Vim tai
Cu khun Vim tai Amox+ Cephalospori Ciprofloxacin
Gr(-) Vim xoang clavulanat n II- III Tetracyclin
Moraxella Vim phi Ampi+ Erythromycin
catarrhalis sulbactam
TMP + SMZ
Neisseria Pen. G- Ceft. Cefot. Ciprofloxacin
meningitis Rifampin minocyclin
Trckhun Vim hng Erythromycin Clindamycin Cephalosporrin I
Gr(+) Vim phi Rifampin
Corynebacteriu Vim thanh ph
m qun
diphteriae
CorynebacteriuVim ni tm Penicilin G + Rifampicin +
m species, i mc aminoglycosi penicilin G
kh Nhim khun d Ampicilin +
huyt Vancomycin sullactam
Trc khun Nhim khun TMP- SMZ Pen + c ch Aztreonam
Gr(-) tit niu Ciprofloxacin penicilinase Nitrofurantoin
Escheria coli Ampi+ Aminoglycos Doxycycline
Aminogl id
Proteus Nhim khun Ampi/ Amox Cephalospori Ciprofloxacin hoc
tit niu n Ofloxacin
Aminoglycos
id
Pseudomonas Nhim khun Pen. ph rng Aminoglycos Imipenem
aeruginosa tit niu Ceftazidim id
Ciprofloxacin Aztreonam
Vim phi Pen.ph rng Imipenem + aminogl
Nhim khun Aminoglycos Ceftazidim +
huyt id Aminogl Aztreonam +
Ciprofloxacin aminoglycosid
Salmonella Thng hn Ciprofloxacin Ampicilin Chloramphenicol
Ph thng hn Ceftriaxon
Nhim khun TMP + SMZ
huyt
Shigella Vim rut cp Ciprofloxacin TMP + SMZ Amoxicilin
Hemophilus Vim tai gia TMP + SMZ Cefuroxim Ciprofloxacin
influeuzae Vim xoang Amoxicilin + Amox/ Ampi Azithromycin
Vim phi clavulinat
Vibrio T Doxycyclin TMP + SMZ Chloramphenicol
cholerae Ciprofloxacin
Cu hi t lng gi
1. Trong cc thuc di y, thuc no l khng sinh? Khng sinh dit khun? Khng sinh
km khun?
Penicilin, Streptomycin, Sulfonamid, Iod, Tetracycli n, Erythromycin, Thuc tm (KMnO 4),
Quinolon, Phenol.
2. Hy phn loi nhm lactam theo cu trc ha hc v nu c im.
3. Hy phn tch c ch tc dng v tc dng ca Penicilin v Cephalosporin.
4. Trnh by c ch tc dng v p dng iu tr ca aminoglycos id.
5. Trnh by c ch tc dng v p dng iu tr ca:
- Nhm cloramphenicol
- Nhm tetracyclin
- Nhm macrolid
- Nhm quinolon
- Thuc phi hp sulfamid- trimethoprim
- Nhm 5- nitro imidazol.
6. Hy phn bit c tnh ca cc nhm khng sinh lactam, aminoglycosid,

cloramphenicol, tetracyclin v quinolon.
7. Trnh by 6 nguyn tc s dng khng sinh an ton v hp l.
8. Phn tch cc nguyn nhn tht bi trong vic dng khng sinh v cch khc phc.
Bi 15: thuc khng virus

(Nhm khng virus sao chp ngc)

1. Trnh by c cc giai on pht trin ca virus sao chp ngc v v tr c th tc ng
ca thuc.
2. Trnh by c c ch tc dng v c tnh ca zidovudin, nevirapin v indinavir.
Virus gm c loi 1 hoc 2 chui ADN hoc ARN c bc trong mt v protein gi l capsid.
Mt s virus c c v lipoprotein, v ging nh capsid, v ny c th cha cc protein khng
nguyn. Virus bt buc phi sng k sinh trong t bo vt ch, s sao chp ca chng ph thuc
ch yu vo cc qu trnh tng hp ca t bo vt ch.
- Loi ADN virus nh poxvirus (gy bnh u ma), herpesvirus (gy thu u, herpes, zona),
adenovirus (vim kt mc, vi m hng), hepa AND virus (vim gan B) v papillomavirus (ht
cm). Sau khi thm nhp c vo nhn t bo vt ch, ADN virus c sao m sm vo ARN m
bi ARN m polymerase ca t bo vt ch, ARN m c dch m theo cch thng thng ca t bo
vt ch thnh cc protein c hiu ca virus. Ring virus u ma, do c ARN polymerase
ring nn c th sao chp ngay trong bo tng ca t bo vt ch.
- Loi ARN virus gm rubellavirus (gy bnh si c [German measles], rubeon), rhabdovirus
(bnh di), picoARNvirus (bnh bi lit, vim mng no, cm lnh), arenavirus (vim mng no,
st Lassa), arbovirus (st vng), orthomyxovirus (cm), paramyxovirus (si, quai b).
Vi ARN virus, vic sao chp trong t bo vt ch s da vo hoc l cc enzym trong virion (ht
virus) tng hp ARN m cho n, hoc l ARN virus c dng nh chnh ARN m ca n. ARN m
c dch m thnh cc protein virus, k c ARN polymerase, enzym chi phi s tng hp nhiu
ARNm virus.
Mt nhm ARN virus trong loi ny l retrovirus c cha enzym re verse transcriptase (enzym
sao m ngc), to ADN t ARN virus. Sau , bn sao ADN tch hp vo genom (b gen) ca
vt ch (lc c coi nh provirus) v c sao m thnh c ARN genom v ARN m dch
m thnh cc protein virus (HIV).
Trong nhiu bnh nhim virus, nh im ca s sao chp ca virus l vo ngay trc lc triu
chng lm sng xut hin. V vy, hiu qu iu tr lm sng ti u l phi bt u iu tr sm.
Cc thuc khng virus cn phi: ngn cn s xm nhp ca virus vo t bo v phi c hot tnh
vi virus trong t bo, ngha l phi c tnh c hiu.
Da vo cc bc trong qu trnh sao chp, nhn i ca virus m nghin cu cc thuc khng
virus, theo bng 15.1
Thuc khng virus sao chp ngc (Antiretroviral agents): thuc chng HI V.
HIV (human immunodeficiency virus) l virus sao chp ngc. ARN tn cng vo cc t bo
lympho CD 4, i thc bo v t bo thn kinh si nhnh (dendritic cells). Nghin cu vng i
ca HIV trong t bo chnh l tm mc tiu tc ng ca thuc.
Hnh 15.1 di y trnh by cc giai on pht trin ca HIV v mc tiu c th tc ng ca

thuc.
Bng 15.1: Cc giai on sao chp ca virus v mc tiu tc ng

ca thuc chng virus
Giai on sao chp Cc nhm thuc
- Bm dnh v xm nhp
Bm dnh - By receptor ha tan, khng receptor khng
th c ch protein kt hp.
Xm nhp
- Chn knh ion, cht lm vng bn mng
- Tho v
capsid
Gii phng genom ca virus
c ch cc enzym ca virus: ADN polymerase,
- Sao m ca genom virus ARN polymerase, reverse transcriptase,
helicase, primase hoc integrase.
- Interferon, antisense oligonucleotid ribozym.
- Dch m ca protein virus - Cc cht c ch protein iu ha
Cc protein iu ha (sm)
Cc protein cu trc (mun) - Cc cht c ch protease
- Thay i sau dch m - Interferon, cc cht c ch protein tp hp
- Tp hp cc thnh phn ca Cht c ch neuraminidase, khng th khng
virion virus.
- Thot khi t bo vt ch
Hnh 15.1. Qu trnh pht trin

ca HIV trong t bo vt ch
1) Virus gn vo cc receptor CD 4
2) Ha mng v thot v ca virus
3) Sao chp ngc t ARN
ADN 4) Tch hp ca ADN virus
vo ADN vt ch
5) Sao m mun hay s tng hp
protein ca virus
6) Lp rp hay t hp li ca
virus v ny chi; : ARN virus;
. ARN v enzym reverse
transcriptase.
Qua hnh trn, v l thuyt, c th nghin cu cc thuc tc ng vo cc khu sau:

- Ngn cn virus gn vo cc receptor t bo (1)
- Ngn cn s ha mng v thot v ca virus (2)
- Km hm s sao chp ngc t ARN (3)
- Ngn cn s tch hp ca ADN virus vo ADN ca t bo vt ch (4).
- Ngn cn s sao m mun hay s tng hp protein ca virus (5)
- Km hm s lp rp hay s t hp li ca virus v s ny chi (6).
mi giai on trn u c nhn g c ch c hiu v nhng enzym c hiu ring cho HIV, v
nh vy c th tm ra cc thuc c ch thch hp cho tng giai on. Tuy nhin, do nhiu kh
khn, cc nghin cu hin nay phn ln tp trung vo cc loi thuc c ch enzym sao chp
ngc (reverse transcriptase- RT), protease v integrase.
RT l enzym c tc dng chuyn mch n ARN ca HIV thnh mch kp ADN (giai on 3
trn s ) trc khi xm nhp vo nhim sc th ca t bo vt ch. Thuc c ch RT c 2 loi:
- Thuc c ch nucleosid revers e transcriptase (NRTI): tc dng rt sm giai on sao chp ca
HIV, ngn cn nhim khun cp tnh ca t bo, rt t tc dng trn t bo nhim HIV. Cc
thuc ny u l tin thuc, c cu trc tng t nh mt thnh phn cu to ca ADN nhng
phi c enzym bo tng ca t bo vt ch phosphoryl ha mi tr nn c hot tnh l nhm
thuc quan trng nht trong cng thc phi hp thuc iu tr HIV.
- Thuc c ch nonnucleosid reverse transcriptase (NNRTI): Thuc c ch enzym sao chp
ngc khng phi nucleosid l thuc tng hp c kh nng gn vo cnh v tr tc ng ca RT,
lm thay i hnh dng ca v tr ny nn enzym b mt hot tnh. Thuc khng cn qua giai on
phosphoryl ha nh NRTI v ch c tc ng trn HIV - 1. Tt c u chuyn ha gan qua Cyt.
P450, gy cm ng enzym nn lm tng chuyn ha ca chnh n (phi tng liu khi dng ko di)
v mt s thuc dng cng.
Integrase l enzym c tc dng gm ADN ca provirus vo nhim sc th ca t bo vt ch. Nu
c ch c enzym ny s lm HIV khng nhn ln c trong t bo k sinh v s b tiu dit.
Hin cn l bc nghin cu phng th nghim.
Cc protease l cc enzym tham gia trong qu trnh tng hp nhiu protein cu trc ca li virus
v cc enzym ch yu, trong c c RT v chnh bn thn protease. c ch protease th HIV ch
l cc virion (ht virus) khng trng thnh v khng gy bnh c. V vy, hng nghin cu
ny rt hp dn.
Trong vng i ca HIV, cc enzym tc ng nh sau:
. Mch n ARN RT mch kp ADN
integrase
. ADN virus nhp vo ADN vt ch
. ADN ho nhp c ch phin m bnh ARN mi ca virus

(provirus)
thng ca t bo vt ch
protease
protein ca virus
Cc thuc chng HIV ang c dng (bng 15.2) hin cn rt t v nhiu thuc cn ang
giai on th lm sng.
Bng 15.2: Cc thuc chng HIV
Tn gc Tn thng mi Hiu qu khng HIV

c ch nucleosid
reverse transcriptase(NRT)
Zidovudin AZT, Retrovir, Videx EC ++
Didanosin ddI, Videx ++
D4T, Zerit ++
Stavudin ddC, Hivid +

Zalcitabin 3 TC, Epivir ++
Lamivudin
c ch nonnucleosid
reverse transcriptase (NNR T) Viramune +++
Nevirapin Sustiva +++
Efavirenz
c ch protease Invirase, Fortovase ++
Saquinavir Crixivan +++
Indinavir Norvir +++
Ritonavir Viracept +++
Nelfinavir Agenerase +++
Amprenavir Kaletra +++
Lopinavir
Cc thuc ny phn ln cn ang c nghin cu v nh gi trn lm sng. Di y l mt s
thuc i din, hin c Vit Nam.
1. Thuc c ch NRT
1.1. Zidovudin (azidothymidin, AZT)
Zidovudin l cht tng hp tng t thymidin, lc u chng ung th (Horwitz - 1964), sau
thy c tc dng chng virus (Ostertag, 1974) v n 1985 th Mitsuya ln u tin thy c tc
dng c ch c HIV-1 in vitro
1.1.1. C ch tc dng
Sau khi nhp vo t bo, zidovudin cng phi c phosphoryl ha 3 ln thnh zidovudin 5 -
triphosphat mi c hot tnh. Trong t bo, dng hot tnh c t/2 3 gi. Zidovudin 5-
triphosphat c ch tranh chp vi deoxythymidin triphosphat ca RT. Ngoi ra cn tranh chp vi
thymidin triphosphat tch hp vo ADN provirus, lm kt thc sm chui ADN, to ra ADN
provirus khng hon chnh. In vitro, zidovudin chng c HIV - 1, HIV- 2 v cc virus hng
lympho T (T cell lymphotropic viruses) ca ngi.
1.1.2. Dc ng hc
Hp thu nhanh qua tiu ha v phn b vo mi m, nng trong dch no tu bng 60% trong
huyt tng. Sinh kh dng khong 65%; t/2 huyt tng l 1,1 gi, nhng dng hot tnh trong
t bo c t/2 3 gi. Thi tr 90% qua thn di dng chuyn ha v khng chuyn h a.
- c tnh chnh l thiu mu thng xy ra trong 4 tun u (7%), gim bch cu (37%), gim
tiu cu.
- Cc tc dng khng mong mun khc l nhc u, mt ng, chn n, bun nn, mt mi, au
c xy ra trong vi tun u. Dng thuc cha triu chng.
- Tc dng ph xut hin chm hn, sau 6 - 17 thng l t sc t cc mng, cn co git, hi
chng ging vim nhiu c.
- Cc thuc c ch phn ng glucuronyl transferase gan (phn ng ging ha AZT) nh
acetaminophen, aspirin, in dometacin, probenecid s lm tng tai bin c tnh v mu ca AZT
nn cn trnh dng chung.
Ung 200 mg, cch 8 gi/ ln; hoc 100 mg 5 ln/ ngy. Dng lin tc. C th phi hp vi
thuc c ch RT khc hoc thuc c ch protease.
Ch phm: AZT, Retrovir vin nang 100 mg; l 200 mg/20 mL.
1.2. Didanosin (ddI)
Didanosin (2', 3' dideoxy inosin - ddI) l cht tng t nucleosid purin, c nghin cu t 1989
v dng iu tr t cui nm 1991. Tc dng c trn HIV - 1 v HIV- 2.
1.2.1. C ch tc dng
Sau khi thm nhp vo t bo, di tc dng ca enzym chuyn ha ni bo, didanosin c 3
ln phosphoryl ha thnh dng c hot tnh l dideoxyadenosin triphosphat (dd ATP), tranh
chp vi dATP (deoxyadenosin triphosphat) c ch RT ca virus, ng t hi ngn cn ko di
chui ADN, ngn cn tng hp ADN provirus.
1.2.2. Dc ng hc
Didanosin b ph hu nhanh mi trng acid, v vy mi ch phm ung u cha cht trung
ha pH ca dch v. Cn ung lc i. Ung sau ba n, lm gim hp thu ti 50%. Nng nh
huyt tng ca liu ung 300 mg l 1 g/ mL. Nng trong dch no tu bng 20% nng
huyt tng. Thi gian bn thi l 0,6 - 1,5 gi, nhng t/2 trong t bo ca ddATP l 8 - 24 gi
nn ch cn ung 2 ln/ ngy. Thi tr qua thn.
- Vim ty v vim thn kinh ngoi bin thng gp nht, lin quan n liu dng, nht l khi
liu > 12,5 mg/ kg. T l thng gp l 6 - 28%.
- Tiu chy: 17%, gn 2% l trng hp nng
- Cc ri lon khc: khong 2% gm bun nn, nn, st, rt run, nhc u, au c, i acid uric...
- Mt s ri lon sinh ha - huyt hc gim bch cu, gim tiu cu, thiu mu, tng
transaminase. Khng lin quan n liu iu tr.
1.2.4. Ch nh, liu lng
Dng cho tr em trn 6 thng tui v ngi ln b nhim HIV k hng dung np vi AZT hoc
dng AZT 4 thng nhng bnh t thuyn gim.
Ngi ln: 200 mg 2 ln/ ngy. Gim liu nu nh cn.
Tr em, da theo din tch c th:
0,8- 1,2 m2 : 75 mg 2 ln/ ngy

0,5- 0,7 m2 : 50 mg 2 ln/ ngy
Phi ung lc i, trc ba n 1 gi. Nhai nt vin thuc hoc ha vo nc cho tht tan ri
ung ngay.
Didanosin (Videx) vin nn 25, 50, 100, 150 mg; bt ho tan dng cho tr em: 100, 200 mg.
2. Thuc c ch NNRT
Nevirapin
2.1. C ch tc dng: Nevirapin khuch tn vo trong t bo , gn vo RT, lm thay i hnh
dng v bt hot enzym. Tc ng mnh trn HIV - 1, k c cc virion ngoi t bo.
2.2. Dc ng hc. D hp thu qua ng tiu ha, thm c qua rau thai v sa. Nng
trong dch no tu bng 45% nng huyt tng. Thi gian bn thi l 25- 30 gi.
Chuyn ha gan qua cytocrom P 450.
2.3. Tc dng khng mong mun: pht ban, st, nhc u ng g v tng transaminase.
2.4. Liu lng: Nevirapin (Viramune) vin 200 mg 1- 2 vin/ ngy.
3. Thuc c ch protease
3.1. Indinavir
c ch c hiu HIV- 1 protease
Dng kt hp vi mt thuc c ch RT lm chm khng thuc. Ung 800 mg, cch 8 gi ung
1 ln; c hp thu tt, nn ung cch ba n 2 gi. Vin 200, 400 mg.
Tc dng khng mong mun: tng bilirubin mu, si thn (nn ung nhiu nc), bun nn, tiu
chy, gim tiu cu. Indinavir c ch mnh cytochrom P 450 nn c tng tc vi nhiu thuc
chuyn ha qua cytochrom ny.
3.2. Ritonavir
c ch c hiu HIV- 1 protease
Sinh kh dng 60- 80%. Ung liu 600 mg 12 gi/ ln.
Tc dng khng mong mu n: ri lon tiu ha, t b, tng transaminase, tng triglycerid mu.
Cng c ch mnh cytochrom P 450 nh indinavir nn c tng tc vi nhiu thuc.
Ritonavir (Norvir): vin nang 100 mg, dung dch ung 80 mg/mL.
Nguyn tc s dng thuc chng HIV
Sau nhiu nm theo di iu tr, WHO a ra mt s khuyn co sau:
- Cc liu php iu tr phi theo hng dn ton quc. Liu php hng u c th l:
AZT + 3 TC + Nevirapin
AZT + 3 TC + Nelfinavir
AZT + 3 TC + Lopinavir/ indinavir/ Saquinavir
- S dng 2 thuc khng cn c coi l thch hp.

- S tun th c ngha quan trng hn s la chn thuc.
- Ph n mang thai v tr nh cng phi c iu tr phi hp thuc ti u.
cu hi t lng gi
1. Trnh by cc giai on pht trin trong t bo vt ch c a virus sao chp ngc (HIV)
v cc v tr c th tc ng ca thuc.
2. So snh c ch tc ng v c tnh ca zidovudin, nevirapin v indinavir.
Bi 16: Thuc khng nm

1. Trnh by c c ch tc dng, tc dng v c tnh ca nhm thuc chng nm ton
thn: amphotericin B, griseofulvin.
2. Trnh by c c ch tc dng, dc ng hc v c tnh ca 3 thuc trong nhm azol.
Thnh cng ca khng sinh chng vi khun v virus dn n s tng ng k t l nhim nm.
Nhim nm thng c chia lm 2 loi, nhim nm ton thn v nhim nm ngoi da, nim
mc. Cc thuc chng nm v th cng c chia lm 2 loi, ton thn v ti ch. Nhng thc ra
thuc ton thn cng c tc dng ti ch v ngc li.
1. Thuc chng nm ton thn
1.1. Amphotericin B
1.1.1. c im: Amphotericin c tm ra t nm 1956 (Gold) l mt trong s 200 cht thu c
h khng sinh polyen macrolid, khng tan trong nc, v vy thuc tim dng di dng dch
treo.
Tc dng trn cc loi Candida albicans v Cryptococcus neoformans, Blastomyces dermatitidis,
Histoplasma capsulatum, Coccidioides immitis, Aspergillus.
Amphotericin B gn vo ergosterol ca vch t bo nm, to nn cc ng dn lm r r cc ion v
cc phn t nh t trong t bo nm ra ngoi, gy cht t bo. Sterol ca vch t bo nm l
ergosterol, cn sterol chnh ca vch vi kh un v t bo ngi li l cholesterol, v vy
amphotericin B khng c tc dng dit khun v khng c vi ngi.
1.1.3. Dc ng hc
Khng hp thu qua ng ung. Gn vo protein huyt tng ti 95%, ch yu vo -lipoprotein.
Ch dng ng truyn tnh mch, thm nhiu vo cc m gan, lch phi, thn. Nng trong
dch bao khp bng khong 2/3 nng huyt tng, nhng ch 2 -3% vo c dch no tu.
Thi gian bn thi khong 15 ngy. Thi tr chm qua thn trong vi ngy.
1.1.4. c tnh
- c tnh lin quan n vic truyn thuc: run, st, nn, nhc u, h huyt p. Cn gim tc
truyn hoc gim liu. C th lm test bng tim 1mg vo tnh mch. Dng thuc h st, khng
histamin hoc corticoid trc khi truyn.
- c tnh mun:
Tn thng ng thn, tng ur-huyt (80%), toan huyt, tng thi K +, Mg++. Truyn dung dch
NaCl 0,9% c th lm gim c tnh cho thn.
Ngoi ra c th thy bt thng test chc phn gan, thiu mu do gim sn xut erythropoietin
ca thn.

- Amphoterincin B (Fungizon) tim, truyn tnh mch. L 50 mg bt ng kh pha thnh dch
treo trong glucose 5%, truyn 0,5 -0,6mg/kg trong 4gi.
- Vin nn 100 mg. Ngm (nm ming) hoc ung (nm rut) 1 - 4 vin/ ngy.
- Kem bi 3%.
1.2. Flucytosin
1.2.1. c im
Flucytosin (5-FC) c tm ra nm 1957 trong khi nghin cu cc thuc chng ung th (gn
ging 5-FU). Flucytosin d tan trong nc, ph khng nm hp hn amphotericin B v khng c
tc dng chng ung th.
Ch c tc dng trn Cryptococcus neoformans v vi loi candida. V c tc dng hip ng vi
thuc chng nm khc nn thng c dng phi hp trnh khng thuc.
Flucytosin c nhp vo t bo nm nh enzym cytosin permease. Trong t bo, 5 -FC c
chuyn thnh 5-FU (5 fluorouracil), sau thnh 5 fluorodeoxyuridin monophosphat (F -dUMP)
c ch tng hp DNA, v thnh fluorouridin tri phosphat (FUTP) c ch tng hp RNA. T bo
ngi v t bo ng vt c v khng chuyn c 5 -FC thnh 5-FU, v th 5-FC c tc dng
chn lc trn nm.
1.2.3. Dc ng hc
Hp thu d dng qua ng tiu ha (>90%), t pic huyt tng sau 1 -2gi, t gn vo protein
huyt tng, thm d vo cc dch trong c th, vo dch no tu vi nng bng 65 -90% nng
huyt tng. Thi qua thn 80% di dng khng chuyn ho. Thi gian bn thi l 3 -6gi,
ngi suy thn, c th ko di ti 200 gi.
1.2.4. c tnh
C kh nng l vi khun rut chuyn ho flucytosin thnh hp cht c, gy c ch tu xng,
dn n thiu mu, gim bch cu , gim tiu cu, ri lon chc nng gan (5%) ri lon tiu ho
(nn, tiu chy).
1.2.5. Ch phm
Ancobon: vim nang 250 -500mg. Ung 100-150mg/kg/ngy chia lm 4ln. Dng phi hp vi
amphotericin B (0,3mg/kg/ngy) cha nm Candida.
Khng dng dng tim.
1.3. Nhm azol: Imidazol v Triazol
1.3.1. c im
Imidazol v triazol u thuc nhm azol chng nm, c cng c ch v cng ph tc dng.
Triazol dng ng ton thn chm b chuyn ho v t tc dng trn tng hp sterol ca ngi
hn l imidazol. V vy, cc dn xut mi u phn ln l t triazol ch khng phi t imidazol.
Vic tm ra azol (1980) l mt bc tin quan trng trong nghin cu thuc chng nm.
X = C: Imidazol: ketoconazol, miconazol,

clotrrimazol
X = N: Triazol; itraconazol, fluconazol
Nhn triazol
Ph tc dng rng, gm: cc loi Candida, Cryptococcus neoformans, Blastomyces dermatitidis,
cc bnh nm da.
Cc azol c ch enzym cytochrom P 450 ca nm nn lm gim tng hp ergosterol ca vch t
bo nm, km hm s ln ln v pht trin ca nm.
1.3.3. Dc ng hc, c tnh v p dng
Ba thuc thng dng ca nhm azol l:
1.3.3.1. Ketoconazol (Nizoral)
- Ung d hp thu, nhng cn mi trng acid (nu dng cng khng H 2 s lm gim hp thu
mnh). Gn vo protein huyt tng 84%, vo hng cu 15%, cn 1% dng t do. Thi gian
bn thi tng theo liu, ung 800mg th t/2 = 7 -8gi. Vo dch no tu bng 1% liu dng.
- c tnh: Km fluconazol v itraconazol l c ch c cytocrom P450 ca ng vt c v nn
dn n 2 hu qu:
. Lm cn tr sinh tng hp hormon thng thn, sinh dc, n ng gy chng v to, gim tnh
dc; ph n gy lon kinh nguyt, v sinh.
. Lm tng c tnh ca thuc kt hp cng chuyn ho qua P450.
Ngoi ra cn gp bun nn, chn n (20%), d ng (4%) tng transferase (5 -10%).
V th khng dng liu cao.
- Ch nhv liu dng:
Vin 200mg, kem bi 2%.
Candida m o: ung 400mg/ngy 5 ngy
Candida thc qun: ung 400mg/ngy 10-14 ngy
Histoplasmosis, blastomycosis: 400mg/ngy 6-12 thng.
Khng dng khi c thai v ang nui con bng sa m.
1.3.3.2. Itraconazol (Sporanox, Sporal)
Ph rng, t c hn ketoconazol v ch c ch cytochro m P450 c hiu ca nm.
- Hp thu qua ng ung khong 30%, hp thu ti a ngay sau khi n. Pic huyt tng sau 3 -4
gi, t/2 khong 1-1,5 ngy. Gn vo protein huyt tng ti 99,8%. Gn vo cc m sng (da,
mng) vi nng cao hn huyt tng 4ln v gi rt lu t vi tun n vi thng sau ngng
iu tr. Nng trong m mm (phi, thn, gan, lch) cng cao hn huyt tng 2 -3 ln.
- Ch nh v liu lng:
Vin nang 100mg, ung ngay sau ba n.
. Candida m o: Ung 1 ngy duy nht 400mg chia 2 l n, hoc 200mg/ngy3 ngy.
. Nm da, lang ben: ung 200mg/ngy 7 ngy.
. Candida ming: 100mg/ngy 15 ngy.
. Nm mng: ung 2 t cch nhau 3 tun. Mi t 7 ngy. Mi ngy ung 400mg chia 2 ln.
1.3.3.3. Fluconazol (Flunaz, Diflucan, Triflucan)
C gn thm 2 nguyn t Fluo.
- Ung hp thu hon ton, khng chu nh hng ca thc n hay acid dch v. Rt tan trong nc
nn c th tim tnh mch. Nng trong huyt tng ca ng ung gn bng ng tim tnh
mch. Gn vo protein huyt tng 11 -12%, t/2 = 25 gi, khong 90% thi qua thn di dng
khng i. Thm vo mi dch ca c th, nng trong dch no tu t 50 - 90% nng
huyt tng.
- Thuc d dung np. C th gp phn ng d ng.
- Ch nh v cch dng:
Vin nang 50, 100, 150 mg. Li u 100 - 400mg/ngy.
L 200 - 400 ml, cha 2mg/ml.
Candida nim mc (ming, m o), nm da, nm mng, nm Cryptococcosis (mng no, phi,
da), nhim nm trong AIDS (lm tng sinh kh dng ca Zidovudin khong 20% v lm gim
chuyn ha Zidovudin).
Thi gian iu tr tu tng loi nm, tng t itraconazol.
Khng dng cho ph n c thai hoc ang cho con b.
Khng dng cho tr di 16 tui v l thuc mi, cha s liu theo di.
1.4. Griseofulvin
1.4.1. c im
Khng sinh ly t nm Penicillium griseof ulvum, khng tan trong nc, vng bn vi nhit.
Tc dng trn nm da, biu b, tc, mng: Microsporum, Epidermophyton v Trichophyton.
Khng c tc dng trn vi khun.
Griseofulvin gn vo protein tiu qun, lm gy thoi phn bo nn km hm s pht trin ca
nm.
1.4.3. Dc ng hc
Hp thu qua tiu ha thay i theo dng thuc v thc n.

Ch phm siu vi tinh th (ultramicrocristalline preparation) c sinh kh dng gp ri loi bt vi
tnh th. Thc n c m s d hp thu v thuc khng tan trong nc. t pic sau 4 gi v t/2 = 24
gi. Thuc tch lu trong t bo tin thn ca keratin lm n khng li s xm nhp ca nm, do
tc, mng mi mc s khng b bnh.
1.4.4. c tnh
Thng nh: nhc u (15%), vim thn kinh, ng g, khng lm c vic kho lo, mt mi,
nhn m, ri lon tiu ha...
1.4.5. Ch phm, liu dng
Griseofulvin (Fulvicin, Grisactin) vin nang 125 -250 mg; vin nn 250-500mg.
Liu tr em 10mg/kg; ngi ln 0,5 - 1,0 g.
Thi gian iu tr t nht l 1 t hng cho bnh nm tc v 6 -9 thng cho bnh nm mng.
2. Thuc chng nm ti ch
2.1. Nystatin
Nystatin l khng sinh macrolid, tng t amphotericin B c v cu trc v c ch tc dng,
nhng c hn nn ch dng ngoi v khng hp thu qua da hoc m o.
Tc dng iu tr cc loi nm Candida nim mng v k da.
Nystatin (Mycostatin, Nilstrat), dng pomat, kem bi, thuc bt, dng phun, cha 100.000 n
v/g. Bi 2 - 3 ln/ngy 7 ngy.
2.2. Clotrimazol v miconazol
Thuc nhm azol dng ngoi. Bi ngoi da ch hp thu 0,5%; bi m o, hp thu 3 - 10%.
Dng thuc: Kem 1%, thuc ra, dung dch (Lotrimin, Mycelex), vin nn t m o 100 - 500
mg, thuc phun 2%.
Nm da: bi 2 ln/ngy.
Nm m o: t vin 500mg/ngy; kem 5g/ngy, dng trong 7 - 14 ngy.
Nm ming: vin ngm 10mg 5 ln/ngy.
Cu hi t lng gi
1. Trnh by c ch tc dng v c tnh ca amphotericin B v griseofulvin.
So snh ketoconazol, itraconazol v fluconazol v dc ng hc, c tnh v p dng iu tr.
Bi 17: Thuc chng lao - thuc iu tr phong

1. Trnh by c 5 thuc chng lao thng dng v cc mt tc dng, c ch tc dng,
nhng im chnh v dc ng hc v tc dng khng mong mu n.
2. Trnh by c nguyn tc v phc iu tr lao hin nay.
3. Trnh by c tc dng, c ch tc dng, nhng im chnh v dc ng hc v tc
dng khng mong mun ca dapson v clofazimin.
4. Nu c 3 nguyn tc v phc iu tr phong hin nay.
1. Thuc chng lao
Lao l bnh nhim khun ph bin do trc khun lao gy nn v c th cha khi hon ton.
Trc khun lao gy bnh lao phi v cc c quan khc l loi vi khun khng cn, khng acid,
sng trong mi trng a kh, pht trin chm (chu k ph n chia khong 20 gi).
Mng t bo ca trc khun lao c cu to bi 3 lp: phospholipid trong cng, polysACharid
lin kt vi peptidoglycan. Cc peptidoglycan c gn vi arabingolactose v acid mycolic lp
gia. Acid mycolic lin kt vi cc lipid p hc tp nh myosid, peptidoglycolipid,
phenolglycolipid ngoi cng.
dy, mng v s cha nhiu hay t lipid ca mng t bo nh hng r rt n s khuych tn
ca cc thuc chng lao vo trong t bo v sc khng ca vi khun vi cc tc nhn ha hc
v l hc t bn ngoi.
Trong c th, vi khun lao c th tn ti di 4 dng qun th nhng vng tn thng khc
nhau. Cc qun th ny chu s tc ng ca thuc chng lao mc rt khc nhau.
- Qun th trong hang lao cn gi l qun th A. Trong hang lao c pH trung tnh, lng oxy di
do, vi khun nm ngoi t bo v pht trin nhanh, mnh nn s lng vi khun nhiu, d xut
hin t bin khng thuc. Qun th ny b tiu dit nhanh bi rifampicin, INH v streptomycin.
- Qun th trong i thc bo cn gi l qun th B. Trong i thc bo pH acid, s lng vi
khun t v pht trin chm nhng c kh nng sng st cao nn tn ti dai dng gy nguy c ti
pht bnh lao. Pyrazinamid c tc dng tt nht vi qun th ny. Rifampicin c tc dng, I NH
rt t tc dng cn streptomycin khng c tc dng vi loi qun th ny.
- Qun th nm trong b u gi l qun th C. b u l vng rt t oxy, c pH trung tnh,
vi khun chuyn ha tng t ngn nn pht trin rt chm, ch c rifampicin c t c dng vi
qun th vi khun ny.
- Qun th nm trong cc tn thng x, vi ha gi l qun th D. S lng vi khun lao khng
ln khng pht trin c gi l trc khun ng. Cc thuc chng lao khng c tc dng trn
qun th vi khun ny.
Mc tiu quan trng trong iu tr lao l dng cc thuc tiu dit tt c cc qun th, c bit
l qun th B, C. Ngoi ra, tu theo th bnh c th dng mt s phng php iu tr thch hp
nh phu thut, ct lc, b bt hoc chc ht v.v...
Hin nay thuc chng lao c chia thnh 2 nhm:
Nhm I: L cc thuc chng lao chnh thng dng, c ch s iu tr cao, t tc dng khng
mong mun : isoniazid (INH, Rimifon), rifampicin, ethambutol, streptomycin v pyrazinamid.
Nhm II: L nhng thuc t dng hn, d ng thay th khi vi khun lao khng thuc, c phm vi
iu tr hp, c nhiu tc dng khng mong mun: ethionamid, para -aminosalicylic (PAS),
cycloserin, amikacin, kanamycin, capreomycin, thiacetazon, fluorquinolon v azithromycin,
clarythromycin.
1.1. Cc thuc chng lao thng dng
1.1.1. Isoniazid (Rimifon, INH, H)
L dn xut ca acid isonicotinic, va c tc dng km khun, va c tc dng dit khun.
Nng c ch ti thiu i vi trc khun lao 0,025 - 0,05 mcg/ml. Khi nng cao trn
500mcg/ml, thuc c tc dng c ch s pht trin ca cc vi khun khc. Thuc c tc dng trn
vi khun ang nhn ln c trong v ngoi t bo, k c trong mi trng nui cy.
1.1.1.1. C ch tc dng:
Mc d isoniazid c s dng iu tr lao vi thp k v n nay vn c coi l thuc s
mt trong iu tr tt c cc th lao nhng c ch tc dng ca thuc vn cn cha c gii thch
y . Theo Takayama v cng s (1975), acid mycolic l mt thnh phn quan trng trong cu
trc mng ca trc khun lao. Giai on u ca qu trnh tng hp mycolic l s ko di mch
ca acid nh desaturase. Vi nng rt thp ca INH, enzym ny b c ch lm ngn cn s ko
di mch ca acid mycolic dn dn gim s lng lipid ca mng vi khun, vi khun khng pht
trin c.
Ngoi ra, mt s tc gi cn cho rng, INH to chelat vi Cu 2+ v c ch cnh tranh vi
nicotinamid v pyridoxin lm ri lon chuyn ha ca trc khun lao.
1.1.1.2. Dc ng hc
Thuc c hp thu nhanh qua ng tiu ha. Sau khi ung 1 -2 gi, nng thuc trong mu
t ti 3-5mcg/ml. Thc n v cc thuc cha nhm lm gim hp thu thuc.
Isoniazid khuch tn nhanh vo cc t bo v cc dch mng phi, dch c trng v nc no
tu, cht b u, nc bt, da, c. Nng thuc trong dch no tu t ng ng vi nng
trong mu.
Thuc c chuyn ha gan nh phn ng acetyl ha, thu phn v lin hp vi glycin. S
acetyl ha ca isoniazid thng qua acetyltransferase c tnh di truyn.
ngi c hot tnh enzym mnh, thi gian bn thi ca thuc khong 1 gi, nhng ngi c
hot tnh enzym yu thi gian bn thi ca thuc khong 3 gi.
Thuc c thi tr ch yu qua thn. Sau dng thuc 24 gi, thuc thi tr khong 75 - 95%
di dng chuyn ha. Gn y, mt s tc gi cho rng dng acet yl ha ca INH c kh
acetyl trong c th to thnh dng cn hot tnh.
- D ng thuc, bun nn, nn, chng mt, to bn, kh ming, thoi ho bch cu ht, thiu
mu.
- Vim dy thn kinh ngoi vi chim 10 - 20%, c bit hay gp bnh nhn dng liu cao, ko
di, nghin ru, suy dinh dng v tng glucose mu. Vitamin B6 c th lm hn ch tc dng
khng mong mun ny ca isoniazid.
- Vim dy thn kinh th gic.
- Vng da, vim gan v hoi t t bo gan thng hay g p ngi trn 50 tui v nhng ngi c
hot tnh acetyltransferase yu. C ch gy tn thng gan ca isoniazid n nay vn cha c
gii thch y . C gi thuyt cho rng, acetylhydrazin cht chuyn ha ca isoniazid b
chuyn ha qua cytocrom - P450 sinh ra gc t do gy tn thng t bo gan.
Mt s thuc gy cm ng cytocrom - P450 nh phenobarbital, rifamycin gy tng tn thng gan
ca INH.
- Isoniazid c ch s hydroxyl ha ca phenytoin, c th gy ng c phenytoin khi iu tr phi
hp thuc.
- Rimifon: vin nn 50 - 100 - 300 mg; ng tim 2ml cha 50mg hoc 100mg/ml; Siro 10
mg/ml.
- Phi hp vi cc thuc chng lao khc iu tr tt c cc th lao. Ngi ln dng 5mg/kg th
trng, tr em 10-20mg/kg th trng, ti a 300mg/24 gi.
- Thuc c th dng d phng cho nhng ngi c test tuberculin dng tnh hoc bnh nhn
sau iu tr tn cng bng cc thuc chng lao. Ngi ln dng 300mg/ 24 gi, tr em 10mg/kg
th trng, ti a 300mg/24 gi ko di 3 - 6 thng. Khi iu tr, cn dng km vitamin B 6 10-
50mg /24 gi gim bt tc dng khng mong mun ca INH.
1.1.2. Rifampicin (RMP,R)
Rifamycin l t ch c mt h khng sinh c cu trc ging nhau c chit xut t Streptomyces
mediterranei. Rifampicin l khn g sinh bn tng hp t rifamycin B c tc dng dit khun c
trong v ngoi t bo, chuyn ha v thi tr chm so vi cc cht cng nhm.
1.1.2.1. Tc dng
Thuc khng ch c tc dng dit trc khun lao, phong, m cn dit c cc vi khun gram m,
E-coli, trc khun m xanh, Haemophilus influenzae, Nesseria meningitis.
Rifampicin dit vi khun c trong v ngoi t bo. Trong mi trng acid, tc dng ca thuc
mnh gp 5 ln.
1.1.2.2. C ch tc dng
Rifampicin gn vo chui ca ARN - polymerase ph thuc ADN ca vi khun lm ngn cn
s to thnh chui ban u trong qu trnh tng hp ca ARN. Thuc khng c ch ARN -
polymerase ca ngi v ng vt liu iu tr. Khi dng liu cao gp nhiu ln liu iu tr,
thuc c th gy c ch ARN - polymerase ty th t bo ng vt.
1.1.2.3. Dc ng hc
Thuc c hp thu tt qua ng tiu ha. Sau khi ung 2 - 4 gi, t c nng ti a trong
mu. Acid amino salicylic lm chm hp thu thuc.
Trong mu, thuc gn vo protein huyt tng khong 75 - 80%. ng thi tr ch yu ca

thuc l qua gan v thn. Ngoi ra, thuc cn thi tr qua nc bt, m, nc mt, lm cho cc
dch ny c mu da cam. Thi gian bn thi ca thuc khong 1,5 - 5 gi. Khi chc nng gan
gim, thi gian bn thi ca th uc ko di. Ngc li, do t gy cm ng h enzym oxy ha
thuc gan, sau iu tr khong 14 ngy thi gian bn thi ca thuc b rt ngn li. Thuc c
chu k gan - rut.
Rifampicin lm tng chuyn ha mt s thuc thng qua tc dng gy cm ng cytoc rom - P450
nh: thuc trnh thai, phong ta - adrenergic, chn knh calci, diazepam, quinidin, digitoxin,
prednisolon, sulfonylurea, mt s thuc chng ng mu...
1.1.2.4. Tc dng khng mong mun:
Thuc t c tc dng khng mong mun, song c th gp mt s ngi:
- Pht ban 0,8%; bun nn, nn (1,5%); St (0,5%); ri lon s to mu.
- Vng da, vim gan rt hay gp ngi c tin s bnh gan, nghin ru v cao tui. Tc khng
mong mun ny tng ln khi dng phi hp vi isoniazid.
- Ch phm Rifampicin (Rifampin, Rimactan, Rifadin) vin nang hoc vin nn 150 - 300
mg, siro 100mg/Ml, dung dch tim truyn 300 - 600 mg/l.
- Phi hp vi cc thuc chng lao khc iu tr cc th lao, khng dng n c rifampicin
trong iu tr lao. Ngoi ra thuc cn c ch nh trong mt s bnh nhim khun do cc vi
khun cn nhy cm gy nn.
- Liu dng cho ngi ln 1 ln trong 1 ngy 10 - 20mg/kg th trng, ti a 600mg/24 gi.
-Khng dng thuc ngi gim chc nng gan v khi iu tr cn theo di chc nng gan
thng xuyn.
1.1.3. Ethambutol (EMB, E)
1.1.3.1. Tc dng
L thuc tng hp, tan mnh trong nc v vng bn nhit cao, c tc dng km khun lao
mnh nht khi ang k nhn ln, khng c tc dng trn cc vi khun khc.
1.1.3.2. C ch tc dng:
Theo Takayama v cng s (1979), ethambutol c tc dng km khun l do c ch s nhp acid
mycolic vo thnh t bo trc khun lao, lm ri lon s to mng trc khun lao. Ngoi ra, mt
s tc gi cn cho rng ethamb utol gy ri lon s tng hp acid nhn thng qua c ch cnh
tranh vi cc polyamin v to chelat vi Zn 2+ v Cu2+.
1.1.3.3. Dc ng hc:
Thuc c hp thu tt qua ng tiu ha, sau khi ung 2 - 4 gi, t c nng ti a trong
mu. Trong c th, thuc tp trung cao trong cc m cha nhiu Zn 2+, Cu2+, c bit l thn,
phi, nc bt, thn kinh th gic, gan, ty v.v... Sau 24 gi, mt na lng thuc ung vo c
thi ra ngoi qua thn, 15% di dng chuyn ha.
1.1.3.4. Tc dng khng mong mu n:
Khi iu tr lao bng ethambutol c th gp mt s tc dng khng mong mun nh: ri lon
tiu ha, au u, au bng, au khp, pht ban, st, vim dy thn kinh ngoi vi, nhng nng
nht l vim dy thn kinh th gic gy ri lon nhn bit mu sc. Ct ngha cho tn thng th
gic, c tc gi cho rng dy thn kinh th gic cha nhiu Zn 2+, ethambutol to chelat vi Z 2+
gy vim.
1.1.3.5. p dng iu tr:
Ethambutol vin nn 100 n 400mg c phi hp vi cc thuc chng lao iu tr cc th
lao, ngi ln ung liu khi u 25mg/kg/ngy trong 2 thng sau gim liu xung
15mg/kg/ngy. Tr em ung 15mg/kg/ngy. Khng dng cho ngi c thai, cho con b, tr em
di 5 tui v ngi c vim thn kinh th gic v gim th lc.
1.1.4. Streptomycin (SM , S).
L khng sinh thuc nhm aminoglycosid c tc dng dit khun lao mnh c bit vi khun
trong hang lao v mt s vi khun Gram (+) v Gram ( -). Nng 10mcg/ml c tc dng dit
trc khun lao.
c phi hp vi cc thuc chng lao khc iu tr lao. Tim bp hng ngy hoc cch ngy
liu 15mg/kg th trng, ti a khng vt qu 1g/ngy. i vi ngi cao tui, liu dng 500 -
750mg/ngy.
Dc ng hc, c ch tc dng, tc dng khng mong mun v chng ch nh ca thuc xin
c bi khng sinh nhm aminoglycosid.
1.1.5. Pyrazinamid(Z, PZA)
1.1.5.1. Tc dng:
L thuc c ngun gc tng hp, t tan trong nc, tc dng mnh trong mi trng acid c tc
dng km khun lao c cu trc tng t nh nicotinamid. Thuc dit trc khun lao trong i
thc bo c pH acid v t bo n nhn vi nng 12,5mcg/ml, c bit khi vi khun ang
nhn ln.
C ch: cha bit d cu trc gn ging acid nicotinic v INH.
1.1.5.2. Dc ng hc:
Thuc hp thu nhanh qua ng tiu ho. Ung sau hai gi t c n ng ti a trong mu v
khuch tn nhanh vo m dch c th. Thuc i qua hng ro mu no tt nn c hiu qu iu tr
cao trong lao mng no. Thi gian bn thi ca thuc khong 10 n 16 gi.
Thuc c th gy mt s tc dng khng mong mun nh: au bng, chn n, bun nn, nn,
st, nhc u, au khp. c bit lu , thuc c th gy tn thng t bo gan, vng da 15%
s bnh nhn. Do vy, khi iu tr cn kim tra chc nng gan trc v trong iu tr. Nu c d u
hiu gim chc nng gan phi ngng thuc. Do cnh tranh vi acid uric h vn chuyn tch cc
ti ng thn, pyrazinamid c th gy tng acid uric mu.
Pyrazinamid lm gim tc dng h acid uric ca probenecid, aspirin, vitamin C v lm tng tc
dng h glucose mu ca cc thuc nhm sulfonylure.
1.1.5.4. p dng iu tr:
Vin nn 500mg.
Pyrazinamid thng phi hp vi cc thuc chng lao khc iu tr lao trong 6 thng u, sau
thay bng thuc khc. Liu trung bnh ngi ln 1,5 -2,0 g/ngy v tr em 35mg/kg/ngy.
1.2. Cc thuc chng lao khc
1.2.1. Ethionamid
- L thuc va km khun va dit khun (do c ch tng hp acid mycolic). Ung hp thu t t
qua ng tiu ha, sau 3 gi t nng ti a trong mu v thi tr ch yu qua thn di
dng chuyn ha.
- Thuc c ch nh khi vi khun lao khng vi cc thuc nhm I. Ngoi ra, ethionamid cn
c dng phi hp vi dapson, rifampin iu tr phong vi liu 10mg/kg th trng.
- Mt s tc dng khng mong mun c th gp nh: chn n, bu n nn, nn, i lng, ri lon
thn kinh trung ng (au u, co git, mt ng), vim dy thn kinh ngoi vi. Ethionamid c th
gy ri lon chc nng gan, cn phi theo di chc nng gan trc v trong khi iu tr.
- Thuc c dng vi liu tng dn. Kh i u 500mg cch 5 ngy tng 125mg n khi t 15 -
20mg/kg th trng v khng vt qu 1gam/24gi.
1.2.2. Acid paraaminosalicylic (PAS)
L thuc km khun lao c c ch tc dng ging sulfonamid, nhng khng c tc dng trn cc
vi khun khc. Liu dng: 200- 300mg/kg/ngy, ti a 14 - 16g/ngy. PAS c th gy a lng,
nn, au bng. hn ch tc dng khng mong mun, cn ung vo lc no.
1.2.3. Mt s khng sinh khc c tc dng chng lao
- Kanamycin v amikacin c nng v c ch ti thiu vi trc k hun lao 10 g/ ml. Liu iu
tr lao 1g/ 24 gi.
- Capreomycin l 1 peptid vng c tc dng chng lao vi liu 15 - 30 mg/ kg/ 24 gi.
- Ofloxacin v ciprofloxacin l 2 khng sinh nhm fluorquinolon c nng trong t chc phi
cao hn trong huyt tng c nng c ch ti thiu trn trc khun lao rt thp t 0,25 - 3 g/
ml. Trong iu tr lao ciprofloxacin ung 1,5g chia 2 ln/ngy; ofloxacin ung 600 - 800 mg/
ngy.
- Azithromycin v clarythromycin l 2 macrolid mi cng c tc dng trn trc khun la o c
ch nh khi trc khun lao khng cc thuc chng lao chnh.
- Cycloserin c ch nh iu tr lao vi liu 15 - 200 mg/ kg/ ngy.
Chi tit xin xem bi Thuc khng sinh.
1.2.4. Thiacetazon (Amithiozon)
L thuc km khun. C hot tnh chng lao v i nng c ch ti thiu (MIC) l 1 g/ml. Trong
lm sng c th phi hp vi INH iu tr lao. Liu dng hng ngy 150mg.
1.2.5. Clofazimin
Thuc c dng cho nhng bnh nhn c trc khun lao a khng thuc vi liu dng
200mg/24 gi.
(Chi tit xin c bi "thuc iu tr phong").

1.3. S khng thuc ca vi khun lao
T l vi khun lao khng thuc ngy cng tng, nguyn nhn ch yu l do dng thuc khng
ng phc phi hp, liu lng v thi gian dng thuc hoc cht lng thuc km.
S khng thuc c th xp thnh 3 loi:
- Khng thuc tin pht: l s khng thuc xy ra bnh nhn cha c dng thuc chng lao
ln no. Nguyn nhn l do vi khun lao khng thuc lan truyn t bnh nhn khc sang.
- Khng thuc mc phi hay cn gi l khng t huc th pht l s khng thuc sau khi dng cc
thuc chng lao t nht mt thng. Nguyn nhn do dng thuc khng ng liu lng v phi
hp thuc khng ng gy nn s chn lc vi khun khng thuc.
- a khng thuc l hin tng vi khun lao khng li t nht 2 loi thuc chng lao trong c
khng rifampicin v INH v khng cng vi cc thuc chng lao khc.
i ph vi s khng thuc ca vi khun lao, ngn nga s chn lc to ra chng khng thuc
v s lan truyn cc chng khng thuc trong cng ng, cn phi p dng ng nguyn tc iu
tr lao.
1.4. Nguyn tc dng thuc chng lao v mt s phc iu tr lao
1.4.1. Nguyn tc dng thuc chng lao
- gim t l khng thuc v rt ngn thi gian iu tr, cc thuc chng lao lun dng cng
mt lc (vo thi gian nht nh trong ngy) t nht 3 loi thuc trong 24 gi v c th phi hp
4-5 thuc trong giai on tn cng 2 - 3 thng u, sau chuyn sang iu tr duy tr.
- Cn phi cy vi khun v lm khng sinh chn khng sinh thch hp.
- Phi hp thuc theo tnh nng tc dng nhm nng cao hiu qu iu tr v gim tc dng
khng mong mun. Thng phi hp thuc va dit khun trong t bo v ngoi t bo cng vi
thuc dit khun th ang pht trin v th bnh.
- iu tr lin tc, khng ngt qung, t nht 6 thng v c th ko di 9 - 12 thng.
- Tr liu ngn ngy c kim sot trc tip (DOTS =directly observed treatment short course).
- Liu php d phng bng INH trong 6 thng cho nhng ngi tip xc vi bnh nhn c k h
nng b lao, nhng cha c du hiu nhim khun v ngi c test tuberculin rng trn 10mm v
ngi trc kia b lao nhng hin nay th khng hot ng v hin ang dng thuc c ch
min dch.
- Thng xuyn theo di tc dng khng mong mun ca thu c.
- Trong trng hp trc khun lao khng vi cc thuc chng lao chnh thng dng hoc c tc
dng khng mong mun m bnh nhn khng th chp nhn c th la chn cc thuc chng
lao khc.
1.4.2. Mt s phc iu tr lao hin nay Vit Nam
Da trn phc iu tr lao ca t chc Y t Th gii, chng trnh chng lao Quc gia
xut mt s phc p dng cho iu tr lao hin nay Vit nam.
1.4.2.1. Ngi bnh cha cha lao bao gi:
2SRHZ / 6HE
- iu tr tn cng 2 thng lin tc dng 4 l oi thuc S (SM); H (INH); R (RMP); Z (PZA) hng
ngy.
- iu tr duy tr hng ngy lin tc trong 6 thng vi 2 thuc l H v E (EMB).
1.4.2.2. Ngi bnh c lao ti pht hoc tht bi iu tr:
2SHRZE/1HRZE/5H 3 R3 E3 *
- iu tr tn cng hng ngy lin tc trong hai thng vi 5 loi thuc SHRZE, mt thng tip
theo dng hng ngy 4 loi thuc HRZE.
- Sau iu tr duy tr 3 loi thuc H, R, E mt tun dng ba ln cch qung trong 5 thng lin
tc.
* H: Isoniazid Z: pyrazinamid S: Streptomycin
R: Rifampicin E: Ethambutol
S trc ch ci ch thi gian iu tr tnh bng thng; ch s di sau ch ci ch s ngy
dng thuc trong 1 tun, nu khng c cc ch s ny th dng thuc hng ngy.
2.Thuc iu tr phong
Bnh phong l bnh nhim khun Myc obacterium leprae. Nu c iu tr sm v ng, bnh
phong c th khi, khng li di chng. Hin nay, ba thuc ch yu iu tr phong l: dapson,
rifampicin v clofazimin.
2.1. Dapson (DDS)
L dn xut 4-4 diamino diphenyl sulfon cu trc gn ging pa ra-aminobenzoic acid c tc dng
km trc khun phong. Mc d, c tng hp t nhng nm 1940, nhng n nay DDS vn
c coi l thuc quan trng nht trong iu tr phong.
2.1.1. Dc ng hc
Thuc c hp thu gn hon ton qua ng tiu ha. Ung 1 00mg, sau 24 gi t c nng
trong mu gp 50 - 100 ln nng c ch ti thiu. Trong mu, thuc gn vo protein huyt
tng khong 50% v khuch tn nhanh vo cc t chc: da, c, gan, thn v dch no tu.
Dapson c chuyn ha gan nh phn ng acetyl ha to thnh monoacetyl -DDS khng c tc
dng km khun. S chuyn ha ca DDS mang tnh di truyn. Thn v mt l ng thi tr ch
yu ca thuc. Do c chu k gan - rut, nn thuc tn ti rt lu trong c th, thi gian bn thi
ca thuc khong 28 gi.
2.1.2. Tc dng v c ch tc dng
Dapson ch c tc dng km khun phong, khng dit khun. C ch tc dng ging sulfonamid.
C ch chi tit xin c bi Thuc khng sinh, phn sulfamid.
Dng Dapson c th gp mt s tc dng khng mong mun sau:
- Bun nn, nn, au u, pht ban da.
- Ri lon tm thn, vim dy thn kinh ngoi vi.
- Thiu mu, tan mu, c bit hay gp ngi c thiu ht G 6PD.

- Methemoglobin
- Hi chng sulfon hay Jarish - Herxheimer. Hi chng ny thng xut hin sau khi dng
thuc 5-6 tun. Biu hin: st, vng da, hoi t gan, vim da, met -Hb v thiu mu.y l hi
chng rt nng, cn phi ngng thuc ngay v hi sc tch cc trnh t vong.
2.1.4. p dng iu tr
Do t l trc khun phong khng thuc ngy cng cao, nn t nm 1982 Vit Nam khng dng
ring dapson iu tr m thng phi hp vi clofazimin hoc rifampin.
Thuc dng vin nn 25mg, 100mg ung khi u liu thp 50mg/24 gi. Nu bnh tin trin
khng tt, tng liu ln 100 mg/24 gi v duy tr t nht trong 2 nm. Trong iu tr cn theo di
cng thc mu thng xuyn. nhng bnh nhn c d ng vi thuc, suy gim chc nng gan,
thiu ht G 6PD hoc met-hemoglobinreductase, chng ch nh dng thuc.
2.2. Rifampicin
L khng sinh khng ch dit khun lao v cc vi khun Gram (+), Gram ( -) khc, m cn c kh
nng dit trc khun phong mnh. So vi dapson, thuc khuch tn vo m thn kinh km nn
khng lm gim c triu chng tn thng thn kinh do trc kh un phong gy nn.
Thuc c phi hp vi cc thuc iu tr phong khc vi liu 600mg/24 gi.
Chi tit v rifampicin xin c bi Thuc khng sinh v bi Thuc chng lao.
2.3. Clofazimin (Lampren)
Thuc c tc dng km khun phong v mt s vi khun g y vim lot da (Mycobacterium
ulcerans) v gy nn vim ph qun mn tnh (Mycobacterium avium). Ngoi ra, clofazimin cn
c tc dng chng vim v ngn chn s pht trin ca cc nt sn trong bnh phong.
Theo Morrison v Marley (1976), clofazimin c tc dng km khun l do thuc gn vo ADN
ca trc khun lm c ch s nhn i ca ADN.
Ung hp thu nhanh v tch ly lu trong cc m. Thn l ng thi tr ch yu ca thuc.
Ngoi ra, thuc cn c thi qua m hi.
Trong qu trnh dng thuc, c th g p mt s tc dng khng mong mun nh: mt mu da,
vim rut, tng bch cu a acid.
Vin 100mg - phi hp vi dapson v rifampin iu tr mt s th phong vi liu 50mg/24 gi
hoc 100-300mg/24 gi/tun. Khi iu tr, cn theo di chc nng gan v thn.
2.4. Cc thuc iu tr phong khc
2.4.1. Sulfoxon
Thuc c cu trc tng t nh dapson, nhng hp thu khng hon ton qua ng tiu ha v
thi tr ch yu qua mt v qua phn.
C ch tc dng v tc dng khng mong mun ca thuc ging dapson. Thuc c th dng thay
dapson iu tr phong vi liu 330mg/24 gi.
2.4.2. Thalidomid
L thuc an thn, nhng c tc dng iu tr phong, c bit th phong c. Liu dng 100 -
300mg/24 gi. Do gy qui thai, c bit giai on 24 - 36 tun u ca k thai nghn, nn thuc
t c dng.
2.4.3. Ethionamid
C tc dng va km khun va dit khun lao v phong c th thay th clofazimin trong nhng
trng hp khng clofazimin. Liu dng hng ngy 250 - 375mg.
Chi tit xin c thm bi Thuc chng lao.
2.5. Nguyn tc v mt s phc iu tr phong hin nay
Nhm tng hiu qu iu tr, rt ngn thi gian dng thuc v hn ch s khng thuc ca trc
khun phong t 1982, T chc Y t Th gii khuyn co mt s nguyn tc iu tr phong nh
sau:
- a ha tr liu, khng dng mt loi thuc iu tr phong v thng dng 3 thuc dapson,
rifampicin v clofazimin.
- Phi hp ha tr liu vi vt l liu php v th dc liu php trnh tn ph.
- Ung thuc ng liu lng, ng phc , thi gian v nh k theo di tc dng trn lm
sng, xt nghim vi khun v tc dng khng mong mun.
- Thi gian iu tr ko di tu thuc vo mc nhim trc khun.
2.5.1. Phc iu tr nhm c nhiu trc khun
Dapson Rifampicin Clofazimin Thi gian iu tr Theo di

100mg t 600mg mi 300mg mi thng t nht 2 nm hoc cho Sau 1-2-6
ung mi thng ung 1 ung 1 ln c gim n khi xt nghim thng
ngy ln c gim st + 50mg hng ngy tm trc khun m tnh (trong 5
st t ung nm)
Phc iu tr nhm t vi khun
Dapson Rifampicin Thi gian iu Theo di

tr
100mg t ung 600mg mi thng ung 1 6 thng Sau 1-2-4-6 thng
hng ngy ln c gim st (trong 3 nm)
Phc iu tr nhm bnh nhiu vi khun tr em
Rifampicin Clofazimin Dapson Thi gian

Cn hng thng Hng thng Hng tun, t ung iu tr
nng tr c kim tra c gim st hng ngy hng ngy
(ung) (ung) t ung
20 kg 150mg 100mg 100mg 25mg t nht
(hng tun) 2 nm hoc
21-30kg 300mg 150-200mg 150mg 25-50mg n khi
(hng tun)
31-50kg 450mg 200-300mg 50mg 50-75mg xt nghim

(hng tun) m tnh
2.5.4. Phc iu tr nhm bnh t vi khun tr em

Cn nng tr Rifampicin hng thng c Dapson hng ngy t Thi gian iu
gim st (ung) ung tr
20kg 150 mg 25mg
21 30 kg 300mg 25 50 mg 6 thng
31 50 kg 450 mg 50 70 mg
Cu hi t lng gi
1. Trnh by tc dng, c ch tc dng, c im dc ng hc v tc dng khng mong
mun ca INH v cc nguyn tc iu tr lao.
2. Trnh by tc dng, c ch tc dng, c im d c ng hc v tc dng khng mong
mun ca rifampicin, v phc iu tr lao hin nay.
mun ca ethambutol v pyrazinamid.
4. Trnh by tc dng, c ch tc dng, c im d c ng hc v tc dng khng mong
mun cu streptomycin.
mun cu dapson.
mun cu clofazimin.
7. Trnh by nguyn tc v phc iu tr phong hin nay.
Bi 18: thuc iu tr st rt

1. Trnh by c tc dng, c ch tc dng ca cc thuc chng st rt.
2. Trnh by c tc dng khng mong mun v p dng iu tr ca cc thuc
chng st rt.
3. Gii thch c nguyn nhn khng thuc st rt ca plasmodium falciparum.
1. i cng
Bnh st rt c Hypocrate m t cch y hn 2000 nm, l bnh truyn nhim, do
plasmodium gy ra, plasmodium l mt loi k sinh trng khng nhng gy bnh cho
ngi m cho c sc vt. Bn loi k sinh trng st rt gy bnh cho ngi l: P.
falciparum, P.vivax, P.malariae v P.ovale.
Vit nam, st rt do P.falciparum chim khong 70 - 80%, do P.vivax 20- 30%,
P.malariae 1- 2% cn P.ovale hu nh khng c. Dch s t rt do P.falciparum thng xy
ra t ngt, din bin nng, t vong cao nhng thi gian tn ti ca dch ngn.
Ngi c th nhim bnh st rt theo 3 phng thc:
- Do mui truyn: y l phng thc nhim ch yu v quan trng nht.
- Do truyn mu.
- Truyn qua rau thai.
Vic iu tr st rt hin nay cn gp nhiu kh khn v k sinh trng st rt (c bit l
P.falciparum) khng li nhiu thuc chng st rt. Hn na, Vit nam c khong 35
triu ngi sng trong vng st rt lu hnh (trong c 15 triu ngi sng trong vng
st rt lu hnh nng), nn mun iu tr st rt c hiu qu phi trit tun th phc
iu tr ca chng trnh phng chng st rt quc gia.
2. Chu k sinh hc ca k sinh trng st rt
2.1. Chu k pht trin trong c th ng i (chu k sinh sn v tnh)
2.1.1. Giai on gan
Khi mui t ngi, thoa trng ( trong tuyn nc bt mui) chui qua mch mu lu
thng trong mu. Sau 30 pht, thoa trng vo gan pht trin trong t bo gan thnh th
phn lit (10 - 14 ngy), sau ph v t bo gan v gii phng ra cc mnh trng. Giai
on ny gi l giai on tin hng cu.
Vi P.falciparum, tt c mnh trng u vo mu v pht trin . Cn P.vivax v
P.ovale, ngoi s pht trin tc th ca cc thoa trng thnh th phn li t, cn c s
pht trin mun hn ca mt s thoa trng khc. Nhng thoa trng ny khng pht trin
ngay thnh th phn lit m to thnh cc th ng. Cc th ng pht trin tng t thnh
phn lit, v ra v gii phng nhng mnh trng vo mu gy nn nh ng cn ti pht xa
(th ngoi hng cu).
2.1.2. Giai on mu
Cc mnh trng t gan xm nhp vo hng cu, lc u l th t dng ri pht trin
thnh phn lit non, phn lit gi. Th phn lit gi s ph v hng cu gii phng ra
nhng mnh trng. Lc ny tng ng vi cn st xy ra trn lm sng.
Hu ht cc mnh trng ny quay tr li k sinh trong cc hng cu mi, cn mt s bit
ha thnh nhng th hu gii, l nhng giao bo c v giao bo ci.
2.2. Chu k pht trin trong c th mui (chu k sinh sn h u tnh)
Giao bo c v ci c mui ht vo d dy s pht trin thnh nhng giao t c v
ci, qua sinh sn hu tnh sinh ra thoa trng. Cc thoa trng n tp trung trong tuyn
nc bt ca mui l tip tc truyn bnh cho ngi khc.
Chu k ca k sinh trng st rt v v tr tc dng

ca cc thuc iu tr st rt
1a: Thoa trng vo t bo gan

2a,3a: Th phn lit pht trin trong t bo gan
4: Gii phng cc mnh trng
5: Mnh trng vo hng cu
6: Th t dng trong hng cu
7,8: Th phn lit pht trin trong hng cu
9: Ph v hng cu v gii phng cc mnh trng
10,11,12: Pht trin thnh giao bo c v giao bo ci
1b, 2b, 3b: Pht trin ca th ng.
3. Cc thuc iu tr st rt thng dng
3.1. Thuc dit th v tnh trong hng cu
3.1.1. Cloroquin (Aralen, Avloclor, Malarivon, Nivaquin)
L thuc tng hp, dn xut ca 4 amino quinolein
3.1.1.1. Tc dng
Cloroquin c hiu lc cao i vi th v tnh trong hng cu ca c 4 loi k sinh trng

st rt, tc dng va phi vi giao bo ca P.vivax, P.malariae v P.ovale. Khng nh
hng ti giao bo ca P.falciparum.
C ch tc dng: tn ti, k sinh trng st rt "nut" hemoglobin ca hng cu vt ch
vo khng bo thc n. , hemoglobin c chuyn thnh heme (ferriprotoporphyrin
IX) l sn phm trung gian c c tnh gy ly gii mng. Heme c chuyn thnh sc t
hemozoin t c hn nh enzym polymerase. Cloroquin c ch polymerase, lm tch ly
heme, gy c vi k sinh trng st rt, lm ly gii k sinh trng.
Thuc tp trung trong khng bo thc n ca k sinh trng st rt, lm tng pH v
nh hng n qu trnh ging ha hemoglobin, lm gim cc amino acid cn thit cho s
tn ti ca k sinh trng.
Cloroquin cn c th gn vo chui xon kp DNA c ch DNA v RNA polymerase, cn
tr s tng hp nucleoprotein ca k sinh trng st rt.
3.1.1.2. Dc ng hc
Cloroquin hp thu nhanh v gn nh hon ton ng tiu ha, sinh kh dng khong
90%. Sau khi ung 3 gi, thuc t c nng ti a trong mu, 50 - 65% thuc gn
vi protein huyt tng. Khu ch tn nhanh vo cc t chc. Thuc tp trung nhiu hng
cu, gan, thn, lch v phi. hng cu nhim k sinh trng st rt, nng thuc cao
gp 25 ln hng cu bnh thng.
Chuyn ha chm gan, cho desethylcloroquin vn dit c plasmodium. Thi tr
chm, khong 50- 60% qua nc tiu. Thi gian bn thi 3 - 5 ngy, c khi ti 12- 14
ngy.
Vi liu iu tr, thuc thng dung np tt, t gp cc tc dng khng mong mun: au
u, chng mt, bun nn, nn, au bng, a chy, ri lon th gic, pht ban, nga (c
bit lng). Ung thuc khi no c th lm gim cc tc dng ny.
Khi dng liu cao v ko di thuc c th gy tan mu ( ngi thiu G 6PD), gim thnh
lc, nhm ln, co git, nhn m, bnh gic mc, rng tc, bin i sc t ca tc, da xm
nu en, h huyt p.
Ch nh:
- Cloroquin c dng trong iu tr v phng bnh st rt
- Thng dng trong st rt th nh v trung bnh ( nhng vng v k sinh trng cn
nhy cm vi thuc) khng dng khi st rt nng hoc c bin chng.
iu tr d phng cho nhng ngi i vo vng c st rt lu hnh.
- Thuc cn c dng dit amp gan, trong vim a khp dng thp, lupus ban .
Chng ch nh:
- Chng ch nh: bnh vy nn, ri lon chu yn ha porphyrin, tin s ng kinh v bnh
tm thn, ph n c thai.
- Thn trng: cn khm mt trc khi dng thuc di ngy v theo di trong sut qu
trnh iu tr.
Ch ti nhng ngi c bnh v gan, thn, c bt thng v thnh gic v th gic,
nghin ru, ri lon v mu v thn kinh, thiu ht G 6PD.
Liu lng:
Chng trnh phng chng st rt Vit nam dng vin cloroquin phosphat 250 mg 150
mg cloroquin base
- iu tr st rt: ung cloroquin phosphat 3 ngy
Ngy u: 10 mg cloroquin base/ kg, chia 2 ln
Ngy th 2, 3: 5 mg cloroquin base/ kg
- iu tr d phng; 5 mg cloroquin base/ kg/ tun cho c ngi ln v tr em.
- Cc thuc khng acid hoc kaolin c th lm gim hp thu cloroquin, v vy ch ung
cloroquin sau khi dng thuc ny 4 gi
- Cimetidin lm gim chuyn ha v thi tr, tng th tch phn b ca Cloroquin
- Dng cloroquin kt hp vi proguanil lm tng tai bin lot ming.
- Cloroquin lm gim kh nng hp thu ampicilin
3.1.2. Quinin
L alcaloid chnh ca cy Quinquina, c dng iu tr st rt hn 300 nm (t 1630)
3.1.2.1. Tc dng
Quinin c tc dng nhanh, hiu lc cao i vi th v tnh trong hng cu ca c 4 loi k
sinh trng st rt. Thuc dit c giao bo ca P.vivax v P.malariae nhng t hiu lc
i vi giao bo ca P.falciparum.
C ch tc dng ca quinin tng t nh cloroquin. Ngoi tc dng dit k sinh trng st
rt, quinin cn c mt s tc dng khc.
- Kch ng ti ch: khi ung thuc kch ng d dy, gy bun nn, nn. Tim di da rt
au, c th gy p xe v khun, v vy nn tim bp su.
- Tim mch: liu cao quinin gy gin mch, c ch c tim, h huyt p (khi tim tnh
mch nhanh).
- C trn: lm tng co bp t cung u n trong nhng thng cui ca thi k c thai, t
tc dng trn t cung bnh thng hoc mi c thai.
3.1.2.2. Dc ng hc
Thuc c hp thu nhanh v hon ton qua rut, sau khi ung 1 - 3 gi thuc t c
nng ti a trong mu, nng trong huyt tng thng gp 5 ln trong hng cu.
Gn vi protein huyt tng khong 80%, qua c rau thai v sa, 7% vo dch no ty.
80% thuc c chuyn ha qua gan v thi tr phn ln qua thn. Thi gian bn thi 7 -
12 gi trn ngi bnh thng v 8 - 21 gi ngi b st rt.
- Hi chng quinin; thng g p khi nng thuc trong mu trn 7 - 10 g/ mL vi cc
biu hin: au u, nn, chng mt, tai, ri lon th gic. Phi ngng thuc khi cc triu
chng tin trin nng hn.
- c vi mu: thuc c th gy tan mu (hay gp ngi thiu enzym G 6PD). Gim
bch cu, gim prothrombin, mt bch cu ht... l nhng du hiu t gp hn.
- H ng huyt c th gp khi dng quinin vi liu iu tr.
- c tnh nghim trng (do qu liu hoc dng lu di): st, phn ng da (nga, pht
ban...), ri lon tiu ha , ic, gim th lc (nhn m, ri lon mu sc, nhn i...), tc
dng ging quinidin.
- Khi dng liu cao quinin c th gy xy thai, d tt bm sinh thai nhi.
- Trong mt vi trng hp, khi tim tnh mch quinin c th gy vim tnh mch huyt
khi.
Ch nh:
- iu tr st rt nng do P.falciparum v st rt c tnh, hay dng nhng vng m
P.falciparum khng cloroquin. Ung quinin sulfat kt hp vi cc thuc chng st rt
khc nh tetracyclin (hoc doxycyclin), fancidar, mefloqui n hoc artemisinin.
- Quinin cn c ch nh cho ph n c thai (thay th cloroquin khi b khng thuc). V
hiu lc km hn cloroquin nn quinin khng dng iu tr t cp do P.vivax,
P.malariae v P.ovale; khng dng khi P.falciparum cn nhy cm v i cloroquin.
- Phng bnh: v c nhiu c tnh nn quinin t c dng phng bnh. Tuy nhin
nhng vng P.falciparum khng cloroquin, khi khng c mefloquin v doxycyclin, c th
phng bnh bng quinin.
Chng ch nh, thn trng:
- Chng ch nh: ngi nhy cm vi thuc, tin s c bnh v tai, mt, tim mch.
Khng dng quinin phi hp vi mefloquin bnh nhn thiu G 6PD.
- Thn trng: bnh nhn suy thn phi gim liu thuc
Liu lng:
- iu tr st rt do P.falciparum khng cloroquin (th nh v trung bnh): ung quinin

sulfat 30 mg/ kg/ ny, chia 3 ln. Mt t iu tr 7 ngy.
- iu tr st rt nng v st rt c tnh: tim bp hoc truyn tnh mch quinin
hydroclorid.
Tim bp: 30 mg/ kg/ ngy, trong 7 ngy
Truyn tnh mch: quinin hydroclo rid 10 mg/ kg mi 8 gi (vi 10 mL/ kg dch truyn)
Theo di n khi bnh nhn tnh, chuyn sang tim bp hoc ung cho liu iu tr.
- Cc thuc khng acid cha nhm lm chm hp thu quinin
- Quinin lm tng nng digoxin trong mu d o gim thanh thi ca thuc.
- Lm tng tc dng ca warfarin v cc thuc chng ng mu khc khi dng phi hp.
- Cimetidin lm chm thi tr quinin, acid ha nc tiu lm tng thi quinin.
3.1.3. Fansidar
L thuc phi hp gia sulfadoxin 500 mg v pyrimet hamin 25 mg.
3.1.3.1. Tc dng
Sulfadoxin thuc nhm sulfamid thi tr rt chm. Thuc c tc dng dit th v tnh
trong hng cu ca P.falciparum, tc dng ch yu vi P.vivax, khng nh hng ti giao
bo v giai on gan ca P.falciparum v P.vivax.
Pyrimethamin l dn xut ca diaminopyrimidin, c tc dng chm i vi th v tnh
trong hng cu ca bn loi k sinh trng st rt. Thuc cn c ch cc th hu tnh pht
trin trong c th mui nn c tc dng ngn chn s lan truyn st rt trong cng ng.
Sulfadoxin v pyrimethamin c ch 2 enzym ca 2 giai on khc nhau trong qu trnh
tng hp acid folic ca k sinh trng. V vy, khi phi hp hai thuc ny s c tc dng
hip ng tng mc, lm c ch s tng hp acid folic, nn k sinh trng khng tng hp
c DNA v RNA.
Dihydrofolat Dihydrofolat DNA
synthetase reductase
(-) sulfadoxin (-) pyrimethamin
PABA + dihydropteridin Acid Acid Tng hp

dihydrofolic tetrahydrofolic cc purin
RNA
3.1.3.2. Dc ng hc
Fansidar hp thu tt qua ng tiu ha, sau khi ung 2 - 8 gi thuc t c nng ti
a trong mu, khong 90% gn vi protein huyt tng. Thi tr ch yu qua nc tiu.
Thi gian bn thi l 170 gi i vi sulfadoxin v 80 - 110 gi i vi pyrimethamin.
Khi dng Fansidar c th b d ng vi sulfamid (nga, m ay...), ri lon v mu (tan
mu, gim bch cu ht), ri lon tiu ha, ri lon ch c nng thn.
Dng Fansidar phng bnh (di ngy) c th gy phn ng da nghim trng: hng ban,
hi chng Stevens- Johnson, hoi t biu b...
Ch nh:
- iu tr st rt do P.falciparum khng cloroquin, thng phi hp vi quinin (v tc
dng ca fansidar chm)
- D phng cho nhng ngi i vo vng st rt lu hnh nng trong thi gian di.
Chng ch nh, thn trng
- Chng ch nh: d ng vi thuc, ngi b bnh mu, bnh gan, thn nng, ph n c
thai.
- Thn trng: ph n cho con b, tr em di 2 thng tui, ngi thiu enzym G 6PD, c
a d ng, hen ph qun.
Liu lng:
iu tr st rt: ung 25 mg sulfadoxin + 1,25 mg pyrimethamin/ kg
D phng st rt: ngi ln: ung 1 vin/ tun hoc 3 vin/ thng
Sulfadoxin lm tng tc dng ca warfarin v thiopenton, lm gim hp thu digoxin qua
ng tiu ha.
3.1.4. Mefloquin (Eloquin, Lariam, Mephaquin)
L thuc tng hp, dn xut ca 4 - quinolin methanol. Cu trc ha hc c lin quan
nhiu vi quinin.
3.1.4.1. Tc dng
Mefloquin c tc dng mnh i vi th v tnh trong hng cu ca P.falciparum v
P.vivax nhng khng dit c giao bo ca P.falciparum hoc th trong gan ca P. vivax.
Mefloquin c hiu qu trn cc k sinh trng a khng vi cc thuc st rt khc nh
cloroquin, proguanil, pyrimethamin... Tuy nhin, vng ng Nam cng c chng
P.falciparum khng mefloquin.
Hin nay cn c nhiu gi thuyt khc nhau v c ch tc dng ca mefloquin. Tc dng

khng k sinh trng st rt lin quan nhiu ti kh nng c ch enzym polymerase ca
thuc.
3.1.4.2. Dc ng hc
Mefloquin c hp thu tt qua ng ung. Nng ti a trong huyt tng (0,2 - 1,4
g/ mL) t c khong 2 - 12 gi sau khi ung mefloquin vi liu duy nht 250 mg.
Gn mnh vi protein huyt tn g (98%). Thuc tp trung nhiu trong hng cu, phi,
gan, lympho bo v thn kinh trung ng.
Thuc c chuyn ha gan, cht chuyn ha chnh l acid quinolin carboxylic khng
cn hot tnh. Thi tr ch yu qua phn, c th c chu k gan - rut. Thi gian bn thi
khong 21 ngy (t 13 n 33 ngy).
Mc v tn sut ca cc phn ng c hi lin quan nhiu vi liu dng. Tc dng
khng mong mun ph bin nht l chng mt (20%) v bun nn (15%).
- liu phng bnh tc dng c hi thng nh v thong qua, bao gm ri lon tiu ha
(bun nn, nn, au bng, tiu chy), au u, chng mt, ngoi tm thu. t gp cc triu
chng thn kinh tm thn (co git, ng g, lon tm thn), tng bch cu, tng amino -
transferase.
- Khi dng liu cao (> 1000 mg) khong 1% bnh nhn thy bun nn, nn, au u,
chng mt, tai, ri lon th gic, lon tm thn cp... t gp: nga, pht ban, rng tc, au
c.
Ch nh:
iu tr v d phng st rt do P.falci parum khng cloroquin v a khng thuc
Chng ch nh, thn trng
- Chng ch nh: Mefloquin khng s dng cho nhng ngi c tin s bnh tm thn,
ng kinh, lon nhp tim, ngi nhy cm vi mefloquin hoc cc thuc c cu trc tng
t nh cloroquin, quinin, quinidin,
Tr em di 3 thng tui, ngi suy gan hoc suy thn nng khng c dng mefloquin
- Thn trng: cn thn khi dng cho ngi li xe, vn hnh my mc v nguy c gy
chng mt, ri lon thn kinh - tm thn c th xy ra trong khi iu t r v 2- 3 tun sau
khi ngng thuc.
Trong d phng st rt bng mefloquin, nu xut hin cc ri lon nh lo u, trm cm,
kch ng hoc l ln phi ngng thuc v y l tin triu ca nhng tc dng ph
nghim trng hn.
Khng nn dng cho tr em di 15 kg hoc di 2 tui, ph n c thai trong 3 thng

u.
Khng dng mefloquin lu qu 1 nm. Nu dng lu, phi nh k kim tra chc nng
gan v mt (thuc c th lm gim chc nng gan v gy tn thng mt)
Liu lng:
- iu tr st rt: ngi ln v tr em; 15 mg/ kg, chia lm 2 ln, cch nhau 6 - 8 gi.
Liu dng ti a ngi ln l 1000 mg
Phng bnh
Ngi ln: ung 1 vin mefloquin 250 mg/ tun, vo mt ngy c nh, bt u dng t
trc khi i vo vng c st rt v ko di 4 tun sau khi ra kh i vng st rt lu hnh.
i vi ngi i vo vng st rt nng trong thi gian ngn: tun u ung 1 vin 250 mg
mi ngy, ung lin 3 ngy. Sau mi tun ung 1 vin
Tr em: ung tu theo tui.
- Phi ht sc thn trng khi d ng mefloquin cho ngi bnh ang dng cc thuc chn
beta, chn knh calci, digitalis hoc cc thuc chng trm cm (c th xy ra tng tc
bt li)
- Dng mefloquin cng vi valproic acid lm gim nng valproat trong huyt thanh.
- Phi hp mefloquin vi quinin s lm tng c tnh trn thn kinh (gy co git) v tim
mch
Mefloquin c th dng cho ngi sau khi tim quinin nhng phi cch 12 gi sau liu
cui cng ca quinin trnh c tnh.
3.1.5. Artemisinin v cc dn xut
Artemisinin c phn lp t c y Thanh hao hoa vng Artemisia annua L. h Asteraceae.
Artemisinin t tan trong nc, ch dng ng ung hoc t trc trng. Cc dn xut nh
artesunat tan c trong nc, c th ung hoc tim (bp, tnh mch), artemether v
arteether tan trong du, c h dng tim bp.
3.1.5.1. Tc dng
Artemisinin v cc dn xut c hiu qu cao trong iu tr st rt. Thuc c tc dng dit
th v tnh trong hng cu ca c 4 loi k sinh trng st rt, k c P.falciparum khng
cloroquin.
Thuc khng c tc dng trn giai on gan, trn thoa trng v giao bo ca
plasmodium.
Artemisinin l mt sesquiterpen lacton c cu ni endoperoxid, cu ni ny rt quan
trng i vi tc dng chng st rt ca thuc.
Hin nay, ngi ta cha hon ton hiu r v c ch tc dng ca thuc. Thuc tp trung
chn lc vo cc t bo nhim k sinh trng v phn ng vi hemozoin trong k sinh
trng. Phn ng ny to ra nhiu gc t do hu c c c th ph hu mng ca k sinh
trng.
Mt s cng trnh nghin cu cho thy bnh nhn dng artemisini n c thi gian ct st v
thi gian sch k sinh trng trong mu nhanh hn dng cloroquin , quinin hoc
mefloquin. Song t l ti pht cao.
Artemisinin, artemether v arteether c tc dng mnh hn artemisinin.
3.1.5.2. Dc ng hc
Artemisinin hp thu nhanh sau khi ung, t nng cao sau 1 gi, phn b vo nhiu t
chc: gan, no, phi, mu, thn, c, tim, lch.
Artemisinin gn 64% vo protein huyt tng, dihydroartemisinin 43%, artemether 76%
v artesunat 59%. Chuyn ha ch yu qua gan, cho 4 cht chuyn h a: deoxyartemisinin
v crystal- 7 khng cn hot tnh.
80% liu dng c thi qua phn v nc tiu trong vng 24. Thi gian bn thi khong
4 gi.
Artemisinin v cc dn xut l nhng thuc c c tnh thp, s dng tng i an ton.
Cc tc dng khng mong mun thng nh v thong qua nh ri lon tiu ha (bun
nn, nn, au bng, tiu chy), nhc u, chng mt, hoa mt, c bit l sau khi ung.
Mt vi ngi dng artesunat, artemether c th b c ch nh tim, chm nhp tim. Sau
t trc trng, artemisinin c th kch thch gy au rt, au bng v tiu chy.
Trn sc vt, thuc gy c ch tu xng v c vi thn kinh trung ng.
Ch nh
- L thuc st rt c dng nhiu Vit nam, thng dng i u tr st rt th nh v
trung bnh do c 4 loi plasmodium.
- iu tr st rt nng do P.falciparum a khng thuc hoc st rt c tnh. Thuc c bit
hiu qu trong st rt th no.
Chng ch nh:
Khng c chng ch nh tuyt i cho artemisinin v c c dn xut. Tuy vy, khng nn
dng cho ph n c thai 3 thng u tr khi b st rt th no hoc st rt c bin chng
vng m P.falciparum khng nhiu thuc.
Liu lng:
Artemisinin: ngy u ung 20 mg/ kg
ngy th 2 n ngy th 5: mi ngy 10 mg/ kg

Artesunat: ngy u ung 4 mg/ kg
ngy th 2 n ngy th 5 : mi ngy 2 mg/ kg

- Artemisinin hip ng tc dng vi mefloquin hoc tetracyclin trong iu tr st rt .
- S phi hp gia artemisinin vi cloroquin v pyrimethamin c tc dng i khng.
3.1.6. Halofantrin (Halfan)
Thuc tng hp, dn xut phenanthrenmethanol.
3.1.6.1. Tc dng
Halofantrin c hiu lc i vi th v tnh trong hng cu ca P.falciparum. Thuc khng
c tc dng trn giai on gan, th t hoa trng v giao bo ca k sinh trng st rt
C ch tc dng ca halofantrin cn cha r, c th thuc tc ng nh cloroquin, quinin
trn ferriprotoporphyrin IX v gy tn hi mng k sinh trng.
3.1.6.2. Dc ng hc
Hp thu km qua ng tiu ha, t huc t c nng ti a trong mu sau khi ung 6
gi. M trong thc n lm tng hp thu ca thuc
Cht chuyn ha chnh l N - debutyl- halofantrin vn c tc dng dit k sinh trng st
rt. Thi tr ch yu qua phn. Thi gian bn thi t 10 - 90 gi.
Halofantrin t c, thnh thong bnh nhn c th b bun nn, nn, au bng, tiu chy,
nga, ban . Tiu chy thng xy ra ngy th 2, th 3 sau dng thuc v lin quan ti
liu dng.
nh hng ca thuc trn tim p h thuc vo liu: liu iu tr, c th ko di khong
QT v PR, khi dng liu cao halofantrin c th gy lon nhp tht.
Ch nh: iu tr st rt do P.falciparum khng cloroquin v a khng thuc.
Chng ch nh, thn trng : halofantrin khng c dng cho ph n c thai, ph n cho
con b, ngi c tin s bnh tim mch, ngi dng mefloquin trc 2 - 5 tun.
Khng phi hp halofantrin vi nhng thuc c c tnh trn tim mch.
Khng s dng halofantrin phng bnh st rt.
Liu lng: vin nn 250 mg
Ngi ln v tr em > 40 kg: ung 24 mg/ kg/ ngy, chia lm 3 ln, cch nhau 6 gi.

Phi hp halofantrin vi mefloquin , cloroquin, quinin, thuc chng trm cm loi 3
vng, dn xut phenothiazi n, thuc chng lon nhp tim (aminodaron, quinidin,
procainamid), Cisaprid, khng histamin (astemizole, terfenadin), thuc li tiu, s lm
tng c tnh trn tim.
3.2. Thuc dit giao bo: primaquin
L thuc tng hp, dn xut 8 amino - quinolein
3.2.1. Tc dng
Thuc c tc dng tt i vi th ngoi hng cu ban u gan ca P.falciparum v cc
th ngoi hng cu mun (th ng, th phn lit) ca P.vivax v P.ovale, do trnh c
ti pht. Primaquin dit c giao bo ca c 4 loi plasmodium trong mu ngi bnh
nn c tc dng chng ly lan.
C ch tc dng ca primaquin cha r rng. C th cc cht trung gian ca primaquin
(quinolin- quinin) tc ng nh nhng cht oxy ha, gy tan mu v methemoglobin.
3.2.2. Dc ng hc
Primaquin hp thu nhanh, sau khi ung 1-2 gi thuc t nng ti a trong mu, phn
phi d vo cc t chc. Chuyn ha hon ton gan. Thi tr nhanh qua nc tiu sau
24 gi. Thi gian bn thi 3 - 8 gi. Carboxyprimaquin (cht chuyn ha chnh ca
primaquin) c nng trong huyt tng cao hn nhiu so vi cht m v c tch ly v
thi tr chm (thi gian bn thi 22 - 30 gi).
Vi liu iu tr thuc dung np tt, tuy vy bnh nhn c th b au bng, kh chu vng
thng v, au u nu ung primaquin lc i. Vi liu cao hn c th gy bun nn v
nn.
Him gp cc triu chng nng nh tng huyt p, lon nhp tim, mt bch cu ht.
c tnh thng gp i vi primaquin l c ch tu xng, gy thiu mu tan mu (hay
gp ngi thiu G 6PD) v methemoglobin (hay xy ra ngi thiu NADH bm sinh)
3.2.4. p dng iu tr
Ch nh: iu tr st rt do P.vivax v P.ovale, thng dng phi hp vi cc thuc dit
th v tnh trong hng cu
- iu tr cho cng ng ct ng lan truyn ca k sinh trng st rt, c bit
P.falciparum khng cloroquin.
Chng ch nh:
Khng dng primaquin cho ngi c bnh tu xng, bnh gan, tin s c gim bch
cu ht, methemoglobin, ph n c thai, tr em di 3 tui.
Trong qu trnh iu tr, phi ngng thuc ngay khi c cc du hiu tan mu hoc
methemoglobin.
Liu lng:
Ung 0,5 mg primaquin base/ kg/ ngy
iu tr st rt do P.vivax v P.ovale: ung 5 ngy lin trnh ti pht.
Dit giao bo ca P.falciparum: ung 1 ngy
3.2.5. Tng tc thuc
Primaquin lm tng thi gian bn t hi ca antipyrin khi dng phi hp.
4. K sinh trng khng thuc
K sinh trng st rt khng thuc l vn ht sc nghim trng. Trong nhng thp k
gn y c s gia tng nhanh chng v s lan rng k sinh trng P.falciparum khng li
cc thuc st rt hin c, ch yu l s dng cho phng bnh, t iu tr khng ng phc
, hoc dng khng liu...
4.1. nh ngha
Theo WHO, khng thuc l kh nng mt chng k sinh trng c th sng st v pht
trin mc d bnh nhn c iu tr v hp thu mt lng thuc, hoc chnh xc
trong mu bnh nhn c nng thuc m trc y vn ngn cn v dit c k
sinh trng s rt . S khng nh vy c th l tng i (vi liu lng cao hn m vt
ch dung np c vn dit c k sinh trng) hoc khng hon ton (vi liu lng ti
a m vt ch dung np c nhng khng tc ng vo k sinh trng).
Khng thuc st rt c th c chia lm hai nhm:
- khng t nhin: K sinh trng c tnh khng t trc khi tip xc vi thuc, do
gen ca k sinh trng bin d t nhin, tnh khng thuc c di truyn qua trung gian
nhim sc th. K sinh trng c th khng cho nh P.falciparum khng cloroquin cng
c th khng vi amodiaquin.
- khng mc phi: K sinh trng nhy cm vi thuc, sau mt th i gian tip xc, tr
thnh khng nhy cm na, do t bin nhim sc th, tip nhn gen khng t bn
ngoi qua plasmid hoc transposon (gen nhy) ca k sinh trng.
4.2. C ch khng thuc
Cho n nay cha c mt gii thch hon ton sng t v c ch khng thuc ca k sinh
trng st rt, c mt s gi thuyt nh sau:
4.2.1. K sinh trng khng cloroquin
- Do FPIX c i lc yu vi cloroquin, nn cloroquin khng to c phc FPIX -
cloroquin, v vy thuc khng hy c mng v dit k sinh trng.
- chng k sinh trng khng cloroquin protein gn heme (hemin -binding-protein),

tng s lng v i lc vi FPIX, protein ny s cnh tranh vi cloroquin to phc vi
FPIX, lm mt tc dng ca cloroquin.
- P.falciparum c th c 2 gen m ha cht v n chuyn a khng thuc MDR (multi drug
resistant) l Pfmdr 1 v Pfmdr 2, gen ny lm tng s vn chuyn P -glycoprotein qu mc
trn mng v gy tng thi tr cloroquin. Pfmdr 1 c trong chng k sinh trng khng vi
mefloquin, halofantrin nhng khng tn g trong chng k sinh trng khng cloroquin.
4.2.2. K sinh trng khng fansidar
Ging nh c ch vi khun khng bactrim.
- K sinh trng tng tng hp PABA, tng sn xut dihydrosynthetase.
- Gim tnh thm vi sulfonamid v pyrimethamin.
5. Nguyn tc iu tr st rt
- iu tr sm: iu tr cng sm cng tt, ngay sau khi cc triu chng bnh xut hin
(tr em trong vng 12 gi, ngi ln trong vng 24 gi).
- iu tr ng thuc, liu, thi gian (theo ng phc ). Phi m bo bnh nhn
ung c v ung liu thuc cn thit.
- Theo di cht ch kt qu iu tr c bin php x l kp thi v thch hp.
Cu hi t lng gi
1. Trnh by chu k ca k sinh trng st rt v v tr tc dng ca cc thuc
chng st rt.
2. Trnh by tc dng, c ch tc dng, tc dng khng mong mun v p dng
iu tr ca Cloroquin.
3. Trnh by tc dng, tc dng khng mong mun v p dng iu tr ca quinin.
4. Trnh by tc dng, c ch tc dng v p dng iu tr ca Fansidar.
5. Trnh by tc dng, tc dng khng mong mun v p dng iu tr ca
Mefloquin.
artemisinin.
primaquin.
halofantrin.
9. Phn tch nguyn nhn khng thuc ca k sinh trng st rt.
Bi 19: thuc chng giun sn

1. Trnh by c c ch tc dng, tc dng khng mong mun ca cc thuc
iu tr giun, sn.
2. Trnh by c p dng iu tr ca cc thuc iu tr giun sn th ng dng
1. i cng
L mt nc vng nhit i, kh hu nng m nn Vit nam c t l nhim giun sn kh
cao. nc ta, bnh do giun thng trm trng hn do sn. Cc loi giun c t l nhim
cao Vit nam l giun a, giun tc, giun kim, giun mc (m) v giun ch.
Bnh sn thng do sn l v sn dy gy ra. Cc loi sn l gy bnh cho ngi l sn l
gan nh, sn l phi v sn l rut. nc ta bnh sn dy b thng gp hn sn dy
ln.
Thuc chng giun sn c nhiu loi, c sp xp da theo hnh th chung ca k sinh
trng. a s thuc u hiu qu cao, t tc dng khng mong mun v d s dng.
2. Thuc chng giun
2.1. Mebendazol (Fugacar, Vermox, Mebutar, Nemasole)
L dn xut benzimidazol, t tan trong nc v dung mi hu c. Khng ht m, n nh
khng kh.
2.1.1. Tc dng
Thuc c hiu qu cao trn cc giai on trng thnh v u trng ca giun a, giun
kim, giun tc, giun mc, giun m. Mebendazol cn dit c trng ca giun a v giun
tc. Vi liu cao, thuc c tc dng i vi nang sn.
C ch tc dng ca mebendazol ging nh cc dn xut benzimidazol khc: thuc lin
kt vi cc tiu qun ca k sinh trng, c ch s trng hp tiu qun thnh cc vi tiu
qun (l thnh phn thit yu cho s hot ng bnh thng ca t bo k sinh trng), do
lm gim hp thu glucose, cn d tr glycogen, gim ATP (ngun cung cp nng
lng cho k sinh trng). Cui cng k sinh trng b bt ng v cht.
2.1.2. Dc ng hc
Thuc t hp thu qua ng tiu ha, sinh kh dng qua ng ung di 20%. S hp thu
s tng ln khi ung mebendazol cng vi thc n c cht bo. Sau khi ung 4 gi, thuc
t c nng ti a trong mu. Khong 95% thuc gn vi protein huyt tng.
Chuyn ha ch yu gan thnh cc cht hydroxy v amino ha mt hot tnh. Thi tr
qua phn, ch mt lng nh (5- 10%) thi qua nc tiu.

Thuc dung np tt, t tc dng ph. i khi gp ri lon tiu ha (au bng, tiu chy),
au u nh.
Dng liu cao iu tr nang sn, thuc c th gy c ch tu xng, rng tc, vi m
gan, vim thn, st v vim da trc vy. V vy, khi dng liu cao, phi theo di u n
nng transaminase trong huyt thanh, bch cu v tiu cu.
2.1.4. p dng iu tr
2.1.4.1. Ch nh
iu tr nhim mt hoc nhiu loi giun nh giun a, giun kim, giun tc, g iun mc,
giun m...
Khi khng c albendazol, c th dng mebendazol trong bnh nang sn.
2.1.4.2. Chng ch nh
Khng dng mebendazol cho nhng ngi mn cm vi thuc, ph n c thai, tr em
di 2 tui, suy gan.
2.1.4.3. Liu lng
Ngi ln v tr em trn 2 tui dng li u nh nhau
- Nhim giun a, giun tc, giun mc, giun m: ung mi ln 100 mg, ngy 2 ln trong 3
ngy lin, hoc c th dng liu duy nht 500 mg.
- Nhim giun kim: liu duy nht 100 mg, ung nhc li sau 2 tun v giun kim rt d b ti
nhim.
- Bnh nang sn: ung 40 mg/ kg/ ngy, trong 1 - 6 thng
2.1.5. Tng tc thuc
- Cimetidin c ch chuyn ha mebendazol, c th lm tng nng mebendazol trong
huyt tng.
- Dng ng thi vi phenytoin hoc carbamazepin s lm gim nng mebendazol
trong mu.
2.2. Albendazol (Albenza, Eskazole, Zeben, Zentel)
Albendazol l mt dn xut benzimidazol carbamat, cu trc ha hc c nhiu lin quan
vi mebendazol.
2.2.1. Tc dng
Thuc c tc dng tt vi nhiu loi giun nh giun a, giun kim, giun tc, giun mc,
giun m, giun ln, giun xon v sn dy. Albendazol c tc dng trn c giai on
trng thnh v giai on u trng ca cc loi giun sn k sinh trong ng tiu ha, dit
c trng giun a v giun tc.
C ch tc dng tng t nh mebendazol.

2.2.2. Dc ng hc
Sau khi ung, albendazol c hp thu rt km (5%). V chuyn ha ln u ti gan rt
nhanh nn khng thy albendazol hoc ch thy dng vt trong huyt tng. Albendazol
sulfoxid (cht chuyn ha vn cn hot tnh ca albendazol) gn 70% vi protein huyt
tng, qua c hng ro mu no v c nng trong dch no tu bng 1/3 nng
trong huyt tng. Thi tr phn ln qua thn, mt lng nh qua mt. Thi gian bn thi
khong 9 gi.
Khi iu tr trong thi gian ngn (1 - 3 ngy) khong 6% bnh nhn gp mt vi tc dng
khng mong mun nh, thong qua nh: au bng, tiu chy, chng mt, mt, mt ng.
Dng liu cao, ko di iu tr bnh nang sn hoc bnh u trng sn ln c tn
thng no, tc dng c hi thng gp nhiu v nng hn; au u, ri lon tiu ha
(nn, bun nn, au bng), rng tc, ban , nga, gim bch cu...
2.2.4. p dng iu tr
2.2.4.1. Ch nh
- Nhim mt hoc nhiu loi giun nh giun a, giun kim, giun tc, giun mc, giun m,
giun ln.
- iu tr bnh nang sn v bnh u trng sn ln c tn thng no.
2.2.4.2. Chng ch nh
Ph n c thai, tr em di 2 tui, ngi c bnh gan nng
2.2.4.3. Liu lng

Ngi ln v tr em trn 2 tui dng liu nh nhau. Khng cn phi nhn i hoc dng
thuc ty.
- Nhim giun a, giun kim, giun tc, g iun mc: ung liu duy nht 400 mg. Giun kim
thng hay b ti nhim, c th dng nhc li sau 2 - 4 tun.
- Nhim giun ln, sn dy; mi ngy ung 400 mg, trong 3 ngy
- Bnh nang sn: dng 4 t, mi t 28 ngy, mi ngy 10 - 15 mg/ kg chia lm 3 ln.
Cc t cch nhau 14 ngy. Tuy nhin thi gian iu tr cn tu thuc vo tnh trng bnh
v s dung np ca ngi bnh.
- Nhim u trng sn ln c tn thng no: mi ngy 15 mg/ kg chia lm 3 ln, trong 28
ngy.
2.2.5. Tng tc thuc
Dexamethason, cimetiin, p raziquantel lm tng nng albendazol sulfoxid trong mu

khi dng phi hp
3. Thuc chng sn
3.1. Niclosamid (cestocid, Yomesan, tredemine, niclocide)
L dn xut salicylanilid c clor, bt mu vng nht, khng mi, khng v, khng tan
trong nc.
3.1.1. Tc dng
Thuc c hiu lc cao i vi sn b, sn ln, sn c (Diphyllobothrium latum), sn dy
rut (Hymenolepis nana) khng c tc dng trn u trng sn ln.
Thuc c tc dng ti ch, khi tip xc vi thuc, u v thn sn b "git" ngay v
niclosamid c ch s o xy ha. Thuc cn nh hng n chuyn ha nng lng ca sn
do c ch s sn sinh ra adenosin triphosphat (ATP) ty lp th. Niclosamid cng c ch
s thu nhp glucose ca sn. Sn khng bm c vo rut, b tng ra ngoi theo phn
thnh cc on nh.
3.1.2. Dc ng hc
Thuc hu nh khng hp thu qua ng tiu ha. Thm vo thn sn qua tn thng m
niclosamid to v sn, sn b dit ngay ti rut ca vt ch.
Thuc dung np tt, t gy tc dng khng mong mun. C th gp cc ri lon nh
ng tiu ha nh bun nn, nn, au bng, tiu chy. Cc triu chng: au u, hoa
mt, ban v nga him gp hn v c th do gii phng cc khng nguyn t k sinh
trng b phn hu.
3.1.4. p dng iu tr
3.1.4.1. Ch nh
Niclosamid c dng khi b n him sn b, sn c v sn ln (nn dng praziquantel khi
b nhim u trng sn ln)
Dng iu tr sn dy rut khi khng c praziquantel
3.1.4.2. Chng ch nh
Trng hp nhim sn b, sn c, sn ln: ung liu duy nht vo sau ba n sng, nn
nhai k vin thuc.
- Ngi ln: 2,0 g
- Tr em 11- 34 kg: 1,0 g
- Tr em > 34 kg: 1,5 g
- Tr em < 11 kg: 0,5 g
Trng hp nhim sn dy rut (Hymenolepis nana): dng trong 7 ngy lin tip
- Ngi ln: mi ngy 2g ung 1 ln.
- Tr em 11- 34 kg: ngy u ung 1 g, 6 ngy sau mi ngy 0,5 g ung 1 ln
- Tr em > 34 kg: ngy u ung 1,5g, 6 ngy sau mi ngy 1g, ung 1 ln
Khi b to bn, cn lm sch rut trc khi iu tr. Sau khi dng thuc, nu mun tng
sn ra nhanh hn v nguyn con, nn dng thuc ty mu i c tc dng mnh nh
magnesisulfat (ung 2- 4 gi sau khi dng niclosamid)
3.1.5. Tng tc thuc
Ru lm tng kh nng hp thu ca niclosamid qua ng tiu ha, gy c. V vy, khng
c dng ru trong khi iu tr.
3.2. Praziquantel (Biltricid, Cysticid, Dronci t, Cesol)
L dn xut isoquinolein - pyrazin tng hp, c ph tc dng rng, thng c la chn
iu tr cc bnh sn l, sn dy.
3.2.1. Tc dng
Thuc c hiu qu cao i vi giai on trng thnh v u trng ca sn mng, cc loi
sn l (sn l gan nh, sn l phi, sn l rut) v sn dy (sn c, sn ch, sn mo, sn
b, sn ln)
Praziquantel khng dit c trng sn, khng phng c bnh nang sn.
C ch tc dng: thuc lm tng tnh thm ca mng t bo sn vi ion calci, lm sn co
cng v cui cng lm lit c ca sn.
Khi tip xc vi praziquantel, v sn xut hin cc mn nc, sau v tung ra v phn
hu. Cui cng sn b cht v b tng ra ngoi.
3.2.2. Dc ng hc
Thuc c hp thu nhanh khi ung (ngay c khi ung trong ba n), trn 80% liu d ng
c hp thu. Sau khi ung 1- 3 gi, thuc t nng ti a trong mu.
Gn vi protein huyt tng khong 80%. Nng thuc trong dch no tu bng 15 -
20% nng trong huyt tng. Thi gian bn thi l 1- 1,5 gi. Thi tr ch yu qua
nc tiu, di dng chuyn ha (60 - 80%).
Cc phn ng c hi thng nh, xy ra mt vi gi sau ung thuc v c th ko di ti 1
ngy, hay gp: au u, chng mt, chong vng, bun nn, nn, au bng, nga, m
ay, st nh, au c- khp, tng nh enzym gan.
Cc du hiu st nh, nga, pht ban i khi i cng vi tng bch cu a acid c th do
gii phng protein ngoi lai t sn cht.
Cc phn ng c hi thng gp nhng bnh nhn nhim sn nng, mc v tn sut

ca phn ng c hi tng theo liu lng thuc dng.
3.2.4. p dng iu tr
3.2.4.1. Ch nh
- Nhim cc loi sn mng gy bnh ngi, bnh sn l gan nh, sn l phi, sn l
rut, sn dy ln, sn dy b.
- Bnh do u trng sn ln (bnh go sn) no
3.2.4.2. Chng ch nh
- Bnh go sn trong mt, bnh go sn tu sng
- Nn thn trng khi dng praziquantel ngi b suy gan (phi gim liu), ph n c
thai, ph n cho con b (ngng cho b trong nhng ngy iu tr v 72 gi sau iu tr v
thuc qua c sa m)
Khng c li xe, iu khin my mc... trong khi dng thuc v praziquantel gy chng
mt, chong vng.
3.2.4.3. Liu lng
- Nhim sn mng: liu thng dng cho ngi ln v tr em trn 4 tui l 60 mg/ kg,
chia lm 3 ln, cch nhau 4 - 6 gi trong ngy.
- Nhim sn l gan nh, sn l phi, sn l rut: ung 75 mg/ kg, chia lm 3 ln, trong 1 -
2 ngy.
- Nhim sn dy ln, sn dy b, sn dy ch... dng liu duy nht 10 mg/ kg cho c
ngi ln v tr em.
i vi bnh u trng sn ln no: ung 50 mg/ kg/ ngy, chia lm 3 ln , trong 14 n
15 ngy (c th n 21 ngy i vi mt s ngi bnh).
Praziquantel thng ung ngay sau ba n, nut nguyn vin thuc, khng c nhai
(thuc c v kh chu, c th gy bun nn)
C th dng phi hp praziquantel vi dexamethason (6 - 24 mg/ ngy) hoc prednisolon
(30- 60 mg/ ngy) gim tc dng ph trn thn kinh trung ng nhng ngi bnh
mc u trng sn ln no.
3.2.5. Tng tc thuc
Carbamazepin, phenytoin v corticoid lm gim ng k nng praziquantel trong huyt
tng trong khi cimetidin c tc dng ngc li.
3.3. Metrifonat (Bilarcil)
L mt phc hp phospho hu c, c dng trong iu tr t 1960, tc dng ch yu vi
cc loi sn mng gy tn thng bng quang.
3.3.1. Tc dng
Thuc c tc dng dit sn mng gy bnh bng quang c giai on trng thnh v u
trng, khng c hiu lc i vi trng sn l do trng vn tn ti trong nc tiu mt
vi thng sau khi sn trng thnh b dit.
C ch tc dng ca thuc cha hon ton bit r, c th do metrifonat c ch enzym
cholinesterase, lm lit tm thi sn trng thnh. Cui cng sn b y t m ri mch
bng quang n cc tiu ng mch ca phi, mc li v cht.
3.3.2. Dc ng hc
Thuc hp thu nhanh qua ng tiu ha, nng ti a trong mu t c sau khi ung
1- 2 gi. Thi gian bn thi khong 1,5 gi. Metrifonat v dichlorvos (cht chuyn ha
cn hot tnh ca metrifonat) c phn phi vo nhiu t chc v thi tr hon ton qua
nc tiu trong vng 24- 48 gi.
Metrifonat c th gy ra c c triu chng cng h cholinergic nh: bun nn, nn, au
bng, tiu chy, co tht ph qun, au u, hoa mt, chng mt, v m hi... Cc du hiu
ny c th bt u 30 pht sau khi ung thuc v ko di ti 12 gi.
3.3.4. p dng iu tr
3.3.4.1. Ch nh
- Nhim sn mng gy tn thng bng quang. Thuc c gi thnh r nn c th p
dng rng ri cho cng ng trong chng trnh iu tr sn mng bng quang.
- Phng bnh cho tr em nhng vng c t l nhim bnh cao.
3.3.4.2. Chng ch nh
Ph n c thai khng c dng m etrifonat.
Sau giai on tip xc vi cht dit cn trng loi phospho hu c hoc cc thuc c ch
cholinesterase khng nn dng metrifonat
Trong 48 gi sau khi ung metrifonat khng c dng cc thuc gin c.
3.3.4.3. Liu lng
Mi ln ung 7,5- 10 mg/ kg, ngy 3 ln, trong 14 ngy.
3.3.5. Tng tc thuc
Metrifonat hip ng vi tc dng gin c ca succinylcholin
3.4. Triclabendazol (Egaten)
L dn xut benzimidazol, tn ha hc l 6 - chloro- 5- (2, 3- dichlorophenoxy)- 2-
methylthiobenzimidazol.
3.4.1. Tc dng
Triclabendazol c hiu lc cao vi sn l gan ln (Fasciola) v sn l phi (paragonimus).
Thuc c a vo danh mc thuc thit yu iu tr sn l gan ln t 1997.

C ch tc dng: thuc gn c chn lc vi cc tiu qun ca sn l, ngn cn s trng
hp tiu qun thnh cc vi tiu qun, lm gim hp thu glucose v cn d tr glycogen
ca sn.
3.4.2. Dc ng hc
Thuc c hp thu nhanh qua ng tiu ha. S hp thu s tng ln khi ung
triclabendazol sau ba n. Thi tr ch yu qua phn (90%), mt phn qua nc tiu
(10%). Thi gian bn thi khong 11 gi.
Thuc c th gy mt s tc dng khng mong mun nh v thong qua: au bng vng
h sn phi, v m hi, chng mt, nhc u, st nh, ho, bun nn, nn, ni m n, nga.
3.4.4. p dng iu tr
3.4.4.1. Ch nh
Triclabendazol c ch nh trong nhim sn l gan ln cp v mn tnh.
3.4.4.2. Chng ch nh
Ph n c thai, ph n ang cho con b, bnh nhn qu mn vi thuc; ngi ang vn
hnh my mc, tu xe.
3.4.4.3. Liu lng
Ngi ln dng liu duy nht 10 mg/ kg, ung sau khi n no.
Cu hi t lng gi
1. Trnh by tc dng, c ch tc dng, tc dng khng mong mun v p dng
iu tr ca mebendazol.
albendazol.
3. Trnh by tc dng, tc dng khng mong mun ca niclosamid.
4. Trnh by tc dng, p dng iu tr ca praziquantel.
Trnh by tc dng, tc dng khng mong mun v p dng iu tr ca metrifonat.
Bi 20: Thuc chng amp - trichomonas

1. Trnh by c tc dng, c ch tc dng ca cc thuc chng amp.
2. Trnh by c tc dng khng mong mun v p dng iu tr ca cc thuc
chng amp.
1. Thuc chng amip

Amp k sinh ngi c nhiu loi, nhng ch c Entamoeba histolytica l loi duy nht
thc s gy bnh cho ngi. Amp c th gy bnh rut (l amp, vim i trng mn
tnh do amip) hoc cc m khc (p xe gan, amip phi, no, da...)
Ngi nhim E. histolytica l do n phi bo nang. Bo nang nhim vo ngi qua ng
tiu ha bng nhiu cch: thc n, nc ung hoc do rui, gin vn chuyn mm bnh ...
Cc bnh do amp ch yu l iu tr ni khoa, nu iu tr khng trit , bnh d tr
thnh mn tnh. Th bo nang (th kn) l th bo v v pht tn amp nn rt nguy him
v d lan truyn bnh (bo nang c thi ra theo phn v c th sng nhiu ngy trong
nc). Amp th bo nang khi gp iu kin thun li s chuyn s ang th hot ng
1.1. Thuc dit amip m
Cc thuc ny rt c hiu qu i vi cc th n hng cu ca amp.
1.1.1. Emetin hydroclorid
L alcaloid ca cy Ipeca.
V c nhiu c tnh nn hin nay rt t dng
1.1.2. Dehydroemetin (Dametin, Mebadin)
L dn xut tng hp ca emetin, c tc dng dc l tng t nhng t c hn emetin.
1.1.2.1. Tc dng
Thuc c tc dng dit amp trong cc m, t c tc dng trn amip rut.
Dehydroemetin c tc dng dit amp trc tip do cn tr s chuyn dch phn t ARN
thng tin dc theo ribosom nn c ch khng phc hi s tng hp protein ca amp.
1.1.2.2. Dc ng hc
Thuc hp thu km qua ng tiu ha. Sau khi tim bp dehydroemetin c phn b
vo nhiu m, tch lu gan, phi, lch v thn.
Dehydroemetin thi tr qua nc tiu nhanh hn em etin nn t tch lu hn v do t
c hn emetin.

Tc dng khng mong mun ca thuc cng tng t nh khi dng emetin nhng nh v
t gp hn.
- Cc phn ng ti ch: ti vng tim thng b au, d to thnh p xe v trng. C th
gp ban kiu eczema.
- Tc dng trn thn kinh c: thng gp mt mi v au c, c bit chn tay v c.
Cc triu chng ny ph thuc vo liu dng v l du hiu bo trc c tnh trn tim.
- Tc dng trn tim: h huyt p, au vng trc tim, n hp tim nhanh v lon nhp l
nhng biu hin thng gp khi b tn thng tim. Nhng thay i trn in tim (sng T
dt hoc o ngc, ko di khong Q - T) l cc du hiu n sm hn.
- Tc dng trn h tiu ha: bun nn, nn, au bng, tiu chy
Cn c th gp cc triu chng: nga, run, d cm.
Ch nh
- L amp nng
- p xe gan do amp
Ch nn dng dehydroemetin khi khng c cc thuc khc an ton hn hoc b chng ch
nh
Chng ch nh
Ph n c thai khng c dng dehydroemeti n v thuc c vi thai nhi.
Ht sc thn trng khi dng thuc bnh nhn c bnh tim, thn, thn kinh c, th trng
chung qu yu hoc tr em. Khi dng dehydroemetin, ngi bnh phi lun lun c
thy thuc theo di. Phi ngng luyn tp cng thng tro ng 4- 5 tun sau khi iu tr.
Liu lng
- Ngi ln: 1 mg/ kg/ ngy, khng dng qu 60 mg/ ngy. Cn gim liu ngi cao
tui v ngi b bnh nng (c th gim ti 50%). t iu tr 4 - 6 ngy.
- Tr em: 1mg/ kg/ ngy, khng dng qu 5 ngy.
Thuc nn dng qua ng tim bp su, khng tim tnh mch v d gy c cho tim,
khng dng ng ung v kch ng gy nn. Cc t iu tr phi cch nhau t nht 6
tun.
Trong iu tr l do amp, dng thm tetracyclin gim nguy c bi nhim. Khi iu tr
p xe gan do amp phi ung thm cloroquin ng thi hoc ngay sau . Sau iu tr tt
c cc bnh nhn nn ung thm diloxanid loi tr amip cn sng st kt trng,
phng ti pht.
1.1.3. Metronidazol (Elyzol, Flagyl, Klion, Trichazol)
L mt dn xut 5- nitroimidazol, c ph hot tnh rng, t tan trong nc, khng ion
ha pH sinh l, khuch tn rt nhanh qua mng sinh hc.
1.1.3.1. Tc dng
Metronidazol c hiu qu cao trong iu tr nhim amp ngoi rut (p xe gan, amp
no, phi- lch) v amp thnh ru t. Thuc c tc dng dit amp th hot ng nhng t
nh hng n th kn.
Thuc cn c dng iu tr trichomonas ng niu - sinh dc, bnh do Giardia
lamblia v cc vi khun k kh bt buc.
C ch tc dng: trong cc vi khun k kh v ng vt nguyn sinh (n bo), nhm 5 -
nitro ca thuc b kh thnh cc cht trung gian c vi t bo. Cc cht ny lin kt vi
cu trc xon ca phn t DNA, lm v cc si DNA v cui cng lm t bo cht.
Qu trnh kh nhm 5 - nitro ca thuc c s tham gia " tch cc" ca ferredoxin - mt
protein xc tc c nhiu trong cc vi khun v n bo nhy cm vi thuc. Mt s
nghin cu cho thy, cc chng khng metronidazol c cha t ferredoxin.
1.1.3.2. Dc ng hc
Metronidazol hp thu nhanh v hon ton qua ng tiu ha. Sau khi ung 1- 3 gi, thuc
t nng ti a trong mu (6 - 40 g/ mL). Metronidazol gn rt t vo protein huyt
tng (10- 20%) v c th tch phn phi ln (Vd 0,6- 0,8 lt/ kg) nn thuc khuch tn
tt vo cc m v dch c th, c nng cao tro ng nc bt, dch no tu, sa m...
Thi gian bn thi l 7,5 gi. Trn 90% liu ung c thi tr qua thn trong 24 gi, ch
yu l cc cht chuyn ha hydroxy (30 - 40%) v dng acid (10 - 22%). 10%
metronidazol thi nguyn vn qua nc tiu, 14% qua ph n.
Phn ng c hi thng ph thuc vo liu dng. Vi liu iu tr n bo, cc tc dng
khng mong mun ca thuc thng nh, c phc hi v gp 4 - 5% bnh nhn c
iu tr.
Hay gp cc ri lon ng tiu ha: bun nn, c hn n, kh ming, li c v kim loi,
au vng thng v v cc triu chng trn h thn kinh trung ng: au u, chng mt,
bun ng.
C th gp tiu chy, vim ming, phng rp da, pht ban, nga, d cm.
Khi dng liu cao, ko di, thuc c th gy c n ng kinh, ri lon tm thn, vim a
dy thn kinh ngoi bin, vim ty.
Nc tiu c mu nu xm do cht chuyn ha ca thuc
Ch nh
- L amp cp rut
- p xe gan do amp, amp trong cc m

- Nhim trichomonas vaginalis : cn iu tr cho c v v chng.
- Bnh do Giardia Lamblia
- Nhim khun k kh; vim mng trong tim, nhim khun ton thn, p xe no, vim
mng no c m, vim lot li cp, vim quanh thn rng...
Chng ch nh
Khng nn dng Metronidazol cho ph n c thai (c bit trong 3 thng u), ph n
cho con b, ngi c tin s qu mn vi thuc.
Cn thn trng khi dng thuc bnh nhn c tin s ri lon th tng mu, bnh h
thng thn kinh trung ng. Phi gim liu ngi b suy gan nng.
Liu lng
Metronidazol c th ung di dng vin nn (250 mg, 500 mg) hoc dung dch treo
metronidazol benzoat. Trng hp bnh nhn khng ung c, c th truyn tnh mch
(dung dch 5 mg/ mL), tc truyn 5 mL/ pht.
- iu tr l a mp cp: c th dng n c hoc tt hn nn phi hp vi iodoquinol
hoc vi diloxanid furoat. Liu thng dng cho ngi ln l 750 mg, ngy ung 3 ln
trong 5- 10 ngy, ung sau ba n.
- p xe gan do amp: ngi ln ung 500 - 750 mg/ ln, ngy 3 ln trong 5 - 10 ngy.
i vi tr em liu thng dng l 30 - 40 mg/ kg/ 24 gi, chia lm 3 ln, ung lin 5 - 10
ngy.
- Bnh do Giardia:
. Ngi ln: ung 250 mg, ngy 3 ln, trong 5 - 7 ngy hoc ung 1 ln 2g/ ngy, trong 3
ngy.
. Tr em: ung 15 mg/ kg/ ngy, chia lm 3 ln, trong 5- 10 ngy.
Tinidazol (Fasigyne): vin nn 500 mg. L dn xut th ca imidazol (C 8H13N3O4). Tc
dng v c ch tc dng tng t metronidazol, ch khc nhau v dc ng hc: hp thu
nhanh v hon ton qua ng tiu ha, nng ti a trong mu t c sau 2gi, t/2 =
12- 14 gi, gn vo protein huyt tng 8 - 12%, thm vo mi m, thi tr ch yu qua
thn, phn nh qua phn (t l 5: 1).
Liu lng: liu duy nht 2g. Hoc iu tr cc nhim khun k kh dng ngy u 2g;
ngy sau 1g (hoc 500 mg 2 ln) trong 5- 6 ngy.
Metronidazol lm tng tc dng chng ng mu ca cc thuc khng vitamin K, c th
gy chy mu nu dng ng thi metronidazol vi warfarin.
Phenobarbital v cc thuc gy cm ng microsom gan lm tng chuyn ha

metronidazol nn metronidazol thi tr nhanh hn.
Metronidazol c tc dng kiu disulfiram (cai ru)v vy, khng nn ung ru trong
thi gian dng thuc trnh tc dng c trn thn kinh: au u, bun nn, nn, chng
mt, ri lon tm thn, l ln...
1.2. Thuc dit amp trong lng rut (dit amp do tip xc)
Thuc tp trung trong lng rut v c tc dng vi th minuta (sng hoi sinh trong
lng rut) v bo nang (th kn).
1.2.1. Diloxanid (Furamid)
Diloxanid Furoat l dn xut dicloro acetamid c tc dn g ch yu vi amp trong lng
rut.
1.2.1.1. Tc dng
Thuc c tc dng dit trc tip amp trong lng rut nn c dng iu tr cc bnh
amp rut.
Diloxanid c hiu lc cao i vi bo nang amp. Khng c tc dng i vi amp trong
cc t chc.
C ch tc dng ca thuc cha c sng t. Diloxanid c cu trc gn ging
cloramphenicol (u l dn xut dicloro acetamid) nn thuc c th c ch s tng hp
protein ca vi sinh vt.
1.2.1.2. Dc ng hc
Nhng nghin cu trn ng vt cho thy diloxanid hp thu rt chm nn nng thuc
trong rut kh cao. Ti rut thuc (Diloxanid furoat) b thu phn thnh diloxanid v acid
furoic. Lng thuc hp thu c thi tr trn 50% qua thn di dng glucuronid
trong 6 gi u tin. Di 10% liu dng thi tr qua ph n.
Thuc dung np tt ngay c khi dng liu cao. Diloxanid t gy cc phn ng c hi
nghim trng.
Hay gp cc ri lon trn ng tiu ha: chng bng (87%), chn n (3%), nn (6%),
tiu chy (2%), co cng bng (2%).
t gp cc triu chng trn h thn kinh trung ng: nhc u, ng lm, chng mt, hoa
mt, nhn i, d cm...
Ch nh
Diloxanid c la chn iu tr amp th bo nang (khng c triu chng lm sng
nhng vng khng c dch bnh lu hnh).
Thuc cn c phi hp vi metronidazol dit amp th hot ng trong lng rut.

Chng ch nh
Khng nn dng thuc cho ph n c thai (3 thng u) v tr em di 2 tui.
Liu lng
Diloxanid ch dng theo ng ung
- iu tr cho ngui bnh man g kn amp khng triu chng:
. Ngi ln: mi ln ung 500 mg, ngy ung 3 ln trong 10 ngy. Nu cn, iu tr c
th ko di n 20 ngy.
. Tr em: 20 mg/ kg/ ngy, chia lm 3 ln, ung lin 10 ngy.
- iu tr l amp cp: cn iu tr bng metronidaz ol trc, sau tip theo bng
diloxanid furoat liu nh trn.
1.2.2. Iodoquinol (Yodoxin, Moebequin)
1.2.2.1. Tc dng
Iodoquinol (diiodohydroxyquin) l mt dn xut halogen ca hydroxyquinolein c tc
dng dit amp trong lng rut nhng khng nh hng n amp th nh rut v trong
cc t chc.
C ch tc dng ca thuc cha c r rng.
1.2.2.2. Dc ng hc
Thuc hp thu rt km qua ng tiu ha (90% thuc khng c hp thu). Phn thuc
vo c vng tun hon c thi gian bn thi khong 11 - 14 gi v thi tr qua n c tiu
di dng glucuronid.
Khi dng liu cao v ko di, iodoquinol c th gy nhng phn ng c hi trn h thn
kinh trung ng. Thuc d gy phn ng c hi tr em hn ngi ln.
Vi liu iu tr, iodoquinol c th gy m t s tc dng khng mong mun nh v thong
qua nh: bun nn, nn, tiu chy (thng ht sau vi ngy), chn n, vim d dy, kh
chu vng bng, au u, ban , nga...
Ch nh
Phi hp iu tr cc trng hp nhim amp rut (t h nh v trung bnh)
Chng ch inh
Khng nn dng thuc cho nhng ngi c bnh tuyn gip, d ng vi iod, ph n c
thai, tr em di 2 tui.
Liu lng
Ung 650 mg/ ln, ngy 3 ln, trong 10 - 20 ngy. Nn ung thuc sau ba n.
2. Thuc dit Trichomon as
Trichomonas k sinh ngi c 3 loi:
Trichomonas hominis (Trichomonas intestinalis)
Trichomonas bucalis (Trichomonas tenax)
Trichomonas vaginalis
Trichomonas vaginalis k sinh ch yu m o, trong nc tit m o, cc np nhn
ca da b phn sinh dc ngi. Khi k sinh m o, Trichomonas chuyn pH t acid
sang base, nn to iu kin cho vi khun trong m o sinh sn, gy vim m o cp v
mn tnh.
Thuc dit T.vaginalis gm c cc dn xut ca 5 - nitroimidazol nh metronidazol
(Flagyl), tinidazol (Fasigyn), ornidazol (Tibral, Secnidazol, Flagentyl), nimorazol... (xin
xem bi khng sinh)
Trong iu tr bnh do Trichomonas cn m bo cc nguyn tc sau:
- V sinh b phn sinh dc thng xuyn l rt cn thit v tng cng v sinh s gim
mc vim nhim ca b phn sinh dc
- iu tr cho c v v chng (v y l mt bnh ly truyn t v sang chng v ngc
li)
- Trong thi gian ang iu tr khng c giao hp bnh khi truyn t v sang chng
hoc ngc li.
- Phi phi hp dit Trichomonas vi dit vi khun v nm men (Candida albicans) v
thuc khng dit trc khun D derlein (l vt ch bnh thng v cn ca m o), khng
tc ng vi candida albicans. V vy, nn dng km acid boric trong iu tr
Trichomonas chng s p ht trin ca nm men v phi hp vi khng sinh dit vi
khun.
Liu lng: ung 1 liu duy nht 2 g hoc dng 7 ngy, mi ngy 3 ln, mi ln 250
mg.
Cu hi t lng gi
1. Trnh by tc dng, c ch tc dng, tc dng khng mong mun ca
dehydroemetin.
2. Trnh by p dng iu tr ca dehydroemetin.
3. Trnh by tc dng, c ch tc dng, tc dng khng mong mun ca
metronidazol.
4. Trnh by ch nh, chng ch nh v cch dng metronidazol.

diloxanid.
Trnh by tc dng, tc dng khng mong mun v p dng iu tr ca iodoquinol .
Bi 21: Thuc st khun - thuc ty u
1. Pht biu c nh ngha thuc st khun, cht ty u. Tiu chun ca mt thuc

st khun l tng.
2. Trnh by c c ch tc dng ca cc thuc s t khun thng thng
3. Nu c tc dng, tc dng ngoi (hoc c tnh) v p dng trn lm sng ca
cc thuc st khun thng thng
1. i cng
1.1. nh ngha
- Thuc st khun, thuc kh trng (antiseptics) l thuc c tc dng c ch s pht trin
ca vi khun c in vitro v in vivo khi bi trn b mt ca m sng (living tissue) trong
nhng iu kin thch hp.
- Thuc ty u, cht ty u (disinfectants) l thuc c tc dng dit khun trn dng c,
c, mi trng.
1.2. c im
- Khc vi khng sinh hoc cc ha tr liu dng ng ton thn, cc thuc ny t hoc
khng c c tnh c hiu.
- Tc dng khng khun ph thuc nhiu vo nng , nhit v thi gian tip xc:
nng rt thp c th kch thch s pht trin ca vi khun, nng c ao hn c th c
ch v nng rt cao c th dit khun.
- lm v khun, c th dng cc phng php khc:
+ Nhit
+ Dung dch khng chu nhit, c th lc qua mng c l d = 0,22 micron, hoc chiu
tia cc tm c bc sng 254nm vi liu khong 20 0.000 microwatt-sec/cm 2, hoc chiu
tia , hoc tit trng lnh (cho qua kh ethylen oxyd hoc ngm trong dung dch
glutaraldelhyd, ru formaldehyd)
1.3. Cc thuc st khun l tng cn t c cc tiu chun sau
- Tc dng nng long
- Khng c vi m hoc lm hng dng c
- n nh
- Khng lm mt mu hoc khng nhum mu
- Khng mi
- Tc dng nhanh ngay c khi c mt protein l, dch d vim
- R
Hin cha c cht no t c!
1.4. Phn loi theo c ch tc dng
- oxy ha: H 2O2, phc hp c clo, KMnO 4
- Alkyl ho: Ethylenoxyd, Formaldehyd, Glutaraldehyd
- Lm bin cht protein: cn, phc hp phenol, iod, kim loi nng
- Cht din hot: cc phc hp amino bc 4
- Ion ho cation: cht nhum
- Cht gy tn thng mng: clorhexidin
1.5. Nguyn tc dng thuc st khun
1.5.1. da lnh
- Ra sch cht nhn
- Bi thuc st khun
1.5.2. Trn vt thng
- o pH ch cn bi. Xc nh vi khun (nu cn)
- Lm sch vt thng
- Ra bng nc dit khun
- Bi thuc tu theo pH vt thng
2. Cc thuc st khun thng thng
2.1. Cn
Thng dng cn ethylic (C 2H5OH) v isopropyl (isopropanol) [CH 3CH(OH)CH 3] 60 -
70%. Tc dng gim khi cn <60% v >90%.
C ch: gy bin cht protein
Tc dng: dit khun, nm bnh, siu vi. Khng tc dng trn bo t.
Dng ring hoc phi hp vi tc nhn dit khun khc. nng thp cn c th c
s dng nh cc c cht cho mt s vi khun, nhng nng cao cc phn ng kh
hydro s b c ch.
2.2. Nhm halogen
2.2.1. Iod
- C ch: Iod lm kt ta protein v oxy ha cc enzim ch yu theo nhiu c ch: phn

ng vi cc nhm NH, SH, phenol, cc carbon ca cc acid bo khng bo ho, lm ngn
cn to mng vi khun.
- Iod c tc dng dit khun nhanh trn nhiu vi khun, virus v nm bnh. Dung dch 1:
20.000 c tc dng dit khun trong 1 pht, dit bo t trong 15 pht v tng i t c
vi m.
- Ch phm v cch dng:
Iod c dng nh thuc st khun v ty u.
+ Cn iod: c iod 2% + kali iodid 2,4% ( lm iod d tan) + cn 44 -50%. Nhc im
l hi kch ng da, st v nhum mu da.
+ Povidon - iod, l cht dn iod (iodophore), ch to bng cch to phc iod vi
polyvinyl pyrolidon. Iod s c gii phng t t. Hin c dng nhiu v vng bn hn
cn iod nhit mi trng, t kch ng m, t n mn ki m loi. Tuy nhin gi thnh
t. Vi vt thng m, do c vi nguyn bo si (fibroblast) nn c th lm chm lnh.
Ch phm:
- Betadin
- Povidin
2.2.2. Clo
- Tc dng v c ch: clo nguyn t phn ng vi nc to thnh acid hypoclor (HOCl).
C ch dit khun cn cha r.
+ C th HOCl gii phng oxy mi sinh ra oxy ha cc thnh phn ch yu ca
nguyn sinh cht:
2 HOCl = H 2O + Cl2 + O
+ Hoc, Cl kt hp vi protein ca mng t bo to thnh phc hp N - Clo lm gin
on chuyn ha mng t bo.
+ Hoc, oxy ha nhm - H ca mt s enzym lm bt hot khng hi phc.
Tc dng pH trung tnh hoc acid nh (ti u l 5) nng 0,25 ppm (phn triu) Clo
c tc dng dit khun trn nhiu chng, tr vi khun lao c sc khng 500 ln mnh
hn.
Clo khng cn c dng nh mt thuc st khun v c tc dng kch ng v b mt hot
tnh bi cc cht hu c do chng d kt hp vi cc cht hu c. Tuy nhin, n cn c
dng nhiu lm thuc ty u v kh trng nc v r.
- Cc ch phm:
. Cloramin: l cc dn xut Cl N ca sulfonamid, dn xut guanidin, phc hp N d
vng, cha 25 - 29% Clo. Tc dng ko di, t kch ng m, nhng yu.
Thng dng Cloramin T (Na -p-toluen sulfon cloramid), dung dch 1 -2% ra vt
thng.
. Halazon (acid p-dicloro sulfamidobenzoic): vin 4mg st khun cho 1 lt nc,
ung c sau 30 pht.
3. Cc cht oxy ha
Thng dng peroxyd hydro (H 2O2, nc oxy gi), thuc tm (KMnO 4). Do c tc dng
oxy ha, to gc t do, nn cc thuc ny lm tn hi mng vi khun, ADN v mt s
thnh phn ch yu khc ca t bo.
Nc oxy gi 3- 6% c tc dng dit khun v virus, nng cao hn (10 - 25%) dit
c bo t. Khi tip xc vi m s gii phng oxy phn t. Khng thm vo m nn ch
dng sc ming v ra cc vt thng, c c b phn gi. Catalase lm bt hot thuc.
Nc oxy gi c vi nguyn bo si nn c th lm chm lin so vt thng. Khng
c dng H 2O2 di p lc ra cc vt thng su c rch nt v c th to hi di
da.
- Thuc tm: vi nng 1:10.000, c tc dng dit nhiu loi vi khun trong 1 gi. Nng
cao hn d kch ng da. Thng dng ra cc vt thng ngoi da c r nc.
4. Cc kim loi nng
Mi kim loi nng u c tc dng dit khun. Thng dng l Hg, Ag.
4.1. Thu ngn
- Tc dng v c ch: ion Hg ++ lm kt ta protein v c ch cc enzym mang gc SH. V
vy cc vi khun b c ch bi Hg, c th hot ng tr li khi tip xc vi cc phc hp
c nhm SH. Thu ngn hu c c tc dng km khun v yu hn cn, km c hn Hg
v c.
- Ch phm: Thuc (mercurochrom) dung dch 2%, ch dng bi ngoi da.
Khng nn bi din rng vng mt da.
Khng c ung, c th gy c cho ng thn.
Dng thn trng tr s sinh.
4.2. Bc
- Tc dng v c ch: Bc ion kt ta protein v ngn cn cc hot ng chuyn ha c
bn ca t bo vi khun. Cc dung dch mui bc v c c tc dng st khun.
- Cc ch phm:
. Bc nitrat dung dch 1% dng nh mt cho tr mi , chng c bnh lu cu gy
vim mt. Hin ang thay th bng pomat khng sinh.
. Bc - Sulfadiazin 1% di dng kem bi cha bng, lm gii phng t t c bc v

sulfadiazin, c tc dng dit khun tt v lm gim au. Bi din rng v ko di, i khi
c th gy gim bch cu.
. Cc ch phm bc di dng keo (collargol, protargol, arg yrol) c tc dng km khun
tt, t gy thng tn cho m. Ch phm cha 20% bc dng st khun nim mc. Thuc
b hu bi nh sng nn phi trong l mu.
Mi ch phm bc dng lu gy chng nhim bc (argyrism).
5. X phng
X phng l cht din hot l oi anion, thng l cc mui Na hoc K ca mt s acid
bo. V NaOH v KOH l cc base mnh trong khi phn ln acid bo li l cc acid yu,
v vy cc x phng khi tan trong nc u l cc base mnh (pH 8.0 - 10.0), d kch ng
da (pH ca da = 5,5 - 6,5). Mt s x phng c sn xut vi pH = 7.
Cc x phng loi b trn b mt da cc cht bn, cc cht xut tit, biu m trc vy v
mi vi khun cha trong . lm tng tc dng st khun ca x phng, mt s cht
dit khun c cho thm vo nh hexaclorophan, phenol, carbanilid, l nhng cht s
trnh by di.
6. Cc hp cht cha phenol
Phenol c Lister dng u tin t nm 1867 tit khun. Do lm bin cht protein v
kch ng da nn c, ch dng ty u. Ngy nay dng cc cht thay t h.
6.1. Hexaclorophen
L cht km khun mnh.
X phng v cht ty u cha 3% hexaclorophen c tc dng km khun mnh v lu bn
v gi li lp sng ca da. Nhng dng nhiu ln c th b nhim c, nht l tr nh.
6.2. Carbanilid v Salicylanilid
Hin dng thay th hexaclorophen trong x phng st khun.
Dng thng xuyn x phng ny c th lm gim mi ca c th do ngn nga c s
phn hu ca vi khun vi cc cht hu c cho trong m hi.
Cc loi x phng ny c th gy d ng hoc mn cm vi nh sng.
6.3. Clohexidin
L dn xut ca biguanid, c tc dng lm ph v mng bo tng ca vi khun, c bit
l chng gram (+). Dng trong x phng st khun, nc sc ming. Dung dch 4%
dng ra vt thng. Thuc c th c gi li lu da n n tc dng km khun ko di.
Tuy nhin t c vi ngi v khng kch ng v khng hp thu qua da v nim mc lnh.
Cu hi t lng gi
1. Pht biu nh ngha v thuc khng sinh, thuc st khun v thuc ty u.

2. K c tiu chun ca mt thuc st khun l tng v nguyn tc dng thuc st
khun
3. Trnh by c ch tc dng v phn tch u nhc im ca cc thuc st khun:
cn, iod, clo.
Trnh by c ch tc dng, p dng v phn tch u nhc im ca H 2O2, KMnO 4, Ag,
x phng.
Bi 22: thuc tr tim

1. Nu c mi lin quan gia cu trc ha hc v dc ng hc ca thuc loi
glycosid
2. Phn tch c c ch tc dng v c tnh ca digitalis
3. Phn bit c ch nh v chng ch nh ca digitalis v strophantus
4. Trnh by c c ch tc dng v p dng iu tr ca hai nhm thuc tr tim do
lm tng AMPv
Thuc tr tim l nhng thuc c tc dng lm tng lc co bp ca c tim, dng trong cc

trng hp suy tim. Cc thuc c chia lm 2 nhm:
- Thuc loi glycosid c ch nh trong suy tim mn.
- Thuc khng phi glycosid dng trong suy tim cp tnh.
1. Thuc loi glycosid ( glycosid tr tim): digitalis
Cc thuc loi ny u c 3 c im chung:
- Tt c u c ngun gc t thc vt: cc loi Digitalis, Strophantus
- Cu trc ho hc gn ging nhau: u c nhn steroid ni vi vng lacton khng bo
ha C 17, gi l aglycon hoc genin, c tc dng chng suy tim. V tr C 3 ni vi mt
hoc nhiu phn t ng( ose), khng c tc dng dc l nhng nh hng n dc
ng hc ca thuc.
- Hin ch cn digoxin v digitoxin c dng lm sng. Digitoxin khc digoxin l
khng c OH C 12 v th t tan trong nc hn.
- Cc thuc tc dng trn tim theo cng mt c ch.
Digoxin
1.1. Dc ng hc
1.1.1. Hp thu
Glycosid khng ion ho, c khuch tn th ng qua ng tiu ha (d dy, t trng,

rut non): thuc cng tan trong lipid, cng d khuch tn. Cc nhm OH ca genin l
nhng cc a nc, lm hn ch tan trong lipid ca thuc:
- Digitoxin ch c mt nhm OH t do C 14, nn d tan trong lipid, c hp thu hon
ton khi ung.
- Uabain c 5 nhm OH t do, khng hp thu qua ng tiu ho, nn phi tim tnh
mch. Hin khng cn c dng na.
- Digoxin c 2 nhm OH t do, hp thu qua ng tiu ha tt hn uabain, nhng
khng hon ton nh digitoxin.
1.1.2. Phn phi
Thuc cng d tan trong lipid, cng d gn vo protein huyt tng, song khng vng
bn v d dng c gii phng ra dng t do.
Glycosid gn vo nhiu t chc, c bit l tim, gan, phi, thn, v nhng c quan ny
c ti mu nhiu; vi c tim, thuc gn vng bn theo kiu lin kt cng ho tr. Kali -
mu cao, glycosid t gn vo tim v ngc li khi kali- mu gim, glycosid gn nhiu vo
tim, d gy c. Digitalis c th qua c hng ro rau thai.
1.1.3. Chuyn ho
Digitoxin chuyn ho hon ton gan, digoxin 5%, cn uabain khng chuyn ho.
Nhng phn ng chuyn ho quan trng ca digitoxin v digoxin l:
- Thu phn, mt dn phn ng, cui cng cho gennin
- Hydroxyl ho genin v tr 5 -6 bi micrsm gan
- Epime ho: chuyn -OH v tr 3 t bta sang alpha
- Lin hp vi cc acid glucuronic v sulfuric.
1.1.4. Thi tr
Digitoxin v digoxin thi tr qua thn v qua gan, nhng ni , mt phn thuc c
ti hp thu, nn lm tng tch ly trong c th. Uabain khng b chuyn ho, thi tr qua
thn di dng cn hot tnh.
Bng 22.1: So snh chuyn ha ca ba glycosid
Digitoxin Digoxin Uabain
Ngun gc D.purpurea D.laineuse Strophanthus
S OH gn vo sterol 1 2 5
Tan trong m +++ + 0
Hp thu qua tiu ha 100:100 80:100 0
Gn vo protein huyt tng 90:100 50:100 0
Thi gian c tc dng sau 2h (khng dng) 20 pht 5 pht
(t/m)
Phn hu gan +++ + 0
Digitoxin Digoxin Uabain

Thi tr Chm Nhanh Rt nhanh
T l mt hot tnh trong ngy 7:100 18-20:100 40:100
Thi gian tc dng 2-3 ngy 12-24 gi 12 gi
Thi gian bn thi 110 gi 33 gi 6 gi
Lu li trong c th 2-4 tun 1 tun 1-2 ngy
Trnh by - Dung dch ru Vin 0,25mg ng 0,25mg
1:1000 - t/m
1ml = 50 git = ng 0,5mg-t/m
1mg
vin 0,1mg =
5git
1.2. Tc dng ca digitalis
1.2.1. Tc dng trn tim
y l tc dng ch yu: digitalis lm tm thu ngn v mnh, tm trng di ra, nhp tim
chm li. Nh , tim c ngh nhiu hn, mu t nh vo tht thi k tm trng c
nhiu hn, cung lng tim tng v nhu cu oxy gim. Do bnh nhn kh th v
nhp h hp tr li bnh thng. Digitalis cn lm gim dn truyn ni ti v tng tnh tr
ca c tim nn nu tim b lon nhp, thuc c th lm u nhp tr li.
C ch tc dng:
Cc glycosid tr tim u c ch cc ATPase mng, l enzym cung cp nng lng cho
bm Na + K+ ca mi t bo. Bm ny c vai tr quan trng trong kh cc mng t
bo, do y 3 ion Na + ra trao i vi 2 ion K + vo trong t bo. Tc dng ca glycosid
ph thuc vo tnh nhy cm ca ATPase ca tng m. Trn ngi, c tim nhy cm nht,
v vy: vi liu iu tr, glycosid c tc dng trc ht l trn tim.
Khi ATPase b c ch, nng Na + trong t bo tng s nh hng n mt h thng
khc, h thng trao i Na + - Ca++. Bnh thng, h thng ny sau mi hiu th hot ng
s y 1 ion Ca ++ v nhp 4 ion Na + vo t bo. Di tc dng ca glycosid, nng Na +
trong t bo s tng cn tr s trao i ny v lm nng Ca ++ trong t bo tng cao, gy
tng lc co bp ca c tim, v ion Ca ++ c vai tr hot ha myosin ATPase cung cp
nng lng cho s co c (cc si actin trt trn si myosin). (Hnh 22.1)
Hnh 22.1. Tc dng ca digitalis trn cc lung ion

(-) c ch
Sau c tim ATPase ca cc t bo nhn cm p lc ca cung ng mch ch v xoang

ng mch cnh cng rt nhy cm vi glycosid. Khi ATPase b c ch, tn s phng
xung tc gim p hng tm t ng, kch thch trung tm ph giao cm v lm gim
trng lc giao cm s lm tim p chm li v lm gim dn truyn nh - tht.
1.2.2. Cc tc dng khc
- Trn thn: digitalis lm tng thi nc v mui nn lm gim ph do suy tim.
C ch ca tc dng ny l: mt mt, digitalis lm tng cung lng tim, nn nc qua cu
thn cng tng; mt khc, thuc c ch ATPase mng t bo ng thn lm gim ti hp
thu natri v nc.
- Trn c trn: vi liu c, ATPase ca bm Na + - K+ b c ch, nng Ca ++ trong t
bo thnh rut tng lm tng co bp c trn d dy, rut (nn, i lng), co tht kh qun
v t cung (c th gy xy thai).
- Trn m thn kinh: digitalis kch thch trc tip trung tm nn sn no tht 4 v do
phn x t xoang cnh, quai ng mch ch.
1.3. Nhim c
Cc du hiu nhim c digitalis rt a dng. Khi iu tr, cn ch pht hin cc du
hiu, triu chng sau:
- Tm thn: m sng, kh chu, mt mi, l ln, chong vng.
- Th gic: nhn m, c qung sng.
- Tiu ha: chn n, bun n n, nn, au bng.
- H hp: th nhanh.
- Tim mch: nhp xoang chm, lon nhp ngoi tm thu nh, tht; ri lon dn truyn nh -
tht; nghn nh- tht cc loi; rung tht.
Digitalis l thuc b tch lu trong c th, phm vi nng huyt tng c tc dng iu
tr li hp, v vy trong lm sng, tuy dng liu iu tr vn c th gp nhim c do nhiu
yu t tng tc nh: ri lon in gii (h K + mu, h Mg ++ mu, tng Ca ++ mu); nhim
kim chuyn ha; suy gan, suy thn lm gim chuyn ha v thi tr th uc.
Trong gim st iu tr, cn o nng ca thuc trong huyt tng hiu chnh liu.
1.4. p dng lm sng
- Ch nh:
+ Gin tm tht.
+ Nhp nhanh v lon.
+ Suy tim do tn thng van.
- Chng ch nh:
+ Nhp chm.
+ Nhp nhanh tm tht, rung th t.
+ Vim c tim cp (bch hu, thng hn...)
+ Nghn nh tht.
+ Khng dng cng vi cc thuc sau, c th gy cht t ngt hoc tng c ca
digitalis: calci (nht l khi tim tnh mch), quinidin, thuc kch thch adrenergic,
reserpin.
1.5. Ch phm v liu lng
- Digitoxin:
Nng iu tr trong huyt tng l 10 - 25 ng/ mL, nng c l > 35 ng/ mL
Liu iu tr: 0,05- 0,2 mg/ ngy.
Ch phm: vin nn 0,05 v 0,1 mg
- Digoxin:
Nng iu tr trong huyt tng l 0,5 - 1,5 ng/ mL, nng c l 0,2ng/ mL.
Liu iu tr: 0,125- 0,5 mg/ ngy
Ch phm: vin nn 0,125 - 0,25- 0,5 mg
ng tim 0,1- 0,25 mg/ mL
1.6. iu tr ng c
Ng c do tch lu thuc hoc ung qu liu, v digitalis gn rt cht vo c tim, cho nn

khi ng c phi dng thuc c ch gn tip tc digitalis vo tim (kali), thi tr calci l
cht hip ng tc dng vi digitalis trn c tim (EDTA) v cc thuc cha triu chng
lon nhp tim (diphenylhydantoin, thuc phong to bta vv...)
- KCl ung 20-80mEq/L/ngy; hoc 40-60mEq/L chuyn tnh mch trong 2 -3gi u.
Truyn tnh mch th d kim tra v khi cn c th ngng ngay. Tuyt i khng dng khi
suy thn.
- Diphenylhydantoin: lm tng ngng kch thch ca tim, i khng vi tc dng in
tim ca digital. Tim tnh mch 125-250mg trong 1-3pht. Tc dng nhanh v gi c
4-6 gi. C th truyn lidocain 2mg/ pht.
Nu c nhp chm, thm atropin 0,5 -1,0mg tim tnh mch.
- EDTA (acid etylen diamino tetraacetic) c tc dng gp calci ra khi c th. Dng khi
kali v diphenylhydantoin khng c ch nh. Truyn tnh mch 3,0g pha trong 200ml
glucose 5%.
- Min dch tr liu khng digoxin (antidigoxin immuno therapy). Hin c thuc gii c
c hiu cho digoxin v digitoxin di dng khng th, l cc phn on Fab tinh khi t t
khng huyt thanh khng digoxin (antidigoxin antisera) ca cu (DIGIBIND). Pha trong
dung dch nc mui, truyn tnh mch trong 30 - 60 pht. Liu lng tnh theo nng
hoc tng lng digoxin c trong c th.
Ch phm: Digibind l bt ng kh cha 38 mg Fab v 75 mg sorbitol. Mi l gn c
khong 0,5 mg digoxin hoc digitalin.
1.7. Strophanthus
Ht cy Strophanthus c glycosid l strophantin (genin l strophantidin). Trong lm sng,
c dng nhiu l G. strophantin (tc uabain) ly Strophanthus gratus, v K.
strophantin ly Strophanthus kombe.
Tc dng ca strophantin xut hin nhanh, 5 - 10 pht sau khi tim tnh mch, tc dng ti
a sau khong 1 gi v thi tr nhanh.
Thuc t tc dng trn dn truyn ni ti c tim, c th dng khi nhp ch m. Ch nh
trong suy tim l khi digitalin t ra khng hiu lc, v trong cp cu (v tc dng nhanh).
Nhc im l tim bp khng c tc dng v ung th b thu phn nhanh.
Mi ngy tim tnh mch 0,25 mg - 1 mg. v thuc thi nhanh, nn c th tim hn g ngy
nu dng liu 0,25 mg.
Strophantin cng c th gy nn, a chy v rung tm tht (c bng A). Hin ang c
thay th bng cc thuc cng 1 giao cm.
2. Thuc tr tim khng phi digitalis: Thuc lm tng AMPv
Thuc loi ny c dng cho suy tim cp tnh v t cp tnh ca suy tim mn, biu hin
bng cn kh th nng, ph ngoi bin hoc ph phi. Vic iu tr trc tin l phi lm
gim gnh nng cho tim bng thuc gin mch, thuc li niu (xin xem phn tng ng);
sau l dng thuc lm tn g sc co bp ca c tim. Cc thuc loi ny u l thuc
tim v bnh nhn thng phi nm vin.
Thuc tng co bp tim loi digitalis, khng c dng trong shock v c nhiu tc dng
ph, cng d xy ra khi c tng catecholamin ni sinh (stress), thiu ox y, acid huyt.
Thng xy ra lon nhp.
Hin a dng loi lm tng AMPv mng t bo c tim, tc dng lm m knh calci nn
lm tng co bp tim:
ATP
(+) (+)
Cc Adnylcyclase cng 1, 2
protein (+)
kinase 3- 5- AMPv
(+) (-) Xantin
Tc dng Phosphodiesterase Amrinon
sinh l 5 AMP Enoximon
Thuc kch thch adenylcyclase, enzym tng hp AMPv, v c ch phosphodiesterase,

enzym ging ho AMPv, u c tc dng lm tng AMPv (s ). Cc thuc ny lm
tng bin co bp ca c tim, tc co bp nhanh v thi gian co ngn li, c tc dng
tt trong iu tr suy tim cp, sc. Cc glycosid tim cng lm tng bin co bp ca c
tim, nhng tc co bp ch tng va phi v thi g ian co bp li ko di (hnh 22.2), c
tc dng ci thin c tnh trng suy tim mn
Tc dng qua trung gian AMPc Tc dng ca glycosid tim
Hnh 22.2. Chu k co bp ca tim b suy ( )

v di nh hng ca thuc ( ----------)
2.1. Cc thuc cng adrenergic

(Xin xem thm mc ny bi Thuc tc dng trn h adrenergic)
2.1.1. Isoprenalin
- Tc dng dc l:
+ Cng 1: tc dng ln c 4 tnh cht ca tim, lm tim p mnh, p nhanh, tng tnh
dn truyn v tnh chu kch thch. Do lm tim p nhanh, lm tng nhu cu oxy ca c
tim. Lu lng tim tng, huyt p ti a tng.
+ Cng 2: lm gin kh qun, gin mch (gim sc cn ngoi bin, gim hu gnh).
Huyt p ti thiu gim.
Lu lng tim tng v gin mch l 2 tc dng quan trng lm ci thin c s ti mu,
c bit l cho vng tng ni chu nh hng nhiu ca shock.
Ngoi tc dng tim mch, isoprenalin cn lm tng ng huyt, tng hu lipid v do
sinh nng lng.
- Tc dng khng mong mun v c tnh:
+ H huyt p, lon nhp, au vng trc tim, nhi mu c tim. Cn theo di bng in
tim.
Khng dng cng thuc m nh cyclopropan, fluothan, lm tng c tnh vi tim.
- Ch nh chnh:
+ Shock c h huyt p, cn tr mu ti cc mch do co mch ngoi bin v thiu nng
tim, th hin bng tng p lc tnh mch trung tm.
+ Ngng tim, kt hp vi xoa bp tim ngoi lng ngc.
- Ch phm:
+ Isoprenalin clohydrat (Isuprel)
+ Isoprenalin sulfat (Aleudrine)
ng 1ml = 0,2mg.
Truyn tnh mch 2-6 ng trong 250- 500ml huyt thanh ngt ng trng, khng c
base. Khi ngng tim tim 2 ng vo tim.
2.1.2. Dobutamin
Tc dng chn lc ch trn 1 receptor.
- c im tc dng trn h tim - mch:
+ Trn tim: lm tng co bp c tim, c bit l vi liu lm tng bin nh isoprenalin

th dobutamin ch lm tng nhp tim rt t, do ch lm tng t nhu cu s dng oxy ca
c tim, tuy lm tng c lu lng ca tim.
+ Lm gim nh sc cn ngoi vi v p lc mao mch phi.
- Ch nh:
+ Shock - tim, nht l sau m tim vi tun hon ng oi c th.
+ Cc suy tim nng, khng b tr, khng p ng vi cc cch iu tr khc.
- Ch phm:
+ Dobutrex l 20ml = 250mg
Pha trong dung dch glucose hoc mui ng trng, khng c base, truyn tnh mch
vi tc 2- 15 mg/ kg/ pht, tu tnh trn g bnh v t/2 = 2- 3pht. Khi xut hin nhp tim
nhanh v lon nhp, cn gim liu.
2.2. Dopamin
Dopamin l cht tin thn ca noradrenalin v l cht dn truyn thn kinh ca h
dopaminergic. Trn tim mch, tc dng ph thuc vo liu (xin xem Thuc cn g h
adrenergic). Tuy nhin, ngay c vi liu trung bnh (2 - 5 g/ kg/ pht- liu kch thch
1), dopamin lm nhp tim nhanh nn d gy thiu mu c tim, nht l trn bnh nhn
c bnh mch vnh. Cn cn nhc khi ch nh.
2.3. Cc thuc phong ta p hosphodiesterase
Nhm thuc mi phong ta phosphodiesterase c u im hn nhm thuc c in (nhm
xantin) l:
- Tc dng ch yu trn isoenzym F typ III ca phosphodiesterase c nhiu mng t bo
c tim.
- Khng kch thch thn kinh trung ng.
2.3.1. Dn xut bipyridin: amrinon (Inocor) v milrinon (Primacor)
- Lm tng co bp c tim, tng lu lng tim
- Lm gin mch nn lm gim tin gnh v hu gnh
- Tc dng ph: t. C th gp st, nhc u, ri lon tiu ho, gim v gic v khu gic.
Gim tiu cu, ngng thuc s khi, him gp vi milrinon
- Ch dng thuc cho bnh nhn nm vin
- Cch dng:
+ Amrinon (Inocor) ng 20mL c 100mg amrinon lactat pha trong dung dch mui ng
trng dng ngay trong ngy. Tim tnh mch liu tn cng 0,5 g/kg, sau truyn vi
tc 2-20 g/kg/pht; t/2 = 2-3gi.
+ Milrinon (Primacor) 5mg/mL. ng tim tnh mch. Khong 10 ln mnh hn amrinon.

Liu tn cng 50g/kg tim tnh mch, sau truyn vi tc 0,25 - 1,0g /kg/ pht;
t/2 = 30-60pht. ang l thuc c la chn v c ch c hiu PDE III.
2.3.2. Dn xut benzimidazol
L cc dn xut c ch PDE III ang c nghin cu:
- Pimobendan: ngoi c ch c ch PDE III cn c c ch lm mn cm cc yu t co tht
ca c tim vi Ca ++ ni bo.
2.3.3. Vesnarinon: l quinolinon tc dng theo ng ung lm tng lc co bp tim mch
v gin mch theo nhiu c ch: c ch PDE III, tng nhp Ca ++, ko di in th hot
ng, lm chm nhp tim. Tuy nhin phm vi an ton hp, nhiu nc khng dng na.
2.4. Cc thuc khc
2.4.1. Spartein
Alcaloid chit xut t hoa cy Kim tc (Spartium junceum L.), thng dng spartein
sulfat. Lm tim p mnh u, v chm li.
Ch nh:
- e da try tim mch do chn thng nhim c.
- nh trng ngc, nhi vng tim (khng phi hi chng ng mch vnh).
- Tr tim gia hai t dng digitalis hay strophanthus.
- C th phi hp vi morphin, scopolamin trong tin m; spartein cn c ch bi tit
catecholamin. Nn dng, nu gy m bng cloroform.
- Thc : lm t cung co bp mnh v u.
Liu lng: ung hay tim di da 0,05g/ ln, 1 -3 ln/ ngy.
2.4.2. Long no
Lm nhp tim p mnh, u, kch thch h hp, gy tit m hi v h nhit (rt t).
Ch nh:
- Try tim mch.
- Nhim khun, nhim c.
Liu lng:
- Dung dch du 10%: tim di da 2- 5 mL.
- Long no tan trong nc (natri camphosulfonat): dung dch 10%. Tim di da 1 - 10
mL.
Hai thuc trn ngy cng t dng v tc dng khng mnh.
2.4.3. Amino- 2- methyl- 6 heptaminol- 6
Lm tng cung lng ng mch vnh, cung lng tim, li niu, tng huyt p. t c.
Thng dng cng digitalis cha suy tim. c ch nh trong try tim mch, bin chng
tim trong phu thut, vim c tim cp, nhim khun, nhi mu c tim.
Ung mi ngy 0,3- 0,5g.
Tim bp, tnh mch: 0,05 - 0,1g (dung dch 5%).
cu hi t lng gi
1. Phn tch v sao c s khc bit v dc ng hc gia digitoxin, digoxin v
uabain.
2. Phn tch c ch tc dng trn tim ca digitalin, t gii thch tc dng v c
tnh ca thuc.
3. So snh cc thng s dc ng hc ca digitoxin v digoxin, t suy ra cch
dng trong lm sng.
4. Cc du hiu nhim c digitalis v cch iu tr.
5. So snh ch nh v chng ch nh ca thuc tr tim digitalis v khng phi
digitalis.
So snh c ch tc dng v tc dng ca dobutamin v dopamin trn tim mch.
Bi 23: Thuc iu tr cn au tht ngc

1. Nu c cc yu cu mt thuc cha cn au tht ngc
2. Phn bit c thuc loi nitrit v thuc chn knh calci v mt c ch v p dng
iu tr
Nguyn nhn ca cn au tht ngc l do c tim b thiu oxy t ngt v mt thng bng
gia s tng nhu cu oxy ca c tim v s cung cp khng oxy ca mch vnh.
C tim ch chim 0,5% trng lng c th, nhng khi ngh ngi cng lu gi 5% lu
lng tim. C tim ly 80- 90% oxy ca dng mu qua c tim. Khi c gng, khi xc ng
hoc dng catecholamin, tim phi lm vic tng, nhu cu oxy ch c tho mn bng
tng lng mu cung cp cho tim.
T lu, chng cn au tht ngc, vn dng thuc lm gin m ch vnh. Tuy nhin,
nhiu thuc ngoi tc dng lm gin mch vnh, li ng thi lm gin mch ton thn, v
vy mt khi lng mu ng l cn cung cp cho tim th li chy ra cc vng khc. Mt
khc, p lc tnh mch gim, i hi tim phi lm vic nhi u hn, v v vy li cng tng
s dng oxy ca tim. Khi mt phn mch vnh b tc, vng di ch tc b thiu mu,
chuyn ho lm vo tnh trng k kh, lm tng to thnh acid lactic, adenosin, kali l
nhng cht gy gin mch mnh ti ch. Nu cho thuc gin mch, s cung cp mu s
tng ln vng lnh, khng c li g cho vng b thiu mu, tri li, s ti mu cho vng
b thiu mu li cn b gim i. Hin tng ny c gi l ly trm ca mch vnh
(vol coronarien).
Trong cn au tht ngc m n guyn nhn l do thiu mu t ngt ca c tim th vic cn
trc ht l lm gim nhu cu oxy ca c tim, v hn na l loi tr tt c nhng tc ng
i hi tim phi lm vic nhiu ln v chuyn ho tng ln.
V vy, cc thuc chng cn au tht ngc tt cn t c nhng yu cu sau:
- Tng cung cp oxy, ti mu cho c tim.
- Gim s dng oxy bng cch gim cng nng tim (tnh trng co bp ca c tim, nhp
tim).
- Lm gim cn au. Tuy nhin cn thy rng v tr ca vng thiu mu c tim khng
hon ton c lin quan n s c mt hoc mc ca cm gic au, ngha l c th thiu
mu c tim m khng c au.
Cc thuc iu tr c chia thnh hai loi:
- Loi chng cn: cc nitrat v nitrit
- Loi iu tr cng c lm gim cng nng tim v gim s d ng oxy: thuc phong to
recptor adrenergic, thuc chn knh calci (c c tc dng gin mch)
1. Loi chng cn: Nitrat v nitrit
Cc nitrat hu c l cc este polyol ca acid nitric, cn cc nitrit hu c l cc este ca
acid nit. Este nitrat (C ONO2) v este nitrit (CONO) c c trng bi chui C
ON, trong khi cc hp cht nitro l C NO2. Nh vy, nitroglycerin l tn gi khng
ng ca glyceryl trinitrat v khng phi l hp cht nitro, nhng do dng quen v qu
ph bin nn khng sa c!
Cc thuc nhm ny hoc l dung dch bay hi (amylnitrit), hoc l dung dch bay hi
nh (nitroglycerin), hoc l th rn (isosorbid dinitrat). Tt c cc hot cht trong nhm
ny u gii phng nitric oxid (NO) ti m ch c trn thnh mch
Cc loi thng dng lm sng l:
Tn chung v bit dc Cu trc ha hc Liu lng v ng

dng
Amyl nitrit H3C Ht: 0,18- 0,3 ml
CHCH 2CH2ONO
H3C
Nitroglycerin Vin: 0,15- 0,16 mg,
(glyceryl trinitrat H 2C O NO2 ngm
Nitrostat, Nitro - Phun: 0,14 mg/ nht bp
bid HC O NO2 Vin gii phng chm:
2,5- 9 mg
H 2C O NO2 Dn: 2,5- 15 mg/ ngy
Isosorbid dinitrat H 2C Vin ngm: 2,5- 10 mg
(Isorrdil, sorbitrat) HC O NO2
Vin nhai: 5- 10 mg
O Vin ung: 10- 40 mg
CH Vin gii phng chm:
O O2N O C 40- 80 mg
CH2
Erythrityl tetranitrat H2C O NO2 Vin ngm: 5- 10 mg

(cardilat) HC O NO2 Vin ung: 10 mg
HC O NO2
H2C O NO2
1.1. Tc dng dc l v c ch
Nitrat lm gin mi loi c trn do bt k nguyn nhn gy tng trng lc no. Khng
tc dng trc tip trn c ti m v c vn.
Trn mch, nitrat lm gin mch da v mt (gy mt) lm gin mch ton thn. Tnh
mch gim, lm gim dng mu chy v tim (gim tin gnh). ng mch gin, lm
gim sc cn ngoi bin (gim hu gnh). Mc d nhp tim c th nhanh mt cht do
phn x gin mch, nhng th tch tm thu gim, cng nng tim gim nn vn gim s
dng oxy ca c tim. Mt khc, s phn b mu cho c tim cng thay i, c li cho
vng di ni tm mc.
Trn c trn khc, nitrat lm gin ph qun, ng tiu ho, ng mt, ng tit niu sinh
dc.
C ch lm gin c trn: Cc nitrit, nitrat v hp cht nitroso gii phng nitric oxyd (NO)
trong t bo c trn di tc dng ca h enzim cha hon ton bit r. NO c gii
phng ra s hot ha guanylyl cyclase v lm t ng tng hp GMPv, dn n kh
phosphoryl chui nh ca myosin, gy gin c trn (hnh 23.1). Myosin chui nh
(myosin light chain) phosphoryl ha (Myosin LC PO4) th gy co c.
Nitrat T bo ni mc mch
NO
Guanylyl Guanylyl
cyclase cyclase hot ha
GTP GMPv
Myosin- LC- PO4 Myosin LC
Co c Gin c
Hnh 23.1: c ch gy gin c trn ca nitrat
Tc dng gin c ca nitrat ging tc dng ca yu t gin c ca t bo ni m (EDRF:

Endothelium- derived relaxing factor). T bo ni m mch mu tit EDRF, chnh n l
NO hoc l tin cht ca NO (nitrosothiol). EDRF thm t ni m mch vo t bo c
trn thnh mch v hot ha guanylyl cyclase ti .
Cc cht ni sinh gy gin mch c th cng do thng qua c ch gii phng EDRF
(hnh 23.2) nh con ng chung cui cng.
Hnh 23.2. Tc dng gin c thng qua EDRF

Vng gin mch ph thuc vo sinh kh dng v chuyn ho khc nhau ca thuc.
Nitroglycerin cn c cystein mi chuyn thnh n itrosothiol. V vy, dng lu tc dng s
gim (quen thuc), cn dng ngt qung hi phc cystein. Nitroprussiat trong qu trnh
chuyn ha khng cn cystein nn khng c hin tng quen thuc.
1.2. Dc ng hc
Cc nitrat hu c chu nh hng rt mn h ca enzim gan glutathion - organic nitrat
reductase, thuc b kh nitrat tng bc v mt hot tnh.
Nitroglycerin t di li, t nng ti a sau 4 pht, t/2 = 1 -3 pht. Cht chuyn ho
dinitrat c hot tnh gin mch km 10 ln v t/2 khong 40 p ht.
Isosorbid dinitrat t di li c pic huyt tng sau 6 pht v t/2 = 45 pht. Cc cht
chuyn ho ban u l isosorbid - 2 - mononitrat v isosorbid - 5 - mononitrat vn cn tc
dng v c t/2 l t 2 5 gi.
1.3. c tnh
c tnh cp tnh lin q uan n tc dng gin mch: tt huyt p th ng, nhp tim
nhanh, au nhi u. Cc ch phm nitrat vn c th dng cho ngi c tng nhn p, tuy
nhin khng dng c cho ngi c tng p lc ni s.
1.4. Cc ch phm v liu lng
Bng di y ghi cc ch phm ca nitrat v nitrit dng trong iu tr cn au tht ngc.
Thuc Liu lng Thi gian

tc dng
Loi tc dng ngn
Nitroglycerin, t di li 0,15- 1,2 mg 10- 30 pht
Isosorbid dinitrat, di li 2,5- 5,0 mg 10- 60 pht
Amyl nitrit, ngi 0,18- 0,3 mL 3- 5 pht
Loi tc dng di
Nitroglycerin, ung tc dng chm 6,5- 13 mg mi 6- 8 gi 6- 8 gi
Nitroglycerin, thuc m 2% 2,5- 5 mg mi 4- 8 gi 3- 6 gi
Nitroglycerin, gii phng chm, ung 2 mg mi 4 gi 3- 6 gi
Nitroglycerin, gii phng chm qua da. 10- 25 mg(1 ming cao)/24 gi 8- 10 gi
Isosorbid dinitrat, ung 10- 60 mg mi 4- 6 gi 4- 6 gi
Isosorbid dinitrat, nhai 5- 10 mg mi 2- 4 gi 3 gi
Isosorbid dinitrat, ung 20 mg mi 12 gi 6- 10 gi
2. Loi iu tr cng c
2.1. Thuc phong to adrenergic
Lm gim cng nng tim do lm chm nhp tim. i khng vi tng nhp tim do gng
sc. Lm tng th tch tm tht v ko di thi k tm thu. Tuy vy, tc dng chnh vn l
tit kim s dng oxy cho c tim. Mt khc, thuc lm h huyt p trn ngi tng huyt
p.
Khng dng cho ngi c suy tht tri, v c th gy try tim mch t ngt. Khng nn
ngng thuc t ngt v c th gy hin tng bt li lm nhi mu c tim, t t.
- Ch phm: cc thuc thng dng l timolol, me toprolol atenolol v propranolol. Xin
xem mc ny trong bi thuc tc dng trn h thn kinh thc vt.
2.2. Thuc chn knh calci
Trong hiu th hot ng ca tim, Ca 2+ c vai tr trong giai on 2 (giai on cao nguyn)
v c bit l trong kh cc ca nt dn nhp (pacemaker), nt xoang v nt nh tht.
Calci vo t bo theo knh chm. Trong c tim, Ca 2+ gn vo troponin, lm mt hiu qu
c ch ca troponin trn b co tht, do actin v myosin c th tng tc vi nhau
gy ra co c tim. V th, c c thuc chn knh calci lm gim lc co bp ca c tim (xim
xem thm mc ny trong bi Thuc cha tng huyt p), lm chm nhp tim v gim
dn truyn nh tht.
2.2.1. C ch tc dng chng cn au tht ngc
- Cc thuc chn knh calci do lm gim lc co bp ca c tim nn lm gim nhu cu oxy

ca c tim (c ch chnh).
- Trn thnh mch, cc thuc lm gin mao ng mch, lm gim sc cn ngoi bin,
gim huyt p v gim p lc trong tm tht, gim nhu cu oxy.
- i khng vi co tht mch vnh. Tc dng tt trong iu tr cc cn au tht ngc cha
n nh. Tc dng phn phi li mu trong c tim, c li cho vng di ni mc, l vng
rt nhy cm vi thiu mu.
2.2.2. Ch nh
- D phng cc cn co tht mch vnh
- Cn au tht ngc do co tht mch vnh (Prinzmetal) l ch nh tt nht.
- Cn au tht ngc do co tht ngc khng n nh: tc dng tng t vi thuc chn .
C th dng phi hp vi cc dn xut nitro
Cc tc dng khng mong mun thng lin quan n tc dn g gin mch nh nhc u,
cn bc ho, tt huyt p th ng, thu. Nng hn l cc du hiu c ch trn tim: tim
nhp chm, nh tht phn ly, suy tim sung huyt, ngng tim.
2.2.4. Cc thuc
Bng 23.1: So snh tc dng trn tim ca mt s thuc
Tn thuc Gin mch c ch co c ch tnh c ch s

vnh bp tim t ng (nt dn truyn
xoang) nh tht
Nifedipin 5 1 1 0
Nicardipin 5 0 1 0
Nimodipin 5
1 1 0
Diltiazem 3
2 5 4
Verapamil 4
4 5 5
Ghi ch: Thang im cho t 0 (khng tc dng) n 5 (tc dng mnh n ht).
Qua bng trn cho thy nifedipin v cc thuc cng nhm (xem Thuc cha tng huyt
p) lm gin mch vnh mnh, t nh hng n hot ng ca c tim. Verapamil c ch
hot ng ca c tim mnh nht, dng tt cho iu tr lon nhp tim.
Bng 23.2: Dc ng hc v liu lng mt s thuc thng dng

Tn thuc Sinh kh Khi pht tc t/2 (h) Liu lng (ung)

dng (%) dng
Nifedipin 45- 70 5- 20 pht 4 20- 40 mg, cch 8gi/ ln
(ngm, ung)
Nicardipin 35 20 pht ung 2- 3 20- 40mg, cch 8gi/ ln
Amlodipin 65- 90 - 30- 50 5- 10 mg/ ln/ ngy
Diltiazem 40- 65 > 30 pht 3- 4 30- 80 mg, cch 6gi/ ln
Verapamil 20- 35 30 pht (ung) 6 80-160 mg, cch 8gi/ ln
3. Thuc khc
Cc hng nghin cu thuc mi ang pht trin v c n ang trong bc th nghim:
- Yu t pht trin ni mc mch (VEGF: vascular endothelial growth factor) nhm pht
trin cc mch bng h cho vng thiu mu.
- Tremetazidin (Vastarel): duy tr chuyn ho nng lng cc t bo b thiu oxy hoc
thiu mu do trimetazidin ngn nga s gim st mc ATP trong t bo, v vy m bo
c chc phn ca cc bm ion qua mng t bo, duy tr c tnh hng nh ni mi.
Dng iu tr di ngy.
Vastarel vin nn 20mg. Mi ln ung 1 vin vo ba n, mi ngy ung 2 -3 ln.
cu hi t lng gi
1. Trnh by c ch bnh sinh ca cn au tht ngc v nhng yu cu ca 1 thuc
cha cn au tht ngc tt.
2. Trnh by c ch tc dng ca thuc loi nitrit.
3. Phn tch dc ng hc v cch dng ca loi nitrit tc dng ngn v n itrit tc
dng di. Cho th d tng loi.
Phn tch c ch thuc chn knh calci la chn thuc cho tim mch
Bi 24: Thuc iu tr tng huyt p

1. Phn loi c cc thuc h huyt p
2. Trnh by c c ch tc dng v p dng iu tr ca cc thuc chn knh calci:
nifedipin v verapamil.
1. Trnh by c c ch tc dng v p dng iu tr ca nhm thuc c ch enzym
chuyn dng angiotesin.
1. Huyt p v bnh tng huyt p

1.1. Huyt p
Huyt p
T iu ho
Huyt p = cung lng tim sc cn mch ngoi vi
Th tch Tn s d lng mch

tm thu
Tng HA
tin gnh co tht Ph i thnh mch

cng g/c
V mu tng stress
Tng nhp Thn gi Renin

Na+ Na+ angiotensin
Vai tr ca thn trong kim tra th tch tun hon:

Khi p lc ti mu cho thn b gim, s c s phn phi li mu trong thn, km theo
lm gim p lc mao mch thn v hot tnh giao cm (thng qua receptor ) dn n
sn xut renin t tng sn xut angiotensin, gy ra:
- Co mch
- Kch thch sn xut aldosteron lm gi Na + v nc

Tng huyt p thng c chia thnh hai loi:
- Tng huyt p th pht: khi huyt p tng ch l mt triu chng ca nhng tn thng
mt c quan nh: thn, ni t it, tim mch, no... iu tr nguyn nhn, huyt p s tr li
bnh thng.
- Tng huyt p nguyn pht: khi nguyn nhn cha r, lc c gi l bnh tng
huyt p.
C ch bnh sinh ca tng huyt p rt phc tp. Huyt p ph thuc vo lu lng ca
tim v sc cn ngoi vi. Hai yu t ny li ph thuc vo hng lot cc yu t khc, nh
hot ng ca h thn kinh trung ng v thn kinh thc vt, ca v v tu thng thn,
ca hormon chng bi niu (ADH), ca h renin - angiotensin - aldosteron, ca tnh trng
c tim, tnh trng thnh mao mch, khi lng mu, thng bng mui v th dch v.v...
Mt yu t quan trng trong tng huyt p l lng cc ng mch nh v mao mch thu
hp li. Phn ln khng tm c nguyn nhn tin pht ca tng huyt p, v vy phi
dng thuc tc ng ln tt c cc khu ca c ch iu ha huyt p lm gin mch,
gim lu lng tim dn n h huyt p (xem hnh). Tt c u l thuc cha triu chng
v nhiu thuc c trnh by trong cc phn c lin quan (xem bng b).
Bng 24.1: Phn loi cc thuc h huyt p theo v tr hoc c ch tc dng
1. Thuc li niu: lm gim th tch tun hon

- Nhm thiazid
- Thuc li niu quai
2. Thuc hu giao cm
- Tc dng trung ng: methyldopa, clonidin
- Thuc lit hch: trimethaphan
- Thuc phong to nron: guanethidin, reserpin
- Thuc chn : propranolol, metoprolol
- Thuc hu : prazosin, phenoxybenzamin
3. Thuc gin mch trc tip
- Gin ng mch hydralazin, minoxidil, diazoxid
- Gin ng mch v tnh mch: nitroprussid
4. Thuc chn knh calci
Nifedipin, felodipin, nicardipin, amlodipin.
5. Thuc c ch enzym chuyn angiotensin
Captopril, enalapril, ramipril.

6. Thuc i khng ti receptor angiotesin II
Losartan, Irbesartan
2. Thuc chn knh calci

2.1. Khi nim v knh calci
Nng Ca ngoi t bo 10.000 ln hn trong t bo (10 -3 M so vi 10 -7 M) v khi ngh
mng t bo hu nh khng thm vi Ca, ng thi c bm Ca cng vi s trao i Na + -
Ca++ y Ca ++ ra khi t bo.
Ca vo t bo bng 3 ng (knh):
2.1.1. Knh hot ng theo in p (voltage operated chanel-VOC hoc cn gi l POC:
potential operated channel): hot ng theo c ch tt c hoc khng c g (hoc
hon ton m hoc hon ton khp kn) gy ra do s kh cc mng (t -90mV ln -
40mV). Thuc h knh loi ny cn c c knh Na+, K+. Tu vo s dn (conductance) v
s cm th (sensitive) vi in th, knh VOC cn c chia thnh 4 loi knh:
- Knh L (long acting): c nhiu trong c tim v c trn thnh mch
- Knh T (transient): c trong cc tuyn tit
- Knh N (neuron): c trong cc nron
- Knh P (purkinje): c trong purkinje tiu no v nron.
Knh T, N v P t cm thu vi thuc chn knh Ca.
2.1.2. Knh hot ng theo receptor (receptor operated channel -ROC): p ng vi cc
cht ch vn.
2.1.3. Knh d :
Tri vi 2 knh trn, knh ny lun c m cho qua lung Ca nh, nhng lin tc.
Ca t bo hoc vo li bo tng v t li bo tng ra, lm cho nng Ca trong bo
tng t 10 -7 M (nng gin c) tng ln 10 -5M (nng co c), s kt hp c vi
calci protein (troponin/calmodulin-CaM) v gy ra nhiu tc dng sinh l.
2.2. Vai tr sinh l ca Ca trn tim mch
10-3 M Ca++ VOC
S.R
Dn truyn nh tht Ca++ 10-7M 10-5M
Troponin Calmodulin
Tnh t ng tim nhp bo/ xut bo
Prot. Co bp Proteinkinase
enzyme gii phng TGHH
Co bp tim Ch.ha co c trn thnh mch
VOC: knh hot ng theo in p

SR: li bo tng
Hnh 24.1: Vai tr ca Ca++ sau khi qua knh
Trn c tim, Ca++ gn vo troponin, lm mt tc dng c ch ca troponin trn chc nng
co bp, do cc si actin c th tng tc vi myosin, gy co c tim. Trn c trn thnh
mch, khi calci ni bo tng s to phc vi calmodulin, phc hp ny s hot ha cc
protein-kinase (phosphoryl ha myosin kinase chui nh), thc y s tng tc gia
actin v myosin, gy co c trn thnh mch (Hnh 24.1)
Sau khi tc ng, nng Ca 2+ ni bo s gim do Ca 2+ c bm li vo ti li ni bo
hoc y ra khi t bo do bm v do trao i vi Na +.
S trao i Na +/Ca2+ c th thc hin c hai chiu: Na + vo Ca2+ ra, hoc Na + ra Ca2+ vo.
Trong iu kin sinh l bnh thng Na + vo v Ca 2+ ra, ngha l s trao i ny c vai
tr chnh trong vic gi nng Ca 2+ thp trong t bo. Khi c tr Na + trong t bo (th
d digitalis phong ta bm Na +) th hot ng theo chiu ngc li: Ca 2+ vo t bo
trao i vi Na + i ra, gy tc dng tng co bp tim.
Khc vi knh Na +, knh calci chu nh hng rt mnh ca cc yu t ngoi lai (trung
gian ha hc, hormon) v cc yu t ni ti (pH, ATP). Ni chung, cc knh Ca ch hot
ng khi trc c phosphoryl ha. S phosphoryl ha ph thuc vo hot tnh ca
adenylcyclase.
2.2. Cc thuc chn knh calci
Fleckenstein (1964) ln u tin a ra khi nim chn knh calci khi m t tc dng ca
verapamil trn t bo c tim, l thuc c tng hp phng theo cng thc cu to ca
papaverin. Cc thuc thuc nhm ny gn c hiu trn knh v phong ta knh, tuy cu
trc ha hc rt khc nhau.
2.2.1. Phn loi
Theo cu trc ha hc v c im iu tr, c 3 nhm thng thng.

Sau li chia thnh th h: th h 1 l thuc chn knh Ca mng t bo v mng ti
li ni bo; th h 2 tc dng nh th h 1 nhng chn lc trn t bo c trn thnh
mch hoc tim hn. Tc dng ko di.
Bng 24.2: Cc thuc chn knh calci
Nhm ha hc Tc dng c hiu Th h 1 Th h 2

Felodipin
Nicardipin
Dihydropyridin ng mch > tim Nifedipin Nimodipin
Amlodipin
Benzothiazepin ng mch = tim Diltiazem Clentiazem
Phenyl alkyl amin Tim > ng mch Verapamil Gallopamid

Anipamil
Thuc c tc dng trn ng mch mnh hn trn tim do lm gin mch nhanh v mnh,
d gy h huyt p nhanh, dn n phn x lm tn g nhp tim, khng li, nht l trn c
tim b thiu mu. Verapamil do c tc dng c ch trn tim mch hn trn ng mch
nn thng c ch nh trong lon nhp tim (xin xem thm bi Thuc cha lon nhp
tim).
2.2.2. Dc ng hc
Cc thuc chn knh calci tc dng theo ng ung v chu s chuyn ha qua gan ln
th 1, v vy ngi ta nghin cu thay i cc nhm chc trong cng thc cu to, lm
cho thuc chm b chuyn ha, chm b thi tr hoc n nh hn, c tnh chn lc hn.
Do to ra cc thuc th h 2, 3.
Bng 24.3: Dc ng hc mt s thuc chn knh calci
Thuc Hp thu Khi pht tc t/2 Phn phi

(ung) dng (gi)
Nifedipin 45- 70% - tm: < 1 pht 4 - Gn protein huyt tng90%
- Ngm, ung - B chuyn ha, thi qua thn
5- 20 pht
Nicardipin 35% ung: 20 pht 2- 4 - Gn protein huyt tng 95%
- B chuyn ha, thi qua gan
Felodipin 15- 20% ung: 2- 5 h 11- 16 - Gn protein huyt tng >
99%
- B chuyn ha nhanh gan
Nimodipin 13% cha c ti liu 1- 2 - B chuyn ha nhiu

- Lm gin mch no mnh
Nisoldipin < 10% - 2- 6 - B chuyn ha nhiu
- Lm gin mch vnh mnh
Amlodipin 65- 90% - 30- 50 - Gn protein huyt tng
>90%
- B chuyn ha nhiu
Bepridil 60% Ung: 1 h 24- 40 - Gn protein huyt tng >
99%
- B chuyn ha nhiu
Diltiazem 40- 65% - Tim tnh 3- 4 - Gn protein huyt tng
mch < 3 pht 70-80%
- Ung:>30 pht - B chuyn ha, thi qua phn
Verapamil 20- 35% - Tim tnh 6 - Gn protein huyt tng 90%
mch: < 1,5pht - Thi qua thn 70%
- Ung: 30 pht - Thi qua rut 15%
2.2.3. C ch tc dng
Cc thuc chn knh Ca gn ch yu vo knh L, l knh c nhiu t bo c tim v c
trn thnh mch. Nifedipin v cc thuc nhm dihydropyridin (DHP) gn vo mt v tr
mt trong knh, trong khi verapamil v diltiazem gn vo tr tr khc. Knh L c nhiu
di n v 2, , v . DHP gn ch yu vo . Ngoi ra, DHP c th cn c ch
nucleotid phosphodiesterase vng nn lm tng nucleotid vng, gy gin c trn: thuc
cng phong ta knh hot ng theo receptor, nhng mc km hn.
Knh T v N rt km nhy cm vi thuc nn nron v cc tuyn tit t chu nh hng
ca cc thuc ny.
2.2.4. Cc tc dng trn c quan
2.2.4.1. Trn c trn
Lm gin cc loi c trn: kh - ph qun, tiu ha, t cung, nhng c bit l thnh mch
(mao ng mch nhy cm hn mao tnh mch).
2.2.4.2. Trn c tim
Hot ng ca tim ph thuc nhiu vo dng Ca (xem in sinh l ca tim). Thuc chn
knh Ca lm gim to xung tc, gim dn truyn v gim co bp c tim, v th lm gim
nhu cu oxy trn bnh nhn c co tht mch vnh. Mc tc dng gia cc thuc c
khc nhau.
2.2.4.3. Mch no
Nimodipin c i lc cao vi mch no, v vy c dng cho bnh nhn c tai bin mch
no (chy mu di mng nhn gy co mch do chn p; t qu c vim tc mch).
Nhng cn cha r kt qu iu tr l do gin mch no hay l do lm gim nhu cu oxy

ca nron.
2.2.5. Tc dng khng mong mun v c tnh
- Tc dng nh, khng cn ngng iu tr: cn nng bng, nhc u, chng m t (do phn
x gin mch, tng nhp tim nn dng cng vi thuc chn giao cm), bun nn, to.
- Tc dng nng hn, lin quan n tc dng iu tr do c ch qu mnh knh Ca: tim
p chm, nghn nh tht, suy tim xung huyt, ngng tim. Him gp.
2.2.6. p dng lm sng trong iu tr THA
- Do lm gim lc co bp c tim, gim nhu cu oxy ca c tim, gim trng lc v sc
cn mch ngoi bin nn cc thuc ny c dng iu tr THA. Cho ti nay, cc
thuc chn knh calci c coi l thuc iu tr THA an ton v c hiu qu. Verpamil,
nifedipin, nicardipin v diltiazem u c hiu qu h p nh nhau. Tuy nhin, do c s
khc nhau v hiu qu huyt ng hc nn vic chn la iu tr c khc nhau:
Nifedipin c tc dng chn lc nht trn mch v tc dng c ch tim li yu nht. Phn
x giao cm hi lm tng nhp tim v lm tng hiu sut tim.
Verapamin c tc dng trn tim mnh nht, lm gim nhp tim v gim hiu sut tim.
Diltiazem c tc dng trung gian
- Ngn cn co tht mch vnh khu tr, c ch ch nh ca cn au tht ngc
- Verapamil, diltiazem lm gim dn truyn nh tht, c ch nh trong nhp tim nhanh
trn tht do ti nhp (xin xem bi Thuc chng lon nhp tim).
2.2.7. Ch phm
- Amlodipin: vin nn 2,5- 5- 10 mg
- Diltiazem: vin nn 30- 60- 90- 120 mg
Vin nang gii phng chm: 60 - 90- 120- 180 mg
Thuc tim 5 mg/ mL
- Felodipin (Plendil): vin gii phng chm 2,5 - 5- 10 mg
- Nifedipin (Adalat): vin nang 10- 20 mg
Vin gii phng chm 30 - 60- 90 mg
- Nimodipin (Nimotop): vin nang 30 mg
- Verapamil: vin nn 40- 80- 120 mg
Vin gii phng chm 120 - 180- 200 mg
Thuc tim 5 mg/ 2mL
3. Thuc c ch enzym chuyn angiotensin (ECA)
Enzym chuyn angiotensin (ECA) hay bradykinase II l mt peptidase c tc dng:

- Chuyn angiotensin I (decapeptid khng c hot tnh) thnh angiotensin II (octapepetid
c hot tnh) l cht c tc dng co mch v chng thi tr Na + qua thn.
- Lm mt hot tnh ca bradykinin, l cht gy gin mch v tng thi Na + qua thn.
Sau khi c hnh thnh, angiotensin II s tc ng trn cc receptor ring, hin c bit
l AT1, AT2, AT3, AT4, trong ch c AT 1 l c bit r nht (s ).
Hnh 24.2: Tc dng ca ECA v thuc c ch ECA
Cc receptor AT 1 c nhiu mch mu, no, tim, thn, tuyn thng thn. Vai tr sinh l :
co mch, tng gi Na +, c ch tit renin, tng gii phng aldosteron, kch thch giao cm,
tng co bp c tim v ph i tht tri.
Cc receptor AT 2 c nhiu tuyn thng thn, tim, no, c t cung, m bo thai. Vai tr
sinh l: c ch s tng trng t bo, bit ha t bo, sa cha m, kch hot
prostaglandin, bradykinin v NO thn.
3.1. C ch v c im tc dng
Cc thuc do c ch ECA nn lm angiotensin I khng chuyn thnh angiotensin II c
hot tnh v ngn cn ging ha bradykin, kt qu l lm gin mch, tng thi Na + v h
huyt p.
Trong iu tr tng huyt p, cc thuc ny c cc c im sau:
- Lm gim sc cn ngoi bin nhng khng lm tng nhp tim do c ch trng lc giao
cm v tng trng lc ph giao cm.
- Khng gy tt huyt p th ng, dng c cho mi la tui.
- Tc dng h huyt p t t, m du, ko di.
- Lm gim c huyt p tm thu v tm trng.
- Lm gim thiu mu c tim do tng cung cp mu cho mch vnh.
- Lm chm dy tht tri, gim hu qu ca tng huyt p.
- Trn thn kinh trung ng: khng gy trm cm, khng gy ri lon gic ng v khng
gy suy gim tnh dc.
3.2. Ch nh
- Thuc c tc dng iu tr tt cho mi loi tng huyt p:
. Trn ngi c tui, h huyt p khng nh hng n tun hon no v kh ng nh
hng n phn x p lc.
. Trn ngi c i tho ng: khng nh hng n chuyn ha glucid, lipid. Mt khc,
insulin lm K + vo t bo, gy h K + mu; thuc c ch ECA lm gim aldosteron nn gi
li K+.
. Trn ngi c bnh thn, do angiotens in II gim, lm lu lng mu qua thn tng nn
lm gim bi tit
- Suy tim sung huyt sau nhi mu c tim.
3.3. Tc dng khng mong mun
- H huyt p mnh c th xy ra khi dng liu u trn nhng bnh nhn c th tch mu
thp do ang s dng thuc l i niu, ch n gim mui hoc mt nc qua tiu ha.
- Suy thn cp nht l trn bnh nhn c hp mch thn.
- Tng Kali mu khi c suy thn hoc i tho ng.
- Ho khan v ph mch l do bradykinin khng b ging ha, prostaglandin tch lu
phi gy ho (nhiu khi lm bnh nhn phi b thuc).
- Khng dng cho ph n c thai 3 - 6 thng cui v thuc c th gy h huyt p, v
niu, suy thn cho thai, hoc gy qui thai, thai cht.
3.4. Phn loi v dc ng hc
3.4.1. Thuc c ch ECA
Thuc Captopril Enalapril Perindopril Benezepril Lisinopril
Cc thng s
Sinh kh dng % 70 40 70 17 25
Gn protein huyt 30 50 9- 18 95 3- 10
tng %
t/2 (h) 2 11 9 11 12
Khi pht tc dng 0,25 2- 4 1- 2 0,5 1- 2
(h)
Thi gian tc dng 4- 8 24 24 24 24
(h)
Liu ung 24h (mg) 75- 300 5- 20 2- 8 5- 20 5- 20
Enalapril, perindopril, benezepril u l tin thuc, vo c th phi c gan chuyn

ha mi c tc dng.
3.4.2. Thuc c ch ti receptor ca angiotensin II
Do vic chuyn angiotensin I thnh II cn c s tham gia ca cc enzym khc (nh
chymase) khng chu tc ng ca thuc c ch ECA nn s to thnh angiotensin II vn
cn. Mt khc, do thuc c ch ECA ngn cn s ging ha ca bradykinin nn
bradykinin phi tng, kch ng gy cn ho khan rt kh tr. V vy kch thch vic
nghin cu cc thuc c ch angiotensin II ngay ti receptor ca n: thuc c ch AT 1.
Cc thuc ny cn ang c nghin cu, nh gi trn cc th nghim lm sng. V
nguyn tc, do c tc dng ch n lc trn AT 1 nn trnh c tc dng ph ca bradykinin
(ho, ph mch).
Bng 24.4: Mt s c im dc ng hc ca cc thuc c ch AT 1
Thuc Losartan Valsartan Irbesartan Telmisartan

Cc thng s
i lc gn vo AT 1 + +++ ++++ +++
Sinh kh dng 33 25 70 43
t/2 (h) 2 (6- 9)* 9 11- 15 24
Thi tr Thn v gan Gan 70%; thn Gan 80%, thn Gan
30% 20%
Liu ung (mg/ 24 h) 50- 100 80- 320 150- 300 40- 80
* t/2 ca loscartan l 2 gi, nhng ca cht chuyn ha cn hot tnh l 6-9 gi.
4. Cc thuc h huyt p khc
4.1. Clonidin (2,6 diclorophenyl - amino - 2 imidazolin - catapres)

L thuc kch thch receptor 2 ca h giao cm trung ng nn lm gim trng lc giao
cm ngoi bin.
4.1.1. Tc dng
- Lm h huyt p do:
. Lm gim cng nng tim, gim nhp tim
. Lm gim sc cn ngoi bin, nht l khi trng lc giao cm tng.
. Lm gim sc cn mch thn, duy tr dng mu ti thn.
. Nh methyl dopa, clonidin rt t khi gy tt huyt p th ng.
- Cc tc dng khng lin qu an n h huyt p:
. An thn (do hu giao cm trung ng?) khong 50% trng hp.
. Kh ming do c ch trung ng: khong 50% trng hp.
. Gim au do gim hot tnh nron sng sau tu sng.
Nhng tc dng ny l do thuc gn vo receptor imidazolin c trong thn kinh trung
ng.
4.1.2. Dc ng hc
Thuc tan nhiu trong m, vo thn kinh trung ng nhanh. Ung hp thu tt, sinh kh
dng ti 100%, t c pic huyt tng sau 1 -3gi, t/2 khong 12gi. Thi tr qua thn
50% di dng nguyn cht.
4.1.3. Ch nh
- Tng huyt p
- Tin m: do c tc dng an thn, gim au nn lm gim c lng thuc m v tng
n nh huyt ng.
- Cai nghin: ma tu, ru, thuc l.
4.1.4. c tnh
- Kh ming, an thn: l tc dng trung ng, lin quan n liu dng.
- Ngng thuc sau dng lu v liu cao (>1mg/ngy) c th gp cn tng huyt p kch
pht do tng trng lc giao cm: bun nn, tim nhp nhanh, nhc u, v m hi.
Cn gim liu dn v dng thuc thay th. iu tr nn tng huyt p ny bng dng li
clonidin v dng cc thuc chn , chn giao cm.
Clonidin (Catapres)
Vin nn: 0,1 - 0,2 - 0,3mg
Ung 0,2 -1,2 mg/ngy, chia lm 2 ln

Cao dn: Gii phng 0,1 - 0,2 - 0,3mg/24gi. C tc dng 7 ngy cho 1 ln dn. C th c
phn ng ti ch dn.
4.2. Natri nitroprussid
L thuc gin mch mnh dng theo ng tim iu tr cp cu cn tng huyt p v
suy tim nng. Lm gin c ng mch v tnh mch. C ch: hot ho guanyl cyclase do
tc dng kch thch trc tip hoc th ng qua gii phng NO, dn n lm tng GMPv, gy
gin c trn.
Nitroprussid l mt phc hp ca st,

cc nhm cyanid v phn nitroso. c CN
tnh nng nht lin quan n s tch lu
cyanid; ngoi ra cn gp nhim acid, CN
lon nhp, tt huyt p.
Hydroxocobalamin (vitamin B 12) kt
hp vi cyanid to cyanocobalamin 2Na NC Fe CN
khng c, do c dng gii
c nitroprussid.
ON CN
Natrinitroprussid c ch nh trong cn tng huyt p, suy tim sung huyt (do lm gim
c tin gnh v hu gnh) v lm gim nhu cu oxy ca c tim sau nhi mu c tim.
Trong ngoi khoa cn dng lm h huyt p c kim tra khi gy m lm gim chy
mu do phu thut.
Nitroprussid (Nipride): l 50mg. Khi dng pha trong dextrose 5% - 250 - 1000 ml, truyn
tnh mch 0,5 g/kg/pht, c th tng ti 10 g/kg/pht. Chai thuc phi bc trong giy
mu, trnh nh sng. Kim tra huyt p thng xuyn.
5. Chin thut iu tr tng huyt p v cn
V THA v cn mang tnh cht rt a dng nn vic iu tr cng cn c th ha va
c hiu qu, va c th dung np c.
5.1. Ai cn c iu tr
- Mi ngi khi c HA 140- 90 mmHg
- Khi c tn thng c quan ch hoc c i tho ng, mc du HA cn gii hn
trn (130-139/85-89 mmHg).
Mc tiu iu tr l a HA v chun < 140/99mmHg, nhng khng n gin, M ch
27% bnh nhn THA t c ch t iu ny.
5.2. Cch iu tr
5.2.1. Phng php khng dng thuc
- n gim mui, gim ru, gim cn (bo)...
- Th dc u, nh nhng
5.2.2. Thuc
Cn c th ha, vi th cn iu tr th
- Lc u dng li niu, chn , chn knh calci v thm ch c cc t huc khc (chn 1
c ch ECA).
iu cn tu thuc vo bnh km theo: thuc c ch ECA khi c i tho ng; chn
khi c bnh mch vnh; chn knh Ca (loi dihydropyrindin) khi c THA tm thu ring
bit ngi cao tui. Lc u nn chn mt loi thu c.
- Khi mt thuc khng cho kt qu mong mun:
Khng nn tng liu v s c tc dng ph: thuc li niu (ri lon chuyn ha), chn
(tc dng trung ng, chm nhp tim), chn knh Ca (ph, nh trng ngc, nhc u,
nng mt), chn 1 (h HA th ng).
Thay thuc khc
Phi hp thuc c c ch khc nhau
Mt thuc h HA c th gy phn ng b tr, lm gim tc dng ca chnh n. Dng
thuc phi hp ngn chn phn ng b tr. Th d thuc li niu lm thi Na, gy tng
renin (dng thm thuc c ch EC A); thuc chn knh Ca gy tng nhp tim phn x
(dng chn ).
Hin c vin thuc phi hp sn. Tin dng nhng khng hay v khng c th ha
c.
Trong nhng nm gn y, vic iu tr THA tr nn n gin hn trc rt nhiu nh
c nhiu loi thuc hiu qu. Vn l phi c th ha trong iu tr mi bnh nhn c
th tm c cho mnh mt thuc thch hp va c hiu qu, va dung np tt.
5.3. Tiu chun thuc h huyt p l tng
- C tc dng h huyt p tt
. H HA t t, m du, ko di
. Gim c s ti a v s ti thiu
. Gim c ngi tr v ngi cao tui
. Lm mt nh tng huyt p trong ngy
- Khng lm mch nhanh do khng lm tng cng c tim v tng nhu cu oxy.
- Khng lm mch chm, trnh c nghn nh - tht
- Khng lm gim sc co bp ca c tim, nht l tht tri

- Dng c cho nhiu i tng: suy thn, tiu ng, tng lipid mu
- Khi ngng thuc, khng c nguy c "phn hi".
cu hi t lng gi
1. Phn loi cc thuc iu tr tng huyt p theo c ch tc dng ca th uc
2. Trnh by c ch tc dng v phn loi cc thuc chn knh calci.
3. Trnh by cc tc dng iu tr v tc dng khng mong mun ca thuc chn
knh calci.
4. Trnh by c ch tc dng ca thuc c ch enzym chuyn angiotensin (ECA).
5. Nu c im tc dng v ch nh iu tr ca ECA.
6. So snh u- nhc im ca thuc chn knh calci v ECA trong iu tr tng
huyt p.
Bi 25: Thuc li niu

1. Trnh by c c ch tc dng v p dng iu tr ca 4 nhm thuc li niu:
nhm thuc c ch enzym carbonic anhydrase, nhm thiazid, nhm thuc li niu
quai v nhm lu kali mu.
2. Nu c cc tai bin ri lon v ion khi dng cc thuc li niu ko di
3. Trnh by c c ch tc dng v p dng iu tr ca thuc li niu thm thu
1. i cng
Tt c cc cht lm tng khi lng nc tiu u c coi l c tc dng li niu (ung
nc nhiu lm i nhiu). Song nu ch nh vy th khng gii quyt c ph, l tnh
trng ng Na + dch ngoi t bo. Cho nn thuc li niu phi l thuc lm tng thi
tr Na+, km theo l thi tr nc ly t dch ngoi t bo.
Trn ngi khng c ph, thuc li niu vn c tc dng. l c s s dng n trong
iu tr cao huyt p: lm gim Na + ca thnh mch s lm tng tc dng ca thuc h p
v gim tc dng ca cc hormon gy co mch (nh vasopressin).
Ngoi tc dng c ch chn lc ti hp thu Na +, cc thuc li niu cn c nh hng trc
tip hoc gin tip n s bi xut ca mt s in gii hoc cc cht khc: K +, Cl-, HCO3-
, acid uric... v gy ra cc ri lon khi dng ko di.
hiu r c ch v cc tc d ng khng mong mun ca thuc li niu, cn nhc li qu
trnh vn chuyn ca mt s ion khi qua thn.
1.1. Vn chuyn ca Na +
- ng ln gn, khong 70- 80% Na + c ti hp thu cng vi cc cht hu c ha tan
(ng, acid amin), vi cc anion (acetat, phosphat, citrat, Cl -), vi bicarbonat di nh
hng ca carbonic anhydrase.
- on ln ca quai Henle, Na + tip tc c ti hp thu khong 15 - 20%, theo c ch
cng vn chuyn 1 Na +, 1 K+ v 2 Cl-.
- ng ln xa, ti hp thu Na + (0- 10%) ph thuc vo bi xut K + v H+:
. Trao i Na + v K+ di nh hng ca aldosteron, hormon lm tng ti hp thu Na + v
tng thi K +
. Trao i gia Na + v H+ ph thuc vo trng thi thng bng acid - base. Trong nhim
acid, c s tng thi tr H + nn lm tng ti hp thu Na +: c 1 ion H + thi tr vo lng ng
thn th 1 ion Na + c ti hp thu.
Trong nhim base c hin tng ngc li.

Kt qu cui cng l sau khi lc qua cu thn (25.000 mEq/ 24h), Na + c ti hp thu ti
98- 99%, ch thi tr 20- 400 mEq/ 24h.
1.2. Vn chuyn K +
K+ qua cu thn c ti hp thu hon ton ng ln gn. S c mt ca K + trong nc
tiu l do c bi xut ng ln xa bng cc qu trnh sau:
- nh hng ca aldosteron: thi K + v ti hp thu Na +
- nh hng ca trng thi thng bng acid- base: H + v K+ l 2 ion c thi tr tranh
chp ng ln xa. Trong nhim acid, khi tng thi tr H + trao i vi ti hp thu Na +
th s gim bi xut K +. Trong nhim base th ngc li, ion H + c to ra phn ln l do
enzym carbonic anhydrase (CA). ng ln xa, CA ng vai tr ch yu trong acid ha
nc tiu.
1.3. Bicarbonat
ng ln gn, 4/5 bicarbonat lc qua cu thn c ti hp thu do nh hng ca
enzym CA (hnh 25.1). Phn cn li hu nh s b ti hp thu nt ng ln xa (p H ca
nc tiu l acid nn khng cha bicarbonat).
1.4. Vn chuyn nc
- ng ln gn, nc c ti hp thu th ng theo cc cht in gii. Nc tiu trong
lng ng ng trng.
- nhnh xung ca quai Henle, nc c ti hp thu n thun, khng km theo in
gii, nc tiu ngy cng u trng.
Hnh 25.1. Ti hp thu bicarbonat ng ln gn
- nhnh ln ca quai Henle, nc khng thm qua c, trong khi Na + li c ti hp

thu, nn nc tiu dn dn tr thnh nhc trng. V vy, phn cui ca nhnh ln v
phn u ca ng ln xa c gi l on pha long.
Hnh 25.2. Vn chuyn nc v in gii n v thn

= : Nc tiu ng trng
+ : u trng
- : Nhc trng
- Trong ng gp, tnh thm vi nc c thay i ph thuc v o ADH, hormon chng bi

niu ca thu sau tuyn yn. Vi s c mt ca ADH, ng gp thm nc mnh, nc
c ti hp thu khng km theo ion, nc tiu c c c dn v tr thnh u trng.
Khi khng c ADH th ng gp khng thm nc, nc tiu t ng ln xa n vn gi
trng thi nhc trng trong ng gp (H.29).
Nh vy, cu thn lc 130 ml/ pht v bi xut nc tiu l 1 ml/ pht (1440 ml/ 24h).
Ngha l trn 99% nc tiu lc qua cu thn c ti hp thu. R rng l mun c tc
dng li niu nhanh khng phi l lm tng sc lc ca cu thn m l cn c ch qu
trnh ti hp thu ca ng thn.
2. Cc thuc li niu
Mi thuc li niu thng tc dng mt v tr nht nh ca ng thn, lm thay i
thnh phn ion ca nc tiu trong lng ng th n. S thay i s gin tip hoc trc
tip gy ra cc phn ng trong s vn chuyn cc ion v nc cc phn khc, v s l
nguyn nhn ca cc ri lon in gii, thng bng acid - base ca thuc. tin theo di
lm sng khi dng thuc li niu ko d i, ta chia thnh 2 nhm ln:
- Thuc li niu lm gim K + mu (tng thi tr K +)
- Thuc li niu gi K + mu (gim thi tr K +)
- Ngoi ra, c loi thuc li niu thm thu, khng gy ri lon ion.
2.1. Thuc li niu lm gim K + mu
Cc thuc ny do tc dng lm tng thi Na + on trn ca ng ln nn on cui
ca ng ln c phn ng tng thi K + gi Na +, gy cc ri lon gim K + mu v lm
tng c tnh ca thuc dng cng (nh loi digitalis).
2.1.1. Thuc phong to carbonic anhydrase (CA)
Cn gi l sulfamid li niu. Tt c u c nhm sulfonamid ( -SO2NH2) trong cng thc,
nhng khng c tc dng km vi khun.
2.1.1.1. Tc dng v c ch
ng ln gn, trong t bo ng thn, CA c tc dng lm gii phng ion H + vo lng
ng thn theo phn ng sau:
CA
H2O + CO 2 H2CO3 HCO 3- + H+

H+ c gii phng vo lng ng thn s trao i vi Na + c ti hp thu (hnh 1). Khi

enzym CA b phong ta, lng ion H + bi xut b gim nn Na + khng c ti hp thu,
thi tr ra nc tiu di dng bicarbonat, ko theo nc nn li niu. Mt khc, do s bi
xut tranh chp gia H + v K+, khi thiu H +, K+ s b tng thi tr. Tm li, thuc lm
tng thi tr Na +, K+ v bicarbonat (c th lm thi tr ti 45% lng HCO 3- qua thn), do
lm gim K + mu v gy nhim acid chuyn ha. Tnh trng nhim acid ny ch b tr
sau 3- 7 ngy v sau l nguyn nhn t gii hn hiu qu ca thuc: dng thuc lin
tc, tc dng b gim nhanh. Do qu trnh b tr, nng Cl - huyt tng tng (do tng
ti hp thu NaCl)
Ngoi ra mt (cun m) v thn kinh trung ng cng c enzym CA. Thuc c ch
enzym lm gim tit thu dch ca mt, gim sn xut dch no ty v gy toan chuyn
ha trn thn kinh trung ng.
2.1.1.2. Ch nh
- V c nhiu thuc li niu tt hn nn thuc ny khng cn c dng vi mc ch li
niu. Ch nh ca thuc lin quan n tc dng thi tr bicarbonat v tc dng ngoi
thn.
- iu tr tng nhn p (glcm gc m) do thuc lm gim tit dch nhn cu.
- iu tr chng ng kinh: ngoi tc dng lm gim to thnh dch no tu, thuc cn c
tc dng chng co git. Trong no, cc qu trnh oxy ha xy ra rt nhanh cho nn CO 2
cng c sinh ra nhanh. Thuc phong to enzym CA bo tng, lm tch lu H 2CO3
gy nhim acid t bo nn lm thay i chc phn t bo thn kinh.
2.1.1.3. Chng ch nh
- Bnh tim phi mn tnh, hoc cc bnh phi mn tnh c suy h hp v tng CO 2
mu, v cc thuc phong to CA ngn cn ti hp thu bicarbonat cn thit nh l cht m
trung ha trng thi qu tha CO 2 trong m.
- X gan v suy gan, v thuc gy acid mu, d lm xut hin hn m gan.
2.1.1.4. Tai bin
- Gy acid huyt do lm gim d tr base, khi tc dng ca thuc cng b gim i nu
dng thuc nhiu liu lin nhau, cho nn cn d ng ngt qung.
- Gim K + mu, gy mt mi, hoc d xy ra nhim c khi ang iu tr bng digitalis.
2.1.1.5. Ch phm
Vin 0,25 g. Mi ngy ung 1 vin. Trong bnh tng nhn p, c th ung 4 - 6 vin mt
ngy. Hp thu nhanh qua ng tiu ha, gn v i protein huyt tng 92%. Thi gian bn
hy ngn, khng b chuyn ha. Thi tr hon ton qua nc tiu trong 24 gi.
2.1.2. Nhm thiazid (benzothiadiazid)
Trong phn t c 2 nhm sulfonamid ( -SO2NH2), 1 t do v 1 nm trong d vng.
Tc dng c ch CA km acetazolamid (Diamox), nhng tc dng li niu li nhanh hn
v vy cn c nhng tc dng khc m c ch cn cha hon ton bit r. L thuc tc
dng trc tip trn thn, tim vo 1 thn th gy li niu ch cho thn (tuy nhin cha
tm thy receptor hay enzym c hiu).
Thiazid c ch ti hp thu Na + v km theo l c Cl - (v tr ng vn chuyn) on pha
long (phn cui ca nhnh ln quai Henle v phn u ca ng ln xa), thi tr Na + v
Cl- vi s lng gn ngang nh au nn cn gi l thuc li niu thi tr mui (saluretics).
Khong 5- 10% Na + lc qua cu thn b thi tr nn thuc loi thuc c tc dng li niu
trung bnh.
Thuc c tc dng c mi trng acid v base.
- Lm tng thi tr K +, theo 2 c ch: mt ph n do thuc c ch enzym CA, lm gim bi
tit ion H + nn tng thi K + (c ch thi tr tranh chp ng ln xa); mt phn do c ch
ti hp thu Na + lm m Na + tng cao ng ln xa, gy phn ng b tr bi xut K +
ko Na + li.
- Khng lm tng thi tr bicarbonat nn khng gy acid mu.
- Lm gim bi tit acid uric qua ng thn nn c th lm nng thm bnh gut. Cc
thiazid c thi tr qua h thi tr acid hu c ca ng thn nn tranh chp mt phn vi
thi tr acid uric qua h ny.
- Dng lu, lm gim calci niu do lm tng ti hp thu Ca ++ ng ln gn v c xa nn
c th dng d phng si thn. Tuy nhin, him khi gp tng calci mu do thiazid v c
th c cc c ch b tr khc.
- Lm h huyt p trn nhng bnh nhn b tng huyt p v ngoi tc dng lm tng thi
tr mui, cc thuc cn c ch ti ch tc dng ca thuc co mch trn thnh mch, nh
vasopressin, noradrenalin. Mt khc, do lng Na + ca m thnh mch gim nn dch
gian bo ca thnh mch cng gim, lm lng mch rng ra , do sc cn ngoi vi gim
xung (huyt p ti thiu h).
2.1.2.2. Ch nh
- Ph cc loi: tim, gan, thn, c th gy thiu mu thai v teo thai, khng dng cho ph
v tng huyt p khi c thai. C th dng cho ph tim, gan, thn ngi c thai.
- Tng huyt p: dng ring hoc dng cng vi cc thuc h p khc, v c tc dng hip
ng.
- Tng calci niu khng r nguyn nhn d dn n si niu.

2.1.2.3. Chng ch nh hoc dng thn trng
- Trng thi gim kali- mu trn bnh nhn b x gan (v d l m xut hin hn m gan),
trn bnh nhn ang iu tr bng digital (s lm tng c tnh ca digital). Khc phc
bng ung KCl 1- 3 g mt ngy.
- Bnh gut: do thiazid lm tng acid uric mu
- Suy thn, suy gan, khng dung np sulfamid (gy bnh no do gan ).
2.1.2.4. Tai bin
Khi dng lu, thuc c th gy cc tai bin sau:
- Ri lon in gii: h Na + v K+ mu (theo c ch trnh by trn), gy mt mi,
chn n, nhc u, bun nn, chut rt.
- Tng acid uric mu gy ra cc cn au ca bnh gut. iu tr bng probenecid.
- Lm nng thm i ng ty. C ch cha r.
Mt s tc gi thy thiazid c ch gii phng insulin v lm tng bi tit catecholamin
u dn ti tng ng huyt.
- Lm tng cholesterol v LDL mu khong 5 - 15%. Tuy nhin khi dng k o di th c 2
mc li tr v bnh thng.
- Mt s biu hin d ng hoc khng chu thuc.
- Cc thiazid lm gim tc dng ca cc thuc chng ng mu, thuc lm tng thi tr
uric iu tr gut, cc sulfonylure v insulin.
- Cc thiazid lm tng tc dng ca thuc t, diazoxid, glycosid tr tim, lithi, thuc li
niu quai v vitamin D.
- Tc dng li niu ca thiazid b gim khi dng cng vi thuc chng vim phi steroid.
Amphotericin B v corticoid lm tng nguy c h kali mu ca thiazid.
2.1.2.6. Ch phm: mt s thuc thng dng
Chc halogen C 6 v nhm sulfamid C 7 rt
cn cho tc dng li niu ca c nhm. Thay
nhm -SO2 NH2 C7 bng Cl, c diazoxid
c tc dng ngc vi chlorothiazid, gi Na +,
nhng c tc dng gin mch, h huyt p.
Hydrochlorothiazid do bo ha ng ni 3 - 4,
c tc dng thi tr Na + mnh gp 10
chlorothiazid.
Bng 25.1: Mt s ch phm

Tn thuc X ng Y Z Thi Mc Liu lng
ni 3- 4 gian tc thi tr
dng mui
Chlorothiazid Cl Ni kp H H 8- 12h 1 0,5- 2,0g
Hydrochlorothiazid Cl Bo ha H H 8- 12h 10 0,025- 0,1
(hypothiazid)
Hydroflumethiazid
CF3 Bo ha H H 8- 12h 10 0,025- 0,1
Methylchlothiazid
Cl Bo ha -CH2Cl CH3 12- 24h 200 0,005- 0,01
Polythiazid
Cl Bo ha -CH2-S- CH2 - CF3 CH3 30h 500 0,002- 0,004
Hin nay c thm mt s ch phm mi:

- Chronexan (Xipamid). Vin 20 mg
D hp thu qua tiu ha. nh huyt tng 45 pht - 2 gi sau khi ung liu duy nht.
T1/2: 6- 8h. Gn vo protein huyt tng 95%. Thi 90% qua thn, ch yu l dng khng
i.
Ung liu duy nht bui sng 10 - 40 mg
- Hygroton (Chlorthalidone) . Vin 25 mg
Hp thu chm. T 1/2 l 50 gi.Thi 1/2 qua thn di dng khng i. Qua c sa.
Ung 1 ln vo bui sng, 1 - 2 vin
- Fludex (Indapamid) vin 2,5 mg, Natrilix vin 1,5 mg.
c im: . Gin mch (thay i dng ion, c bit l Ca)
. Kch thch tng hp PGE 2 v PGI2 (gin mch v chng vn tiu cu)
. Khng nh hng n chuyn ha ng v lipid
ng hc: t c nh huyt tng sau 1 - 2h. Gn 75% vo protein huyt tng, T 1/2 =
14- 24h
2.1.3. Thuc li niu tc dng mnh hay thuc li niu "quai" ("loop diuretics")
l nhm thuc c tc dng rt mnh so vi cc thuc li niu bit v v tr tc dng
l on phnh to ca nhnh ln quai Henl e. on ny c qu trnh ti hp thu ti 35%
lng Na + v Cl- ca nc tiu ban u. Thuc tiu biu l furosemid v acid ethacrynic.
2. 1.3.1. Tc dng v c ch
- c ch c ch cng vn chuyn (cotransport mechanism) ca 1Na +, 1K+ v 2 Cl - on
phnh to ca nhnh ln quai Henle. V vy lm tng thi tr Na +, Cl- (gn ngang nhau) v
K+ (t hn thiazid).
- Furosemid v bumetanid cn c c tc dng c ch carbonic anhydrase do trong cng

thc cng c gc sulfonamid. Nhng tc dng ny ch rt yu.
- Tuy c lm tng thi tr ion H +, nhng pH nc tiu t thay i v tc dng c ch
carbonic anhydrase b tr li.
- Cc thuc nhm ny lm tng thi tr Ca ++ v c Mg ++, tri vi tc dng ca thiazid, v
vy c th dng iu tr tng calci mu triu chng. V Ca++ cn c ti hp thu ng
ln nn thng ch thy h Mg ++ mu khi dng lu.
Kt qu l cc thuc li niu "quai" c th lm thi tr ti 30% s lng nc tiu lc qua
cu thn, vt qu s lng nc ti hp thu ca quai Henle, cho nn c th cn c mt
s c ch ph c ch ti hp thu ng ln gn. Hin l thuc c tc dng li niu mnh
nht.
2.1.3.2. Ch nh
- Nh nhm thiazid
- V c tc dng nhanh nn cn c dng trong cp cu: cn ph nng, ph phi cp,
cn tng huyt p, tng calci huy t cp tnh.
2.1.3.3. Tai bin
- Do thi tr qu nhanh nc v in gii nn c th gy mt mi, chut rt, tin hn m
gan, h huyt p.
- Ging nhm thiazid, c th gp tng acid uric mu, tng ng mu.
- Dng lu, do tng thi tr Cl -, K+ v H+ nn c th gy nhim base gim Cl -, hoc nhim
base gim K +.
- Do lm tng thi tr Mg ++ v Ca++ nn c th gy h Mg ++ mu (d gy lon nhp tim) v
h Ca++ mu (him khi dn n ttani)
- Nhng biu hin khc c th gp: ri lon tiu ha (c khi l chy mu), gim s lng
hng bch cu, ri lon chc phn gan thn, sn da, t b.
- Duy nht vi nhm ny l c tnh vi dy VIII, c th gy ic tai do ri lon ion trong
ni dch hoc do c ng. V vy khng nn dng cng vi khng sinh nhm aminosid.
2.1.3.4. Ch phm v liu lng
* Ethacrynic acid (Edecrin): trong cng thc c cha ceton khng bo ha cho nn d
phn ng vi nhm sulfydril ca cc enzym vn chuyn ion ca ng thn.
- Vin 25 hoc 50 mg. Ung 50 - 200 mg/ ngy
- ng bt Edecrin natri 50 mg. T im tnh mch 50 mg hoc 0,5mg/kg cn nng. Khng
tim bp hoc di da v thuc kch thch ti ch gy au.
Hp thu nhanh qua ng tiu ha. Gn nhiu vi protein huyt tng, t/2 di 1 gi.
Thi tr qua thn 40% di dng khng chuyn ha.
* Furosemid (Lasix, Lasilix, Trofurit)

L dn xut ca acid anthranilic, c cha gc sulfonamid trong cng thc.
- Vin 20, 40 v 80 mg. Ung 20 - 80 mg/ ngy
- ng 2 ml = 20 mg. Tim bp hoc tnh mch: 1 - 2 ng
Trong ph phi cp, sau liu u 60 - 90 pht c th tim nhc li.
Tc dng li niu xut hin nhanh, 3 - 5 pht sau khi tim tnh mch, 20 pht sau khi
ung. Ht tc dng sau 4 - 6h.
Thuc d hp thu qua tiu ha, mt phn gn vi protein huyt tng. Ch yu nm ngoi
t bo v t tan trong m. Thi tr phn ln di dng khng chuyn ha.
* Bumetanid (Bumex):
L dn xut ca acid 3 - aminobenzoic, trong cng thc cng cha nhm sulfonamid.
Mnh hn furosemid 40 ln.
- Vin 0,5- 1,0 v 2,0 mg. Ung 0,5- 2,0 mg
- ng 0,5- 1,0 mg. Tim bp hoc tnh mch 0,5 - 1,0 mg.
2.2. Thuc li niu gi kali - mu (gim thi tr K +)
Cc thuc li niu thuc cc nhm trn khi dng lu u gy gim kali - huyt. Cc thuc
thuc nhm ny tc dng phn cui ng ln xa, do c ch ti hp thu Na + bng c ch
trao i vi bi xut K +, v th lm gim bi xut K +. ng thi thuc lm tng thi tr
bicarbonat, gim bi xut H + cho nn nc tiu nhim base.
Cc thuc ny hu nh khng dng mt mnh v tc dng thi Na + yu v tai bin tng
kali- mu thng bt li. Dng phi hp vi cc t huc li niu lm gim kali - mu s gi
c tc dng thi tr Na + v khc phc c ri lon h K + mu. C nhiu bit dc
phi hp.
2.2.1. Thuc i lp vi aldosteron
Spironolacton (Aldacton) : cng thc gn ging vi aldosteron, tranh chp vi aldostero n
ti receptor ng ln xa, nn cn gi l thuc khng aldosteron. Tc dng thi tr Na +
ca thuc ph thuc vo s lng aldosteron bi tit v b c ch. Tc dng xut hin
chm sau 12- 24 gi.
- Vin 25 mg. Ung mi ngy 2 - 4 vin
- Dng lu c th gy tc dng ph ging hormon: nam gy chng v to, n gy
chng rm lng v lon kinh nguyt.
2.2.2. Thuc khng i lp vi aldosteron
Triamteren (Teriam). Cn gi l khng aldosteron gi (pseudo - anti- aldosterone). Cng
thc hon ton khng ging vi aldosteron nn khng c tc dng tranh chp vi
aldosteron.
Lm tng thi Na +, Cl- do lm gim tnh thm ca ng ln xa vi Na +. Lm gim bi

xut K+ v H+. Tc dng c khi c mt cng nh khi khng c mt aldosteron (ng vt
ct b thng thn). Spiron olacton lm tng tc dng ca triamteren cho nn 2 thuc tc
dng trn 2 receptor khc nhau.
Tc dng ti a t c sau khi ung 2 gi v ch gi c tc dng trong 10 gi.
- Nang 100 mg. Ung 1- 2 nang/ ngy
- C th gy bun nn, nn, chut rt, ng g .
Amilorid (Modamid): tc dng thi Na +, lu K+ mnh hn triamteren. Ngoi c ch tc
dng theo kiu triamteren, amilorid cn tc dng trn c ng ln gn.
Nng ti a trong mu t c 4 gi sau khi ung, thi gian bn hu khong 6 gi,
tc dng ko di 24 gi.
- Vin 5 mg. Ung mi ngy 1 vin. Khng vt qu 20 mg/ ngy
2.3. Thuc li niu thm thu
Thuc li niu thm thu dng ch mt s cht ha tan c cc tnh cht sau:
- c lc t do qua cu thn
- c hp thu c gii hn khi qua ng thn
- Hu nh khng c hot tnh dc l
Nhng cht ny c dng vi s lng tng i ln lm thay i mt cch c
ngha nng osmol trong huyt tng hay trong nc lc cu thn, hoc dch ng thn.
Hin ch c mannitol l c dng nhiu hn c.
2.3.1. Ch nh
Do khng lm tng thi tr Na + nn khng dng c trong cc chng ph.
Thng dng phng nga i t sau m, sau chn thng, tng p lc trong s, hoc
lm tng li niu trong cc trng hp nhim c thi tr cht c.
2.3.2. Chng ch nh
- Mt nc trong t bo
- Suy tim
2.3.3. Ch phm
Mannitol dung dch 10 - 20% ng trong l 250- 500 v 1000 ml dng truyn nh git
tnh mch.
Mannitol thi tr qua cu thn v ch khong 10% c ti p thu ng ln, do lm
tng p lc thm thu trong ng ln, c ch ti hp thu nc, gy li niu.
cu hi t lng gi
1. Trnh by c ch tc dng v p dng iu tr ca thuc c ch enzym carbonic
anhydrase (CA).
2. Trnh by c ch tc dng v tc dng ca nhm thiazid.
3. Phn tch v so snh ri lon in gii ca thuc c ch CA v thiazid.
4. Trnh by c ch tc dng v tai bin ca thuc li niu quai .
5. So snh tc dng v c ch ca 2 nhm thuc li niu gi kali - mu.
6. Trnh by c ch tc dng v p dng iu tr ca mannitol.
Bi 26: cc cht in gii chnh v cc dch truyn

1. Phn bit c cc du hiu tha v thiu Na +, K+, Ca++
2. Trnh by c cc thuc iu chnh ri lon (tha hoc thiu) cc ion trn.
3. Phn tch c s khc nhau gia dch b ion v dch thay th huyt tng.
4. Trnh by c vai tr ca cc dch dinh dng.
1. cc cht in gii chnh

1.1. Natri
1.1.1. Vai tr sinh l
- Gi vai tr sng cn: duy tr nng v th tch dch ngoi t bo. Na + l ion ch yu
ngoi t bo, v vy ri lon Na + bao gi cng km theo ri lon nc.
- Gi tnh kch thch v dn truyn thn kinh - c do duy tr hiu th hot ng gia trong
v ngoi t bo.
- Duy tr thng bng base acid
iu ha Na trong c th d o hormon v thng thn aldosteron (ti hp thu Na + v thi
K+, H+ qua ng thn) v hormon vasopressin (hay ADH, hormon chng bi niu) ca
tuyn hu yn.
Natri mu bnh thng l 137 - 147 mEq/L
1.1.2. Thiu Na (gim natri - mu; hyponatremia)
Khi Na- mu < 137 mEq/L
1.1.2.1. Nguyn nhn
- Nhp nhiu nc, tng tit ADH
- Mt nhiu Na +: do m hi, do dng thuc li niu thi Na (nh loi thiazid), do thiu
aldosteron.
1.1.2.2. Lm sng
- Na+ gim, lm gim p lc thm thu ca huyt tng, nc t ngoi t bo s i vo
trong t bo. c bit l khi t bo thn kinh b "trng", s gy cc triu chng thn kinh
nh: kch thch, mi mt, lo s, run tay, tng phn x co tht cc c, hn m.
Khi Na+ mu t 120- 125 mEq/L: cha c du hiu thn kinh
115- 120 mEq/L: bun nn, u oi, nhc u

< 115 mEq/L : co git, hn m
- Mt Na + c th i km theo mt dch, lm gim th tch dch ngoi t bo
+ Nguyn nhn:
. Tiu ha: tiu chy, nn, c ng thng ht dch
. Thn: dng li niu, suy thng thn
. Da: bng, dn lu vt thng
+ Lm sng: gim th tch mu, gim p lc tnh mch trung tm, gim p lc ng mch
phi v huyt p trung bnh
- Na+ mu gim , nhng th tch dch ngoi t bo vn bnh thng hoc tng.
+ Nguyn nhn
. Hi chng tng ADH, gi nc
. Ph do suy tim, s gan, thn h
. Truyn tnh mch qu nhiu dung dch nhc trng
+ Lm sng: ngc vi cc du hiu trn: th tch mu tng, tng p lc tnh mch trung
tm, tng p lc ng mch phi v huyt p trung bnh.
1.1.2.3. iu tr
-Bo v bnh nhn khi nguy c trc tip: nng ngay Na + ln trn 120 mEq/L, sau dn
dn a v bnh thng v cho thng bng vi dch ngoi t bo (xem 1.3.4.)
- Ch iu chnh in gii khc: K +, HCO3- (khi tiu chy nhiu).
- Ch dng dung dch mui u trng (3 -5%) khi Na + di 115 mEq/L v rt thn trng v
c th lm tng th tch trong mch.
- Nu Na + mu gim m dch ngoi t bo tng th dng "li niu quai" nh furosemid
(Lasix 0,2 - 0,3g/ ngy), v lm mt nc nhiu hn mt mui. Khng dng loi thiazid v
lm mt mui nhiu hn mt nc.
1.1.3. Tha natri (tng natri - mu, hypernatremia)
Khi Na+ mu > 147 mEq/L
do mt nc hoc do nhp nhiu Na +
1.1.3.1. Nguyn nhn
- Mt nc qua da, qua phi, bnh i nht, dng li niu thm thu, tng ng huyt.
- Nhp nhiu mui: truyn dung dch mui u trng, NaHCO 3, tng aldosteron, n nhiu
mui.
1.1.3.2. Lm sng
Tng p lc thm thu, tng trng lc ca dch ngoi t bo, nc trong t bo ra ngoi
t bo, gy kht, mt mi, nhc c, hn m, gim p ng vi ADH.
nh gi tnh trng tng hoc gim khi lng dch ngoi t bo bng o p lc tnh
mch trung ng v p lc ng mch phi.
1.1.3.3. iu tr
Ph thuc vo nguyn nhn
- Nu do mt nc: cho ung v truyn nc vo tnh mch
- iu chnh tng natri mu cn t t, khong 2 ngy tr nh mt lng nc ln vo
no, gy ph no. Cn theo di cc du hiu ph no: tng huyt p, gim nhp tim, lon
cm gic.
1.1.3.4. Tnh lng nc v mui iu chnh
* Thiu nc (trong Na + mu cao):
Th d Na + mu hin c l 160 mEq/L ([Na] 1), mun lm gim xung 150 mEq/L ([Na] 2)
bng pha long, cn bao nhiu nc (TNC 2)?
Gi s ngi bnh nng 50 kg, tng lng nc ca c th (TNC) chim 60%, l 30 lt.
Cng thc tnh l:
TNC1 [Na]1 = TNC 2 [Na]2
30 160 = x 150
30 160
x= = 32 L
150
S nc cn thm l 32L - 30 = 2 L
* Thiu Na +
Th d: Na + mu l 120 mEq/L, cn bao nhiu Na + nng ln 130 mEq/L?
Nh vy, mi lt cn 130 mEq - 120 mEq = 10 mEq. Vi th d trn, tng lng nc
trong c th (TNC) cho c dch trong v ngoi t bo l 30 lt, cn 10 30 = 300 mEq
Na+.
Pmg ha tr mEq phn t lng

Ta bit: mEq = Pmg =
Phn t lng Ha tr
Nh vy, lng Na + tng ng vi 300 mEq l:
300 23
Pmg = = 6900 mg
1
T tnh ra lng dung dch cn truyn tu theo vic ch nh dng nc mui ng

trng (0,9%) hoc u trng.
C th tnh ring cho dung dch ngoi t bo.
Nc chim 60% trong lng c th. Nc trong t bo chim 2/3 v ngoi t bo l 1/3.
1.2. Kali
K+ l ion ch yu trong t bo, c vai tr:
- m bo hiu th mng, tnh chu kch thch ca thn kinh - c
- Trn c tim, K + lm gim lc co bp, gim tnh chu kch thch v gim dn tru yn.
Tc dng i khng vi Ca ++ v glycosid, tim.
- Tham gia vo iu ha acid - base
y l qu trnh phc tp v K + tham gia vo:
+ C ch trao i ion qua mng t bo
+ Chc phn thi tr qua thn; lin quan vi thi tr H +
* Thng bng ion qua mng t bo:
Nng trong t bo ca K + v H+ ln hn ngoi t bo
- Khi H+ thay i l nguyn pht:
. Nu nng H + ngoi t bo tng (acid mu) th H + s i vo t bo, v gi thng
bng ion, K + s ra khi t bo, gy tng K + mu: acid huyt tng kali (hyperkaliemic
acidosis).
. Ngc li, nu H + dch ngoi t bo gim (base mu) th H + trong t bo s i ra. V
gi thng bng ion, K + s i t ngoi vo trong t bo, gy gim kali mu: base mu
gim kali (hypokaliemic alkalosis).
pH huyt tng thay i 0,1 th K + thay i 0,6 mEq/L
- Khi K+ thay i l nguyn pht th lm H + thay i theo: nu K + i t trong ra ngoi t
bo th H + v Na+ s i vo gi thng bng ion, kt qu l ngoi t bo th base v trong
t bo th acid (trng hp mt nhi u K+).
* Chc phn iu ha ca thn:
Khi K+ tng cp tnh trong mu, thn tng thi K +, gim thi H +, nc tiu base v mu
cng acid.
Kali mu bnh thng l 3,5 - 5,0 mEq/L
1.2.2. Thiu kali (gim kali- mu- hypokaliemia)
Khi K+ mu < 3,5 mEq/L
1.2.2.1. Nguyn nhn

- Gim kali ton b c th: hi chng cng aldosteron, dng thuc li niu thi K + (loi
thiazid), mt K +qua ng tiu ha (nn nhiu, tiu chy, dn lu), mt K + qua thm
phn.
- K+ nhp t ngoi t bo vo trong t bo: do dng insulin hoc tng insulin n i sinh,
base mu, thi k phc hi t chc sau bng, sau chn thng.
Trong t bo tp trung mt s lng ln cc cht hu c khng khuch tn qua mng (cc
protein). mi trng pH ca dch th, cc nhm chc ca cc hp cht hu c ny u
tch in m nn gi l anion c nh ca t bo. m bo trung ha in, t bo phi
gi li mt s lng tng ng cation, l K + (chnh) v cc cation khc. T , h qu
l:
. Khi anion c nh tng (tng ng ha, sau n, tng insulin) th K + s i vo t bo.
. Khi anion c nh gim (d ha, i, sc, tng cortisol) th K + s ra khi t bo.
- Stress: do c tng tit aldosteron v adrenalin t thng thn. Adrenalin lm tng nhp
K+ vo t bo.
1.2.2.2. Lm sng
- Lit gc chi, sau l u chi. S thy c chc, g im phn x gn xng, cm gic
cn bnh thng, sau l chut rt v d cm (thm c ri lon Na v Ca)
- Chng bng, lit rut, to, b i
- Tim: mch rng, nhy, tng nh. in tim: ST h dn, T c bin gim dn, ng in
ri m, QT di.
1.2.2.3. iu tr
- Cc ch phm:
. Dung dch KCl: cha 20 mEq/ 15 mL (hoc 1 tha canh)
. Vin bao cha 4- 8 mEq.
. ng tim: 1 mL cha 1 mEq (dung dch 7,5%) hoc 1 mL cha 2 mEq (dung dch
15%); ng ng 10- 20 mL- 30mL.
Khi dng pha long trong huyt thanh ngt ng tr ng.
- Liu lng:
. D phng gim K- mu (khi dng li niu lu): 50 mEq/ ngy (tng ng 4,0g KCl),
chia liu nhiu ln.
. Liu truyn ti a 10- 20 mEq/ h ; 50- 100 mEq/ ngy
Dung dch truyn tnh mch cha 30 - 40 mEq/L. Dung dch m c qu gy huy t khi
v hoi t nu tim chch tnh mch.
- Tai bin khi dng qu liu:

. Du hiu in tm : T rng v nhn, P dt, PR di, phc hp QRS rng.
. X tr: truyn dung dch NaHCO 3, hoc dung dch huyt thanh ngt c thm 10 n v
insulin cho 100 g gluco se (xem phn iu tr tng kali mu)
1.2.3. Tha kali (tng kali mu; hyperkaliemia)
Khi kali mu > 5 mEq/L
1.2.3.1. Nguyn nhn
- Ung hoc truyn qu tha kali
- Tn thng nng m (t bo v, kali c gii phng)
- Acid huyt cp tnh (i khi acid huyt mn tnh)
- Bnh Addison
- Kch thch cp tnh receptor giao cm
- Dng li niu lu kali khng ng liu lng
- ng huyt tng
1.2.3.2. Lm sng
- n v cm. D cm u chi, li, mi.
- Lon vn mch: da lnh, m, ti. Nhc c, t b nht l chi di
- Trn in tim: nu kali tng va phi (5 - 7 mEq/L huyt tng), dn truyn trong c tim
b gim nh: sng T tng cao hoc ko di, PR di, P mt.
- Nu kali tng cao hn (8 -9 mEq/L huyt tng) s c ch mnh hn trn nt dn nhp v
s dn truyn trong ton b c tim: QRS di, c th mt tm thu (asystole), i khi trc
l nhp tht nhanh hoc rung tht.
1.2.3.3. iu tr
- Nha trao i cation: natri polystyren sulfonat (Kayexalate) l nha trao i Na +- K+, c
i lc vi K + mnh hn nhiu so vi Na +. rut, c bit l rut gi, n gii phng Na +
v gn K + ri b thi tr theo phn.
Kayexalat khng c hp thu khi ung v khng b tc dng ca dch tiu ha. Ngoi
K+, n cn gn c c ion ha tr 2 l Mg ++ v Ca++, nn c th gy gim Mg v Ca -
mu.
Thng gy to, nn dng cng vi sorbitol (vin 5 mg, 1 - 2 vin/ ngy, c tc dng
nhun trng).
. Ung 15 g 1- 4 ln/ ngy
. Cn kim tra K +, Mg++, Ca++, mu.
. Khng dng khi K + < 5 mEq/L v cn nh rng 1g nha gii phng 1 mEq Na +.
- Glucose v insulin: insulin lm K + nhp vo t bo, v glucose chng h ng huyt
do insulin gy ra.
Insulin 10- 15 n v
Huyt thanh ngt u trng 5 -%- 250- 500 mL
Tc dng h K + trong 6h.
- Natri bicarbonat: lm K + nhp vo t bo, tc dng tm thi trong 1 - 2h. Tim truyn
tnh mch dung dch 1,4% (c 166,6 mEq HCO 3- v 166,6 mEq Na + trong 1000 mL),
hoc dung dch 4,2% (c 500 mEq HCO 3-, 500 mEq Na/ lt).
- Calci gluconat: khng c tc dng trn nng K + nhng chng li tc dng c ca K +
trn tim.
ng 10 mL cha 4,5 mEq Ca ++. Tim tnh mch (trong khi CaCl 2 cha 13,6 mEq).
- Thm phn: dng nha trao i ion c th thi qu nhiu K +. Thm phn an ton hn, c
th dng cho c ngi suy thn.
1.3. Calci
- To xng, rng di dng calci phosphat
- Co c, dn truyn thn kinh, bi xut ca cc tuyn tit
- ng mu
- Tnh thm ca mng t bo
dch ngoi t bo c 1- 2% tng lng Ca. Trong mu, Ca di 3 dng: 50% di
dng ion Ca ++, gn 50% kt hp vi protein huyt tng, ch yu l albumin v ch cn
rt t di dng phc hp vi phosphat, citrat, carbonat.
Ch calci di dng ion mi c vai tr sinh l quan trng.
iu ho calci do hormon cn gip trng (PTH) v calcitonin.
Calci- mu bnhthng l 4,3- 5,3 mEq/L
1.3.2. Thiu calci (gim calci - mu; hypocalcemia)
Khi calci- mu < 4,3 mEq/L
1.3.2.1. Nguyn nhn
- Gim dng ion ha; base mu, dng nhiu citrat hoc mu long
- Mt Ca qua dch th: dng "li niu quai" loi furosemid
- Gim hp thu qua rut: ch n thiu Ca, thiu vitamin D, tiu chy mn, ct d dy.
- Suy cn gip trng.
- Tng phospho mu (hyperphosphatemia), gim magnesi mu

. P v Ca c tc dng qua li: P - mu tng khi Ca- mu gim v ngc li. l c ch
bo v sinh l quan trng v nu c 2 cng tng s dn ti kt ta calci phosphat vo cc
m. Khi P tng th Ca gim v lm gim sn xut dng hot ng ca vitamin D v lm
gim huy ng calci phosphat t xng.
. Mg gim, th Ca mu cng gim v lm gim tit v gim tc dng ca PTH.
- Vim ty cp cng lm gim calci mu v c th l lm lng ng Ca vo m m hoi
t, gim tit PTH, gim albumin - huyt v tng sn xut calcitonin ca tuyn gip.
1.3.2.2. Lm sng
T, nga cc ngn, tng phn x, chut rt, tetani vi cc du hiu Trousseau (+),
Chvostek (+), co git do ngng kch thch ca thn kinh b gim. Nu mn tnh, gy xp
xng, gy xng, du hiu gim calci nng: co tht thanh qun, kh th, ting th rt
(stridor)
1.3.2.3. iu tr
- Tim tnh mch:
. Calci gluconat: ng 10 mL dung dch 10% cha 4,5 mEq Ca
. Calci clorid: ng 10 mL, dung dch 10% ch a 13,6 mEq Ca
Tim chm 1mL/ pht phng ngt tim v tt huyt p do gin mch nhanh.
- Ung:
. Calci lactat, calci carbonat, calci gluconat: di dng gi bt
. Vitamin D: Ergocalciferol (D 2): calcitriol 1,25 (OH) 2 D3
Khng dng cng vi fluor v phosph at v to phc khng tan, khng hp thu c.
1.3.3. Tha calci (tng calci-mu, hypercalcemia)
Khi calci- mu > 5,3 mEq/L
1.3.3.1. Nguyn nhn
- Ch n nhiu Ca
- Hp thu nhiu Ca: tha vitamin D, cng ph gip trng.
- Tng gii phng ca t xng: ung th cn gip t rng, bnh Paget (tng tit PTH)
- Gim thi tr Ca qua thn; thn suy, dng li niu loi thiazid lu.
- Tng Ca ++ dng ion v acid huyt.
1.3.3.2. Triu chng
Suy nhc, chn nn, bun nn, nn, i nhiu, m mng, l ln, t b, thay i nhn
cch, hn m. in tim: ST v QT ngn, PR di.
1.3.3.3. iu tr
iu tr nguyn nhn: cn gip trng, ch n
Khi calci mu > 7 mEq/L phi iu tr tch cc:
- Ung hoc tim tnh mch thanh huyt mn 0,45% hoc 0,9%, c th ti hng lt/ ngy
vi iu kin chc phn thn bnh th ng: th tch mu tng, pha long c Ca, thn
tng thi Na + (gim ti hp thu), ng thi tng thi Ca. C th cho ung thm 2 - 3 lt/
ngy.
"Li niu quai" furosemid lm tng thi Ca v d phng c tha nc do dng huyt
thanh mn: 40- 60 mg cch 6 h ung 1 ln. Khng dng li niu loi thiazid v gim thi
Ca.
Phosphat tim tnh mch dng cha cc cn cp tnh. Tim tnh mch Na phosphat hoc
K phosphat lm gim nhanh ion Ca ++ v to Ca phosphat. Nhng khi Ca phosphat > 75
mg/ dl th gy lng ng C a vo cc m.
Khng dng qu 1,5g/ ngy v khng qu 2 ngy.
- Ch n t Ca v dng cortison: steroid tranh chp vi vitamin D receptor ca rut,
lm gim hp thu Ca qua tiu ha v tng thi qua thn.
Cn dng liu cao: Prednison 1mg/ kg/ ngy. Tc d ng h calci mu xut hin chm, sau
1- 2 tun dng thuc. Ngng thuc khi c du hiu nhim c.
Mt s thuc lm gim tiu xng:
- Mithracin (Plicamycin) l khng sinh gy c t bo, tc dng c ch trc tip cc hu
ct bo (osteoclastes), lm gim h uy ng Ca t xng ra mu v gim ti hp thu Ca ti
ng thn.
Ch dng trong tng Ca- mu do ung th nng khng vi cc cch iu tr khc, v
mithracin c nhiu tc dng ph, c bit l gim tiu cu, bch cu, gim prothrombin,
gy chy mu c th dn n cht.
ng trong l ng kh 2500 g
Truyn tnh mch 25 g/ kg/ ngy. Pha trong 500 mL huyt thanh ngt ng trng.
Cch 2-3 ngy, truyn li tu thuc vo Ca - mu.
- Cc diphosphonat: l thuc tng hp ca cc pyrophosphat v c c tc dng c ch tiu
xng ca cc hu ct bo. Th d:
Didronel (etidronat disodic): ch nh chnh trong bnh Paget hoc cc di cn ung th vo
xng, gy tiu xng.
Dng liu duy nht, ung 2 gi trc ba n vi liu 5 mg/ kg/ ngy, trong thi gian 6
thng. Khng dng cho ngi suy thn. Dng qu liu gy h Ca - mu (iu tr bng
calci- gluconat tim tnh mch)
Vin 200 mg
- Calcitonin: l hormon ca t bo C tuyn gip trng, lm h calci mu do:

. c ch hu ct bo (ngc vi PTH, kch thch) lm gimtiu x ng
. Tng thi Ca v P qua thn do c ch ti hp thu
Cc ch phm sn xut t ng vt (Staporos, Calcitar t ln, Calsyn, Miacalcic t c hi
salmon) hoc tng p (Cibacalcin). Calcitonin ca c hi mnh hn ca ngi v ln 10 -
40 ln v tc dng lu h n 10 ln.
Liu lng: 4- 8 n v quc t/ kg/ ngy chia lm 4 ln tim di da, tim bp hoc tim
chm vo tnh mch. Tc dng xut hin nhanh
2. Cc dch thay th huyt tng
Khi th tch huyt tng b gim do mt nc v mui n thun (tiu chy, nn nhiu)
th ch cn truyn nc v in gii l . Nhng nu do mt nhiu mu hoc huyt tng
nh trong sc xut huyt, bng nng, th phi truyn mu, huyt tng hoc cc dch thay
th c p lc keo cao.
Cc sn phm thin nhin (mu, huyt tng ca n gi) l tt nht, nhng t v c nhiu
nguy c (phn ng min dch, lan truyn vim gan siu vi khun B hoc C, lan truyn
AIDS). V vy, cc dch thay th huyt tng c nghin cu v s dng. Cc dch
ny cn phi c by tnh cht sau:
- Tn ti trong tun hon lu, ngha l c p lc keo tng t vi huyt tng, c trng
lng phn t tng ong vi albumin huyt tng ( 40.000).
- Khng c tc dng dc l khc.
- Khng c tc dng khng nguyn, khng c ch nhit t.
- Khng c tng tc hoc phn ng cho vi nhm mu.
- Gi n nh lu khi bo qun hoc thay i ca nhit mi trng.
- D kh khun
- nht thch hp vi s tim truyn.
Di y l mt s dch truyn t tiu chun hin ang c dng:
2.1. Gelatin bin cht
c sn xut t colagen ca xng, thu phn cho ti khi t c cc phn t protein
c trng lng phn t khong 3.000. C nhiu dng:
- Plasmion: cha 30g gelatin lng trong 1 lt, c thm thnh phn cc ion Na +, K+, Mg++
v Cl- tng t nh huyt tng, kh ng c Ca ++. Cht m l lactat. ng trong l 500
mL.
- Plasmagel: cha 30g gelatin lng trong 1 lt dung dch mui ng trng, thm 27
++
mEq Ca (cho nn khng c dng cho bnh nhn ang c iu tr bng digitalis).
Khng c cht m. ng tro ng l 500 mL.
- Plasmagel khng mui, c ng (Plasmagel dsod glucos): cha 25 g gelatin trong 1

lt dung dch glucose ng trng, khng c mui, Ca ++ v cht m (trnh b tha mui).
ng trong l 500 mL.
+ u im ca gelatin lng l d bo qun, k hng cn xc nh nhm mu trc khi
truyn.
+ Nhc im:
. Khng gi c lu trong c th, khong 75% b thi tr qua nc tiu trong 24h.
. Vn cn phn ng khng nguyn: d ng biu hin da, him gp phn ng tim mch.
. C ri lon ng mu: gim p rotrombin, fibrinogen, tiu cu, ko di thi gian chy
mu.
. Gy protein- niu gi. Nu dng Plasmagel, ch c th lm tng calci huyt.
. Phi hm nng trc khi dng v rt qunh khi gp lnh.
2.2. polyvinyl- pyrrolidone (PVP)
l cht tng hp, c trng lng phn t khong 40.000.
ng trong l 500 mL (Subtosan)
- u im: tng i d bo qun.
- Nhc im: cn phn ng khng nguyn, gy protein niu gi v nht l b gi lu
trong h lin vng ni mc.
2.3. Dextran
L cht trng phn c trng l ng phn t rt cao, c to ra t glucose di tc ng
ca vi khun Leuconostoc mesenteroides. Phn hai loi:
2.3.1. Loi c trong lng phn t cao
Khong 80.000. ng trong l 250 v 500 mL. Thi tr qua chuyn ha.
- u im: d bo qun, gi khng t lm.
- Nhc im:
. To phc hp fibrinogen - dextran, gn vo hng cu, lm tng dnh tiu cu, v vy c
th gy ri lon ng mu.
Rt t c, nhng c th gy phn ng qu mn ngay t ln truyn u tin v mn cm
vi dextran t nhin gp trong mt s thc n.
2.3.2. Loi c trng lng phn t thp .
Khong 40.000. ng trong l 250 v 500 mL (Rheomacrodex). Thi tr bng chuyn
ha v qua thn.
- u im: lm d dng tun hon ca hng cu trong mao mch.
- Nhc im: gi thnh cn cao v gy ri lon ng mu. Ch l sau khi truyn, c

th lm sai lc vic xc nh nhm mu v glucose mu.
2.4. Dung dch in gii
C 5 loi hay dng
Loi dung dch Nng (mmol/ L) ASTT pH
Na+ K+ Cl- Ca2+ Lactat mOsm/L
NaCl 0,9% 154 154 308 5.7
Ringer 147 4 156 5 309
Ringer lactat 130 4 112 1,82 28 280 5.1
NaCl 10% 1.709 1.709 3.418
NaCl 20% 3,419 3,419 6.836
1g NaCl = 17 mmol Na= 400 mg Na. ASTT: p sut thm thu
2.4.1. Dung dch ng trng:
2.4.1.1. Dung dch nc mui sinh l (NaCl 0, 9%)
- u: R, ph bin.
- Nhc: d gy toan mu do lng Cl - cao. Truyn nhiu v nhanh d gy nc ngoi
bo v ph phi cp.
2.4.1.2. Ringer lactat (dung dch Hartman)
- Vo c th, lactat chuyn thnh bicarbonat (do gan) v kim ha mu (chnh c t oan
nh).
- C thm K + v Ca2+.
- Truyn 1 lt s tng c 200 - 300 mL th tch tun hon, v vy cn truyn 1 lng gp
3 ln th tch b mt. Nhng khng c gi lu trong mu nn cn truyn lin tc.
Ch truyn khi th tch tun hon mt 1 lt. Tng lng truyn khng qu 3- 4
lt/ 24h.
2.4.2. Dung dch u trng
- Cc loi dung dch: NaCl 1,2 - 1,8- 3,6- 7,2- 10 v 20%. Trn th trng c sn loi 10 -
20%, ng 10- 20 mL. Khi dng, pha vi glucose 5% t nng mong mun.
- c im:
. ASTT qu cao, d gy ph.
. Lm gim kt tp tiu cu, tng nguy c chy mu.
. Lm gin mch ni tng: thn, tim. Tng co bp tim.
. Lm gim ph no, gim tng p lc ni s tt hn so vi dung dch keo.

3. Cc dch cung cp glucid, acid amin v l ipid
Dng cung cp nng lng khi khng dinh dng c qua ng tiu ha. Trong sc,
nhu cu nng lng c cung cp giai on u ch yu bng glucid v c hp thu
trc tip, sau l cc acid amin, v trong giai on hi phc l lipid.
3.1. Cc glucid d hp thu
3.1.1. Glucose (dextrose)
- Dung dch ng trng 50g/ 1000 mL (5%)
- Dung dch u trng 100g; 150g v 300g/ 1000 mL.
ng trong l 500- 1000 mL, 100g glucose cung cp 400 kilo calo. Ngoi ra cn dng
iu tr v d phng cc trng hp mt nc nhiu hn mt mui.
Truyn chm vo tnh mch. Cc dung dch u trng d lm vim tc tnh mch ti ni
truyn v gy hoi t nu truyn ra ngoi tnh mch. Glucose huyt tng ph thuc khng
nhng vo nng dung dch tim truyn m cn v o tc truyn v kh nng chuyn
ha ca ngi bnh.
Khi nui dng bng dch truyn, cn phn phi liu u trong ngy v gim liu dn,
trnh ngng t ngt d gy h ng huyt. C th b tr thm bng insulin v kali tu
thuc vo ng- niu, aceton- niu, kali- mu.
3.1.2. Sorbitol
Sorbitol l hexa- alcol khng c chc kh, trong c th, b phn hu nhanh thnh fructose
di tc dng ca sorbitol deshydrogenase gan.
- Dung dch ng trng 50g/ 1000 mL
- Dung dch u trng 100g/ 1000mL.
ng trong l 500- 1000 mL. Tc dng v ch nh ging nh glucose, 100g sorbitl cung
cp 400 Kcal.
Dung dch u trng c th gy ri lon thn kinh hoc l do tng p lc thm thu, hoc
l do tc dng c trc tip trn thn kinh.
3.2. Cc acid amin
L dung dch c cha cc acid amin cn thit nh leucin, isoleucin, lysin, methionin,
arginin di dng L d hp thu.
Truyn chm tnh mch (khng vt qu 50 git/ pht).
Khng dng trong giai on u ca sc. Thn trng khi c suy gan, suy thn nng, suy
tun hon nng v dung dch cha nhiu m v u trng. C th gy ra hoc lm nng
thm phn ng phn v.
Tc dng khng mong mun: nim toan chuyn ha do qu liu acid amin, tng N mu
ngi suy thn, mn cm, d ng, a niu do tng p lc thm thu.
Cc ch phm: Alvesin 40, Amigreen - TPN, Proteolysat, Moriamin.
Phi tuyt i v khun khi tim truyn v khng c trn bt k mt thuc g vo dung
dch truyn.
L thuc dng tim truyn 100 - 250- 500- 1000mL.
3.3. Lipid
L dung dch cung cp nng lng v cc a cid bo cn thit cho c th, khng gy u
trng huyt tng.
Cc phn ng khng mong mun sm c th gp l st, bun nn, nn, h ng huyt,
m phi, gim tiu cu.
Cc phn ng mun: gan to, vng da, do mt, lch to, gim tiu cu, gim bch cu,
tng tm thi cc test chc phn gan.
Ch phm: Intralipid, Lipofundin, Lipovenoes 10% PLR (du u tng - soja).
- Dch nh tng 10% ng trong l 100 v 500 mL, cung cp 1100 Kcal/ lit.
- Dch nh tng 20% ng trong l 100 - 250 v 500 mL, cung cp 2000 K cal/ lt
Liu lng: tng lng lipid cho ngi ln trong 24 gi l 2 - 3g/ kg thn trng; cho tr em
l 0,5- 4g/ kg.
Trong 10 pht u truyn 10 git/ pht; trong 20 pht sau l 20 git/ pht, sau t ti
40 git/ pht.
Khi m l phi dng ht trong 1 ln.
Cu hi t lng gi
1. Trnh by vai tr sinh l ca Na+, cc ri lon do thiu Na+ v cch iu tr
2. Trnh by vai tr sinh l ca Na+, cc ri lon do tha Na+ v cch iu tr.
3. Trnh by vai tr sinh l ca K+, cc ri lon do thiu K+ v cch iu tr.
4. Trnh by vai tr sinh l ca K+, cc ri lon do tha K+ v cch iu tr
5. Trnh by vai tr sinh l ca Ca++, cc ri lon do thiu Ca++ v cch iu tr.
6. Trnh by vai tr sinh l ca Ca++, cc ri lon do tha Ca++ v cch iu tr.
7. Nu v phn tch 7 tnh cht cn c ca 1 dch thay th huyt tng. Cho th d.
8. Nu cc ch nh v cch dng ca dch truyn cung cp glucid.
9. Nu cc ch nh v cch dng ca dch truyn cung cp cc acid amin.
10. Nu cc ch nh v cch dng ca dch truyn cung cp l ipid.

Bi 27: thuc iu chnh ri lon tiu ha

1. Trnh by c c ch tc dng, tc dng khng mong mun v p dng iu tr
ca nhm hydroxyd, magnesi hydroxyd, thuc khng histamin H 2, thuc c ch
H+/ K+- ATPase v cc mui bismuth.
2. Phn tch c v tr, c ch tc dng v ch nh ca cc thuc gy nn v chng
nn
3. Nu c c ch tc dng, tc dng v p dng iu tr ca cc thuc iu ha
chc nng vn ng ca ng tiu ha v thuc chng co tht c trn ng tiu
ha.
4. Trnh by c phn loi, c ch tc dng, p dng iu tr ca cc thuc nhun
trng v thuc ty thng dng.
5. Trnh by c tc dng v p dng iu tr ca cc thuc chng tiu chy: dung
dch ung b nc v in gii; cc cht hp ph, bao ph nim mc rut; thuc
lm gim nhu ng rut; cc vi khun v nm.
6. Phn bit c tc dng ca thuc li mt v thuc thng mt, p dng lm sng.
1. thuc iu tr vim lot d dy - t trng

1.1 i cng
Lot d dy- t trng l bnh l ng tiu ha ph bin, hu qu ca s mt cn bng
gia cc yu t gy lot (acid clohydric, pepsin, xon khun Helicobacter pylori) v cc
yu t bo v ti ch nim mc d dy (cht nhy, bicarbonat, prostaglandin).
Xon khun H.pylori ng vai tr quan trng trong nguy c gy lot: khong 95% ngi
lot t trng v 70- 80% ngi lot d dy c vi khun ny. Chng gy vim d dy mn
v lm tng bi tit acid. Dit tr c H.pylori s lm lot lin nhanh v gim r rt t
l ti pht.
Mc tiu ca iu tr lot d dy - t trng l:
- Chng cc yu t gy lot:
. Cc thuc khng acid: trung ha acid trong lng d dy (magnesi hydroxyd, nhm
hydroxyd...)
. Cc thuc lm gim bi tit acid v pepsin: thuc khng histamin H 2 v thuc c ch
bm proton.
. Thuc dit H.pylori: cc khng sinh, bismuth.
- Tng cng yu t bo v: sucralfat, bismuth, misoprostol.

Vic iu ha bi tit HCl ca t bo thnh d dy l do histamin, acetylcholin v
gastrin thng qua H +/ K+- ATPase (bm proton).
Prostaglandin c vai tr quan trng trong c ch iu ha ngc: PGE 2 c ch
adenylcyclase lm gim AMPv, i khng vi tc dng ca histamin v c ch gii phng
gastrin. PGI 2 kch thch t bo biu m ca nim mc d dy, lm tng tit cht nhy,
bicarbonat bo v nim mc. Cc thuc chng vim khng steroid c ch tng hp
prostaglandin, c th gy lot v chy mu ng tiu ha.
Hnh 27.1. C ch iu ha sinh l v dc l ca bi tit dch v v cc v tr

tc dng ca thuc
Hnh 27.2. Vai tr trung ha acid ca NaHCO 3 ti lp nhy

nim mc d dy
1.2. Thuc khng acid
1.2.1. Tnh cht chung
Cc thuc khng acid l nhng thuc c tc dng trung ho acid trong dch v, nng pH
ca d dy ln gn 4, to iu kin thun li cho ti to nim mc. Khi pH d dy tng,
hot tnh ca pepsin s gim (pepsin b bt hot trong dung dch pH ln hn 4).
Cc thuc khng acid c tc dng nhanh nhng ngn, ch l thuc iu tr triu chng,
ct cn au.
Khi d dy rng, cc thuc khng acid thot khi d dy sau 30 pht, khi c thc n th
khong 2 gi.
Thuc khng acid thng dng nht l cc ch phm cha nhm v magnesi, c tc dng
khng acid ti ch, hu nh khng hp thu vo mu nn t gy tc dng ton thn. Thuc
khng acid cha magnesi c tc d ng nhun trng, ngc li thuc cha nhm c th gy
to bn. V vy, cc ch phm khng acid cha c hai mui magnesi v nhm c th lm
gim tc dng khng mong mun trn rut ca hai thuc ny. Nu chc nng thn bnh
thng, rt t nguy c tch lu ma gnesi v nhm.
Natribicarbonat c tc dng trung ha acid dch v mnh, nhng hin nay hu nh khng
dng lm thuc khng acid na v hp thu c vo mu, gy nhiu tc dng khng mong
mun ton thn v c hin tng tit acid hi ng (tng tit acid sau khi ngng thuc).
Dng thuc khng acid tt nht l sau ba n 1 - 3 gi v trc khi i ng, 3 - 4 ln (hoc
nhiu hn) trong mt ngy. Cc ch phm dng lng c hiu qu hn dng rn nhng thi
gian tc dng ngn hn.
Do lm tng pH d dy, cc thuc khn g acid lm nh hng n s hp thu ca nhiu
thuc khc, phi dng cc thuc ny cch xa thuc khng acid t nht 2 gi.
Mt s ch phm phi hp thuc khng acid vi simeticon (cht chng si bt) lm
gim s y hI hoc lm nh triu chng nc.
1.2.2. Magnesi hydroxyd - Mg(OH) 2
d dy, magnesi hydroxyd phn ng nhanh vi acid clohydric:
Mg(OH) 2 + 2HCl MgCl2 + 2H2O
Xung rut non, Mg 2+ tc ng vi cc ion phosphat (PO 43-) v carbonat (CO 32-) to thnh
mui rt t tan hoc khng tan, do trnh c s hp thu base, trnh c base mu
ngay c khi dng lu.
C th dng cc mui khc ca magnesi nh magnesi carbonat, magnesi trisilicat.
1.2.2.2 Ch nh
- Tng tit acid (au, y bng, kh tiu, nng, chua) ngi c lot hoc khng c
lot d dy- t trng.
- Tro ngc d dy- thc qun.
1.2.2.3. Chng ch nh
Mn cm vi thuc, suy thn nng, tr nh (c bit tr mt nc v suy thn).
Ming ng cht, bun nn, nn , cng bng, a chy, tng magnesi mu (gp ngi suy
thn hoc dng liu cao, ko di).
- Cc thuc gim hp thu khi dng cng thuc khng acid: tetracyclin, digoxin,
indomethacin, cc mui st, isoniazid, benzodiazepin, ranitid in
- Cc thuc tng tc dng do gim thi tr khi dng cng thuc khng acid: amphetamin,
quinidin.
1.2.2.6. Liu lng, cch dng
Ngi ln: mi ln ung 300 - 600 mg, ti a ti 1g, ngy 3 - 4 ln. Nhai k vin thuc
trc khi nut.
1.2.3. Nhm hydroxyd- Al(OH) 3
d dy, nhm hydroxyd phn ng vi acid clohydric:
chm
Al(OH) 3 + 3HCl AlCl 3 + 3H2O
Nhm hydroxyd c tc dng trung ha acid yu nn khng gy phn ng tng tit acid
hi ng.
rut, nhm kt hp vi phosphat t thc n, to phosphat nhm khng tan, hu nh
khng hp thu, thi tr theo phn, khng gy base mu. V phosphat b thi tr, c th
phi huy ng phosphat t xng ra, d gy chng nhuyn xng. V vy, cn n ch

nhiu phosphat v protein.
1.2.3.2. Ch nh: nh magnesi hydroxyd (mc 1.2.2.2)
Tng phosphat mu (t dng)
1.2.3.3. Chng ch nh : nh magnesi hydroxyd. (mc 1.2.2.3)
Gim phosphat mu. Ri lon chuyn ha porphyrin.
Cht ming, bun nn, cng bng, to bn, phn trng, gim phosphat mu. Nguy c
nhuyn xng khi ch n t phosphat hoc iu tr lu di. Tng nhm trong mu gy
bnh no, sa st tr tu, thiu mu hng cu nh.
1.2.3.5. Tng tc thuc: ging nh magnesi hydroxyd (mc 1.2.2.5)
1.2.3.6. Liu lng, cch dng
Ngi ln: dng vin nhai mi ln 0,5 - 1,0g, dng hn dch ung mi ln 320 - 640 mg,
ngy 4 ln.
Tr em: 6- 12 tui: dng hn dch ung mi ln 320 mg, ngy 3 ln.
* Ch phm phi hp magnesi hydroxyd v nhm hydrox yd
- Dng hn dch cha magnesi hydroxyd 195 mg v nhm hydroxyd 220mg trong 5mL.
Ngi ln ung mi ln 10 - 20 mL
- Dng vin: cha magnesi hydroxyd 400 mg v nhm hydroxyd 400 mg. Ngi ln mi
ln nhai 1- 2 vin, ti a 6 ln mt ngy.
* Ch phm phi hp thuc khng acid v simeticon: dng vin hoc dng hn dch (cha
magnesi hydroxyd 195 mg, nhm hydroxyd 220 mg v simeticon 25 mg trong 5 ml.
Ngi ln ung mi ln 5 - 10 mL, ngy 4 ln).
1.3. Thuc lm gim bi tit acid clohydric v pepsin ca d dy
1.3.1. Thuc khng histamin H 2
1.3.1.1. c im chung
C ch tc dng
Do cng thc gn ging vi histamin, cc thuc khng histamin H 2 tranh chp vi
histamin ti receptor H 2 v khng c tc dng trn receptor H 1. Tuy receptor H 2 c
nhiu m nh thnh mch, kh qun, tim, nhng thuc khng histamin H 2 tc dng ch
yu ti cc receptor H 2 d dy. Thuc khng histamin H 2 ngn cn bi tit dch v do bt
k nguyn nhn no lm tng tit histamin ti d dy (cng ph giao cm, thc n,
gastrin, bi tit c s).
Tc dng ca thuc khng histamin H 2 ph thuc vo liu lng, thuc lm gim tit c
s lng v nng HCl trong dch v
Ch nh
- Lot d dy- t trng lnh tnh, k c lot do dng thuc chng vim khng steroid.
- Bnh tro ngc d dy- thc qun.
- Hi chng tng tit acid dch v (Hi chng Zollinger - Ellison)
- Lm gim tit acid dch v trong mt s trng hp lot ng tiu ha khc c lin
quan n tng tit dch v nh lot ming ni d dy - rut
- Lm gim cc triu chng ri lo n tiu ha (nng rt, kh tiu, chua) do tha acid
dch v.
- Lm gim nguy c ht phi acid dch v khi gy m hoc khi sinh (Hi chng
Mendelson).
Chng ch nh v thn trng
- Chng ch nh: qu mn vi thuc
- Thn trng: trc khi dng thuc khng histamin H 2, phi loi tr kh nng ung th d
dy, c bit ngi t trung nin tr ln v thuc c th che lp cc triu chng, lm
chm chn on ung th.
C nhy cm cho gia cc thuc trong nhm khng histamin H 2.
Dng thn trng, gim liu v / hoc ko di khong cch gia cc ln dng thuc ngi
suy thn.
Thn trng ngi suy gan, ph n c thai v cho con b (ngng thuc hoc ngng cho
con b).
Tc dng khng mong mun
a chy v cc ri lon tiu ha khc, tng enzym gan, au u, ch ng mt, pht ban.
Him gp vim ty cp, chm nhp tim, nghn nh tht, ln ln, trm cm, o gic (c
bit ngi gi), ri lon v mu, phn ng qu mn.
Chng v to n ng v thiu nng tnh dc gp ngi dng cimetidin nhiu hn cc
thuc khng histamin H 2 khc.
Tng tc thuc
- Do pH d dy tng khi dng thuc khng histamin H 2 nn lm gim hp thu ca mt s
thuc nh penicilin V, ketoconazol, itraconazol
- Cimetidin c ch cytochrom P 450 gan nn lm tng tc dng v c tnh ca nhiu
thuc nh warfarin, phenytoin, theophylin, propranolol, benzodiazepin
Ranitidin c tng tc ny nhng mc thp hn nhiu (km 2 - 4 ln).
Famotidin v nizatidin khng gy tng tc kiu ny.
Mt s thng s dc ng hc ca thuc khng histamin H 2
Tn thuc Sinh kh Gn Th tch t/2 Qua rau Qua

dng (%) protein phn b Vd (gi) thai sa
huyt (L/ kg)
tng (%)
Cimetidin 60- 70 20 2 1 + +
Ranitidin 50 15 2- 3 1,3 + +
Famotidin 40- 45 15- 20 3 1,2 ? +
Nizatidin > 70 35 1- 2 1,3 ? +
1.3.1.2. Cc thuc
Cimetidin
Hp thu nhanh khi ung. Ung 200 mg cimetidin c tc dng nng pH v gim au trong
1,5 gi. Liu 400 mg trc khi i ng gi c pH ca d dy > 3,5 sut c m. Vi liu
1,0g/ 24 gi, t l ln so l 60% sau 4 tun v 80% sau 8 tun.
Liu dng iu tr lot d dy - t trng ngi ln: ung mi ln 400 mg, ngy 2 ln (vo
ba n sng v trc khi i ng) hoc 800 mg trc khi i ng. Thi gian dng t nht 4
tun i vi lot t trng v 6 tun i vi lot d dy.
Liu duy tr: 400 mg trc khi i ng
Khi lot nng hoc ngi bnh nn nhiu, tim bp hoc tnh mch chm (t nht trong 5
pht) mi ln 200 mg, cch 4 - 6 gi mt ln. Gim liu ngi suy thn.
Liu dng tr em: tr trn 1 tui mi ngy ung 25 - 30 mg/ kg, chia lm nhi u ln. Tr
di 1 tui mi ngy ung 20 mg/ kg, chia lm nhiu ln.
Cimetidin gy nhiu tc dng khng mong mun, c nhiu tng tc thuc hn cc thuc
khng histamin H 2 khc. V vy, trong trng hp cn phi hp nhiu thuc, khng nn
chn cimetidin.
Ranitidin
Tc dng mnh hn cimetidin 4 - 10 ln, nhng t gy tc dng khng mong mun v t
tng tc thuc hn cimetidin.
Liu dng: ung mi ln 150 mg, ngy 2 ln (vo bui sng v bui ti) hoc 300 mg vo
bui ti trong 4- 8 tun. Liu duy tr: 150 m g vo bui ti.
Tim bp hoc tnh mch chm (t nht trong 2 pht, phi pha long 50 mg trong 20
mL): mi ln 50 mg, cch 6 - 8 gi/ ln.
Famotidin
Tc dng mnh hn cimetidin 30 ln.
Liu dng: ung mi ngy 40 mg trc khi i ng trong 4 - 8 tun.

Liu duy tr: 20 mg trc khi i ng.
Tim tnh mch chm hoc truyn tnh mch (pha trong natri clorid 0,9%) mi ln 20
mg, cch 12 gi mt ln cho n khi dng c ng ung.
Nizatidin
Tc dng v liu lng tng t ranitidin, nhng t tc dng khng mong mun hn cc
thuc khng histamin H 2 khc.
1.3.2. Thuc c ch H +/ K+- ATPase (bm proton)
1.3.2.1. c im chung
C ch tc dng
Cc thuc c ch bm proton l nhng tin thuc, khng c hot tnh pH trung tnh.
t bo thnh d dy (pH acid), chng c chuyn thnh cc cht c hot tnh, gn vo
bm proton, c ch c hiu v khng hi phc bm ny. Do , cc thuc c ch bm
proton lm gim bi tit acid do bt k nguyn nhn g v l con ng chung cui
cng ca s bi tit aci d. Thuc rt t nh hng n khi lng dch v, s bi tit pepsin
v yu t ni ti ca d dy. Dng mt liu, bi tit acid d dy b c ch trong khong
24 gi (so snh vi thuc khng histamin H 2 ti a ch 12 gi). Bi tit acid ch tr li sau
khi enzym mi c tng hp.. T l lin so c th t 95% sau 8 tun.
Ch nh
- Lot d dy- t trng lnh tnh.
Phng v iu tr cc trng hp lot do dng thuc chng vim khng steroid.
- Bnh tro ngc d dy- thc qun khi c triu chng nng hoc bin chng.
- Hi chng Zollinger- Ellison (k c trng hp khng vi cc thuc khc).
- D phng ht phi acid khi gy m.
Chng ch nh v thn trng
- Chng ch nh: qu mn vi thuc
- Thn trng: suy gan, ph n c thai hoc cho con b. Phi loi tr kh nng ung th d
dy trc khi dng thuc c ch bm proton.
Tc dng khng mong mun
Ni chung thuc dung np tt. C th gp kh ming, ri lon tiu ha, tng enzym gan,
au u, chng mt, ri lon th gic, thay i v mu, vim thn, lit d ng, phn ng d
ng.
Do lm gim acid trong d dy, nn lm tng nguy c nhim khun ng tiu ha, c
th gy ung th d dy.
Tng tc thuc
- Do pH d dy tng nn lm gim hp thu mt s thuc nh ketoconazol, itraconazol

- Omeprazol c ch cyto chrom P 450 gan nn lm tng tc dng v c tnh ca
diazepam, phenytoin, warfarin, nifedipin Lansoprazol t nh hng n cytochrom P 450,
trong khi pantoprazol khng nh hng n enzym ny.
- Clarithromycin c ch chuyn ha ca omeprazol, lm tng n ng omeprazol trong
mu ln gp hai ln.
1.3.2.2. Cc thuc
Omeprazol
Lot d dy- t trng: ung mi ngy mt ln 20 mg trong 4 tun nu lot t trng, trong
8 tun nu lot d dy. Trng hp bnh nng hoc ti pht c th tng liu ti 40 mg mt
ngy (ung hoc tim tnh mch).
D phng ti pht: 10- 20 mg/ ngy
- Hi chng Zollinger- Ellison: liu khi u 60 mg/ ngy. Sau iu chnh liu trong
khong 20- 120 mg/ ngy tu p ng lm sng.
Esomeprazol
L ng phn ca omeprazol.
Mi ngy ung 20- 40 mg trong 4- 8 tun
Pantoprazol
Ung mi ngy mt ln 40 mg vo bui sng trong 2 - 4 tun nu lot t trng hoc 4 - 8
tun nu lot d dy. Trng hp bnh nng c th tim tnh mch chm hoc truyn tnh
mch mi ngy mt ln 40 mg n khi ngi bnh c th ung li c.
Lansoprazol
- Lot d dy: mi ngy ung 30 mg vo bui sng trong 8 tun.
- Lot t trng: mi ngy ung 30 mg vo bui sng trong 4 tun.
- Liu duy tr: 15 mg/ ngy.
Rabeprazol
Mi ngy ung 20 mg vo bui sng trong 4 - 8 tun nu lot t trng hoc 6- 12 tun nu
lot d dy.
Lu : cc thuc c ch bm proton b ph hu trong mi trng acid nn phi dng di
dng vin bao tan trong rut. Khi ung phi nut nguyn c vin vi nc (khng nhai,
nghin) v ung cch xa ba n (tr c khi n sng, trc khi i ng ti).
1.4. Cc thuc khc
1.4.1. Cc mui bismuth
c dng di dng keo subcitrat (trikalium dicitrato), subsalicylat
Cc mui bismuth c tc dng:

- Bo v t bo nim mc d dy do lm tng tit dch nhy v bicarbon at, c ch hot
tnh ca pepsin.
- Bao ph chn lc ln y lot, to chelat vi protein, lm thnh hng ro bo v lot
chng li s tn cng ca acid v pepsin.
- Dit Helicobacter pylori.
Khi dng ring, cc mui bismuth ch dit c H.pylori khong 20% ngi bnh,
nhng khi phi hp vi khng sinh v thuc c ch bm proton, c th ti 95% ngi
bnh tit tr c H.pylori. V th bismuth c coi l thnh phn quan trng trong cng
thc phi hp thuc.
Bismuth dng keo t hp thu qua ng ung (ch khong 1%) nn t gy c vi liu
thng thng. Nu dng liu cao hoc dng ko di c th gy bnh no.
Chng ch nh: qu mn vi thuc, suy thn nng, ph n c thai.
Tc dng khng mong mun: bun nn, nn, en ming, en li, en phn (thn tr ng
ngi c tin s chy mu ng tiu ha, v d nhm vi i tin phn en).
Ch phm: Bismuth subcitrat vin nn 120 mg
Ung mi ln 1 vin, ngy 4 ln vo 30 pht trc cc ba n v 2 gi sau ba n ti,
hoc mi ln ung 2 vin, ngy 2 ln vo 30 pht trc ba n sng v ti. iu tr trong
4- 8 tun.
Khng dng iu tr duy tr, nhng c th iu tr nhc li sau 1 thng.
* Ch phm phi hp ranitidin v mui bismuth: ranitidin bismuth citrat
d dy ranitidin bismuth citrat c phn ly t hnh ranitidin v bismuth, do c c hai
tc dng ca hp cht bismuth v ca ranitidin.
Ung mi ln 400 mg, ngy 2 ln trong 4 - 8 tun nu lot t trng hoc 8 tun nu lot d
dy lnh tnh. Khng dng iu tr duy tr.
1.4.2. Sucralfat
Sucralfat l phc hp ca nhm hydroxyd v sulfat sucrose. Ging nh bismuth, sucralfat
t hp thu, ch yu c tc dng ti ch.
Thuc gn vi protein xut tit ti lot, bao ph vt lot, bo v lot khi b tn cng
bi acid dch v, pepsin v acid mt. Ngoi ra , sucralfat cn kch thch sn xut
prostaglandin (E 2, I1,) ti ch, nng pH dch v, hp ph cc mui mt.
Thn trng khi dng ngi suy thn (trnh dng khi suy thn nng) do nguy c tng
nng nhm trong mu, ph n c thai v cho con b.
t gy tc dng khng mong mun, ch yu l cc ri lon tiu ha.
Ung mi ngy 4,0g, chia lm 2 - 4 ln vo 1 gi trc cc ba n v trc khi i ng,

trong 4- 8 tun.
Sucralfat lm gim hp thu ca nhiu thuc, v vy phi ung cc thuc ny trc
sucralfat 2 gi.
1.4.3. Misoprostol
L prostaglandin E 1 tng hp, c tc dng kch thch c ch bo v nim mc d dy v
gim bi tit acid, lm tng lin vt lot d dy - t trng hoc d phng lot d dy do
dng thuc chng vim khng steroid.
Do hp thu c vo mu nn gy nhiu tc dng khng mong mun: bun nn, y
bng, kh tiu, au qun bng, tiu chy, chy mu m o bt thng, gy sy thai, pht
ban, chng mt, h huyt p.
Chng ch nh dng misoprostol ph n c thai (hoc d nh c thai) v cho con b.
Thn trng: bnh mch no, bnh tim mch v nguy c h huyt p.
Liu dng:
- Lot d dy- t trng: mi ngy 800 g chia lm 2- 4 ln vo ba n v trc khi i ng,
trong 4- 8 tun.
- D phng lot d dy - t trng do dng thuc chng vim khng steroid: mi ln ung
200 g, ngy 2- 4 ln cng vi thuc chng vim khng steroid.
1.5. Khng sinh dit Helicobacter pylori
Nu xc nh c s c mt ca H- pylori trong lot d dy t trng (bng test
pht hin), phi dng cc phc dit H.pylori vt lot lin nhanh v trnh ti pht.
Phc ph bin nht, t hiu qu cao, n gin, sn c v chi ph hp l l phc
dng 3 thuc trong 1 tun (one - week triple- therapy) gm mt thuc c ch bm proton
v 2 khng sinh: amoxicilin vi clari thromycin hoc metronidazol. Phc ny dit tr
c H.pylori trong hn 90% trng hp.
Gii thiu mt s phc dng 3 thuc trong 1 tun dit tr H.pylori:
Thuc c ch Khng sinh
bi tit acid Amoxicilin Clarithromycin Metronidazol
Esomeprazol Mi ln 1 g, ngy Mi ln 500 mg,
2 ln ngy 2 ln
mi ln 20 mg, ngy 2 ln Mi ln 500 mg, Mi ln 400 mg,
ngy 2 ln ngy 2 ln
Lansoprazol Mi ln 1 g, ngy Mi ln 500 mg,
2 ln ngy 2 ln
mi ln 30 mg, ngy 2 ln Mi ln 1 g, ngy Mi ln 400 mg,
2 ln ngy 2 ln
Mi ln 500 mg, Mi ln 400 mg,
ngy 2 ln ngy 2 ln
Omeprazol Mi ln 1 g, ngy Mi ln 500 mg,
2 ln ngy 2 ln
ngy 3 ln ngy 3 ln
ngy 2 ln ngy 2 ln
Pantoprazol Mi ln 1 g, ngy Mi ln 500 mg,
2 ln ngy 2 ln
ngy 2 ln ngy 2 ln
Rabeprazol Mi ln 1 g, ngy Mi ln 500 mg,
2 ln ngy 2 ln
ngy 2 ln ngy 2 ln
Ranitidin bismuth citrat Mi ln 1 g, ngy Mi ln 500 mg,
2 ln ngy 2 ln
mi ln 400 mg, ngy 2 ln Mi ln 1 g, ngy Mi ln 400 mg,
2 ln ngy 2 ln
ngy 2 ln ngy 2 ln
Nu lot ti pht nhiu ln, lot to, c nhiu lot hoc cc trng hp lot khng p
ng vi phc 3 thuc, dng phc 4 thuc trong 2 tun gm thuc c ch bm
proton, mui bismuth v 2 khng sinh.
Cng c th phi hp tinidazol hoc tetracyclin vi cc khng sinh khc v thuc c ch
bi tit acid dit tr H. pylori.
2. thuc iu chnh chc nng vn ng v bi tit ca ng tiu ha
ng tiu ha c chc nng vn ng hp thu cc cht dinh dng, in gii, nc v
bi tit cc cht cn b. Khi ri lon cc chc nng ny s sinh ra cc triu chng bun
nn, nn, chng bng, kh tiu, to bn, tiu chy Ngoi vic cha triu chng, thy
thuc cn tm nguyn nhn iu tr.
2.1. Thuc kch thch v i u chnh vn ng ng tiu ha
2.1.1. Thuc gy nn
Nn l mt phn x phc hp, bao gm co tht hang - mn v, m tm v, co tht c honh
v c bng, kt qu l cc cht cha trong d dy b tng ra ngoi qua ng ming.
Trung tm nn nm hnh no, c hu s chi phi ca cc trung tm cao hn l m o v
vng nhn cm ha hc sn no tht 4 (area postrema) hay trigger zone
(Hnh 27.3)
Phenothiazin
Butyrophenon
Hyoscin Khng serotonin Metoclopramid
Khng histamin (5-HT3) Domperidon
Khng histamin
(-) (-) (-) (-)
Tin nh Trung tm nn Vng nhn cm Kch thch

Vn ng (+) (tai) (+) (hnh no) (+) ha hc (sn no (+) nn khc
(ACh, H 1) (ACh, H 1, 5- HT3) tht 4) (D 2)
Hng Ly
tm (+) tm
Metoclopramid (-) Receptor hng, Dy thn kinh X, giao

Khng 5- HT3 mn v, rut v cm, c honh v cc
Gim nhy cm ng mt dy thn kinh khc
Metoclopramid
Domperidon (-) M tm v
Tng tc lm rng ng mn v
d dy v tng trng co c bng
lc thc qun
Nn
Hnh 27.3: V tr, c ch tc dng ca nn v thuc chng nn
C 3 loi thuc gy nn:

2.1.1.1. Thuc gy nn trung ng:
L thuc kch thch vng nhn cm ha hc trigger: apomorphin, ng 5 mg tim di
da. Tr em dng liu 1/20- 1/10 mg/ kg.
2.1.1.2. Thuc gy nn ngoi bin
L thuc c tc dng kch thch cc ngn dy thn kinh li, hu v dy ph v ti nim

mc d dy.
- ng sulfat 0,3 g/ 100mL nc, c th ung thm sau 10 - 20 pht.
- Km sulfat 0,6- 2 g/ 200 mL nc.
2.1.1.3. Thuc gy nn c c ch hn hp
Ipeca hoc ipecacuanha: bt vng sm ng trong nang 1 - 2g, hoc ru thuc 5-
20 mL, hoc siro 15 mL, c th dng nhc li tng 15 pht cho n khi nn.
Thuc gy nn c ch nh tro ng cc ng c cp tnh qua ng tiu ha, nhng trong
thc hnh thng ra d dy s tt hn.
Khng dng thuc gy nn cho ngi hn m hoc nhim c cht n da.
2.1.2. Thuc lm tng nhu ng rut
2.1.2.1. Thuc nhun trng
L thuc lm tng nhu ng ch yu rut gi, y nhanh cc cht cha trong rut gi ra
ngoi. Ch dng thuc nhun trng khi chc chn b to bn, trnh lm dng thuc v c
th gy hu qu h kali mu v mt trng lc i trng. Him khi cn iu tr to bn
ko di, tr mt s ngi cao tui.
C th phng to bn bng ch n cn bng, nc v cht x, vn ng hp l.
Theo c ch tc dng, thuc nhun trng c chia thnh 5 nhm chnh. Mt s thuc
nhun trng c c ch tc dng hn hp.
- Thuc nhun trng lm tng khi lng phn: methylcellulose.
- Thuc nhun trng kch thch: kch thch trc tip c trn thnh rut lm tng nhu ng
rut, c th gy co cng bng: bisacodyl, glycerin, nhm anthraquinon, cc thuc cng
ph giao cm, docusat natri
- Cht lm mm phn: paraphin lng, du arachis.
- Thuc nhun trng thm thu, c tc dng gi li dch trong lng rut: mui magnesi,
lactulose, sorbitol, macrogol, glycerin
- Dung dch lm sch rut dng trc khi phu thut i trng, soi i trng hoc chun b
chiu chp X - quang i trng, khng dng iu tr to bn.
Bisacodyl
- Bisacodyl lm tng nhu ng rut do kch thch m ri thn kinh trong thnh rut,
ng thi lm tng tch ly ion v dch trong lng i trng.
- Ch nh:
. To bn do cc nguyn nhn khc nhau.
. Lm sch rut trc khi phu thut.
. Chun b chp X- quang i trng.

- Chng ch nh:
Tc rut, vim rut tha, chy mu trc trng, vim d dy - rut.
- Tc dng khng mong mun:
Thng gp au bng, bun nn. t gp kch ng trc trng khi t thuc. Dng di ngy
lm gim trng lc i trng v h kali mu.
- Liu dng:
. To bn: ung 5- 10 mg vo bui ti hoc t trc trng vin n 10 mg vo bui sng .
Tr em di 10 tui ung 5 mg vo bui ti hoc t trc trng vin n 5 mg vo bui
sng.
. Chun b chp X- quang i trng hoc phu thut: ngi ln ung mi ln 10 mg lc i
ng, trong 2 ngy lin trc khi chp chiu hoc phu thut. Tr em dng na liu ngi
ln.
Lu : dng vin bao bisacodyl phn r rut, do kh ng c nhai hoc nghin
vin thuc.
Khng dng thuc qu 7 ngy, tr khi c hng dn ca thy thuc.
Magnesi sulfat
L thuc nhun trng thm thu. Do t c hp thu, magnesi sulfat lm tng p lc thm
thu trong lng rut, gi nc, lm tng th tch lng rut, gy kch thch tng nhu ng
rut.
Ung magnesi sulfat liu thp (5g) c tc dng thng mt v nhun trng, liu cao (15 -
30g) c tc dng ty.
Tim tnh mch magnesi sulfat c tc dng chng co git trong sn khoa.
Chng ch nh: cc bnh c p ng tiu ha.
Thn trng: suy thn, suy gan, ngi cao tui, suy nhc.
Liu dng nhun trng: ngi ln v tr em trn 12 tui: 10g; 6 - 11 tui: 5g; 2- 5
tui: 2,5g. Pha thuc trong cc nc y (t nht trong 240 ml) ung trc ba n sng.
Thuc tc dng trong 2 - 4 gi.
2.1.2.2. Thuc ty
L thuc tc dng c rut non v rut gi, dng tng mi cht cha trong rut ra ngoi
(cht c, giun sn) nn thng ch dng 1 ln.
Thuc ty mui
L cc mui t c hp thu, lm tng p lc t hm thu, gi nc, lm tng th tch lng
rut.
Thng dng megnesi sulfat, natri sulfat ung 15 - 30g vi nhiu nc.
Thuc ty du
Thng dng du thu du (ricin) c cha triglycerid ca acid ricinoleic. Di tc dng
ca lipase ty tng, triglycerid b thu phn, gii phng acid ricinoleic. Acid ny c tc
dng kch thch nim mc rut non lm tng nhu ng rut v tng xut tit. Mt khc,
khi acid ricinoleic chuyn thnh natri ricinoleat, th cht ny khng b hp thu, c tc
dng nh thuc ty mui. Liu lng ung 15- 30g.
Du ricin c th lm d dng hp thu mt s thuc qua rut, gy ng c: v d khi dng
cng vi mt s thuc chng giun sn.
Khi iu tr ng c thuc cp tnh, thng dng thuc ty mui, khng dng thuc ty
du.
2.1.3. Thuc iu ho chc nng vn ng ng tiu ha
Cc thuc loi ny c tc dng phc hi li nhu ng ng tiu ha b , dng iu
tr chng y bng, kh tiu khng do lot.
2.1.3.1. Thuc khng dopamin ngoi bin
Domperidon
Domperidon l thuc i kh ng vi dopamin ch ngoi bin v khng qua c hng ro
mu no. V vy c tc dng:
- Chng nn trung ng: c ch cc receptor dopamin vng nhn cm ha hc sn no
tht IV (nm ngoi hng ro mu - no).
- Lm tng tc y cc cht cha tron g d dy xung rut do lm gin vng y d
dy, tng co hang v, lm gin rng mn v sau ba n.
- Tng trng lc c tht thc qun, chng tro ngc d dy - thc qun.
- Tng bin v tn s ca nhu ng t trng, iu ho nhu ng ng tiu ha.
Ch nh: iu tr triu chng bun nn v nn cp, c bit ngi bnh ang iu tr
bng thuc c t bo; chng bng, kh tiu sau ba n do thc n chm xung rut.
Chng ch nh: chy mu ng tiu ha, tc rut c hc, nn sau khi m, tr em di 1
tui.
Tc dng khng mong mun: nhc u, tng prolactin mu (chy sa, ri lon kinh
nguyt, au tc v)
Liu dng: ung 10- 60 mg/ ngy, trc ba n 15 - 30 pht. Khng dng thng xuyn
hoc di ngy.
Metoclopramid
Khc vi domperidon, metoclopramid p hong b receptor ca dopamin, i khng vi tc
dng ca dopamin c trung ng v ngoi bin do thuc d dng qua c hng ro
mu no.
ngoi bin, metoclopramid c tc dng tng t nh domperidon. Do c tc dng c

trn trung ng, metoclopramid c tc dng an thn v c th gy phn ng lon trng
lc c cp tnh (co tht c xng v c mt, cc cn vn nhn), thng xy ra ngi
bnh l n tr hoc ngi rt gi.
Ch nh: chng nn, chng tro ngc d dy - thc qun, y bng kh tiu, chun b
chp X- quang d dy hoc t ng thng vo rut non.
Chng ch nh: ng kinh, chy mu ng tiu ha, tc rut c hc hoc thng rut.
Tc dng khng mong mun: a chy, bun ng, phn ng ngoi thp (lon trng lc c
cp), mt mi, yu c.
Liu dng: ung 5- 10mg/ ln, ngy 3 ln. C th dng ng tim (bp, tnh mch) hoc
truyn tnh mch nu bnh nng.
2.1.3.2. Thuc cng ph giao cm ng tiu ha: Cisaprid.
Cisaprid kch thch gii phng ACh u tn cng ca m ri thn kinh tng, khn g
kch thch trc tip receptor M hoc phong to ChE nn tc dng ch khu tr rut, tng.
Khc vi metoclopramid, cisaprid kch thch vn ng tt c cc phn ca ng tiu ha,
k c thc qun v rut gi.
Tc dng: tng nhu ng thc qun, tng p lc qua tm v. Tng nhu ng d dy - t
trng nn lm nhanh rng d dy. Tng chuyn vn ca d dy - rut non- rut gi.
Ch nh: Tro ngc d dy - thc qun. Chm tiu. To bn mn tnh.
Liu dng: ung mi ln 5 - 20mg, ngy 2- 4 ln, trc ba n 30 ph t.
2.1.3.3. Thuc tc dng trn h enkephalinergic ti rut
Cc receptor ca h enkephalinergic ti rut c tc dng iu ha nhu ng: tc dng
kch thch trn c gim vn ng v tc dng chng co tht trn c tng vn ng
Trimebutin
Kch thch receptor enkephalinergic rut khi c ri lon.
Ch nh: hi chng kch thch rut/ lit rut sau m. Ri lon chc nng tiu ha: au
bng, chm tiu, tiu chy/ to bn.
Liu dng: ung mi ln 100 - 200 mg, ngy 3 ln.
Racecadotril
Cht c ch enkephalinase c hi phc ti rut, lm gim tit dch rut v in gii ca
nim mc rut khi b vim hoc c t vi khun kch thch. Khng c tc dng trn rut
bnh thng v khng nh hng n nhu ng rut nn dng trong tiu chy cp.
Liu dng: ung mi ln 10 0 mg, ngy 3 ln trc cc ba n.
Khng dng cho tr em di 15 tui
2.2. Thuc chng co tht v lm gim nhu ng ng tiu ha
2.2.1. Thuc chng nn

Cc thuc chng nn c ch nh trong cc chng nn do c thai, sau m, nhim
khun, nhim c (do nhim acid, do ur mu cao), say tu xe v do tc dng ph ca
thuc, nht l cc thuc chng ung th.
2.2.1.1. Gy t ngn dy cm gic d dy : kh CO 2, natri citrat, procain
2.2.1.2. Thuc c ch ph giao cm : atropin, scopolamin, ben zatropin
2.2.1.3. Thuc khng histamin H 1: diphenhydramin, hydroxyzin, cinnarizin, cyclizin,
promethazin. Ngoi khng H 1, cc thuc ny cn c tc dng khng M cholinergic v an
thn kinh (xin xem bi Histamin v thuc khng histamin H 1)
2.2.1.4. Thuc khng receptor D 2 (h dopaminergic)
Thuc c tc dng c ch receptor dopamin vng nhn cm ha hc sn no tht IV.
Ngoi ra, thuc cn c ch cc receptor D 2 ngoi bin ng tiu ha.
- Loi phenothiazin: clopromazin, perphenazin.
- Loi butyrophenon: haloperidol, droperidol
- Domperidon, metoclopramid.
2.2.1.5. Thuc khng serotonin
Phng v iu tr bun nn, nn do ha tr liu ung th, do chiu x hoc sau phu thut.
Cc thuc:
- Ondansetron: ung hoc tim tnh mch 8 - 32 mg/ ngy.
- Granisetron: ung hoc tim tnh mch 1 - 3 mg/ ngy.
- Dolasetron mesilat: ung hoc tim tnh mch 12,5 - 200 mg/ ngy.
2.2.1.6. Cc thuc khc
- Benzodiazepin: lorazepam, alprazolam
- Corticoid: dexamethason, metylprednisolon. C ch cha hon ton bit r, c mt phn
tc dng c ch trung tm nn.
2.2.2. Thuc chng co tht c trn ng tiu ha
Do c tc dng chng co tht c trn theo cc c ch khc nhau, cc thuc ny c dng
iu tr triu chng cc cn au do co tht ng tiu ha, ng mt v c ng sinh
dc, tit niu.
2.2.2.1. Thuc hu ph giao cm
Atropin sulfat:
Hu ph giao cm c trung ng v ngoi bin (xin xem bi Thuc tc dng trn h thn
kinh thc vt)
Hyoscin N- butylbromid
V mang amin bc 4 nn khng vo c thn kinh trung ng, ch c tc dng hu ph
giao cm ngoi bin.
Tc dng khng mong mun: kh ming, mch nhanh, b i, to bn, ri lon iu tit
mt.
Chng ch nh: glcm gc ng, ph i tuyn tin lit, nhc c, tc lit rut, hp mn
v, ri lon chuyn ha porph yrin.
Liu dng: mi ln ung 10 - 20 mg, ngy 3- 4 ln.
2.2.2.2. Thuc chng co tht c trn trc tip
Papaverin hydroclorid
Papaverin l mt alcaloid trong nha kh ca qu cy thuc phin, khng c tc dng
gim au, gy ng ging morphin. Tc dng ch yu ca papaverin l lm gin c trn
ng tiu ha, ng mt v ng tit niu.
Chng ch nh: qu mn vi thuc, bloc nh - tht hon ton, mang thai (c th gy c
cho thai).
Tc dng khng mong mun: bng mt, nhp tim nhanh, chng mt, nhc u , ng g,
ri lon tiu ha, vim gan.
Liu dng: ung hoc tim (bp, tnh mch) mi ln 30 - 100mg, ngy 2- 3 ln.
Alverin citrat
L thuc chng co tht, tc dng trc tip ln c trn ng tiu ha v t cung. So vi
papaverin, tc dng mnh hn 3 ln n hng c tnh km 3 ln.
Chng ch nh: tc nghn rut hoc lit rut, mt trng lc rut kt.
Tc dng khng mong mun: bun nn, au u, chng mt, phn ng d ng.
Liu dng: mi ln ung 60 - 120 mg, ngy 1-3 ln.
Cc thuc khc: mebeverin, dicycloverin, phloroglucinol, drotaverin.
2.3. Thuc chng tiu chy
Trong iu tr tiu chy, ngoi vic iu tr nguyn nhn, vn u tin trong mi trng
hp l nh gi v x l ng nhng ri lon nc v in gii. Cc thuc lm gim triu
chng (hp ph, bao ph nim mc, gim tit dch, gim nhu ng rut) c th dng trong
mt s trng hp tiu chy ngi ln, nhng khng nn dng tr em v chng khng
lm gim c s mt dch v in gii, m cn c th gy ra nhiu tc dng c hi.
2.3.1. Thuc ung b nc v in gii (ORS, Oresol)
2.3.1.1. Thnh phn v c ch tc dng
- Thnh phn mt gi bt (ORS ca Unicef)
Natri clorid: 3,5g;

Kali clorid: 1,5g;
Natribicarbonat: 2,5g;
Glucose: 20,0g.
Nc ha tan: 1gi/ 1 lt.
- C ch tc dng: s hp thu ca natri v nc rut c tng cng bi glucose (hoc
carbohydrat khc). Glucose hp thu tch cc rut ko theo hp thu natri (h thng ng
vn chuyn glucose- natri rut non).
B kali trong tiu chy cp c bit quan trng tr em, v tr mt kali trong phn cao
hn ngi ln.
Bicarbonat (hoc citrat) c tc dng khc phc tnh trng nhim toan chuyn ha trong
tiu chy.
2.3.1.2. Ch nh: phng v iu tr mt nc v in gii mc nh v va.
2.3.1.3. Chng ch nh :
Gim niu hoc v niu do gim chc nng thn. Mt nc nng (phi truyn tnh mch
dung dch Ringer lactat). Nn nhiu v ko di, tc rut, lit rut.
Nn nh, tng natri mu, suy tim do b nc qu mc.
2.3.1.5. Liu dng:
- Mt nc nh: ung 50 ml/ kg trong 4 - 6 gi u.
- Mt ncva: ung 100 ml/ kg trong 4 - 6 gi u. Sau iu chnh theo mc kht
v p ng vi iu tr.
Cn tip tc cho tr b m hoc n ung bnh thng. C th cho ung nc trng gia
cc ln ung ORS trnh tng natri mu.
2.3.2. Cc cht hp ph, bao ph nim mc rut
Do c trng lng phn t cao, cu trc phin mng, tnh cht do dai nn cc cht ny
c kh nng gn vi protein ca nim mc ng tiu ha, to thnh mt lp mng bao
ph, bo v nim mc.
- Atapulgit: ngoi tc dng to mng bo v nim mc rut, thuc cn hp ph cc c t
ca vi khun, cc kh trong rut, c tc dng cm mu ti ch .
Liu dng: gi bt 3g atapulgit hot ha, ung 2 - 3 gi/ ngy.
Khng dng trong iu tr tiu chy cp tr em.
- Smecta: gi bt 3g, 2- 3 gi/ ngy, ung xa ba n.
2.3.3. Cc cht lm gim tit dch, gim nhu ng rut
Loperamid
Tc dng: loperamid l opiat tng hp nhng c rt t tc dng trn thn kinh trung ng.
Loperamid lm gim nhu ng rut, ko di thi gian vn chuyn qua rut, gim tit dch
ng tiu ha, tng vn chuyn nc v cht in gii t lng rut vo mu, tng trng
lc c tht hu mn.
Ch nh: iu tr triu chng tiu chy cp khng c bin chng hoc ti u chy mn
ngi ln.
Chng ch nh: mn cm vi thuc, khi cn trnh c ch nhu ng rut, vim i trng
nng, tn thng gan, hi chng l, trng bng.
Tc dng khng mong mun: bun nn, to bn, au bng, trng bng, chng mt, nhc
u, d ng.
Liu dng:
- Ngi ln: lc u ung 4 mg, sau mi ln i lng ung 2 mg cho ti khi ngng tiu
chy. Liu ti a: 16 mg/ ngy. Khng dng qu 5 ngy trong tiu chy cp.
- Tr em: khng dng thng qui trong tiu chy cp. Ch dng cho tr em trn 6 tui khi
tht cn thit. Mi ln ung 2 mg, ngy 2 - 3 ln tu theo tui.
Ngng thuc nu thy khng c kt qu sau 48 gi.
2.3.4. Vi khun v nm
2.3.4.1. Lactobacillus acidophilus
Vi khun sn xut acid lactic v 2 cht dit khun: lactocidin v acidophil lin. C kh
nng tng hp vitamin nhm B.
Bnh thng, cc vi khun cng sinh trong lng rut c s cn bng gia vi khun hu
saccharose v cc vi khun hu protein. Mt s cht tn cng vo vi khun hu
saccharose nh ru, stress, nhim khun, khng sin h gy ra s mt cn bng, lm
tng vi khun hu protein, dn n ri lon tiu ha (tiu chy, to bn, trng bng)
Lactobacillus acidophilus c tc dng lp li thng bng vi khun cng sinh trong rut,
kch thch vi khun hu saccharose pht trin, k ch thch min dch khng c hiu ca
nim mc rut (tng tng hp IgA) v dit khun.
Ch nh: cc tiu chy do lon khun rut
Ch phm: Antibio: gi bt 1g cha 100 triu vi khun sng.
Ngi ln ung mi ln 1gi, ngy 3 ln. Tr em ung mi ngy 1- 2 gi.
2.3.4.2. Saccharomyces boulardii
L nm men c tc dng tng hp vitamin nhm B, km khun, dit Candida albicans,
kch thch min dch khng c hiu.
Ch nh: d phng v iu tr tiu chy do dng khng sinh, tiu chy cp.
V nm men l cc t bo sng nn khng c trn vo nc hay thc n nng (trn

500C), qu lnh hoc c ru. Khng dng cng vi cc thuc chng nm.
Ch phm: Ultra- levure, vin nang cha Saccharomyces boulardii ng kh 56,5mg.
Mi ln ung 1 vin, ngy 4 ln.
2.4. Thuc li mt v thuc thng mt
2.4.1. Thuc li mt
Phn bit hai loi:
- Thuc li mt nc (secretin, thuc cng ph giao cm) lm tng bi tit nc v in
gii ca t bo biu m ng mt, gy tng tit mt long.
- Thuc li mt thc th kch thch t bo gan tng bi tit mt ging nh mt sinh l.
Tu theo ngun gc, c:
2.4.1.1. Thuc li mt c ngun gc ng vt
l mui mt, cc acid mt, hoc mt ton phn loi b sc t v cholesterol
Ch phm: Bilifluine, vin nang 0,1g, ung 2 vin trc mi ba n tra v ti.
2.4.1.2. Thuc li mt c ngun gc thc vt : ngh, actiso, boldo.
Thng dng ch phm phi hp nhiu cy thuc
2.4.1.3. Thuc li mt tng hp
- Cyclovalon: vin bao ng 50 mg, ung 6 - 12 vin/ ngy
- Anthol trithion: dng thuc ht c 0,0125g/ ht. Mi ngy ung 3 - 6 ht.
Ch nh chung ca cc thuc li mt
- iu tr triu chng cc ri lon tiu ha: trng bng, y hi, hi, bun nn
- iu tr ph tr chng to bn
Chng ch nh: tc mt v suy gan nng
2.4.2. Thuc thng mt
L nhng thuc gy co tht ti mt, ng thi lm gin c trn Oddi. Mt hon ton thot
khi ti mt.
V mt sinh l, tc dng ny ph thuc vo cholecystokinin pancreatozinin (CCK - PZ)
do t trng tit ra khi lipid v peptid t d dy tr n xung. Hu nh cc thuc c tc dng
thng mt l do lm bi tit CCK - PZ.
Ch nh: cc ri lon tiu ha nh y bng, chm tiu, hi, bun nn
Chng ch nh: si ng mt, c tin s amip.
Cc thuc: Sorbitol gi bt 5g. Mi ln pha 1 gi trong n c, ung trc ba n.
Magnesi sulfat: ung 2 - 5g
Cu hi t lng gi
1. Trnh by c ch tc dng, tc dng khng mong mun v p dng iu tr ca
thuc khng acid magnesi hydroxyd v nhm hydroxyd.
2. Trnh by c ch tc dng, tc dng khng mong mu n v p dng iu tr ca
thuc khng histamin H 2 v thuc c ch H +/ K+- ATPase.
3. Trnh by tc dng, tc dng khng mong mun v p dng iu tr ca cc mui
bismuth.
4. V s phn tch v tr, c ch tc dng v nu ch nh iu tr ca cc thuc
gy nn v chng nn.
5. Trnh by v phn loi v c ch tc dng ca cc thuc nhun trng v thuc ty
thng dng.
6. Trnh by tc dng, tc dng khng mong mun v p dng iu tr ca bisacodyl
v magnesi sulfat.
7. Nu cc nhm thuc iu ha chc nng vn ng ng tiu ha. Mi nhm k
tn 1- 2 thuc i din.
8. Trnh by c ch tc dng, tc dng, tc dng khng mong mun v p dng iu
tr ca domperidon v metoclopramid.
9. Trnh by c ch tc dng, tc dng, tc dng khng mong mun v p dng iu
tr ca hyoscin N- butylbromid, papaverin v alverin citrat.
10. Trnh by tc dng, p dng iu tr ca ORS.
11. Trnh by tc dng, p dng iu tr ca cc thuc chng tiu chy: atapulgit,
loperamid, vi khun lactobacillus acidophilus, nm saccharomyces boulardii.
Phn bit tc dng ca thuc li mt v thuc thng mt, p dng iu tr ca cc thuc
ny.
Bi 28: Thuc iu chnh ri lon h hp

1. Phn bit c c ch tc dng ca thuc lm long m, thuc cha ho, thuc
cha hen, thuc dng trong hi sc h hp.
2. Trnh by c tc dng, tc dng khng mong mun v p dng iu tr ca:
- N- acetylcystein, bromhexin
- Codein, dextromethorphan
- Thuc cng 2 adrenergic, thuc hu ph giao cm (ipratropium),
theophylin.
- Glucocorticoid (trong iu tr hen)
- Cafein v nikethamid
3. Nu c cch s dng thuc trong iu tr hen.
1. Thuc lm thay i bi tit dch kh - ph qun

Dch kh- ph qun c bi tit:
- T cc t bo nim mc: cc t bo hnh i tit dch nhy (do c nhiu mucoprotein v
mucopolysaccharid) v cc t bo thanh dch tit dch lng, qunh thp.
- T cc tuyn tit di nim mc: l tuyn hn hp tit nc hoc dch nhy.
Acetylcholin v cc thuc cng ph giao cm lm tng bi tit dch kh - ph qun.
Dch kh- ph qun l cht lm du t nhin ca nim mc ng h hp. Dch nhy c
tc dng bm dnh cc ht bi, vi khun, sau nh h thng lng mao y chng ra
ngoi.
1.1. Thuc lm gim tit dch
Thuc hu ph giao cm hoc thuc khng histamin H 1. Thc t t dng v c th lm
cht tit c qunh, kh tng ra ngoi, d gy xp ph nang.
1.2. Thuc lm long m
1.2.1. Thuc lm tng dch tit
L thuc lm tng bi tit dch ng h hp, bo v nim mc chng li cc tc nhn
kch thch v khi lm tan c nhng tc nhn s cho php loi tr chng d dng. C
2 c ch tc dng:
1.2.1.1. Kch thch cc receptor t nim mc d dy gy phn x ph giao cm lm

tng bi tit dch ng h hp, nhng liu c tc dng thng lm au d dy v c th
gy nn. Mt s thuc thng dng l:
- Natri iodid v kali iodid: ung 1 - 2g/ ngy. Dng ko di lm tch lu iod. Khng dng
cho ph n c thai, tr em, ngi b bu gip.
- Natri benzoat: ung 1- 4 g/ ngy. Dng ko di lm tch lu Na +.
- Amoni acetat: 0,5- 1g/ ngy. Khng dng ngi suy gan hoc suy thn
- Ipeca hoc ipecacuanha, hot cht l emetin. Dng liu thp (ti a 1,4 mg alcaloid)
trong trng hp ho c m. Liu c ao gy nn.
1.2.1.2. Kch thch trc tip cc t bo xut tit
Thng dng cc tinh du bay hi nh terpin, gaicol, eucallyptol. Nhng tinh du ny cn
c tc dng st khun.
Khng dng gaicol cho tr em di 30 thng tui.
1.2.2. Thuc lm tiu cht nhy
Cc thuc ny lm thay i cu trc, dn n gim nht ca cht nhy, v vy cc
nt nhy c th d dng di chuyn ra khi ng h hp nh h thng lng chuyn
hoc s khc m. Nhng thuc c nhm thiol t do (nh acetylcystein) c tc dng ct
t cc cu ni disulfit S S ca cc si mucopolysaccharid nn lm lng dch tit
ca nim mc ph qun.
Cc thuc lm tiu cht nhy c th lm ph v hng ro cht nhy bo v d dy, phi
thn trng nhng ngi c tin s lot d dy - t trng.
1.2.2.1. N- acetylcystein
Dng lm thuc tiu cht nhy trong bnh nhy nht, cc bnh l h hp c m nhy
qunh nh trong vim ph qun cp hoc mn. Cn dng lm thuc gii c khi dng qu
liu paracetamol.
Khng dng ngi c tin s hen (nguy c p hn ng co tht ph qun)
Tc dng khng mong mun: bun nn, nn, bun ng, nhc u, phn ng d ng.
Khng dng ng thi vi cc thuc chng ho hoc cc thuc lm gim bi tit dch ph
qun.
Liu dng: Ung mi ln 200 mg, ngy 3 ln.
Kh dung 3- 5 mL dng dch 20%, 3- 4 ln/ ngy.
Nh trc tip vo kh qun 1 - 2 mL dung dch 10- 20%, mi gi 1 ln. Do
tc dng nhanh, i khi c th lm trn dch trong kh qun nu ngi bnh khng c kh
nng ho tng ra ngoi kp thi. C th ht m long bng my ht.
1.2.2.2. Bromhexin (Bisolvon)
Dng iu tr nhng ri lon h hp i km vi ho c m. Khi iu tr nhim khun

ng h hp, bromhexin lm tng s xm nhp ca mt s khng sinh vo dch bi tit
ph qun, tng p ng vi khng sinh.
Thn trng ngi c tin s lot d dy - t trng, bnh hen, suy gan hoc suy thn nng.
Tc dng khng mong mun: ri lon tiu ha, tng nh enzym gan, chng mt, nhc
u, pht ban da. Kh dung bromhexin i khi gy ho hoc co tht ph qun nhng
ngi nhy cm.
Liu dng: ung mi ln 8 - 16 mg, ngy 3 ln.
C th dng ng kh dung, tim bp su hoc tim tnh mch chm.
1.2.2.3. Cc thuc khc: Carbocistein, mucothiol, mecystein
2. Thuc cha ho
Ho l c ch t v sinh l quan trng tng ra ngoi cc d vt phn trn ca ng h
hp c th gy tc ng th. Ho cng c th l triu chng ca mt s ri lon trong c
th (hen, tro ngc d dy - thc qun ), m khi iu tr nhng bnh ny s gim ho,
nhng nhiu khi cng cn iu tr triu chng .
Ch dng thuc gim ho trong trng hp ho khng c m (ho khi cm cm, ho do kch
ng, d ng), ho nhiu lm ngi bnh mt mi, mt ng.
Khng dng thuc lm gim ho trong trng hp ho c m (trong bnh vim ph qun
mn, gin ph qun ) v ho c coi nh c ch bo v c li, lm sch ng th.
Cc thuc gim ho c chia lm 2 loi:
2.1. Thuc gim ho ngoi bin
Lm gim nhy cm ca cc receptor gy phn x ho ng h hp
- Thuc lm du ho do c tc dng bo v, bao ph cc receptor cm gi c hng, hu:
glycerol, mt ong, cc siro ng ma
- Thuc gy t cc ngn dy thn kinh gy phn x ho: benzonatat, bc h (menthol),
lidocain, bupivacain.
2.2. Thuc gim ho trung ng
Cc thuc ny c ch trc tip, lm nng cao ngng kch thch c a trung tm ho hnh
tu, ng thi c tc dng an thn, c ch nh trung tm h hp.
2.2.1. Alcaloid ca thuc phin v cc dn xut
2.2.1.1. Codein
Codein (methylmorphin) l alcaloid ca thuc phin. Trong c th, khong 10% codein b
kh methyl thnh morphin.
So vi morphin, codein c hp thu tt hn khi ung, t gy to bn hoc co tht ng
mt, t gy c ch h hp v t gy nghin hn nhng tc dng gim au cng km hn.
Codein c tc dng gim ho do c ch trc tip trung tm ho, nhng lm kh v tng

qunh ca dch tit ph qun. Dng codein trong trng hp ho khan gy kh chu, mt
ng v trong cc chng au nh v va.
Chng ch nh: mn cm vi thuc, tr em di 1 tui, bnh gan, suy h hp, ph n c
thai.
Liu dng iu tr ho khan: ung mi ln 10- 20 mg, ngy 3 4 ln.
2.2.1.2. Pholcodin
Tc dng gim ho mnh hn codein 1,6 ln, t gy tc dng khng mong mun hn.
Liu dng: 5- 15 mg/ ngy
2.2.1.3. Thuc gim ho khng gy nghin
* Dextromethorphan:
L cht tng hp, ng phn D ca morphin nhng khng tc dng ln cc receptor ca
morphin nn khng gy nghin, khng c tc dng gim au v rt t tc dng an thn.
Do c ch trung tm ho, dextromethorphan c tc dng chng ho tng t codein, nhng
t gy tc dng ph hn.
Dextromethorphan ch nh tt trong trng hp ho khan, mn tnh.
Chng ch nh: qu mn vi thuc, tr em di 2 tui, ang iu tr bng thuc c ch
monoaminoxydase (MAO).
Thn trng: ngi c nguy c hoc ang suy gim h hp, tin s b hen, d ng.
Liu dng: ung mi ln 10- 20 mg, 4 gi/ ln hoc mi ln 30 mg, 6 - 8 gi/ ln, ti a
120 mg/ ngy.
* Noscapin:
Tc dng, cch dng, tc dng khng mong mun v thn trng tng t nh
dextromethorphan.
Khng dng cho ph n c kh nng mang thai (v nguy c gy t bin)
Liu dng: mi ln 15- 30 mg, ngy 3 ln.
2.2.2. Thuc gim ho khng histamin
Mt s thuc c tc dng khng histamin H 1 trung ng v ngoi bin (khng H 1 th h
1) ng thi c tc dng chng ho, khng cholinergic, khng serotonin v an t hn.
Ch nh: cc chng ho khan do d ng, do kch thch, nht l v ban m.
Tc dng an thn ca thuc l iu bt li khi dng thuc ban ngy, nhng c th thun
li khi ho ban m.
Cc thuc:
- Alimemazin: ngi ln ung 5 - 40mg/ ngy, chia nhiu l n.
Tr em: 0,5- 1 mg/ kg/ ngy, chia nhiu ln.

- Diphenhydramin: mi ln ung 25 mg, 4 - 6 gi/ ln.
3. Thuc cha hen ph qun
3.1. i cng
Hen ph qun l hi chng vim mn tnh ng h hp, c gia tng tnh phn ng ca
ph qun vi cc tc nhn gy kch thch, gy nn tnh trng co tht, ph n, tng xut tit
ph qun, lm tc nghn ng th.
Hen ph qun c th do d ng (bi, phn hoa, lng v, thc phm ) hoc khng do d
ng (nhim khun, ri lon ni tit, gng sc, dng thuc chng vi m khng steroid )
ngi hen do d ng, khi tip xc vi d nguyn, rt nhiu cht trung gian ha hc c
gii phng t dng bo (t bo mastocyt), gy nhiu tc dng ph qun v cc ni
khc trong c th.
Gii phng t ht Gii phng t mng Sn xut cytokin

Gii phng ngay Chuyn ha lipid, sau Tng hp ARN m v protein
hng pht mi, sau hng gi
Histamin Cc prostaglandin Cc Interleukin (IL)
Protease (PGD 2) IL 1 IL 3
Heparin Cc leucotrien(LTC 4,D4) IL 4 IL 5
Yu t hoi t u (TNF) Yu t hot ha tiu IL 6 IL8
cu(PAF) TNF
Hnh 28.1. Cc cht trung gian ha hc c gii phng khi dng bo trong
phn ng d ng
Nu pht hin c d nguyn gy bnh, c th iu tr bng phng php gim mn cm

c hiu.
iu tr khng c hiu bnh hen, theo c ch bnh sinh, c hai nhm thuc c dng:
- Cc thuc lm gin ph qun: thuc cng 2 adrenergic, thuc hu ph giao cm,
theophylin.
- Cc thuc chng vim: corticoid, cromolyn natri.
Thuc khng leucotrien (montelukast, zafirlukast) lm gim tc dng co tht ph q un v
gy vim ca LTD 4.
3.2. Thuc lm gin ph qun
3.2.1. Thuc cng 2 adrenergic
C trn ng h hp c nhiu receptor 2, khi b kch thch s gy gin c trn kh ph
qun do lm tng AMPv trong t bo.
Khi dng di dng kh dung, cc thuc cng 2 c ch gii phng histamin v
leucotrien khi dng bo phi, lm tng chc phn ca h thng lng mao, gim tnh
thm ca mao mch phi v c ch phospholipase A 2, tng kh nng chng vim ca
corticoid kh dung.
3.2.1.2. Phn loi
Cc thuc cng 2 adrenergic c chia lm 2 loi:
- Loi c tc dng ngn (short acting 2 agonist: SABA): salbutamol, terbutalin,
fenoterol ch yu dng ct cn hen; Dng di dng ht, tc dng sau 2 - 3 pht, ko
di 3- 5 gi.
- Loi c tc dng di (long acting 2 agonist: LABA): salmeterol, formoterol gn vo
receptor 2 mnh hn salbutamol, tc dng ko di khong 12 gi, dng phi hp vi
corticoid d phng di hn v kim sot hen.
3.2.1.3. Tc dng khng mong mun v thn trng
- Tc dng khng mong mun thng gp: nh trng ngc, nhp tim nhanh, run nh (c
bit u ngn tay). Him gp: nhc u, mt ng, gin mch ngoi bin, lon nhp tim,
h kali mu, tng glucose v acid bo t do trong mu, phn ng qu mn. Dng ng
kh dung c th gy co tht ph qun.
Dng nhiu ln s c hin tng quen thuc nhanh do s lng receptor 2 ca ph qun
gim dn (c ch iu ha gim), bnh nhn c xu hng phi tng liu.
- Thn trng: cng tuyn gip, bnh tim mch, tng huyt p, lon nhp tim, i tho
ng, ang iu tr bng MAOI.
3.2.1.4. Cc thuc
- Salbutamol
Ch nh: hen, tc nghn ng h hp hi phc c, chng non.
Liu dng:
. Cn hen cp: ht nh liu mi ln 100 - 200 g (1- 2 xt), ti a 3- 4 ln/ ngy. Hoc:
tim bp hoc tim di da mi ln 500 g, nhc li sau mi 4 gi nu cn.
. Cn hen cp nghim trng: du ng dch kh dung 2,5 5 mg, ti a 4 ln/ ngy hoc tim
tnh mch chm 250 g, dng nhc li nu cn.
. phng cn hen do gng sc: ht 100 - 200 g (1- 2 xt) truc khi vn ng 15 - 30
pht, hoc ung 2- 4 mg trc khi vn ng 2 gi.
Dng ng kh dung, nng thuc trong mu ch bng 1/10 - 1/50 so vi liu ung.
- Terbutalin
Ch nh: ging nh salbutamol
Liu dng: cn hen cp: ht 250 - 500 g (1- 2 ln xt), ti a 3- 4 ln/ ngy, hoc tim
di da, tim bp hoc tnh mch chm 250 - 500 g, ti a 4 ln/ ngy.
Bambuterol l tin thuc ca terbutalin, mi ngy ung mt ln 10 - 20 mg trc khi i
ng
- Salmeterol
Ch nh: iu tr d phng di hn bnh hen, tc nghn ng h hp phc hi c (k
c hen ban m v phng co tht ph qun do gng sc) ngi phi iu tr bng thuc
gin ph qun thng xuyn, bnh phi tc nghn mn tnh.
Liu dng:
. Bnh hen: mi ln ht 50 - 100 g (2- 4 xt), 2 ln/ ngy.
Tr em trn 4 tui: mi ln ht 50 g (2 xt), 2 ln/ ngy.
. Bnh phi tc nghn mn tnh: mi ln ht 50 g (2 xt), 2 ln/ ngy.
3.2.2. Thuc hu ph giao cm
Ipratropium bromid (Atrovent) l dn xut amin bc 4, dng ng ht. Khi kh dung, ch
khong 1% thuc c hp thu, 90% b nut vo ng tiu ha, khng c hp thu,
thi theo phn nn t gy tc dng khng mong mun ton thn.
Tc dng gin ph qun ca ipratropium trn ngi bnh hen thng chm v khng
mnh bng thuc cng 2 tc dng ngn (SABA), nn thng ch c phi hp s dng
khi cc thuc SABA khng mnh hoc c tc dng ph nng. Phi hp ipratropium vi
SABA lm gin ph qun mnh hn, cho php gim liu SABA nn hn ch c tc
dng ph ca SABA. Kh dung ipratropium c tc dng ti a sau 30 - 60 pht, thi gian

tc dng ko di 3- 6 gi.
Ipratropium cng c tc dng tt trong iu tr bnh phi tc nghn mn tnh.
Thn trng: tng nhn p, ph i tuyn tin lit v tc nghn dng chy ra t bng quang,
c thai v cho con b.
Tc dng khng mong mun: kh ming, bun nn, to bn, au u.
Liu dng: ht nh liu: mi ln 20- 40 g (1- 2 xt), 3-4 ln/ ngy.
Berodual (ipratropium bromid + fenoterol): mi ln xt c 20 g ipratropium v 50 g
fenoterol. Liu thng thng 1 - 2 xt/ ln, ngy 3 ln.
Oxitropium c tc dng tng t nh ipratropium.
3.2.3. Theophylin v dn xut
Theophylin l base xanthin (cng vi cafein v theobromin) c nhiu trong ch, c ph, ca
cao.
3.2.3.1. C ch tc dng v tc dng dc l
Do c ch phosphodiesterase - enzym ging ha AMPv, theophylin lm tng AMPv trong
t bo nn tc dng tng t thuc cng adrenergic.
- Trn h hp: lm gin ph qun, ng thi kch thch trung tm h hp hnh no, lm
tng bin v tn s h hp.
- Trn tim mch: lm tng bin , tn s v lu lng tim, tng s dng oxy ca c tim
v tng lu lng mch vnh.
- Trn thn kinh trung ng: tc dng kch thch thn kinh trung ng km cafein, lm d
dng cho cc hot ng ca v no, gy mt ng c th do tc dng ln h thng li kch
thch.
- Lm gin c trn ng mt v niu qun.
- Tc dng li niu km theobromin.
Theophylin c chuyn ha qua gan. Nng trong huyt tng, thi gian bn thi ca
theophylin thay i ng k trong mt s tnh trng sinh l v bnh l (tng trong suy
tim, x gan, nhim virus, ngi cao tui) hoc do tng t c thuc, trong khi gii hn an
ton gia liu iu tr v liu c ca theophylin kh hp. Tc dng gin ph qun ca
theophylin khng mnh bng cc thuc kch thch 2, trong khi nguy c xut hin cc tc
dng khng mong mun kh cao, v vy theophylin khng c la chn u tin trong
ct cn hen.
Hin nay, theophylin ung gii phng nhanh t c dng trong iu tr hen, ch yu
dng theophylin gii phng chm, duy tr nng thuc trong mu trong 12 gi
iu tr d phng v kim sot hen v m. Trong cn hen nng, theophylin c dng
phi hp vi cc thuc cng 2 hoc corticoid lm tng tc dng gin ph qun,

nhng li c th lm tng tc dng khng mong mun ca thuc cng 2 (h kali mu).
Theophylin c th dng ng tim l aminophylin, hn hp ca theophylin v
ethylendiamin, tan trong nc gp 20 ln so vi theophylin n c. Trong iu tr cn
hen nng, tim tnh mch aminophylin rt chm (t nht trong 20 pht).
3.2.3.2. Chng ch nh v thn trng
Chng ch nh: qu mn vi thuc, lot d dy - t trng tin trin, ri lon chuyn ha
porphyrin, ng kinh khng kim sot c.
Thn trng: bnh tim, tng huyt p, cng gip, tin s lot d dy- t trng, suy gan,
ng kinh, c thai v cho con b, ngi cao tui, ang b st, dng cng cc thuc c ch
enzym chuyn ha thuc gan.
3.2.3.3. Tc dng khng mong mun: thng gp nhp tim nhanh, tnh trng kch thch,
bn chn, bun nn, nn. t gp: kch ng ng tiu ha, au u, chng mt, mt ng,
run, co git, lon nhp tim, h huyt p, phn ng d ng.
3.2.3.4. Liu dng:
Vin theophylin gii phng chm (Theostat, Nuelin SA): mi ln ung 200 - 400 mg, cch
12 gi ung 1 ln.
Hen ban m: ung mt ln duy nht vo bui ti vi liu bng tng liu dng trong mt
ngy.
. Aminophylin: ung mi ln 100 - 300 mg, ngy 3- 4 ln, sau ba n.
Tim tnh mch chm t nht trong 20 pht liu 5 mg/ kg.
3.3. Thuc chng vim
3.3.1. Glucocorticoid (GC)
Glucocorticoid c hiu qu rt tt trong iu tr hen, do thuc c tc dng chng vim,
lm gim ph n, gim bi tit dch nhy vo lng ph qun v lm gim cc phn ng d
ng. Glucocorticoid phc hi p ng ca cc receptor 2 vi cc thuc cng 2
adrenergic (xin xem thm bi Hormon v thng thn).
- Dng di dng ht c tc dng tt, iu tr d phng hen khi ngi bnh phi dng
thuc cng 2 nhiu hn 3 ln/ tun, t gy tc dng khng mong mun ton thn. Bt
buc phi dng thuc u n t li ch ti a v lm gim nguy c tng nng ca
hen.
Tc dng khng mong mun ti ch thng gp khi dng GC ht l nhim nm Candida
ming hng, khn ting v ho. Dng liu cao ko di c th gy c ch thng thn, gim
mt khong xng, tng nhn p.
Cc GC dng ng ht: beclometason dipropionat, budesonid v fluticason propionat.
(ba thuc ny c tc dng tng ng nhau), ciclesonid, mometason furoat.
* Beclometason dipropionat (Becotide): kh dung nh liu mi ln 100 - 400 g, 2

ln/ ngy, sau iu chnh theo p ng ca ngi bnh.
* Budesonid (Pulmicort): ht mi ln 200 g, 2 ln/ ngy.
Ch phm phi hp: Symbicort cha formoterol v budesonid vi cc hm lng
formoterol/ budesonid mi ln xt l 4,5 g/ 80 g; 4,5g/ 160 g; 9g/ 320g.
Ngi ln v tr em trn 12 tui: mi ln 1 - 2 xt, ngy 2 ln.
iu tr duy tr: 1 ln xt/ ngy.
* Fluticason propionat: ht nh liu mi ln 100 - 250 g, 2 ln/ ngy.
tr em 4- 16 tui: mi ln 50- 100 g, 2 ln/ ngy
Ch phm phi hp: Seretide cha salmeterol v fluticason propionat vi cc hm lng
salmeterol / fluticason propionat mi ln xt l 25 g/ 50 g; 25 g/ 125 g; 25
g/ 250 g
Ngi ln v tr em trn 12 tui: mi ln 2 xt, ngy 2 ln.
Dng ch phm c hm lng thuc ph hp vi mc nng ca bnh hen.
* Ciclesonid: ngi ln xt mi ngy mt ln 160 g.
* Mometason furoat: ngi ln ht 200 - 400 g vo bui ti hoc chia lm 2 ln trong
ngy.
- Dng ton thn: iu tr cn hen cp nn g hoc kim sot hen mn tnh nng.
. Hen nng cp tnh: ngi ln ung prednisolon 40 - 50 mg/ ngy, t nht trong 5 ngy
(tr em 1- 2 mg/ kg/ ngy, trong 3 ngy), sau iu chnh liu theo p ng ca ngi
bnh, hoc tim tnh mch hydrocortison 400 mg/ ngy, chia lm 4 ln.
. Hen mn tnh nng khng p ng y vi cc thuc chng hen khc, ht GC liu cao
phi hp vi ung GC mi ngy mt ln vo bui sng. Tm liu thp nht kim sot
c triu chng
3.3.2. Cromolyn natri
- Tc dng: c ch dng bo ca phi gii phng cc cht trung gian ha hc do p
ng vi cc kch thch hoc do tng tc khng nguyn - khng th IgE.
c ch tc dng hot ha ca cc peptid ha hng ng trn bch cu trung tnh, a acid
hoc n nhn.
Cromolyn natri ch c tc dng phng cn, ngn nga p ng hen vi cc kch thch do
d ng hoc khng do d ng, c dng iu tr di hn sm trong hen, khng c tc
dng iu tr cn hen cp. Tr em p ng vi thuc tt hn ngi ln.
Nhn chung tc dng d phng hen ca cromolyn natri km hiu qu hn so vi GC
ng ht.
- Cromolyn natri dng theo ng ht, t c hp thu nn t gy c tnh ton thn.

- Tc dng khng mong mun: ho, co tht nh ph qun, nhc u, bun ng, ri lon
tiu ha, phn ng qu mn.
- Liu dng: ht mi ln 10 mg (2 xt, ngy 4 ln cch u nhau).
Phng cn hen do gng sc, kh lnh, tc nhn mi trng: ht 10 mg (2 xt) ngay trc
khi tip xc vi cc yu t gy cn.
3.3.3. Thuc khng leucotrien
Thuc khng leucotrien ngn cn tc dng ca cc cysteinyl leucotrien ng h hp.
Chng c tc dng khi dng ring hoc khi phi hp vi GC ht (tc dng hip ng
cng)
- Ch nh: iu tr d phng hen
Phi hp vi thuc cng 2 v GC ng ht iu tr hen mn tnh nng
- Tc dng khng mong mun: ri lon tiu ha, kh ming, kht, au u, chng mt,
ri lon gic ng, au khp, au c, ph, phn ng nhy cm. C th gp hi chng
Churg- Strauss (c tin s hen, thng vim mi, vim xoang, vim mch v tng bch
cu a eosin).
- Cc thuc:
. Montelukast: Ngi ln: nhai hoc ung 10 mg trc khi i ng.
Tr em 6 thng 5 tui: 4 mg/ ngy, 6- 14 tui: 5 mg/ ngy
Thn trng khi dng ngi mang thai v cho con b
. Zafirlukast: ung mi ln 20 mg, ngy 2 ln.
Khng dng cho tr em di 12 tui, suy gan, cho con b.
Thn trng khi dng ngi cao tui, ngi mang thai, suy then.
3.4. S dng thuc trong iu tr hen
3.4.1. ng dng thuc
Cc thuc iu tr hen c th dng bng cc ng khc nhau:
+ ng ht: thuc c a trc tip vo ng h hp nn t nng cao ti , liu
ht thng thp hn liu ung, gim c tc dng khng mong mun ton thn .
. Ht nh liu l phng php thun tin v c hiu qu khi s dng thuc iu tr hen
mc nh v trung bnh. iu rt quan trng l phi hng dn ngi bnh tht cn thn
v cch s dng ng dng c ht nh liu t kt qu ti u.
. Bung ht (spacing devices) to ra mt khoang gia dng c ht v ming, dng tt hn
ngi gi, tr em, nhng ngi k h s dng dng c ht nh liu ng cch, hoc dng
khi ht corticoid liu cao gim lng ng thuc ming v hng, d gy nhim nm
Candida. Dn ngi bnh phi sc ming sau khi ht thuc.
. Dung dch kh dung thng dng trong cn hen nng cp tn h, dng cng vi oxygen
trong bnh vin.
- ng ung: khi khng th dng bng ng ht hoc ng ht km hiu qu. Dng
ng ung gy nhiu tc dng khng mong mun ton thn hn ng ht.
- ng tim: cc thuc cng 2, corticoid hoc aminophylin ch dng ng tim trong
cp cu cn hen nng, cp tnh, khi ng kh dung khng hoc khng ph hp.
3.4.2. X tr hen
- Ct cn hen: ht thuc cng 2 tc dng ngn (SABA) c hiu qu nht.
- iu tr duy tr, kim so t di hn hen: phi hp corticoid ht v thuc cng 2 tc dng
di (LABA) ht c hiu qu nht.
Nu hen vn cha kim sot c, cn nhc phi hp thm vi ung mt trong cc thuc
sau: theophylin gii phng chm, thuc cng 2 gii phng chm, thuc kh ng
leucotrien hoc corticoid.
Xem xt li iu tr sau mi 3 thng iu chnh ch iu tr cho ph hp.
- Cn hen nng cp tnh: th oxy, kh dung dung dch SABA, corticoid (ung, tim tnh
mch).
- D phng cn co tht ph qun khi gng sc, do kh lnh hoc do tc nhn mi trng:
ht cromolyn natri hoc SABA (ht, ung).
4.Thuc iu tr bnh phi tc nghn mn tnh
Bnh phi tc nghn mn tnh l tnh trng bnh c trng bi ri lon thng kh tc
nghn khng c kh nng phc hi hon ton. S h n ch thng kh thng tin trin t t
v lin quan n phn ng vim bt thng ca phi do cc phn t hoc kh c hi.
Cc yu t nguy c ca bnh phi tc nghn mn tnh: ht thuc l, khi bi do nhim
mi trng, nhim khun ng h hp v yu t di truyn (thiu 1 antitrypsin).
c im ca bnh phi tc nghn mn tnh l tnh trng vim nhim thng xuyn
ton b ng dn kh v nhu m phi, dn n x ha ng th v ph hu ph nang.
V vy, iu tr bnh phi tc nghn mn tnh, tr c ht phi loi b cc yu t nguy
c.
Cc thuc iu tr bnh bao gm:
4.1. Thuc gin ph qun: iu tr triu chng ca bnh
- Ht thuc cng 2 tc dng ngn (salbutamol, terbutalin, fenoterol) hoc thuc khng
cholinergic tc dng ngn (ipratrop ium) khi cn thit.
- Nu bnh tin trin nng: phi hp thuc cng 2, thuc khng cholinergic v/ hoc
theophylin.
- Tiotropium l thuc khng cholinergic tc dng ko di dng iu tr duy tr trong
bnh phi tc nghn mn tnh, khng dng trong co tht ph qun cp.
- Ht mi ngy mt ln 18 g. Khng dng cho ngi di 18 tui.
4.2. Glucocorticoid:
Phi hp LABA v GC dng ht iu tr bnh phi tc nghn mn tnh mc trung
bnh v nng. Ngng phi hp nu khng thy ch li sau 4 tun.
Nu bnh tin trin nng hn: dng thuc gin ph qun (dung dch kh dung) v th oxy,
ung GC trong thi gian ngn.
4.3. Cc thuc khc
- Tim vaccin cm mi nm mt ln, vaccin phng ph cu.
- Dng khng sinh khi c nhim khun.
- Thuc lm long m (a cetyl cystein, carbocistein ) trong t cp c ho khc m dnh
qunh.
- iu tr tng cng 1 antitrypsin.
5. Thuc kch thch h hp
Ngoi cafein l thuc tc dng u tin trn v no, cc thuc khc u c tc dng ch
yu trn hnh no. Vi liu iu tr, trn ngi bnh thng khng c tc dng r rng.
Vi liu cao, cc thuc u gy co git, lc u l co git cng, ri ngay sau chuyn
sang co git rung. C ch ca tc dng co git cha c hon ton bit r, nhng ni
chung l lm gim ngng k ch thch ca thn kinh trung ng. Trn trung tm h hp,
cc thuc u c tc dng kch thch, i lp vi tc dng ca barbiturat.
5.1. Cafein v cc alcaloid dn xut ca xanthin
Ly l ch, ht c ph, ht cla, cacao, hoc c th tng hp t acid u ric. C 3 cht c
dng trong iu tr l cafein, theophylin v theobromin, trong cng thc u c nhn
purin.
5.1.1. Tc dng
- Trn v no, cafein c tc dng r rt lm mt cm gic mt nhc, bun ng, lm tng
qu trnh hng phn, tng cng nhn cm ca cc gic quan, lm kin n nhanh, tr
tu minh mn. Nu dng thuc lin tc v ko di th sau giai on hng phn thng tip
theo giai on c ch, mt mi.
- Trn h thng tim mch: theophylin tc dng mnh hn cafein. Kch thch trc tip trn
c tim lm tim p nhanh, mnh, tng lu lng tim v lu lng mch vnh. Trn c th
nguyn vn, do cn c tc dng kch thch trung tm dy thn kinh X nn c tc dng
ngc li. V vy, tc dng ca cafein trn tim l phc tp, tu theo liu: liu nh l m tim
p chm, liu cao lm tim p nhanh. Liu iu tr t lm thay i huyt p.
- Trn h hp: kch thch trung tm h hp hnh no, lm gin ph qun v gin mch
phi do tc dng trc tip trn c trn. Tc dng cng r khi trung tm h hp b c
ch bi thuc m, thuc ng hay morphin.
- Trn c quan: lm gin mch thn v li niu. Lm tng tit dch v c s, tng tnh acid
ca dch v do trc tip kch thch nim mc d dy v kch thch qua trung tm ph giao
cm.
5.1.2. C ch tc dng
- Gii phng catecholamin
- Huy ng calci v c ch s thu hi calci vo ti li ni bo.
- c ch phosphodiesterase, lm vng bn v tng AMPc. Catecholamin cng lm tng
AMPc nhng l do kch thch adenylcyclase, tng tng hp AMPv t ATP. V vy, gi i
thch c nhiu tc dng ging nhau gia catecholamin v cafein trn tim mch, ph
qun, mt s chuyn ha nh tng ng huyt, tng hu lipid (xin xem trong bi
Thuc tc dng trn h thn kinh thc vt).
Catecholamin Xanthin
(+) (-)
Adenylcyclase Phosphodiesterase
ATP AMPv AMP
Tng ng huyt Tim mch

Tng hu lipid
5.1.3. p dng iu tr
Qu trnh hng phn ca thn kinh trung ng b gim, hen, suy tim (khng dng trong
trng hp vim c tim), phi hp vi thuc h st ( i khng vi tc dng c ch tim
ca cc thuc ny).
Liu lng:
- ng tim cafein natri benzoat 0,07g/ mL, tim di da hoc tim bp 1 - 2 ng/ ngy.
- Theophylin mi ln ung 200 mg, ngy 2 ln.
5.2. Nikethamid
L thuc tng hp, lm nhp th nhanh v su do kch thch qua phn x xoang cnh,
nhng tc dng chnh l kch thch trc tip cc trung tm hnh no. Khng c tc dng
trc tip trn tim v mch mu.
Ch nh trong cc trng hp suy ti m mch v h hp.

Tim di da, bp tht hoc tnh mch chm, mi ln 1 ng 1mL (dung dch 25%), mi
ngy 3 ng. Ung dung dch 25% mi ln X - XX git, ngy 2- 3 ln.
5.3. Bemegrid
Cng thc ha hc gn ging barbiturat, nhng c tc dng i khng vi ba rbiturat.
Bemegrid kch thch trc tip cc trung tm h hp v tun hon hnh no, lm tng
nhp tim, tng huyt p, tng bin h hp.
Liu cao cng gy cc cn co git, nhng phm vi an ton rng hn, d s dng hn, nn
c xu hng c s dng tro ng iu tr mt s bnh tm thn bng cc cn co git.
Ngoi tc dng trn thn kinh trung ng, bemegrid cn kch thch cc si thn kinh vn
ng, lm d dng s vn chuyn xung tc thn kinh qua cc nron, nn cn c dng
iu tr mt s chng vim d y thn kinh, au tht lng hng
Liu lng: nhim c barbiturat c th tim hng gam vo tnh mch lm nhiu ln tu
theo tnh trng nhim c.
Tim bp 25- 50 mg iu tr vim dy thn kinh.
5.4. Doxapran hydroclorid
- Ch nh: dng trong trng h p suy h hp cp, suy gim h hp sau m
- Chng ch nh: tng huyt p nng, tnh trng hen, bnh mch vnh, nhim c do
tuyn gip, ng kinh, tc nghn c hc ng h hp.
- Tc dng khng mong mun: chng mt, tot m hi, tng huyt p v nhp t im. Tc
dng khng mong mun trong giai on sau m bao gm: co cng c cc b, tng hot
ng, ln ln, o gic, ho, kh th, co tht thanh qun, co tht ph qun, nhp nhanh
xoang, nhp tim chm, ngoi tm thu, bun nn, nn, tit nc bt.
- Liu dng:
. Suy gim h hp sau m: tim tnh mch (t nht trong 30 giy) 1 - 1,5 mg/ kg, nhc li
nu cn thit sau 1 gi hoc truyn tnh mch 2 - 3 mg/ pht. iu chnh liu theo p ng
ca ngi bnh.
. Suy h hp cp: truyn tnh mch 1,5 - 4 mg/ pht, iu chnh theo p ng ca ngi
bnh. Dng cng vi oxygen v phi theo di thng xuyn p sut kh trong mu v pH
mu.
Khng dng cho tr em.
Cu hi t lng gi
1. Phn bit c c ch tc dng ca hai nhm thuc lm long m.
2. Trnh by tc dng, tc dng k hng mong mun v p dng iu tr ca N -

acetylcystein v bromhexin.
3. Trnh by c ch tc dng ca cc nhm thuc cha ho.
4. Trnh by tc dng, tc dng khng mong mun v p dng iu tr ca cc thuc
cha ho: codein, dextromethorphan.
5. Trnh by tc dng, tc dng khng mong mun v p dng iu tr ca thuc
cng 2 adrenergic (salbutamol, salmeterol), ipratropium v theophylin.
glucocorticoid trong iu tr hen.
7. Nu cch s dng thuc trong iu tr hen.
8. Trnh by nguyn tc iu tr bnh phi tc nghn mn tnh.
9. Trnh by c ch tc dng, tc dng v ch nh iu tr ca cafein, nikethamid,
doxapram.
Bi 29: thuc iu tr thiu mu

1. Trnh by c vai tr sinh l, dc ng hc v ch nh ca st.
2. Phn tch c ngun gc, vai tr sinh l, ch nh ca vitamin B 12, acid folic,
erythropoitin, v nguyn tc iu tr thiu mu.
1. i cng
1.1. nh ngha thiu mu
Thiu mu l tnh trng gim s lng hng cu hoc huyt sc t hoc hematocrit di
mc bnh thng so vi ngi cng tui, cng gii kho mnh.
- i vi nam gii c coi l th iu mu khi: s lng hng cu di 4 triu hoc
hemoglobin di 12 g/ 100 mL hoc hematocrit di 36%.
- i vi n gii c coi l thiu mu khi: s lng hng cu di 3,5 triu hoc
hemoglobin di 10 g/ 100 mL hoc hematocrit di 30%.
1.2. Nguyn nhn thiu mu
Thiu mu do rt nhiu nguyn nhn c th : do chn thng, sau phu thut, do giun
mc, tc, rong kinh, tr, lot d dy - t trng, do tan mu ngi c bt thng v
hemoglobin, thiu G 6PD, bnh t min, do thuc hoc ha cht, st rt hoc do tu
xng km hot ng hoc khng hot ng hoc do thiu ht cc thnh phn tng hp
hemoglobin, sn xut hng cu.
Da vo ch s nhim sc v kch thc hng cu thiu mu c xp thnh 3 loi:
. Thiu mu nhc sc: hng cu nh v ch s nhim sc < 1
. Thiu mu ng sc: hng cu bnh thng v ch s nhim sc = 1
. Thiu mu u sc: hng cu to v ch s nhim sc > 1
2. Nguyn tc iu tr thiu mu
Trong qu trnh iu tr thiu mu phi kt hp iu tr nguyn nhn vi dng thuc hoc
vi iu tr triu chng v bi dng c th.
- Trng hp mt mu cp vi khi lng ln: cn phi truyn mu ngay. Trong khi ch
i mu phi truyn nc mui sinh l hoc Ringer lactat v tm nguyn nhn, v tr chy
mu iu tr.
- Mt mu mn tnh do giun tc , mc, rong kinh, tr, st rt dng cc thuc iu tr
nguyn nhn kt hp vi b sung st v bi dng c th.
- Thiu mu do gim sn xut hng cu: c th da vo th tch trung bnh hng cu

dng cc thuc. Hng cu nh khi th tch trung bnh di 70 fl. Ngc li hng cu gi
l to khi th tch trung bnh > 110 fl.
. Trng hp thiu mu hng cu nh: dng st kt hp vi vitamin B 6 v tng lng
protid, lipid trong khu phn n v iu tr nguyn nhn.
. Thiu mu hng cu to phi tm nguyn nhn iu tr kt hp dng B 12 hoc acid folic.
. Thiu mu do tan mu: dng cc phng php hn ch nguyn nhn gy tan mu kt
hp vi dng acid folic.
3. Cc thuc cha thiu mu
3.1. St
3.1.1. Vai tr v nhu cu st ca c th
C th ngi ln cha khong 3 - 5 gam st, trong 1,5- 3 gam tn ti trong hng cu,
phn cn li 0,5 gam cha trong sc t c (myoglobulin), mt s enzym xanthinoxidase,
- glycerophosphatoxidase.
ngi bnh thng, nhu cu st hng ngy khong 0,5 - 1 mg . Ph n giai on c kinh
nguyt hoc c thai, cho con b nhu cu st cao hn khong 1 - 2 mg v 5- 6 mg trong 24
gi.
Khi thiu ht st, c th khng ch c thay i s to mu, m cn thay i chc nng ca
nhiu enzym quan trng. Do vy, b sung st l bin php rt quan trng iu tr thiu
mu nhc sc.
3.1.2. ng hc ca st trong c th
Ngun cung cp st hng ngy cho c th ch yu t cc thc n c ngun gc ng vt
v thc vt. Thc n cha lng st trn 5 mg trong 100 gam: gan, tim, trng, tht nc, gi
u, hoa qu.
* d dy: st t ngun thc n c th dng ion Fe 2+ hoc Fe 3+. Fe2+ c hp thu d
dng qua nim mc d dy, rut; cn Fe 3+ s kt hp vi albumin nim mc ng tiu
ha, nn khng hp thu c, gy kch thch nim mc ng tiu ha. Mun hp thu c,
Fe3+ phi c chuyn thnh Fe 2+ nh tc dng ca acid hydrocloric d dy.
* Ti rut: Fe2+ c gn vi mt albumin t bo nim mc rut l apoferritin to
thnh ferritin i vo mu. Apoferritin l cht mang st, c nhim v a st vo mu xong
quay tr li nim mc rut vn chuyn tip st. Khi c th thiu st th s lng
apoferritin tng ln lm tng hp thu st v ngc li. Mt s cht nh vitamin C,
protein c cha nhm- SH lm Fe 3+ chuyn thnh Fe 2+ d hp thu. Nhng c mt s cht
cn tr hp thu nh: phosphat, acid nucleic, acid phytic, tanin, tetracyclin.
* Trong mu: st tch ra t ferritin v c gn vi - globulin, cht vn chuyn st c
hiu to thnh transferritin. Dng phc hp st c chuyn n cc m nh tu xng,
c mt phn dng d tr cn mt phn to ra hng cu v cc enzym (Hnh 28.1).
* m: st i vo trong t bo c phi thng qua transferritin receptor mng t bo.

Nh qu trnh nhp bo, phc hp transferritin receptor i vo trong t bo gii phng ra
ion st. Sau khi gii phng st trong ni bo, transferritin quay li mng t bo lm
nhim v vn chuyn st tip. Khi thiu ht st th s lng transferritin receptor tng v
gim ferritin (gim d tr st) v ngc li, khi lng st trong c th tng cao th s
lng transferritin receptor gim xung v tng dng d tr st ln (ferritin) v tng thi
tr st qua phn, m hi v nc tiu.
Thc n: Fe2+ hoc Fe 3+

HCl
D dy FeCl2
Nim mc rut
(t trng): Fe2+ + Apoferritin Ferritin(Fe 3+)
Thi theo phn
Mu: Transferritin (Fe 3+) - globulin + Fe 3+
St t hng cu
B hu (Fe 2+)
Tu xng M D tr: Thi tr
(to hng cu) (to enzym, (gan, lch ( m hi, nc
globin c) tu xng) tiu, kinh nguyt)
Hnh 28.1. S vn chuyn st trong c th
3.1.3. S thiu ht st
S thiu ht st c th do:
- Cung cp khng y , gp nhng ngi c mc sng thp.
- Mt cn bng gia cung v cu: ph n c thai, cho con b, tr em ang ln.
- Gim s hp thu st ng tiu ha: gp nhng ngi ct mt phn d dy, vim
rut, thiu apoferritin, dng mt s thuc hoc thc n cha mt s cht ngn cn s hp
thu st.
- Chy mu: ng tiu ha (giun tc, giun mc, tr), t cung cp hoc mn tnh (rong
kinh)...
3.1.4. Ch nh
- Thiu mu thiu st do cc nguyn nhn khc nhau.
- Ph n c thai, cho con b, chng xanh lt ca ph n.

Trong iu tr st c th dng ring r hoc phi hp vi mt s ion hoc v cc vitamin.
Trn lm sng st c th dng ng ung hoc tim tnh mch chm. Tim tnh mch
khi bnh nhn khng dung np hoc ri lon hp thu st theo ng ung hoc ngi suy
thn mn tnh km theo phi lc mu. Hin c 2 ch phm st dextran v st sucrose dng
tim chm tnh mch hoc truyn tnh mch. Khi dng cn phi th vi liu thp trc
phng phn ng phn v. Cc ch phm st thng dng ng ung trn lm sng
u dng mui sulfat, clorid, fumarat, gluconat, aminoat v ascorbat.
- Ngi ln liu trung bnh 2 -3 mg/ kg cn nng tng ng 200 mg/ ngy.
- Tr nh liu trung bnh 5 mg/ kg cn nng/ ngy.
- Ph n c thai hoc cho con b liu trung bnh 4 - 6 mg/ kg cn nng/ ngy.
Trong qu trnh iu tr cn theo di lng hemoglobin. Khi hemoglobulin mu tr v
gi tr bnh thng cn tip tc ung thuc trong 3 -4 thng to s bo ho d tr st.
- Khi dng ng ung: lm ging, bun nn, nn, to bn, a chy, kch ng ng tiu
ha.
- Khi dng ng tim: au ti ch tim , au u, bun nn, nn, st, shock kiu phn v
khi tim tnh mch do vy khi dng cn phi tim tnh mch chm.
3.1.7. S qu liu lng
Ng c st do qu liu t gp ngi ln, nhng hay gp tr em. tr em liu 1- 2 g
c th gy t vong. Triu c hng ng c c th xut hin sau khi ung nhm 30 pht n
vi gi.
- Khi gp ng c, ngoi bin php iu tr tch cc v iu tr triu chng, cc bin php
loi tr cht c nh gy nn, ra rut bng dung dch natribicarbonat hoc phosphat
cng c s dng. Khi st trong mu cao trn 3,5 mg/ L phi dng deferoxamin tim
tnh mch hoc tim bp hoc c th dng deferipron ng ung. Hai thuc ny c tc
dng to chelat vi ion st.
3.2. Vitamin B 12
3.2.1. Ngun gc
Vitamin B 12 l tn chung ch 5 cobalami d: cyanocobalamin, hydroxycobalamin, methyl
cobalamin v 5- deoxyadenosylcobalamin.Vitamin B 12v cyanocobalamin c dng
ch tt c cc cobalamid c hot tnh ngi. Nhng trn thc t ch c 2 cobalamid:
cyanocobalamin v hydroxycobalamin c dng trong iu tr v cc cobalamid ny
ng vai tr coenzym ca nhiu phn ng chuyn ha, c bit l s tng hp ADN. Hn
th na, cc cobalamid ny n nh hn cc cobalamid khc.
T bo c th khng t tng hp c vitamin B 12. Ngun cung cp vitamin B 12 nhiu

nht l gan, tht, c, trng. Trong thc vt khng c vitamin B 12.
3.2.2. Dc ng hc ca vitamin B 12
Trong thc n vitamin B 12 (yu t ngoi lai) c dch v v protease gii phng ra khi
cc lin kt vi protein v c gn ngay vi glycopro tein d dy (yu t ni). Phc hp
vitamin B 12- yu t ni xung rut tc ng ln receptor c hiu trn nim mc hng
trng v c chuyn vo mu. Trong mu vitamin B 12 gn vo - globulin c ngun gc
gan gi l transcobalamin II. Phc hp vitamin B12- transcobalamin nhanh chng c
phn phi vo cc m c bit l nhu m gan. Ngoi transcobalamin II, vitamin B 12 cn
c gn vo transcobalamin I v III. Phc hp transcobalamin I - B12 l dng d tr ca
vitamin B 12. Gan l c quan d tr 90% lng vitamin B 12 ca c th (1- 10 mg). Vitamin
B12 c thi tr qua phn, nc tiu. V c chu k gan rut, cho nn c trng hp sau
ct d dy 3- 4 nm mi c biu hin thiu vitamin B 12.
3.2.3. Vai tr ca vitamin B 12
Vitamin B 12 l cht cho methyl nn r t cn cho s chuyn ha acid folic tng hp acid
nhn gip cho t bo nhn ln pht trin.
- Chuyn homocystein thnh methionin v 5 -methyltetrahydrofolic thnh acid
tetrahydrofolic.
- Chuyn L- methylmalonyl- CoA thnh succinyl - CoA trong chui cc phn ng chuyn
ha glucid, lipid thng qua chu trnh Krebs.
- Duy tr nng myelin bnh thng trong cc neuron ca h thng thn kinh.
3.2.4. Thiu ht vitamin B 12
Nhu cu hng ngy ca vitamin B 12 ph thuc vo tui, gii, tnh trng bnh l v nm
trong khong t 0,3- 2,6 g.
Thiu vitamin B 12 c th do: Cung cp khng y , gim hp thu do gim yu t ni,
vim rut, ct hng trng, bnh ty tng gy thiu protease, t sinh khng th chng yu
t ni, ri lon chu k gan rut hoc do gim s lng, cht lng transcobalamin II do di
truyn. Khi thiu vitamin B 12 gy nn thiu mu u sc hng cu to (thiu mu c tnh
Biermer), tn thng neuron h thn kinh: ph n, mt myelin. C th gy cht neuron
thn kinh tu sng, v no, gy ri lon cm gi c, vn ng chi, ri lon tr nh, ri
lon tm thn. ngi cao tui c th gp tn thng thn kinh do thiu vitamin B 12
nhng khng c du hiu thiu mu.
3.2.5. Ch nh- chng ch nh
- Thiu mu u sc hng cu to Biermer.
- Vim au dy thn kinh, ri lon tm thn.
- Suy nhc c th, chm pht trin, gi yu.
- Nhim c, nhim khun.
- Khng dng thuc cho ngi d ng vi thuc v ung th cc th khc nhau.

Vitamin B 12 c th dng di dng n cht hoc kt hp v i cc vitamin v cc mui
kim loi ung hoc tim bp hay tim di da. Hin nay c 2 ch phm c dng vi
hm lng khc nhau l cyanocobalamin v hydroxycobalamin nhng hydroxycobalamin
c s dng nhiu hn v tn ti trong c th lu hn cyanoco balamin.
Ch nh dng dng thuc v liu lng da vo nguyn nhn v tn thng do thiu
vitamin B 12 gy ra.
- Thiu ht vitamin B 12 do yu t ni phi dng dng tim.
- Trong iu tr thiu mu, suy nhc c th... ch cn dng liu trung bnh 100
g/ ngy, nhng trong trng hp vim dy thn kinh, ri lon tr nh, ri lon tm thn
phi dng dng tim liu 500, 1000, 5000 g/ ngy.
3.3. Acid folic (vitamin L 1, vitamin B 9)
L s kt hp ca pteridin, acid paraaminobenzoic v acid glutamic.
Acid folic khng ch c nhiu trong tht, c, trng, gan, men bia m cn c trong rau
xanh, hoa qu. Khi nu chn thc n, c bit l rau xanh 90% acid folic b phn hy.
3.3.1. Dc ng hc v vai tr ca acid folic
Acid folic trong thc n tn ti di d ng folatpolyglutamat. Dng ny cng l kho d tr
folat trong cc t bo ngi.
* ng tiu ha, folatpolyglutamat b thu phn to thnh folat monoglutamat v b
kh to thnh methyltetrahydrofolat (MTHF). Nh hot tnh ca enzym pteroyl - -
glutamyl- carboxypeptidase nim mc rut, MTHF c hp thu v i vo mu.
* Trong mu, methyltetrahydrofolat c vn chuyn n m v thng qua nhp bo,
MTHF vo trong t bo.
* Trong t bo ca m, methyltetrahydrofolat ng vai tr cht cho methyl ch uyn
vitamin B 12 thnh methylcobalamin. Methylcobalamin gip chuyn homocystein thnh
methionin. Sau khi mt methyl, methyltetrahydrofolat s thnh tetrahydrofolat, tham gia
vo mt s qu trnh chuyn ha quan trng nh:
- Chuyn serin thnh glycin vi s tham gia ca vitamin B 6.
- Chuyn deoxyuridylat thnh thymidylat to ADN - thymin.
Ngoi ra, tetrahydrofolat cn tham gia vo qu trnh chuyn ha histidin v tng hp base
purin.
* gan, methyltetrahydrofolat mt phn tham gia chuyn ha, phn khc c a vo
mt thi xung t trng. t trng, MTHF c ti hp thu tr li. Ru lm gii phng
MTHF t t bo gan vo mt lm gim nng folat trong mu (hnh 29.2)
Hnh 29.2. Vai tr ca acid folic v vitamin B 12 trong chuyn ha
3.3.2. S thiu ht acid folic

- Hng ngy, ngi ln cn 25 - 50 g, ph n c thai, cho con b v tr em cn 100 - 200
g. Khi cung cp khng y hoc do mt cn bng gia cung v cu hoc do mt s
bnh lm gim hp thu hoc do mt s thuc khng chuyn ha trong iu tr ung th,
primaquin, trimethoprim, sulfonamid hoc do tan mu gy nn thiu ht acid folic.
Khi thiu ht acid folic s gy nn thiu mu hng cu to khng km tn thng thn
kinh
3.3.3. Ch nh
- Thiu mu hng cu to khng c du hiu tn thng thn kinh.
- Thiu mu tan mu.
- Gim bch cu ht, mt bch cu ht.
- D phng thiu ht acid folic khi dng mt s thuc, ph n c thai, cho con b.

Acid folic c bo ch di dng ung hoc tim bp hoc tnh mch c dng n cht
hoc phi hp vi cc vitamin khc v cc mui kim loi.
Liu trung bnh t 2- 5 - 15 mg/ 24 gi.
3.4. Cc thuc chng thiu mu khc
Ngoi st, acid folic v vitamin B 12, vitamin B 2 , vitamin B 6, ng v Cobalt cng c tc
dng chng thiu mu.
3.5. Erythropoietin
L yu t iu ha s nhn ln ca t bo gc trong tu xng, kch thch s trng thnh
ca hng cu non v gii phng hng cu khi tu xng i vo tun hon. Yu t ny c
cu trc protein gm 165 acid amin, phn t lng 3040 0, c sn xut ch yu t bo
cnh cu thn, th yu t bo gan.
Trong mu ngi khng thiu mu c nng erythropoietin di 20 UI/L v c gn
vo glucose khng c tc dng dc l. Khi c th thiu mu, thiu oxy s tng hp v
bi tit ca yu t ny tng ln gp 100 ln so vi bnh thng. Khi cu thn b vim cp
hoc mn tnh hay tn thng tu xng hoc thiu st, s bi tit erythropoietin gim
xung r rt, gy nn thiu mu. Chnh v l do , erythropoietin c ch nh ch yu
trong cc trng hp thiu mu do vim thn. Ngoi ra, erythropoietin cn c dng
trong thiu mu do bnh AIDS, iu tr thuc chng ung th, thiu mu do mt mu sau
phu thut v phng thiu mu tr non trng lng thp.
- Ch phm v liu dng:
+ Epoetin alpha (Epogen; Eprex) ng tim cha 2000, 3000, 4000, 5000,6000,8000,
10000 v l cha 40000 n v, l erythropoietin ngi ti t hp nh k thut ti t hp
ADN. Tim tnh mch hoc di da 50 - 100 n v/ kg th trng,3 ln trong mt tun.
ngi c suy thn mn tnh thuc c t/2 t 4 -12 gi.
+ Epoetin beta ( NeoRecormon ) ng tim cha 500,1000, 2000, 4000 5000, 6000, 10000
v l cha 50000,100000 n v. Thuc c th tim di da hoc tim tnh mch liu khi
u 40-60 n v /tun trong 4 tun l in, sau tu theo p ng ca c th m iu
chnh liu ph hp.
Khi dng thuc iu tr, nn cung cp thm st nhm gip tu xng sinh sn nhanh hng
cu. Do thuc c th gy tng th tch mu v hematocrit v tng sc cn ngoi vi, nn
phi chnh liu cho ph hp vi bnh nhn b bnh thn c cao huyt p.
Cu hi t lng gi
1. Trnh by vai tr sinh l, c im dc ng hc v ch nh ca st.
2. Trnh by ngun gc, vai tr sinh l, v ch nh ca vitamin B12.
3. Trnh by ngun gc, vai tr sinh l v ch nh ca acid folic.
4. Trnh by ngun gc vai tr , ch nh ca erythropoietin v nguyn tc iu tr

thiu mu.
Bi 30: Thuc tc dng trn qu trnh ng mu

v tiu fibrin

1. Trnh by c c ch tc dng v p dng iu tr ca vitamin K.
2. So snh c c ch tc dng, ng hc v p dng iu tr ca dn xut
coumarin v heparin.
3. Phn tch c c ch tc dng v p dng iu tr ca thuc lm tiu fibrin v
chng tiu fibrin.
1. Thuc tc dng ln qu trnh ng mu

1.1. C ch ng mu
ng mu l mt qu trnh mu chuyn t th lng thnh th c do chuyn fibrinogen
thnh fibrin khng ha tan v cc si fibrin ny b trng hp to thnh mng li giam
gi cc thnh phn ca mu lm mu ng li.
Bnh thng, trong mu v trong cc m c cc cht gy ng v cht chng ng, nhng
cc cht gy ng dng tin cht, khng c hot tnh. Khi mch mu b tn thng s
hot ha cc yu t ng mu theo kiu dy truyn lm cho mu ng li.
Qu trnh ng mu xy ra qua 3 giai on :
- Giai on to thnh phc hp prothrombinase (1)
- Giai on to thnh thrombin (2)
- Giai on to thnh fibrin (3)
Promthrombinase (1)
Prothrombin Thrombin (2)
Fibrinogen Fibrin (3)

v cc mu ng
1.1.1.Giai on to thnh phc hp prothrombinase
L qu trnh phc tp v ko di nht th ng qua hai c ch ni sinh v ngoi sinh to ra
phc hp prothrombinase.
* C ch ngoi sinh:
Khi mch mu tn thng, mu tip xc vi v tr tn thng. M v tr tn thng gii

phng ra yu t III (thromboplastin m) v phospholipid. Yu t III, IV (calci) cng yu
t VII, v phosphlipid m hot ha yu t X. Yu t X hot ha cng vi yu V,
phospholipid m v ion calci to thnh phc hp prothrombinase.
* C ch ni sinh :
ng thi khi mu tip xc vi v tr tn thng s lm hot ha yu t XII v tiu cu
lm gii phng phospho lipid. Yu t XII hot ha yu t XI v yu t XI hot ha yu t
IX. Yu t IX cng vi yu t VIII hot ha, phospho lipid tiu cu v Ca +2 hot ha yu
t X. Yu t X, yu t V, cng vi phospho lipid tiu cu v Ca +2 to nn phc hp
prothrombinase.
1.1.2. Giai on to thnh thrombin
Prothrombinase to ra theo c ch ngoi sinh v ni sinh cng vi ion calci xc tc cho
phn ng chuyn prothrombin thnh thrombin
1.1.3. Giai on to thnh fibrin v cc mu ng
Di tc dng ca thrombin, fibrinogen dng ha tan chuyn thnh fibrin khng ha tan.
Cc si fibrin ni li vi nhau v di tc dng ca yu t XIII hot ha to ra mng li
fibrin bn vng giam gi cc thnh phn ca mu lm mu ng li.
1.2. Thuc lm ng mu
1.2.1. Thuc lm ng mu ton thn
1.2.1.1. VitaminK (K: Koagulation - ng mu)
+ C 3 ngun cung cp vitamin K :
- Vitamin K 1 (phytonadion, phulloquinon) c ngun gc thc vt.
- Vitamin K 2 (menaquinon) do vi khun gram m ng rut tng hp.
- Vitamin K 3 (menadion) c ngun gc tng hp.
+ Vitamin K tan trong lipid, nhng ring vitamin K 3 dng mui natribisulfit hoc mui
tetra natri tan trong nc vo c th b chuyn ha thnh vitamin K 3.
* Vai tr sinh l :
+ Vitamin K gip cho gan tng hp cc yu t ng mu nh prothrombin (II), VII, IX v
X.
- C ch : Bnh thng, cc yu t II, VII, IX v X dng tin cht. Khi c mt vitamin K
vi vai tr cofactor cn thit cho enzym microsom gan xc tc chuyn cc tin cht
thnh cc cht c hot tnh bi s chuyn acid glutamic gn acid amin cui cng ca cc
tin cht thnh - carboxyglutamyl. Cht ny cng c mt trong protein c bi tit t
ct bo v c vai tr trong s to xng.
* Du hiu ca s thiu ht :
Nhu cu hng ngy khong 1 g/kg. Khi thiu ht s xut hin bm mu di da, chy
mu ng tiu ha, rng ming, i ra mu, chy mu trong s.
* Dc ng hc :
Vitamin K tan trong du, khi hp thu cn c mt ca acid mt. Loi tan trong du thng
qua h bch huyt vo mu, cn d ng tan trong nc hp thu i trc tip vo mu.Vitamin
K1 c hp thu nh vn chuyn tch cc cn K 2, K3 c hp thu nh khuych tn th
ng.
Sau hp thu vitamin K 1 tp trung nhiu gan v b chuyn ha nhanh thnh cht c cc
thi ra ngoi theo phn v nc tiu.
* c tnh :
Mc d c phm vi iu tr rng, nhng c th gp thiu mu tan mu v cht do vng da
tan mu tr di 30 thng tui dng vitamin K 3.
Vitamin K 3 cn gy kch ng da, ng h hp, gy i albumin, gy nn v c th gy
tan mu ngi thiu G 6PD.
* Ch nh v liu dng :
Vitamin K c th ung hoc tim bp, di da hoc tim tnh mch (dng tan trong nc)
vi liu 100 - 200mg/ngy cho nhng bnh nhn :
- Thiu vitamin K do nguyn nhn khc nhau.
- Chun b phu thut ( ph ng chy mu trong v sau phu thut ). Nhng trng hp
ny phi dng thuc trc 2 -3 ngy.
- Gim prothrombin mu
- Ng c dn xut coumarin.
1.2.1.2. Calci clorid:
Ca+2 cn hot ha cc yu t VIII, IX v X chuyn prothrombin sang thrombin .
Liu trung bnh: ung 2- 4g mi ngy, dng cch qung tng thi k 3 - 4 ngy, ri ngh.
Tim tnh mch cho nhng trng hp chy mu: 20ml dung dch 5%. Thuc tim ra
ngoi tnh mch s gy lot. Tuyt i cm tim bp tht.
1.2.1.3. Coagulen
L tinh cht mu ton phn, c bit c tinh cht ca tiu cu. Dng trong ngoi khoa
ngi bnh a chy mu v trong nhng trng thi chy mu (ban chy mu, i ngoi ra
mu v.v...).
Ung 1-5 ng mi ngy (ng 20ml).
Hemocoagulen: ng tim 5ml. Trng hp nng, c th tim ti 4 ng mi ngy.
1.2.1.4. Carbazochrom (Adrenoxyl):
Lm tng sc khng mao mch, gim tnh thm thnh mch, nn lm gim thi gian chy
mu. Tc dng sau khi tim 6 -24 gi (tim bp 1,5 - 4,5 mg mi ngy hoc ung 10 -30
mg mi ngy).
Cha chy mu do gin mao mch hoc phng chy mu sau phu thut to hnh, tai mi
hng, ct b tuyn tin lit.
1.2.1.5. Ethamsylat v dobesilat calci:
Lm tng sc khng mao mch, gim tnh thm thnh mch. Dng phng chy mu cp
trong phu thut to hnh, tai mi h ng, ct b tuyn tin lit, rong kinh.
Mi ngy tim bp 250 -500mg hoc ung 750-1500mg.
1.2.1.6. Vitamin P (flavonoid, rutosid rutin v dn xut):
Rutosid v dn xut ngun gc thc vt c hot tnh vitamin P u gim tnh thm thnh
mch v lm tng sc khng mao mch do c ch s t oxy ha ca adrenalin, v c ch
COMT gan, do ko di tc dng ca hormon ny.. Hot tnh vitamin P biu hin r
trn s tng hp mucopolysacharid v glycoprotein ca m lin kt. Ung 20 -40mg mi
ngy, cha gin mao mch v tng tnh n hi mch mu, c tc dng sau khi ung 6
gi.
1.2.2. Thuc lm ng mu ti ch
1.2.2.1. Enzym lm ng mu
* Thrombokinase (prothrombinase): l tinh cht ca ph tng ngi v ng vt, thng
ly no v phi. Tinh cht ny cha th rombokinase v c nhng yu t ng mu khc.
Tc dng khng chc chn bng thrombin. Dng khi chy mu t, ti ch, thng xuyn
(chy mu cam, rng ming) v c trong trng hp chy mu nhiu (phi hp vi bng
cht).
* Thrombin: Chuyn fibrinogen thnh fibrin n phn, ri thnh fibrin polymer khng tan
trong huyt tng.
Ch dng ti ch, tuyt i khng tim tnh mch (v mu ang chy s gy ng mu
nguy him).
Ung cha chy mu d dy.
1.2.2.2. Nhng loi khc
- Cc keo cao phn t gip tng nhanh ng mu : Pectin, albumin v.v...
- Gelatin, fibrin dng xp tng din tip xc, qua hy tiu cu nhiu hn, mu ng
nhanh hn.
- Mui kim loi nng: Lm bin cht albumin, lm kt ta fibrinogen v cc protein khc
ca mu. Hay dng dung dch F eCl3 10% bi ti ch hoc tm bng FeCl 3 p ln vt
thng.
- Thuc lm sn: Lm co mao mch nh, nn chng ng. Thng dng tanin, mui Al,
Pb, Zn hoc KMnO 4 pha long.
1.3. Thuc chng ng mu
1.3.1. Thuc dng phng th nghim v ngoi c th
- gim v tiu cu, ng nghim phi trng parafin, colodion, phim silicon. ng
nghim bng pyrex lm mu ng chm hn l khi dng loi bnh thng.
- Dng natri oxalat, natri fluorid ngn tc ng ca Ca +2.
- Natri citrat to phc hp vi Ca +2; kt hp vi fibrinogen v cc yu t II, VII, IX, X nn
lm chm ng mu. Mu d tr truyn cho ngi bnh thng c natri citrat (3 -4,0
gam/0,5l mu), vo c th, nng b pha long, khng c tai bin chy mu in vivo.
Nu truyn nhiu, cn ch n c tnh ca natri citrat.
- Cht cng cua (chelating agents) nh dinatri tetracemat (mui natri ca acid etylen
diamin tetracetic, EDTA, Complexon III, Sequestren) c tc dng gp Ca +2.
1.3.2. Thuc dng lm sng
Trong thc t hay dng ba loi :
- c ch s tng hp ca cc yu t ng mu gan (yu t II, VII, IX, X): Loi ny ch
tc dng in vivo: dn xut coumarin v indandion.
- c ch tc dng ca cc yu t ng mu : Loi ny tc dng c in vivo v in vitro:
heparin.
- Chng kt dnh tiu cu: aspi rin, dipyridamol, ticlopidin, clopidogel.
1.3.2.1. Thuc chng ng ng ung : Dn xut ca coumarin v indandion:
L thuc tng hp, c bng B.
- Dn xut 4-hydroxycoumarin c: warfarin, phenprocoumon, acenocoumarol,
dicoumarol, coumetarol, tromexan.
- Dn xut indadion c : phenylindadion, clophenindion.
* C ch tc dng :
Do dn xut coumarin v indandion c cu trc gn ging vitamin K, nn c ch cnh
tranh enzym epoxid-reductase lm cn tr s kh vitamin K -epoxid thnh vitamin K cn
thit cho s carboxyl ha cc tin yu t ng mu di s xc ca carboxylase thnh
cc yu t ng mu II, VII, IX v X.V th cc thuc nhm ny cn c gi l thuc
khng vitamin K.
* Dc ng hc :
Hp thu nhanh qua ng tiu ha, nhng xut hin tc dng sau khi ung 24-36 gi. Cc
thuc gn vo protein t l rt cao, tromexan 90%, warfarin 97%, phenprocoumon 99%.
Nhiu dn xut ca coumarin chuyn ha qua h enzym oxy ha microsom gan nh :

dicoumarol, warfarin, tromexan...
Cht chuyn ha thi tr qua nc tiu v mt - nhiu thuc c chu k gan rut. Thuc c
th i qua rau thai, qua sa. Nng thuc trong rau thai v tr em b m cao c th gy
xut huyt cho thai nhi v tr b m. Nu ung thuc vo 3 thng u thai k c th gy
cho tr s sinh mt s d thng mi, mt, xng.
* c tnh :
- Dng liu cao, ko di gy ri lon thm phn mao mch, xut huyt, rt nguy him
bnh nhn lot d dy t trng, chn thng, cao huyt p.
- D ng, rng tc, vim gan, thn, tng bch cu a acid, nhng li gim hoc mt bch
cu ht.
- Nc tiu mu da cam.
* Khi phi hp dn xut coumarin v indandion vi mt s thuc c th xy ra tng tc
dn n thay i dc ng hc hoc tc dng .
- Thuc lm thay i dc ng hc ca coumarin v indandion :
+ Gim hp thu coumarin qua ng tiu ha:
Thuc lm tng pH d dy, thuc nhun trng, thuc khng cholinergic, du parafin, than
hot, cholestyramin (to phc vi couramin).
+ Thuc y coumarin ra khi protein - huyt tng :
Clofibrat, phenylbutazon, sulfa mid, tolbutamid, salicylat, acid ethacrynic
+ Thuc c ch chuyn ha coumarin microsom gan:
Allopurinol, chloramphenicol, cimetidin, diazepam, metronidazol, phenylbutazon,
sulfinpyrazon, thuc chng trm cm loi ba vng.
+ Thuc cm ng enzym micros om gan lm tng chuyn ha coumarin: barbiturat,
rifampicin
* p dng iu tr :
- Ch nh :
+ Phng hoc cha bnh tc nghn mch nh: vim tnh mch, tc mch phi, nhi mu
c tim.
+ Dit chut : warfarin.
- Chng ch nh: Ph n c thai, cho con b; cao huyt p, vim ty cp; lot d dy - t
trng tin trin; tai bin mch mu no v tng chy mu.
- Liu lng - cch dng :
+ Tc dng chng ng ph thuc vo tng c th.
+ Trong qu trnh iu tr bng dn xut coumarin hoc indandion phi gim l iu dn v

cn theo di thi gian Quick, thi gian Howell chnh liu nhm duy tr t l
prothrombin khong 20% so vi bnh thng. Sau khi dng 36 -48 gi lm xt nghim
nh gi tc dng, chn liu duy tr ph hp. Giai on iu tr duy tr c sau 2 tun cho
xt nghim 1 ln.
+ Tc dng chng ng ca thuc l gin tip, lin quan n s tng hp cc yu t ng
mu gan nn xut hin tc dng chm v ch tc dng trong c th, khng c tc dng
trong ng nghim. Mun t hiu qu chng ng cn ph i c thi gian.
+ Cn theo di nhng triu chng chy mu nh chng t qu liu : Chy mu cam, chy
mu li, chy mu tr, nc tiu c vt mu, t mu da v.v...
+ Khi qu liu hoc ng c dn xut coumarin hoc indandion dng vitamin K iu
tr.
+ Da vo thi gian xut hin tc dng, cng tc dng cc thuc chn thi gian
dng thuc ph hp. Hin nay c 3 nhm chnh :
Liu duy tr cc thuc i khng vitamin K c tp hp trong bng 30.1.
Bng 30.1: Liu duy tr ca cc d n xut coumarin v indandion
Tn thuc Bit dc Thi gian bn Liu duy tr
thi (gi) (mg/ngy)
Acenocumarol Sintrom, 24 1-8
Dicumarol 24-96 50-100
Phenindion Pindione 5-10 50-150
Ethylbiscoumacetat Tromexan 1-2 450 - 600
Warfarin Coumadin 36 3-9
1.3.2.2. Heparin
Thuc c bng B, va c tc dng trong c th v ngoi c th.
* Ngun gc:
Heparin lc u tm thy nm 1916 bi McLean v c nhiu gan nn t tn heparin.
Ngoi gan ra, heparin cn c tm thy thn, phi, hch bch huyt, nim mc rut.
Hin nay heparin c chit xut t nim mc rut ln hoc phi tru, b hoc bn tng
hp.
* Cu trc :
Heparin khng phi n cht. L mt anion mucopolysacharid hoc glycosaminoglycan.
Trong cu trc c nhm sulfat v carboxylic. Nhm sulfat cn thit cho s gn
antithrombin vi thrombin. T l lu hunh trong phn t heparin chim 13,6%.
* Tnh cht :
+ L acid ni sinh mnh nht, c ion ha mnh, rt tan trong nc v tch in m

pH sinh l.
+ Vng bn pH trn 6,5. un si trong 20 pht nhit 120 oC vn cn tc dng.
Nhng ung b phn hy ng tiu ha mt hot tnh.
+ Trng lng phn t khc nhau dao ng t 2 -20 kDa nhng tc dng sinh hc ging
nhau. Khi heparin c trng lng phn t t 2 -7 kDa gi l heparin trng lng ph n t
thp.
* Tc dng :
- Chng ng mu.
- Chng ng vn tiu cu do kch thch tng hp v bi tit yu t hot ho plasmin t
chc (t-PA).
- H lipoprotein mu c bit l triglycerid do gii phng lipase gip thu phn
triglycerid thnh acid bo v g lycerol. Tc dng ny xut hin nhng liu thp hn liu
c tc dng chng ng mu. C hin tng tng lipoprotein hi ng (rebound) khi ngng
heparin.
- Tng tc dng ca cc yu t pht trin nguyn bo si c tnh acid hoc base (aFGF v
bFGF) lm tng s phn bo t bo ni m mao mch, t bo c trn, t bo trung m gy
ra s tn to mch.
* C ch chng ng mu :
- Bnh thng antithrombin III trong huyt tng phn ng chm chp vi thrombin v
cc yu t ng mu IX, X, XI, XII hot ha lm mt tc dng ca cc yu t ny. Khi
c mt heparin, heparin to phc vi antithrombin III. Phc hp heparin - antithrombin III
thc y nhanh phn ng gia antithrombin v thrombin; antithrombin vi cc yu t IX,
X, XI v XII. Hu qu cc yu t chng n g t hot ha mt hiu lc nhanh, mt
kh nng chuyn fibrinogen thnh fibrin.
- Nh tch in m do c cha cc gc sulfat nn heparin lm bin dng thrombin v
prothrombin lm chng d dng to phc vi antithrombin.
* Dc ng hc
Ung khng hp thu v b phn hu ng tiu ha. Do vy, phi tim di da, tim
tnh mch, khng tim bp. Heparin b heparinase ph hu v thi tr nhanh. Sau khi tim
1 gi, 30-50% c thi qua nc tiu. Khng i qua rau thai.
Thi gian bn thi ph thuc vo l iu lng. Liu cao v ngi suy gan, thn th thi
gian bn thi ca thuc di.
* Tc dng khng mong mun.
- Chy mu, gim tiu cu, triu chng ny thng xut hin sau khi tim heparin 7 -14
ngy v hi phc sau khi ngng thuc.
- D ng, nhc u, nn, gy nt au, hoi t gn nu tim di da di ngy. Dng ko

di vi liu trn 15000 n v/ngy gy long xng.
- Tng AST, ALT.
* p dng iu tr :
- Ch nh: phng, chng huyt khi. Tc dng tng khi dng kt hp vi cc thuc chng
ng vn tiu cu nh: aspirin, cc thuc chng vim phi steroid khc, dipyridamol,
ticlopidin v.v...v s mt tc dng khi trn ln vi gentamicin, colistin, cefaloridin do b
kt ta.
- Chng ch nh:
+ Tng a chy mu; lot d dy - t trng tin trin; vt t hng.
+ Gim chc nng gan, thn; c th suy nhc, vim ni tm mc, nhim trng, lao tin
trin.
- Ch phm v liu dng :
+ L 5000 - 25000 n v/ml
Mt n v heparin l lng heparin ngn cn c s ng c 1ml huyt tng c
lm mt calci bi citrat.
+ Liu dng tu thuc vo tng bnh nhn. Thng thng truyn tnh mch 6000 n
v/trong 6 gi vi tc 1000 n v/gi.
Hoc truyn tnh mch khi u 5000 - 10000 n v, sau cch 4 -6 gi truyn 5000 -
10000 n v. Liu tip theo ph t huc vo thi gian ng mu v thi gian Howell.
- Khi qu liu phi ngng haparin ngay v tim tnh mch chm protamin sulfat trung
ha vi tc 50 n v/pht.
Protamin sulfat l protein kim trng lng phn t thp, thi tr nhanh hn heparin
nhng c kh nng phn ly phc hp antithrombin III -heaprin v kt hp vi heparin lm
mt tc dng chng ng.
Mt mg protamin sulfat trung ha c 100 n v heparin.
* Hin c heparin trng lng phn t thp, nhng c tc dng sinh hc ch nh, chng
ch nh v tai bin gn ging heparin ngun gc t nhin. Tuy nhin, c tc dng i
khng yu t X hot ha mnh v thi gian tc dng di hn heparin thng thng. Do
vy, ch cn tim di da mt ln/ngy. Mt s heparin trng lng phn t thp ang
c s dng tm tt trong bng 30.2.
Bng 30.2: Ch phm v liu lng mt s heparin trng lng phn t thp
Tn gc Bit dc Hm lng Liu dng/ngy
Certoparin Alphaparin 3000 n v/0,3ml 3000 n v
Dalteparin Fragmin 12500, 25000n v /ml 2500 n v
Enoxaparin Clexan 100mg/ml 20 mg(2000 n v)
Reviparin Clivarin 1432 n v/ 0,25ml 1432 n v

Tinzaparin Innohep 10000 n v /ml 3500 n v
1.3.2.3. Heparinoid tng hp:
L polysacharid b ester ha bi acid sulfuric, c cng th c ha hc gn ging heparin, c
ch tc dng ging heparin nhng tc dng chng ng yu hn.
- Partiol tc dng km heparin 7 ln.
- Trebuton tc dng yu hn heparin 3 -4 ln.
1.3.2.4. Hirudin
L a peptid c 65 acid amin, trng lng phn t 7000 - 9000 c cha trong tuyn n
bo trong thc qun ca a, vt, c tc dng chng ng mu do ngn cn tc dng ca
thrombin thng qua s to phc vi thrombin lm cho fibrinogen khng chuyn thnh
fibrin.
Thrombin
(-)
Hirudin
Fibrinogen Fibrin
Dng Hirudin trong chn on xc nh hot tnh ca cc yu t ng mu nh thrombin
(Hirudin-toleranz-test; Hirudin test). Hin cha c dng iu tr v s lng tch chit
cn hn ch.
Trong tng lai nh k thut gen c th sn xut c hiru din s dng trong iu tr,
chng huyt khi.
1.4. Thuc chng kt dnh tiu cu
Tiu cu l nhng t bo khng nhn, hnh a, tch in m mnh. Trn b mt mng tiu
cu c cha cc yu t ng mu I, V, VII. C cc fibrinogen receptor (Gp IIb/IIIa) v
c tnh kt dnh v kt t nn khi thnh mch b tn thng cc tiu cu dnh vo ni b
tn thng v dnh vo nhau thnh tng lp to ra nt trng tiu cu cn gi l inh cm
mu Hayem. Trong qu trnh kt dnh, tiu cu cn gii phng ra phospholip id gip thc
y qu trnh to ra phc hp prothrombinase.
S kt dnh tiu cu l yu t to ra mng x va ng mnh v gy nn tc mch.
Hin c mt s thuc chng kt dnh tiu cu c s dng trong lm sng phng v
iu tr huyt khi nh: thuc chng vim phi steroid (aspirin), dipyridamol, ticlopidin,
clopidogrel v thuc c ch glycoprotein IIb/IIIa.
1.4.1. Aspirin (acid acetylsalicylic)
Ngoi tc dng h st, gim au, chng vim, aspirin cn c tc dng chng ng vn
tiu cu.
- C ch : xin xem bi Thuc h st, gim au, chng vim.

- Dng liu thp duy nht 10mg/kg cn nng, cch qung 48 gi, aspirin c ch 90%
cyclooxygenase ca tiu cu, rt t nh hng n cyclooxygenase ca ni m mao mch
nn nh hng khng ng k s tng hp c a prostacyclin I 2. Do vy, tc dng chng
kt dnh tiu cu v ko di thi gian chy mu liu ny l ti a. Dng liu cao aspirin
khng ch c ch COX tiu cu m cn c ch COX ni m mao mch nn hiu qu
chng kt dnh tiu cu khng cao.
- Ngoi c ch COX tiu cu, aspirin cn lm n nh mng tiu cu, hn ch s gii
phng ADP v phospholipid nn gim s kt dnh tiu cu v tng thi gian chy mu.
- Ch nh: dng aspirin trong phng v iu tr huyt khi ng - tnh mch vi liu duy
tr 75 mg/ngy..
- Chng ch nh v tc dng khng mong mun (xin xem bi thuc h st, gim au v
chng vim).
- Ht sc thn trng khi phi hp aspirin vi thuc chng kt dnh tiu cu khc v thuc
chng ng mu nh heparin, dn xut coumarin.
1.4.2. Dipyridamol (Persantone, Peridamol)
Va c tc dng gin mch vnh, va c tc dng chng ng vn tiu cu do :
+ c ch s nhp adenosin vo tiu cu v c ch adenosin desaminase lm tng adenosin
trong mu. Adenosin tc ng ln A 2-receptor lm gim s ng vn tiu cu.
+ c ch phosphodiesterase lm tng AMP v trong tiu cu.
- Ch nh: thuc c phi hp vi warfarin trong phng huyt khi bnh nhn thay
van tim nhn to.
1.4.3. Ticlopidin (Ticlid)
- Do ticlopidin tng tc vi glycoprtein IIb/III a receptor ca fibrinogen lm c ch s
gn fibrinogen vo tiu cu hot ha, ngn cn s kt dnh tiu cu.
Ngoi ra, thuc cn lm tng prostaglandin D 2 v E2 gp phn chng ng vn tiu cu v
tng thi gian chy mu.
- Thuc c dng phng huyt k hi bnh nhn b bnh tn thng mch no hoc
mch vnh vi liu 500mg/ngy. Khng dng thuc cho tr em. Khi dng c th gp mt
s tc dng khng mong mun: chy mu, bun nn, a chy, gim bch cu trung tnh.
1.4.4. Clopidogrel (Plavix)
- Thuc c tc dng chng ng vn tiu cu do:
+ c ch chn lc th th ADP ca tiu cu.
+ Ngn cn s hot ha glycoprotein IIb/IIIa ca fibrinogen trn tiu cu, lm gim s
gn fibrinogen vo tiu cu.
- Ung liu duy nht 75mg/ngy phng ng vn tiu cu.

1.4.5. Cc cht c ch glycoprotein IIb/IIIa receptor:
Glycoprotein IIb/IIIa c vai tr lm tng s gn ca fibrinogen vo receptor trn tiu cu.
Mt s thuc gn vo glycoprotein IIb/IIIa receptor ngn cn s gn ca fibrinogen vo
tiu cu c tc dng chng ng vn tiu cu.
+ Abcimab (Reopro): l mt khng th n dng, khi u tim chm tnh mch 250
mcg/kg, sau truyn tnh mch 125 nanogam/kg/pht (ti a 10mcg/pht).
+ Eptifibatid (Integrilin): l peptid tng hp, khi u tim tnh mc h 180 mcg/kg, sau
truyn tnh mch 2 mcg/kg/pht lin tc trong 72 -96 gi.
+ Tirofiban (Aggrastat): khi u tim chm tnh mch 400 nanogam/kg/pht trong 30
pht, sau truyn tnh mch 100 mcg/kg/pht trong t nht 48 gi.
2. Thuc tiu fibrin
Cc mu ng c th tan tr li nh qu trnh tiu fibrin. l qu trnh ngc vi ng
mu. Bnh thng, enzym plasmin xc tc cho s tiu fibrin trong mu th khng hot
tnh gi l plasminogen. Trong iu kin nht nh, cc cht hot ha (kinase, act ivator)
c gii phng ra khi t chc, hot ha plasminogen to thnh plasmin. Plasmin va
to thnh gip fibrin tr thnh cht phn hu tan c.
2.1. Urokinase ( Abbokinase)
L endopeptidase, gm 2 chui a peptid cha 411 acid amin, trng lng phn t
53000, c phn lp t nc tiu ngi (URO = urine = nc tiu) hoc t nui cy t
bo phi thn ngi.
Urokinase xc tc cho phn ng ct lin kt peptid ca plasminogen (plasminogen c 791
acid amin) to thnh lys -plasminogen v chuyn thnh plasmi n. Lysin cui cng ca
plasmin l v tr gn c i lc cao vi fibrin gip cho s thu phn fibrin.
UK b chuyn ha gan v c thi gian bn thi 15 -20 pht. Thuc ch c tim tnh
mch, khi u 1.000 - 4.500 n v/kg th trng, sau duy tr 4.400 n v/gi. Thuc
hu nh khng c tnh khng nguyn, khng b trung ha bi khng th, nhng c th gy
st.
2.2. Streptokinase ( SK, Streptase)
Gm mt chui apeptid, phn t lng 48000, c phn lp t lin cu tan mu nhm
A.
Streptokinase kt hp v i plasminogen theo t l ng phn t (equimolar) to thnh phc
hp SK-plasminogen. Phc hp ny ct lin kt arginin -valin v tr 560 ca plasminogen
chuyn thnh SK-plasmin c hot tnh tiu fibrin.
Ngoi tiu fibrin, streptokinase cn xc tc cho ph n ng thu phn nucleoprotein thnh
cc base purin t do v pyrimidin nucleotid, do vy lm long cc dch ng c nh m.
Sau khi tim tnh mch vi liu thp thi gian bn thi khong 18 pht, nhng khi tim
liu cao hoc liu thp ko di th thi gia n bn thi t 83 pht v ht hin tng kt hp
khng th khng streptokinase do bo ha. Thuc b chuyn ha v thi tr qua thn.
- Trong qu trnh dng thuc c th gp mt s tc dng khng mong mun: chy mu, d
ng hay gp vo ngy th 8, nn s au khi dng thuc 8 ngy, cn phi chuyn sang dng
thuc khc.
- Liu dng :
+ Khi u tim tnh mch 500.000 n v trong 30 pht, sau mi gi tim 100.000 -
150.000 n v v dng trong 24 - 48 gi lin. Trong nhi mu c tim c th truyn tnh
mch1500000 n v trong 60 pht.
+ C th ha tan 20.000 - 100.000 n v vo 5-20ml nc mui sinh l tim thng vo
ti m sau 6 - 24 gi ht ra.
2.3. Anitreplase (Aminase)
L phc hp ca plasminogen ngi tinh khit v streptokinase ca vi khun c
acetyl ho bo v v tr hot ng ca enzym. Khi s dng, nhm acetyl c thu
phn, gii phng phc hp streptokinase - cht tin hot ho thnh phc hp, hot ho
plasminogen thnh plasmin. Thuc c tc dng trn plasminogen ca cc mu ng mn h
hn plasminogen t do nn lm tan cc huyt khi nhanh. Ngoi c ch trn thuc cn
lm gim yu t V,VIII v cht c ch tiu fibrin -2-antiplasmin.
2.4. Cht hot ho plasminogen m(t -PA, Alteplase)
L mt protease sn phm ca ca k thut ti to ge n cha 527 acid amin c tc dng
trn plasminogen gn vi fibrin mnh gp vi trm ln plasminogen t do. Khi lng
fibrin thp tc dng chuyn plasminogen thnh plasmin thp. Thuc c thi gian bn thi
ngn 5-10 pht. Trong nhi mu c tim cp tim tnh mch 15 mg sau truyn tnh
mch 50 mg trong 30 pht v trong 60 pht tip theo truyn 35 mg (tng liu truyn trong
90 pht khng vt qu 100 mg).
2.5.Reteplase (r-PA, Retavase, Rapilysin)
L cht hot ho plasminogen ti t hp thuc th h th 3, t c dng ging Alteplase
nhng cng v thi gian xut hin tc dng nhanh hn. Thuc c dng trong nhi
mu c tim cp khi u tim chm tnh mch 10 n v trong 2 pht sau c 30 pht
tim thm 10 n v.
2.6. Tenecteplase (Metalyse)
Thuc mi c tc dng tiu fibrin v ch nh nh r eteplase, tim tnh mch ton b liu
500-600 mcg/kg nhng khng vt qu 50mg.
2.7. Ch nh v chng ch nh ca cc thuc tiu fibrin
* Ch nh:
- Tc nghn ng, tnh mch
- Nhi mu c tim
- Vim m, ng mu mng phi hoc cc khp xng hay cc hch dng streptokinase
ti ch.
- Bm vo ng dn lu m trnh tc (streptokinase).
* Chng ch nh:
Sau khi phu thut cha qu 8 ngy; mi hoc sy thai cha qu 4 ngy; cao huyt p
nghim trng, qu trn h cm mu bt thng; c a d ng; mi dng streptokinase cha
qu 6 thng; mi b bnh do lin cu; c thai (thuc khng qua rau thai, nhng phng
bong rau sm); chy mu ng tiu ha nng trong vng 3 thng; tin s tai bin mch
mu no; vim mng ngoi tim cp; phu thut ng mch ch; vim ty cp; bnh gan
nng.
2.8. Cht hot ha plasminogen
L nhng cht gip gii phng cht hot ha (kinase, activator) hot ha plasminogen
hoc tng tng hp plasminogen v cui cng lm cho fibrin tr th nh cht phn hy tan
c. Thng dng ethylestrenol, phenformin, nicotinamid. Dng khi c th khng t
gii phng c cht hot ha, v d khi mu tnh mch do tai bin huyt khi tnh
mch, hoc phng ti pht vim tnh mch (dng ethylestrenol cng phenformin).
3. Thuc chng tiu fibrin
C trng thi bnh lm tiu nhanh fibrin, gy chy mu trm trng, v d khi ngi b
bnh tng plasmin trong mu.
Plasmin khng nhng lm tiu fibrin, m cn kt hp vi mt s yu t ng mu v hy
hoi chng, lm c ch ng mu cng ri lon.
Nhng phn t mi sinh do fibrin b hy cng kt hp li vi fibrin cho phc hp
khng ng c na. Nhng cht phn hu ny cn lm cho tiu cu khng ngng kt
thnh cc c. Kt qu lm chy mu trm trng.
Thuc lm gim s tiu fibrin s c tc dng cm mu. Hin c mt s thuc chng tiu
fibrin ang c s dng trn lm sng cm mu.
3.1. Aprotinin (Trasylol)
L thuc c ch protease gm 58 acid amin, c 3 cu ni disulfur, phn t lng 6500,
ly t tuyn mang tai, phi, gan. iu ch t tin, thi gian bn thi ngn:150 pht; ch
tim tnh mch hoc truyn tnh mch vi liu lng tu thuc vo ch nh. Phng chy
mu khi phu thut tim m liu 2000000 n v, chy mu do tng plasmin mu khi u
500000-1000000 n v.
Thuc to phc vi plasmin cho phc hp mi aprotinin -plasmin khng c hot tnh
plasmin. Aprotinin cn c ch c cc enzym hu protein khc na, nh trypsin,
chymotrypsin, kalikrein.
Aprotinin thi qua nc tiu di dng mt hot tn h, nn khng dng chng tiu
fibrin ng tit niu. Dng nhiu ln c th gy nhng phn ng qu mn ngi c c
a d ng.
3.2. Thuc tng hp
3.2.1. Acid - aminocaproic
C cu trc ging lysine c tc dng chng tiu fibrin nh hai nhm amin v carboxyl
cch nhau 0,7nm, c ch s hot ha ca plasminogen, km hm khng cho plasmin tc
ng ln fibrin, lm cho fibrin khng b ging ha bi plasmin na.
Thuc khng c ch c cc cht hot ha plasminogen (kinase, activator). Thuc c th
ung 24 gam chia lm 4 ln trong ngy hoc tim chm tnh mch 5 -7,5g d phng
hoc iu tr chy mu.
3.2.2. Acid tranexamic (Cyclokapron )
L ng ng v c tnh cht, tc dng ging acid - aminocaproic, c th tim tnh
mch hoc ung phng ch y mu sau m tuyn tin lit, nh rng ngi b
hemophilia hoc qu liu thuc tiu cc mu ng hoc ph n b a kinh vi liu 2 -
4g/24 gi, chia lm 3 ln .
3.3. p dng iu tr ca thuc chng tiu fibrin
- Ch nh: Dng trong trng thi tiu fibri n nguyn pht, tiu fibrin cp, d phng chy
mu sau phu thut to hnh, tai mi hng, ct b tuyn tin lit v.v...
- Chng ch nh: c tnh ca Acid - aminocaproic v acid tranexamic rt t, tuy nhin
cn dng thn trng khi suy thn nng (c th g y tch lu thuc), khi c tin s hoc
c biu hin huyt khi tc tnh mch hoc ng mch.
V tr tc dng ca thuc tiu fibrin v chng tiu fibrin xin xem trong cun Dc l hc
lm sng.
Cu hi t lng gi
1. Trnh by c ch tc dng v p dng iu tr ca vitamin K.
2. Trnh by c ch tc dng v p dng iu tr ca heparin.
3. Trnh by c ch tc dng v p dng iu tr ca dn xut coumarin.
4. Trnh by c ch tc dng chng ng vn tiu cu v p dng iu tr ca
aspirin.
5. Trnh by c ch tc dng tiu fibrin v p dng iu tr ca urokinase v
streptokinase.
6. Trnh by c ch tc dng tiu fibrin v p dng iu tr ca anistreplase v cht
hot ho plasminogen m.
7. Trnh by c ch tc dng chng tiu fibrin v p dng iu tr ca aprotinin v

acid - aminocaproic.
Hy so snh dc ng hc v c ch tc dng ca heparin v dn xut coumarin .
Bi 31: Thuc iu tr ri lon lipoprotein mu

1. Trnh by c c ch tc dng, tc dng, tc dng khng mong mun v p dng
iu tr ca cc thuc nh hng n hp thu v thi tr lipid mu: cholestyramin,
colestipol .
2. Nu c c ch tc dng, tc dng khng mong mun, p dng iu tr ca
cc thuc nh hng n sinh tng hp lipid: acid nicotinic, dn xut ca
acid fibric, dn xut statin, probucol.
1. i cng
Tng lipoprotein mu l mt yu t gy nn va x ng mch v bnh mch vnh.
iu tr ri lon lipoprotein mu, ngoi thay i ch n, c bit l n t lipid, tng
cng hot ng th lc l nhng bin php rt quan trng, th khng th thiu c cc
thuc h lipoprotein mu.
1.1. Cu trc v phn loi lipoprotein
trong mu, cc lipid khng tan c, v vy phi kt hp vi protein nh lin kt Van -
der-Walls to thnh lipoprotein. Nh to thnh lipoprotein, tan c trong nc vn
chuyn n cc m. Lipoprotei n c dng hnh cu vi ng knh 100 -500 A gm 2
thnh phn chnh:
- Phn a nc (phn v ) cha apoprotein, cholesterol t do v phospholipid .
- Phn k nc (trung tm) cha cholesterol este ho, triglycerid.
Protein gn vo cc lipid c ngun gc t i nim mc rut hoc ti gan gi l
apolipoprotein. Da vo cu trc cc acid amin, phn t lng v cc chc nng,
apolipoprotein c xp thnh cc nhm khc nhau theo th t ch ci A, B, C, D, E.
Trong mi nhm, li c xp thnh di nhm, v d nhm A gm A1, A2, A4; nhm B
gm B48, B100; C gm C1, C2, C4 v nhm E gm E1, E2, E4.
Do t l protein v lipid khc nhau nn t trng dao ng t 0,9 n trn 1,2. Da vo t
trng, lipoprotein c xp thnh 5 loi c chc nng khc nhau.
- Ht vi th dng chp (chylomicron)
- Lipoprotein t trng rt thp (VLDL: very low density lipoprotein)
- Lipoprotein t trng thp (LDL: low density lipoprotein)
- Lipoprotein t trng trung bnh (IDL: intermediate density lipoprotein)
- Lipoprotein t trng cao ( HDL: high density lipoprotein)
Trong mi t bo, c bit l t bo gan, t bo ni m mao mch c cha b phn nhn

cm c hiu LDL gi l LDL -receptor. Receptor ny c chc nng nhp LDL vo trong
t bo v gii phng lipid thng qua enzym trong lysosom . Khi lng cholesterol trong t
bo tng cao so vi nhu cu, s tng hp LDL -receptor mng t bo gim xung. Ngc
li, khi lng cholesterol trong ni bo gim, th s tng hp LDL -receptor mng t bo
tng ln.
Cho n nay, c ch vn chuyn choles terol ca HDL vn cn cha c bit r. Theo
mt s tc gi, th di tc dng ca lecithin cholesterol acyltransferase (LCAT), cng
vi s hot ha apolipoprotein AI, cholesterol t do ca VLDL v LDL b ester ha i vo
phn trung tm khng phn cc ca HDL; HDL s vn chuyn cholesterol ny n gan v
b chuyn ha. HDL c vai tr rt quan trng trong bnh va x ng mch, khi HDL
trong mu < 0,3g/l, th t l va x ng mch cao v ngc li khi nng HDL > 0,76
g/l th t l va x ng mch rt t hp. Mt thuc h lipoprotein tt l thuc lm gim
mnh LDL v gy tng HDL r rt.
Mi t bo cng t tng hp cholesterol t acetyl CoA nh hydroxymethyl glutaryl - CoA
- reductase (HMG - CoA - reductase). Hot tnh ca enzym ny b gim khi lng
cholesterol trong t bo tng cao v ngc li, hot tnh tng khi lng cholesterol trong
ni bo gim xung.
1.2. Tng lipoprotein mu v phn loi s tng lipoprotein mu
c th bnh thng, nng cc lipoprotein trong mu tn ti trong trng thi cn b ng
ng. Khi c ri lon trng thi cn bng ng ny s gy nn ri lon chuyn ha
lipoprotein mu. S ri lon c th do:
- Tng cng cholesterol, triglycerid ngoi sinh.
- Ri lon chc nng xc tc chuyn ha lipoprotein ca lipoproteinase.
- Yu t ton thn lm tng chuyn ha glucid, protid tng hp lipid v tng hot ng
ca s hormon lm gim thu phn lipid trong c, gan v m nh bnh i tho ng,
hi chng thn h, tng ure mu, suy gip, nghin ru, dng thuc trnh thai, corticoid ,
c ch - giao cm...
- Yu t di truyn: mt s ngi c ri lon chuyn ha lipoprotein, mang tnh cht di
truyn. nhng ngi ny, thy c s gim s lng LDL -receptor hoc gim cht lng
receptor ny.
Da vo tng cc loi lipoprotein s tng l ipoprotein mu c chia thnh 6 typ khc
nhau: I, IIa, IIb, III, IV v V.
n nay, 99% hi chng tng lipoprotein mu thuc typ IIa, IIb v IV. Nhiu thuc h
lipoprotein c nghin cu v c dng trn lm sng vi nhiu c ch khc nhau,
nhng cha c thuc no c tc dng tt trn tt c cc typ ca ri lon lipoprotein mu.
2.Thuc iu tr ri lon lipoprotein mu
Da vo c ch tc dng trn lipoprotein, thuc c chia thnh 2 nhm chnh:
- Lm gim hp thu v tng thi tr lipid

- Lm gim tng hp lipid.
2.1. Thuc lm gim hp thu v tng thi tr lipid
L nhng thuc c tnh hp th mnh, to phc vi acid mt, lm gim qu trnh nh ha
cc lipid rut, dn n gim hp thu v tng thi lipid qua phn. Ngoi ra, cc thuc
nhm ny gin tip lm tng chuyn ha cholesterol to thnh acid mt thng qua s
thot c ch hydroxylase microsom gan (hydroxylase l enzym iu ha tng hp acid
mt t cholesterol b c ch bi acid mt), v lm tng s lng v hot tnh LDL -
receptor mng t bo.
2.1.1. Cholestyramin
L cht nha trao i ion, c tnh base mnh, khng tan trong nc, ung hu nh khng
hp thu qua ng tiu ha, nhng khng nh hng n cc enzym cc ng tiu ha.
Do c s trao i ion clo vi acid mt mang in m to nn phc hp nha gn acid mt
khng hp thu lm tng thi acid mt qua phn; c ch chu k gan rut ca acid mt lm
tng s tng hp acid mt t cholesterol bi s thot c ch hydroxylase. Do gim acid
mt nn thuc cng lm gim s hp thu sterol ngun tng hp cholesterol..
Thuc bt u c tc dng h LDL trong mu sau khi dng 4 -7 ngy v tc dng ti a
trong vng 2 tun. Trn hu ht bnh nhn, thuc lm tng triglycerid t 5 - 20% so vi
trc khi iu tr, nhng dn dn s tr v gi tr ba n u trong vng 4 tun.
Cholestyramin lm tng HDL -cholesterol khong 5% v gim LDL - cholesterol khong
10 - 35% tu theo liu lng, v c ch nh tt bnh nhn tng lipoprotein mu typ
IIa.
Do to c phc vi acid mt, nn thuc c th gy ri lon ng tiu ha nh: bun
nn, y bng, to bn, h prothrombin. Ngoi ra do tnh hp thu mnh, nn thuc cn
lm gim hp thu mt s thuc khi dng cng ng ung nh: digitoxin, pheylbutazon,
phenobarbital, clorothiazid, thuc chng ng dn xut c oumarin, thyroxin. trnh
tng tc thuc, nhng thuc trn nn ung mt gi trc hoc 4 gi sau khi dng
cholestyramin.
+ Ch phm v liu dng:
- Cholestyramin (Questran) gi bt 4g, ung 16 -32 gam trong 24 gi chia lm 2 - 4 ln.
2.1.2. Colestipol
L polyme ca diethylpentamin v epiclohydrin, tan trong nc, ht m rt mnh. Tc
dng, c ch tc dng v tc dng khng mong mun ging nh cholestyramin.
Ch phm:
Colestipol (Colestid) gi 5 gam hoc vin 1 gam, ung 10 -30 gam/24 gi, chia 2-4 ln.
Thuc c ch nh trong tng lipoprotein mu typ II.
2.1.3. Neomycin
L khng sinh nhm aminoglycosid, ung lm h lipoprotein mu, c bit l h LDL -

cholesterol (khng ph thuc vo tc dng khng khun) v c ch nh trong tng
lipoprotein mu typ IIa.
- Ung liu 0,5 - 2g/24 gi.
- Tc dng khng mong mun (xin c bi Khng sinh).
2.1.4 .Ezetimib
L thuc c ch s hp thu cholesterol rut c dng ring r hoc phi hp vi dn
xut statin trong trng hp tng cholesterol mu do ch n hoc do di truyn vi liu
10 mg /ngy. Khi dng thuc c th gp mt s tc dng khng mong mun nh: a chy,
au bng, au u, ph mch v pht ban. Khng dng thuc cho tr em di 10 tui v
ngi gim chc nng gan .
2.2. Thuc lm gim tng hp lipid
Gm nhng dn xut ca acid fibric ( bezafibrat, ciprofibrat, fenofibrat v gemfibrozil);
dn xut statin (pravastatin, simvastatin, lovastatin, rosuvastatin); acid nicotinic; probucol.
Cc dn xut acid fibric tng hot tnh lipoproteinlipase, cc dn xu t statin c cu trc
gn ging vi HMG-CoA nn c ch cnh tranh HMG -CoA-reductase
(hydroxymethylglutaryl - CoA- reductase) lm gim tng hp cholesterol, ng thi cng
lm tng sinh LDL-receptor mng t bo.
Acid nicotinic l mt vitamin dng iu t r bnh Pellagra, nhng cng lm h
lipoprotein mu. Tc dng ny c thng qua bi s tng sinh LDL -receptor v c ch
s tch t AMP trong m, tng hot tnh triglyceridlipase lm gim LDL -cholesterol.
Probucol c cu trc ha hc hon ton khc vi nh m thuc trn, c ch tc dng ca
thuc vn cn cha c gii thch y . Nhiu nghin cu chng minh thuc lm
tng chuyn ha LDL-cholesterol khng thng qua LDL -receptor v ngi tng
lipoprotein mu c thiu ht LDL -receptor do di truyn, thu c vn cn tc dng. C tc
gi cho rng probucol ngn cn oxy ha ca acid bo v lm gim kh nng tip nhp
LDL ca t bo ni m.
2.2.1. Acid nicotinic (Vitamin PP, Vitamin B3, Niacin)
L vitamin tan trong nc, c nhiu trong gan, tht, c, rau, qu v ng cc. Vi khun rut
c th tng hp mt lng nh vitamin PP.
Ngoi vai tr NAD, NADP tham gia vo chuyn ha protid, glucid v oxy ha trong
chui h hp t bo cc m, acid nicotinic cn lm h lipoprotein mu r rt. Sau 1 - 4
ngy iu tr, vitamin PP lm gim triglycerid 20 - 80%. i vi LDL-cholesterol, thuc
c tc dng r sau 5 - 7 ngy. Sau 3 - 5 tun iu tr thuc c tc dng ti a. C ch tc
dng ca thuc c th do gim sn xut v tng thi VLDL, c ch phn hu lipid, gim
cung cp acid bo cho gan, gim tng hp triglycerid, gim vn chuyn triglycerid,
VLDL v gim sn xut LDL. Thuc gy tng HDL-cholesterol nhng c ch cha r
rng.
Khi thiu ht vitamin PP nng s gy bnh pellagra c biu hin vim da, a chy v ri
lon tr nh.
- gim tc dng khng mong mun c bit l nng bong ,nga na ngi trn ca
thuc, nn ung thuc vo ba n vi liu tng dn, khi u 300 -600 mg chia lm 3 ln
trong ngy sau 3- 4 tun s dng liu duy tr 2 -6 g/ngy. Mt s tc gi kh uyn nn
ung aspirin 160 - 325 mg/24 gi cng c th lm gim tc dng khng mong mun ca
acid nicotinic.
Thuc c ch nh trong tng lipoprotein mu typ II, III, IV v V. Nn phi hp vi
cholestyramin v colestipol trong iu tr s gim c liu l ng v gim tc dng
khng mong mun ca thuc. Ngoi ra, vitamin PP cn c ch nh trong trng hp
thiu mu v ph n dng thuc trnh thai.
2.2.2. Dn xut ca acid fibric
Cc thuc nhm ny hp thu tt qua ng tiu ha, gn mnh vo protein huy t v c tc
dng rt khc nhau trn lipoprotein mu, nhng c cng mt c ch chung l tng hot
tnh lipoprotein lipase trong t bo c bit l t bo c, dn n lm tng thu phn
triglycerid v tng thoi ha VLDL. S tng HDL -cholesterol vi c ch cha r rng.
Cc ch phm fenofibrat (Lypanthyl), bezafibrat (Bezalip), gemfibrozil (Lopid) v
ciprofibrat ( Lipanor) ang c u tin la chn s dng trong tng triglyceride nhng
do cn c tc dng trn LDL nn cn c dng trong tng lipoprotein t yp II, III, IV v V
vi liu lng t 200 mg -1200 mg tu tng ch phm.Thuc c rt t tc dng khng
mong mun, tuy nhin c th gp ri lon tiu ha, au u, chng mt, mt mi v au
c, tiu c vn( c bit ngi gim chc nng thn), thiu mu, t ng nh transaminase,
gim phosphatase kim.
- Chng ch nh ging nhau vi tt c cc thuc cng nhm:
+ Gim chc nng gan, thn v si mt.
+ Ngi c thai, cho con b, tr em di 10 tui.
2.2.3. Dn xut statin
Cc thuc nhm ny c ch HMG -CoA nn lm gim LDL-cholesterol t 25-45% tu
theo tng thuc v liu lng. Tc dng h triglycerid km hn dn xut acid fibric nn
c la chn u tin trong nhng trng hp tng cholesterol mu c bit typ II, III, IV
v V.
Do i qua c rau thai v sa n n thuc khng dng cho ngi c chc nng gan, thn
gim nng, ph n c thai v cho con b, tr em di 18 tui v thuc c th gy bt
thng xng ca sc vt th nghim . Dng lu di thuc gy tng transaminase gp
3- 4 ln bnh thng, ngng thu c enzym li tr v bnh thng. Khi iu tr cn theo di
chc nng gan v creatinin phosphokinase.
+ Thuc c tc dng khng mong mun ging nhau:
- au c, tiu c vn, sn nga, au u, chng mt, ri lon tiu ha v tng cao

transaminase trong mu.
- Cc thuc trong nhm c tm tt trong bng 30.1.
Bng 30.1: Ch phm v liu lng mt s thuc trong nhm statin
Tn gc Bit dc Liu lng
(mg/ngy)
Atorvastatin Lipitor 10-40
Fluvastatin Lescol 200-400
Lovastatin Mevacor 20- 80
Pravastatin Vasten 10-40
Rosuvastatin Crestor 10-20
Simvastatin Lodales 10- 40
2.2.4. Probucol (Lorelco, Lurselle)

C cu trc hon ton khc vi cc thuc nu t rn. Rt tan trong lipid nhng hp thu
km. Thc n lm tng s hp thu thuc. Do tan trong lipid, nn thuc ng li lu trong
c th. Sau khi ngng thuc 6 thng, nng thuc ch gim 80% so vi nng ti a
trong mu. Thuc lm h LDL -C tht thng, khng lm h triglycerid. Thuc gy h
HDL-cholesterol mnh v ko di nn n ch c la chn trong iu tr sau cc thuc
khc.
Probucol l cht chng oxy ha mnh nn c tc dng chng x va mnh sc vt th
nghim.
Khi dng thuc c th gp mt s tc dng khng mong mun: a chy, y bng, au
bng, bun nn.
Khng dng thuc nhng bnh nhn mi b nhi mu c tim, c khong QT C ko di,
ph n c thai, cho con b, tr em di 18 tui, ang dng cc thuc chng lon nhp tim
nhm I, III, chng trm cm loi 3 vng, dn xut phenothiazin.
- Vin 250 mg, ngy ung 500mg chia 2 ln.
2.2.5. D-Thyroxin
D-Thyroxin l ng phn quay phi ca L -Thyroxin mt mt s tc dng ca hormon
tuyn gip, nhng li c tc dng h lipoprotein mu mnh do tng chuy n cholesterol
thnh acid mt v tng thi sterol qua phn.
c ch nh cho tr em c lipoprotein mu cao. Khng dng cho ngi c bnh tim v
d c cn nhi mu c tim v cn au vng trc tim. Liu khi u 1mg, sau tng
dn, ti a 4-8 mg/24 gi. Vi liu ny, khng thy c phn ng c hi.
2.2.6. Cc acid bo khng no a tr h omega 3

Trong du mt s loi c c bit l c hi, c ng, c trch, c thu c cha mt s acid
bo khng no a tr h Omega 3 c tc dng lm gim triglycerid v VLDL nh ng t nh
hng n LDL v HDL-cholesterol trong mu. C 2 acid bo khng no h Omega 3 hay
dng l:
-Omega-3-acid ethylesters: 1 gam bit dc Omacor 90% omega -3-acid ethylesters
cha 46% acid eicosapentaenolic(EPA) , 38 % acid docosahexaenoic (DHA) v 4 mg -
tocopherol.
-Omega-3-marin triglyceride: 1 gam bit dc Maxepa cha170 mg acid
eicosapentaenolic(EPA), 115 mg acid docosahexaenoic (DHA) v di 100 n v
vitamin A v 10 n v vitamin D.
Liu lng cc ch phm xin xem t hng dn s dng thuc.
hn ch s tng v gip h triglycerid v cc lipoprotein mu, nn tng cng n c,
c bit l c hi, c thu, c ng, c trch trung bnh 30g/ngy hoc 3 ln/tun.
2.2.7.Mt s thuc iu tr ri lon lipoprotein mi
- Hai thuc mi ang c th nghim trn lm sng pha II v III ngi c ri lon
lipoprotein mu:
+ BMS-201038 l cht c ch microsomal triglycerid transfer protein lm gim s
vn chuyn triglycerid v cc lipid khng phn cc n apolipoprotein v gim s bi tit
triglycerid t rut dn n gim triglycerid v VLDL -cholesterol.
+ Avasimibe : thuc c ch ACAT1 v ACAT2(cholesterol acyltransferase) lm gim
s ester ho cholesterol gan, rut, i thc bo v gim tng hp acid mt thng qua s
cm ng hydroxylase gy nn gim chylomicron, VLDL, LDL -cholesterol v triglycerid.
3. Nguyn tc iu tr ri lon lipoprotein mu
hn ch nguy c gy bnh tim mch cn phi h LDL v tng HDL trong mu. Theo
mt s nghin cu cho thy mun ngn chn c bnh mch v nh nguyn pht hoc th
pht cn phi gim cholesterol ton phn trong mu 20 -25 % hoc LDL khong 30 %.
Nhm t hiu qu iu tr cn phi p dng mt s nguyn tc sau:
- Trc tin phi c ch n thch hp duy tr trng lng bnh thng v gi m
lipoprotein mu. nhng ngi c ch s khi c th (BMI body mass index ) cao hn
bnh thng, cn c ch n cha < 300 mg cholesterol, acid bo bo ho chim 10%,
acid bo khng bo ha 10 -15%, glucid 50 - 60% v protein chim 10 - 20% tng s
calo/ngy.
- iu tr nguyn nhn gy tng lipoprotein mu nh: i tho ng, suy gip, hi chng
thn h, tng ure mu.
- Gim hoc chm dt cc nguy c gy tng lipoprotein mu nh: ht thuc l, ung
ru, dng cc thuc corticoid, thuc trnh thai, t huc c ch - adrenergic.
- Tng cng hot ng th lc.

- Sau 3 - 6 thng thay i ch n, tng cng hot ng th lc v iu tr cc nguyn
nhn v loi b cc nguy c m lipoprotein mu vn cao th phi dng thuc h
lipoprotein mu.
- Tu theo c ch tc dng, cc thuc c th c dng ring r hoc phi hp 2 hoc 3
thuc c c ch khc nhau t c tc dng hip ng trong iu tr nh :
+ Cholestyramin vi dn xut statin;
+ Cholestyramin phi hp vi acid nicotinic hoc cho lestyramin phi hp vi dn
xut statin v acid nicotinic.
+ Cc thuc thuc dn xut statin c la chn trc tin cho tng cholesterol cn
dn xut acid fibric u tin cho trng hp tng triglycerid. Hai dn xut ny c th dng
ring r hoc kt hp trong nhng trng hp tng lipoprotein hn hp. Nhng phi thn
trng v theo di tc dng khng mong mun, c bit l du hiu tiu c vn. Do c tng
nguy c tiu c vn nn gemfibrozil v dn xut statin khng dng phi hp trong iu
tr.
- Trong qu trnh iu tr, ngoi vic thng xuyn theo di lng lipoprotein mu
nh gi hiu qu iu tr, bnh nhn cn c theo di tc dng khng mong mun do
thuc gy ra nh vim c, tiu c vn, tng transaminase, ri lon in tim v.v...
Cu hi t lng gi
1. Trnh by tc dng, c ch tc dng v p dng iu tr ca cholestyramin v
colestipol.
2. Trnh by tc dng, c ch tc dng p dng iu tr ca acid nicotinic v
probucol.
3. Trnh by tc dng, c ch tc dng v p dng iu tr ca dn xut acid fibric.
Trnh by tc dng, c ch tc dng v p dng iu tr ca dn xut statin.
Bi 32: Thuc h glucose mu

1. Trnh by c tc dng, c ch tc dng v p dng iu tr ca insulin
2. Trnh by c phn loi, c ch tc dng, v p dng iu tr ca dn xut
sulfonylure v c ch tc dng v p dng iu tr ca dn xut biguanid v
acarbose v cc thuc khc.
1. i cng
c th bnh thng, glucose mu c duy tr nng hng nh nh s cn bng

gia insulin v glucagon, hormon tng trng, cortisol, thyroxin v catecholamin. Khi c
ri lon s cn bng ca h thng ny, c bit l gim s lng, cht lng cng nh s
nhy cm ca cc t bo i vi insulin s gy ra bnh tng glucose mu.
Da vo s lng insulin v mc nhy cm ca t bo vi insulin, b nh i tho ng
c chia thnh hai nhm:
- Nhm ph thuc insulin cn gi l tng glucose mu tp I, thng gp ngi gy, tr,
di 40 tui c gim s lng t bo tuyn tu v nng insulin mu rt thp. iu
tr dng insulin.
- Nhm khng ph thuc insulin cn gi l tng glucose mu tp II, thng gp ngi
ln tui, khng gim s lng nhng c gim chc nng gy nn s ri lon bi tit
insulin ca t bo , nng insulin trong mu bnh thng hoc cao v c hin tng
khng insulin cc m ngoi vi. Ngoi ra, cn c tng glucagon v gim p ng ca t
bo vi GLP1(glucagon like peptid 1)v vi GIP(glucose dependent insulin tropic
peptid ). Theo cc thng k, 80 -90% bnh nhn c tng glucose mu thuc typ II. Thuc
iu tr ch yu l cc thuc chng i tho ng tng hp dng ng ung.
2. Cc thuc h glucose mu
Hin nay c 2 cch phn loi thuc h glucose mu:
* Theo c ch tc dng, thuc h glucose mu c chia thnh 5 nhm chnh:
- Insulin
- Thuc kch thch bi tit ins ulin: sulfonylure, nateglinid.
- Cc thuc lm tng nhy cm ca t bo vi insulin: dn xut biguanid, nhm
thiazolindindion.
- Thuc c ch - glucosidase.
- Cc thuc bt chc incretin (GLP1, GIP) v thuc c ch DPP4(dipeptidyl peptidase 4).
* Theo ng dng v ngun gc, cc thuc h glucose mu c chia thnh 2 nhm

chnh:
- Insulin
- Thuc h glucose mu dng ng ung.
2.1. Insulin
Insulin l mt hormon gy h ng huyt do tuyn tu tit ra. Ngy nay, da vo cu
trc, insulin c th c b n tng hp t insulin ln hoc nh k thut ti t hp gen
thng qua vi khun hoc nm. nh gi tc dng v tinh khit, insulin c quy
thnh n v chun quc t. Mt n v insulin (1 IU) l lng insulin cn lm gim
glucose mu th nng 2,5kg nhn i xung cn 45mg/100ml v gy co git sau khi
tim 5 gi v bng 40g insulin.
2.1.1. Tc dng v c ch tc dng
Tt c t bo ca ngi v ng vt u cha receptor c hiu cho insulin. Receptor ca
insulin l mt glycoprotein gm 2 n v di nm mt ngoi t bo v hai n v di
nm mt trong t bo. Bn n v ny gn i xng nhau bng cu disulfid. Thng qua
receptor ny, insulin gn vo di n v gy kch thch tyrosinkinase ca n v di
lm hot ha h thng vn chuy n glucose mng t bo ( glucose transporters = GLUT),
lm cho glucose i vo trong t bo mt cch d dng, c bit l t bo c, gan v t bo
m. Hin nay ngi ta pht hin ra 5 cht vn chuyn glucose phn b nhng t bo
khc nhau. Tc dng l m h glucose mu ca insulin xut hin nhanh ch trong vng vi
pht sau khi tim tnh mch v b mt tc dng bi insulinase.
C ch tc dng xin c thm bi Hormon.
Nhn chung, insulin rt t c, nhng cng c th gp :
- D ng: C th xut hin sau khi tim ln u hoc sau nhiu ln tim insulin, t l d
ng ni chung thp.
- H glucose mu: Thng gp khi tim insulin qu liu, gy chy m hi, h thn nhit,
co git, thm ch c th hn m.
- Phn ng ti ch tim : Nga, au, cng (teo m di da) hoc u m vng tim. trnh
tc dng ph ny, nn thay i v tr tim thng xuyn.
- Tng ng huyt hi ng (rebound): Gp nhng bnh nhn dng insulin liu cao sau
khi ngng thuc.
2.1.3. Ch phm
Da vo dc ng hc v nhu cu iu tr insulin c xp thnh 3 nhm ch phm
khc nhau:
2.1.3.1. Insulin tc dng nhanh:
+ Insulin hydroclorid: Thi gian xut hin tc dng sau khi tim 1 gi v t ti a sau 3
gi v ko di tc dng khong 6 gi. Thuc c s dng trong hn m do i tho
ng, 1ml cha 20-40 n v, c th tim bp, di da, tnh mch.
+ Nh dch Insulin- km: Ch tim di da; sau khi tim 1 gi bt u xut hin tc dng
v ko di khong 14 gi.
2.1.3.2. Insulin tc dng trung bnh:
- Insophan insulin: (NPH - Neutral Protamin Hagedorninsulin) dng nh dch, l s phi
hp insulin, protamin v km trong mi trng m phosphat. C 100 n v insulin, c
thm 0,4mg protamin. Tim di da, tc dng xut hin sau 2 gi v ko di khong 24
gi.
- Lente insulin: Dng nh dch, tim di da xut hin tc dng sau 2 gi v ko di
khong 24 gi.
2.1.3.3. Insulin tc dng chm:
Insulin protamin km: Ch phm dng nh dch, c 100 n v insulin c km theo 0,2mg
protamin. Thi gian xut hin tc dn g sau khi tim di da 4 -6 gi v ko di ti 37 gi.
Insulin km tc dng chm (Ultralente insulin) tim di da, thi gian xut hin tc dng
v ko di tc dng gn ging insulin protamin - km.
2.1.4. p dng iu tr
- Tt c cc bnh nhn tng glucose mu thuc tp I u c ch nh dng insulin.
Ngoi ra, insulin cn c ch nh cho bnh nhn tng glucose mu tp II, sau khi
thay i ch n v dng cc thuc chng tng glucose mu tng hp khng c tc
dng.
- Tng glucose mu sau ct b ty tng, ph n c thai.
- Tng glucose mu c ceton mu v niu cao.
Trn c s nh lng insulin trong mu ca ngi bnh thng, ta thy lng insulin bi
tit trung bnh vo khong 18 - 40 n v/24 gi, mt na s c gi l insulin c s,
lng insulin cn li c bi tit theo ba n. V vy, duy tr lng glucose mu n
nh, insulin nn dng khong 0,2 - 0,5 n v cho 1 kilogam th trng/24 gi.
Cho n nay, duy nht c insulin l dng ng tim, cn cc thuc h glucose mu
khc c c ch tc dng khc nhau nhng ng dng duy nht l ung iu tr tng
glucose mu typ II sau t nht 3 thng thay i ch n, tng cng tp luyn th lc
khng c kt qu. Cc thuc ny khng thay th ch n gim glucid, gim nng lng
v tng cng hot ng th lc trong qu trnh iu tr. Da vo c ch, cc thuc chng
tng glucose mung ung c chia thnh:
- Thuc kch thch bi tit insulin
- Thuc lm tng nhy cm ca t bo ch vi insulin
- Thuc lm gim hp thu glucose rut.
- Cc thuc bt chc incretin(incretin mimetic) v thuc c ch DPP4(dipeptidyl

peptidase 4 inhibitor).
2.2. Thuc kch thch bi tit insulin
2.2.1. Dn xut Sulfonylure
T nhng nm 1942, Janbon v cng s pht hin c tc dng h glucose m u ca
mt s sulfonamid sc vt th nghim v bnh nhn iu tr thng hn. Nh pht hin
ny, carbutamid, mt sulfonamid c tng hp c tc dng h glucose mu, s dng trn
lm sng. Nhng do c tc dng c ch tu xng, thuc b lng qun. Son g nhu cu
iu tr bnh i tho ng ngy cng cao, khong 20 thuc c tng hp v da
vo cng tc dng v dc ng hc cc thuc xp thnh hai th h I v II.
- Th h I gm: tolbutamid, acetohexamid, tolazamid, clopropamid.
- Th h II: tc dng mnh gp khong 100 ln v c thi gian tc dng di hn th h I
nn ch cn dng 1 ln trong mt ngy, gm: glibenclamid, glipizid, gliclazid.
Bng 32.1: Tm tt mt s thng s dc ng hc v liu dng mt s thuc
nhm sulfonylure
Cng Nng cao Thi gian Thi gian Liu trung bnh
nht trong bn thi ko di tc
Th h Thuc tc dng (gam)/24 gi)
mu sau khi (gi) dng (gi)
ung (gi)
Tolbutamid 1 3-5 5-6 6-12 0,5-2,0
(Orabet)
Th h 1 Acetohexamid 2-4 4-5 12-24 0,25-1,25

(Dymelor)
Tolazamid 4-8 7 12-24 0,1-0,75

(Tolinase)
Clopropamid 5-10 2-4 18-35 40-60 0,1-0,5

(Meldian,)
Glibenclamid 100-200 4-5 4-5 24 0,0025-0,02
(Maninil,)
Th h 2
Glipizid (Glucotrol) 100-200 1-3 4 10-16 0,005-0,02
2.2.1.1. C ch tc dng:
Da vo nhng nghin cu thc nghim trn tuyn ty c lp, o ty c lp v nui cy
t bo , Pfeifer v cng s (1981) chng minh rng, tc dng h glucose mu ca cc
dn xut sulfonylure l do tc dng trn receptor b mt K +ATPase ca t bo o
Langerhans lm chn knh K + nhy cm vi ATP, gy gim K + i vo trong t bo to ra
s kh cc mng dn n m knh calci lm tng lng calci t ngoi bo i vo trong t
bo, kch thch gii phng insulin.
Mt s nghin cu gn y chng minh cc thuc ny cn lm tng s lng v tng tnh

nhy cm receptor ca insulin bch cu n nhn to, t bo m, hng cu, do lm
tng tc dng ca insulin. Theo Krall (1985), cc dn xut sulfonylure c tc dng kch
thch gii phng ra somatostatin, chnh somatostatin c ch gii phng glucagon, cho nn
cng gy h glucose mu.
Ngoi ra, ngi ta cn thy thuc c tc dng c ch insulinase, c ch s kt hp insulin
vi khng th khng insulin v s kt gn vi prot ein huyt tng.
2.2.1.2. Dc ng hc
Thuc c hp thu nhanh qua ng tiu ha. Nng ti a trong mu t c sau
khi ung khong 2-4 gi, gn vo protein huyt tng 92 -99% ch yu l albumin. Gn
mnh nht l glibenclamid, gn km nht l clopro pamid.
Thuc c chuyn ha ch yu gan. Tolbutamid chuyn ha nh phn ng oxy ha
thng qua h enzym chuyn ha microsom gan thnh mt s cht chuyn ha vn cn
tc dng nh hydroxymethyl -tolbutamid, 4-hydroxymethyl-tolazamid. Clopropamid
khng b chuyn ha s thi tr qua thn.
Thn l ng thi tr ch yu ca cc thuc h glucose mu dng ng ung. Ring
glibenclamid thi ch yu qua gan, v vy c ch nh cho nhng bnh nhn tng
glucose mu c chc nng thn suy yu.
2.2.1.3. Ch nh:
- Tt c bnh nhn tng glucose mu typ II, khng ph thuc insulin.
- Ngi bo bu trn 40 tui c insulin mu di 40 n v mt ngy.
2.2.1.4. Chng ch nh:
- Tng glucose mu typ I, ph thuc insulin
- Ngi c thai, cho con b, suy chc nng gan, th n
- Tng glucose mu nng trong tnh trng tin hn m hoc hn m.
- H glucose mu, d ng, ri lon tiu ha, bun nn, nn, vng da tc mt.
- Tan mu, thoi ha bch cu ht.
- Phn ng ging disulfuram khi dng clo propamid cng ru (gp khong 1 -15% bnh
nhn).
- H natri mu hay gp vi clopropamid, do c tc dng ging ADH ( 50% bnh nhn).
2.2.1.6. Tng tc thuc:
Thuc th h I gn mnh vo protein huyt gy nn cnh tranh v tr gn vi mt s
thuc: dicoumarol, diphenylhydantoin, salicylat, phenylbutazon, sulfonamid. Th h II
khng c tng tc kiu ny.
Cloramphenicol, IMAO, probenecid lm tng tc dng h glucose mu ca c hai th h I

v II, nhng corticoid, thuc trnh thai, diphenylhydantoin, rifamp icin, INH, cc
phenothiazin li gy gim tc dng h glucose mu ca thuc.
Thuc c ch -adrenergic dng cng vi cc dn xut sulfonylure gy nhp tim nhanh,
thay i huyt ng hc v tng tc dng h glucose mu v vy trnh dng phi hp.
2.2.2 Loi khng phi sulfonylure
2.2.2.1. Nateglinid:
L dn xut ca D-phenylalanin c tc dng kim sot s tng ng huyt sau ba n,
do vy s ci thin tnh trng tng ng huyt sau khi n bnh nhn tng glucose mu
typ II.
Trong c th, nateglinid gn v o receptor c hiu (SUR 1) t bo ca ty lm chn
knh K+ nhy cm vi ATP, gy kh cc mng t bo lm m knh calci. Calci kch thch
gii phng insulin. Do thuc c c im gn nhanh v tch ra nhanh khi receptor c
hiu nn kch thch bi ti t insulin nhanh, nn nhanh chng kim sot ng huyt sau
khi n. Nhng cng do thuc tch ra khi receptor c hiu nhanh lm rt ngn giai on
kch thch bi tit insulin, lm gim nguy c tng cao insulin trong mu nn trnh c
tnh trng h glucose mu v s suy kit t bo ca ty.
Thuc c hp thu tt qua ng tiu ha, thc n tng hp thu thuc. Sau ung liu duy
nht 60mg, nng ti a trong mu t c sau 55 pht. Thuc gn vo protein huyt
vi t l 99% v c thi gian bn thi 1,4 - 2 gi. Trong c th thuc b chuyn ha qua
Cyt-P450 (CyP3A4, CYP2C9) gan v thi tr qua mt v qua nc tiu.
Thuc c phm vi an ton rng, t c tnh. Nghin cu trn lm sng vi liu 60, 120,
180mg ung trc ba n 20 pht, c tc dng kim so t ng huyt sau n r rt.
Thuc c th dng ring r hoc kt hp vi metformin kim sot s tng ng huyt
sau n ngi tng glucose mu typ II.
2.2.2.2.Repaglinid
Ging nh nateglinid, repaglinid cng c tc dng kim sot ng huyt nhanh sau khi
n do vy cch dng ging nhau vi liu khi u 500 mcg sau iu chnh liu ph
thuc vo p ng ca bnh nhn nhng khng vt qu 16 mg/ngy.
2.3.Thuc lm tng nhy cm ca t bo ch vi insulin
2.3.1. Dn xut ca biguanid
Cc dn xut ca biguanid c cu trc hon ton khc vi dn xut sulfonylure gm:
phenformin (phenethylbiguanid) do gy acid lactic mu, nn b nh ch lu hnh trn
th trng, hin ch cn metformin (dimethylbiguanid) .
Mc d cc thuc ny c tc dng h glucose mu r rt nhng ngi tng glucose
mu, nhng c ch tc dng cn cha c r. Mt s tc gi cho rng, thuc tc dng
thng qua s tng dung np glucose, c ch s tn to glucose v tng tng hp glycogen
gan do tng hot tnh glycogensynthetase v lm tng tc dng ca insulin t bo
ngoi vi. Ngoi ra, thuc cn hn ch hp thu glucose rut. Thuc khng tc dng trc
tip trn t bo ca o Langerhans, v ch c tc dng khi c mt insulin ni sinh, nn
thuc c ch nh bnh nhn ty c n kh nng bi tit insulin.
- Metformin (Glucophage): Hp th km qua ng tiu ha, khng gn vo protein
huyt tng, khng b chuyn ha, thi tr ch yu qua thn. Thi gian bn thi khong
1,3 - 4,5 gi, thi gian tc dng khong 6 -8 gi, liu trung bnh 0,5-2,5g/24 gi, ti a
3g/24 gi v c chia lm 3 ln sau cc ba n hng ngy.
+ Ging nh dn xut sulfonylure, metfomin c ch nh dng ring r hoc kt hp vi
cc thuc khc cho bnh nhn tng glucose mu typ II sau khi iu chnh ch n v
tp luyn th lc khng c hiu qu. Metformin c th kt hp vi mt s thuc khc
kch thch bung trng trong iu tr v sinh. Khng dng thuc ngi tng glucose
mu c ceton mu cao v c ceton niu, ph n c thai, cho con b.
+ Thuc c th gy ri lon tiu ha, acid ha mu do tng acid lactic c bit bnh
nhn c km theo gim chc nng gan, thn.
2.3.2.Cc thuc thuc nhm thiazolidindion
L nhng thuc c cu trc v c ch tc dng hon ton khc vi dn xut sulfonylure
v biguanid. Cc thuc nhm ny l nhng cht ch vn v c i lc cao vi PPAR
(peroxisome proliferator activated receptor ). Receptor ny trong nhn t bo chu
trch nhim iu ha mt s gen lin quan n s chuyn ha lipid v glucose. Khi thuc
gn vo receptor gy nn s tng tc vi ADN c hiu lm hot ha gii m gen, lm
tng nhy cm ca t bo vi insulin gip tng chuyn ho glucid v lipid. Trn thc
nghim, ngi ta thy cc thuc lm tng chuyn ha glucose v tng s lng insulin
receptor mng t bo, tng tng hp glycogen thng qua tng hot tnh
glycogensynthetase v tng s dng glucose ngoi vi.
Cc thuc thuc dn xut thiazolidindion c th dng ring r hoc phi hp vi
metformin hoc cc thuc trong nhm sulfonylure nhng khng phi hp vi insulin
iu tr tng glucose mu typ II. Thuc khng c dng cho ngi b suy gan, suy tim,
ph n c thai, cho con b.Trong qu trnh iu tr cn thng xuyn theo di chc nng
gan. Hai thuc trong nhm s dng nhiu hin nay l :
- Pioglitazon (Actos) vin 15,30,45 mg, ung 15 -45 mg/ngy.
- Rosiglitazon (Avandia) vin 4;8 mg, ung 4 -8 mg/ngy.
2.4. Thuc lm gim hp thu glucose rut: acarbose (Glucobay):
Thuc c ch nh bnh nhn tng glucose mu typ II km theo bo bu. C ch tc
dng ca thuc khng lin quan n s bi tit insulin t bo ca ty m thng qua s
c ch - glucosidase b bn chi nim mc rut non. Ngoi ra, thuc cn c ch,
glucoamylase, maltase rut. Cui cng, lm gim hp thu glucose gy h glucose mu.
Thuc c th gy ri lon tiu ha nh trng bng, tiu chy v au bng.
Khi iu tr, cn iu chnh liu cho ph hp vi tng bnh nhn, nhng nhn chung liu
trung bnh cho ngi ln 300mg trong 24 gi. Cc thuc khng acid, cholestyrami n, mt
s cht hp ph mnh v ch phm cha enzym tiu ha lm gim tc dng ca acarbose.
Khng dng thuc nhng ngi c ri lon chc nng hp thu, ph n c thai, cho con
b v tr em di 18 tui.
2.5. Cc thuc bt chc incretin (incretin mimeti c) v thuc c ch
DPP4(dipeptidyl peptidase 4 inhibitor) .
Gn y ngi ta tm ra 2 peptid hormon GLP1, GIP gi chung l incretin c ngun gc
ti nim mc rut, c tc dng iu ho glucose mu sau khi n thng qua s kch thch
bi tit insulin v lm chm s tho rng d dy. Trn c s pht hin ny liraglutid v
exenatid hai cht ging incretin (incretin mimetic) ang c th nghim lm sng pha II
v III trn bnh nhn tng glucose mu typ II.
GLP1 kch thch bi tit insulin sau khi n rt mn h, ngoi ra cn c ch bi tit
glucagon, lm chm s tho rng d dy, kch thch s sao chp gen glucokinase v
GLUT2 nhng li mt tc dng nhanh do b enzym dipeptidylpeptidase ph hu nn c
thi gian bn thi di 2 pht. Vildagliptin, sitagliptin, s axagliptin l cc cht c ch
DPP4 lm ko di tc dng ca GLP1 ang c th nghim lm sng pha II trn bnh
nhn tng glucose mu typ II.
Cu hi t lng gi
1. Trnh by tc dng, c ch tc dng v p dng iu tr ca insulin.
2. Trnh by cch phn loi, c ch tc dng v p dng iu tr ca nhm
sulfonylure.
3. Trnh by tc dng, c ch tc dng v p dng iu tr ca nhm biguanid v
acarbose.
4. Trnh by tc dng, c ch tc dng v p dng iu tr ca nateglinid v nhm
thiazolidindion.
Bi 33: HIstamin v thuc khng histamin

1. Nu c vai tr sinh l v bnh l ca histamin
2. Trnh by c c ch tc dng, cch phn loi, ch nh v c tnh ca thuc
khng histamin H 1.
1. Histamin
1.1. Sinh tng hp v phn b histamin
Histamin l cht trung gian ha hc quan trng c vai tr trong phn ng vim v d ng,
trong s bi tit dch v v cng c chc nng nh cht dn truyn thn kinh v iu bin
thn kinh, c to ra do s kh carboxyl ca histidin di s xc tc ca decarboxylase.
Do histamin tch in dng nn d dng lin kt vi cht tch in m nh protease,
chondroitin sulfat, proteoglycan hoc heparin to thnh phc hp khng c tc dng sinh
hc. Phc hp ny c d tr trong cc ht trong dng bo, bch cu a base, t bo
nim mc d dy, rut, t bo thn kinh v.v... Da, nim mc, cy kh ph qun l nhng
m c nhiu dng bo nn d tr nhiu histamin.
1.2. S gii phng histamin
Nhiu yu t kch thch s gii phng histamin, nhng ch yu l do phn ng khng
nguyn - khng th xy ra trn b mt dng bo . Khi c phn ng khng nguyn -
khng th lm thay i tnh thm ca mng t bo vi ion calci lm tng calci i vo
trong ni bo, ng thi t ng gii phng calci t kho d tr ni bo. Ca +2 ni bo tng lm
v cc ht d tr gii phng histamin.
nh sng mt tri, bng, nc c ca cn trng, morphin, D -tubocurarin lm tng gii
phng histamin. Ngoi ra, mt s yu t khc cng c gii phng trong phn ng d
ng nh: yu t hot ha tiu cu (PAF); cc prostaglandin, bradykinin, leucotrien.
1.3. Chuyn ha histamin
Histamin c th chuyn ha qua 2 con ng khc nhau nh histaminase v N -
methyltransferase to thnh acid imidazol acetic v met hylhistamin khng c tc dng
sinh hc.
1.4. Receptor ca histamin
Hin nay tm thy 4 receptor khc nhau ca histamin l H 1, H2, H3 v H4. S phn b
s lng receptor v chc nng ca tng loi receptor rt khc nhau.
Khi histamin gn vo receptor H 1 s lm tng IP 3 (inositol 1,4,5-triphosphat) v
diacylglycerol t phospholipid. IP 3 lm tng gii phng calci t li ni bo.
Diacylglycerol (DAG) v calci lm hot ha protein lipase C, protein kinase ph thuc

Ca+2/calmodulin v phospholipasse A 2 cc t bo ch khc nhau gy cc phn ng sinh
hc khc nhau.
Histamin gn vo receptor H 2 kch thch adenylcyclase lm hot ha protein kinase ph
thuc AMP v cc t bo ch gy nn phn ng sinh hc. Receptor H 2 c nhiu nim
mc d dy, khi kch thch gy tng tit dch v acid (xin xem bi Thuc cha vim lot
d dy. Cimetidin, ranitidin, famotidin l nhng thuc khng trn receptor H 2.
Receptor H 3 l receptor trc synap, c mt nt tn cng neuron h histaminergic thn
kinh trung ng, c vai tr iu ha sinh tng hp v gii phng histamin. Cng ging
receptor H 1, H2, receptor H 3 l receptor cp vi protein G v c phn b trong nhiu
m. Hin nay tm c mt s cht ch vn v i khng trn receptor H 3:thioperamid,
iodophenpropit, clobenpropit, Imipromidin, Burimamid.
Receptor H 4 c mt t bo a acid, dng bo, t bo T v t bo hnh cy(dendritic
cell).Thng qua receptor ny histamin lm thay i ho hng ng mt s t bo v s
sn xut cytokin. Cc cht i khng trn recep tor H4 ang nghin cu c tc dng chng
vim invivo v c tc dng chng hen v vim i trng trn m hnh ng vt thc
nghim.
1.5. Tc dng sinh hc ca histamin

1.5.1. Trn h tim-mch
- Histamin lm gin cc mch mu nh, tiu ng mch, mao mch v tiu tnh mch lm
gim sc cn ngoi vi, gim huyt p v tng cng dng mu n m: thng qua
receptor H 1 s xut hin tc dng nhanh, cng mnh nhng khng ko di, cn i
vi receptor H 2 s xut hin tc dng gin mch chm, nhng ko di.
- Thng qua receptor H 1 histamin lm co t bo ni m mao mch, tch s kt gn cc t
bo ni m lm bc l mng c bn to thun li cho s thot dch v protein ra ngoi
bo gy ph n, nng, , au.
- Trn tim: Histamin c tc dng trc tip trn c tim v thn kinh ni ti lm tng co bp
c tm nh, tm tht, chm kh cc nt xoang v chm dn truyn nh tht.
1.5.2. Trn kh-ph qun - phi:
Thng qua receptor H 1 histamin lm co c trn kh ph qun, gy cn hen. Ngoi ra,
histamin cn gy xut tit n im mc kh ph qun, gy vim ph n nim mc v tng
tnh thm mao mch phi.
1.5.3. Trn h tiu ha
Histamin lm tng tit dch acid thng qua receptor H 2, lm tng nhu ng v bi tit dch
rut.
1.5.4. C trn
mt s loi vt, histamin lm tng co bp c trn t cung, nhng t cung ngi, c trn
bng quang, niu o, ti mt rt t b nh hng.
1.5.5. H bi tit
Histamin lm tng bi tit nc mt, nc mi, nc bt, dch ty.
1.5.6. Trn h thn kinh
Kch thch u mt si thn kinh ngoi vi g y nga, au. Trn thn kinh trung ng
histamin gy gim thn nhit, gy mt ng, c th chn n, tng tit ADH. Tc dng ny
thng qua c 2 loi receptor H 1 v H2.
2. Cc thuc khng histamin
2.1. Cu trc - phn loi
C nhiu cht i khng chn lc tr n 3 receptor khc nhau ca histamin. Thuc i
khng H 2 receptor (xin c bi thuc cha vim lot lot d dy). Cc cht i khng H 3
ang trong giai on nghin cu. Trong phm vi bi ny, ch gii thiu thuc i khng
chn lc trn receptor H 1.
Da vo dc ng hc, tc dng, cc thuc khng H 1 c xp thnh 2 th h:
* Th h I: gm cc thuc c th i qua hng ro mu no d dng, c tc dng trn
receptor H 1 c trung ng v ngoi vi, c tc dng an thn mnh, chng nn v c tc
dng khng cholinergic ging atropin.
* Th h II: gm cc thuc rt t i qua hng ro mu no, c thi gian bn thi di, t tc
dng trn H 1 trung ng, ch c tc dng trn H 1 ngoi vi, khng c tc dng khng
cholinergic, khng an thn v khng c tc dng chng nn, c hng say tu xe.
Bng 33.1: Liu lng mt s thuc khng histamin H 1
Tn gc Tn bit dc Liu lng cho ngi ln
(mg)
Th h I
- Alimemazin Allerlene 5 - 20
- Brompheniramin Dimetan 4 - 12
- Carbinoxamin Cardec 4-8
- Clemastin Tavist 1,3 - 2,7
- Clopheniramin Chlor- Trimeton 4 - 12
- Cyclizin Marexin 50
- Dimenhydrinat Dramamin 50 - 100
- Dimethinden Fenistil 4
- Diphenhydramin Benadryl 2,5 - 50

- Hydroxyzin Atarax 25 - 100
- Meclizin Antivert 12,5 - 50
- Promethazin Phenergan 10 - 25
-Pyrilamin Nisaval 25-50
Th h II
- Acrivastin Semprex 24; khng dng cho tr di
12 tui
- Astemizol Hismanal C tc dng khng mong
mun trn tim hin khng
c s dng
- Cetirizin Zyrtec 5 - 10
- Desloratadin (cht Aerius* 5
chuyn ha ca
Loratadin)
- Fexofenadin(cht Telfast 60
chuyn ha ca
terfenadin)
- Loratadin Claritin 10
-Mizolastin Mizollen 10
Terfenadin Seldan C tc dng khng mong
mun trn tim hin khng
c s dng
2.2. Tc dng dc l
2.2.1. Tc dng khng histamin thc th
Thuc khng histamin H 1 c ch c cnh tranh vi histamin ti receptor H 1 lm mt cc
tc dng ca histamin trn recetor. Khi d tha histamin, th histamin y cht i khng
ra khi receptor, t thuc gim hoc ht tc dng khng histamin.
c tc dng dc l ko di, cn tm cht va i khng cnh tranh v khng cnh
tranh, khi thuc chm b y khi receptor bi histamin. Terfenadin, astemizol... c
hai kiu c ch (c cnh tranh v khng cnh tranh) vi histamin ti receptor, nn t c
dng di hn nhng do c nhiu tc dng khng mong mun trn tim nn hai thuc ny
hin nay khng c s dng.
Thuc khng H 1 c tc dng d phng tt hn l cha, v khi histamin c gii phng
to hng lot phn ng v s gii phng ng thi cc cht trung gian khc m thuc
khng H 1 khng i khng c. Tc dng ca thuc mnh nht c trn ph qun, c

trn rut. Thuc cho kt qu khng r rt trong cha hen hoc cha nhng bnh tc nghn
ph qun. Cn phi hp hai loi khng H 1 v khng H 2 c ch ton vn s h huyt p
do histamin gy nn.
2.2.2. Tc dng khc
- Trn thn kinh trung ng: Cc thuc khng histamin th h I c tc dng c ch thn
kinh trung ng, lm du, gim kh nng tp trung t tng, ng g, chng mt. Tc dng
c ch receptor H 1 trung ng ny c th ko theo tc dng khng cholinergic, lm tng
tc dng lm du, gim kh nng nh.
Mt s thuc khng H 1 th h II, do tnh a nc v c i lc vi receptor H 1 ngoi bin,
nn t qua hng ro mu - no, v rt t c tc dng trung ng, v d fexofenadin,
loratidin...
- Trn thn kinh thc vt:
+ Khng cholinergic (c ch h M).
Nhiu thuc khng H 1 th h I nh promethazin, dimenhydrinat, diphenhydramin...) c
tc dng khng cholinergic ngay vi liu iu tr v trong m t s trng hp phi chng
ch nh.
+ Thay i h giao cm: Promethazin c ch receptor -adrenergic, lm h huyt p.
Diphenhydramin, dexclopheniramin... c ch thu hi catecholamin, lm tng tim lc tc
dng ca catecholamin.
- Chng say tu xe chng nn: Do khng cholinergic, an thn, chng nn; tt nht l
promethazin (c hiu lc ngang scopolamin). Hin nay diphenhydramin (Nautamin) v
dimenhydrin hay c dng chng nn trn lm sng.
- Chng ho: Nhiu thuc khng H 1 chng c ho theo c ch ngoi bin do c ch s co
ph qun gy phn x ho (promethazin, oxomemazin, doxylamin, dexclopheniramin...)
nhng hiu lc km thuc chng ho trung ng. Thuc khng H 1 lm tng tim lc ca
thuc gin ph qun khc (nh cc amin cng giao cm loi ephedrin).
- Tc dng khc:
+ Khng serotonin receptor ti vng di i gy kch thch n ngon (cyproheptadin,
doxylamin).
+ Chng nga, gy t (khng c lin h vi tc dng khng histamin), nh mepyramin,
diphenhydramin.
2.3. Tng tc thuc
Thuc dng cng khng H 1 Biu hin tc dng
Ru ethylic, thuc ng, thuc lm du, an thn kinh, Lm tng tc dng
thuc gim au ngun gc trung ng trung ng ca thuc
khng H 1
Thuc khng cholinergic: Lm tng tc dng

- Loi atropin, scopolamin khng cholinergic ca
thuc khng H 1
- Thuc an thn kinh (tr butyroph enon)
- Thuc chng trm cm loi ba vng, c ch
MAO, thuc chng Parkinson, dispyramid, thuc chng
co tht
Thuc cng ph giao cm v c ch cholinesterase: i khng vi tc dng
Ambenoniclorid, neostigminbromid, khng cholinergic ca
pyridostigminbromid, fluostigmin, paraoxon thuc khng H 1
2.4. Tc dng khng mong mun

2.4.1. Do tc dng trung ng
Thay i tu theo tng c th, thng biu hin c ch thn kinh (ng g, kh chu, gim
phn x, mt), mt kt hp vn ng, chng mt. Nhng biu hin trn tng mnh nu
dng thuc khng H 1 cng ru ethylic hoc thuc c ch thn kinh trung ng. Cm
dng khi li xe, ang vn hnh my mc hoc lm vic ni nguy him (trn cao).
mt s ngi, tc dng biu hin dng kch thch (nht l tr cn b): Mt ng, d
kch ng, nhc u, c khi co git nu liu cao.
hn ch tc dng khng mong mun trn thn kinh trung ng c th gim liu hng
ngy hoc dng lc chiu ti, hoc dng loi khng H1 th h II.
2.4.2. Do tc dng khng cholinergic
Kh ming, hu hng; khc m kh; kh tiu tin, b i, lit dng; ri lon iu tit
th gic, tng p lc trong mt c bit ngi c glcm gc ng, nh trng ngc;
gim tit sa.
2.4.3. Phn ng qu mn v c ng
C th gp qu mn nghim trng sau khi dng thuc khng H 1 bi ngoi, nht l khi c
xc da. C qu mn cho gia cc loi khng H 1. Biu hin ngoi da (ban , chm)
ngay c khi ung hoc tim, mt phn c ct ngha bi vai tr l m gii phng histamin
ca thuc khng H 1.
2.4.4. Tc dng khng mong mun khc
- Trn tim mch: terfenadin, astemizol ko di khong QT c th a n hin tng xon
nh, hin nay khng dng .
- Khng dung np, thay i huyt p, ri lon mu (thiu mu tan mu, gim bch cu,
thoi ha bch cu ht) tng nhy cm vi nh sng.
2.5. Ch nh v chng ch nh
2.5.1.Ch nh
- Thuc khng H 1 ch thun tu cha triu chng m khng cha c nguyn nhn gy
ra d ng.
Thuc khng lm thay i phn ng khn g nguyn - khng th; khng i khng vi
nhng cht trung gian khc c vai tr rt quan trng trong d ng, shock phn v, hen ph
qun (nh leucotrien). Nh vy, thuc khng H 1 hn ch trong cha hen, mt s thuc
phng c cn hen (promethazin, clophen iramin, thiazinamin, diphenhydramin,
clemasin...) c l do khng cholinergic. Khng H 1 th h II khng khng cholinergic nh
mepyramin dng d phng co tht ph qun khi tp luyn.
- Thuc khng H 1 t hiu qu khi cn tc dng nhanh v mnh (ph thanh m n, phn v
c h thng).
* Ch nh tt nht l:
- D ng: s mi ma, bnh da d ng (my ay cp tnh, ph n ban ; nga do d ng
(nh trong chm); ph Quincke; nga do cn trng t; d ng thuc.
- Bnh huyt thanh.
- Ch nh khc: Cha say tu xe (promethazin, diphenhydramin, diphenhydrinat...); gy ng
(promethazin); phi hp vi thuc ho lm tng tc dng chng ho; kch thch n ngon
(doxylamin, cyproheptadin) hin nay khng dng; dng cng thuc khng cholinergic
phng tai bin do phn x khi thm d bng ni soi hoc khi phu thut (nh khi chc
mng phi).
2.5.2. Chng ch nh
+ Lin quan ti tc dng khng cholinergic: Ph i tuyn tin lit, glcm gc hp,
nghn ng tiu ha v ng niu, nhc c, khi dng IMAO.
+ Do tc dng gy d ng ca thuc khng histamin: Qu mn vi thuc; khng dng
thuc khng H 1 ngoi da khi tn thng da.
+ ngi c thai, khng dng cyclizin v dn xut (c th gy qui thai).
+ Khng dng cc thuc th h II nh terfenadin, astemizol vi erythromyci n,
ketoconazol, itraconazol.
+ Khi li tu xe, vn hnh my mc.
Cu hi t lng gi
1. Trnh by vai tr sinh l v bnh l ca histamin.
2. Trnh by c im dc ng hc, tc dng ca thuc khng histamin th h I.
3. Trnh by c im dc ng hc, tc d ng ca thuc khng histamin th h II.
4. Trnh by cc tc dng khng mong mun v p dng iu tr ca thuc khng
histamin th h I v th h II.
Bi 34: Vitamin

1. Trnh by c vai tr sinh l v p dng iu tr ca 3 vitamin tan trong du:A,
D, E.
2. Trnh by c vai tr sinh l v p dng iu tr ca 4 vitamin tan trong nc :
B1, B2, B6 v vitamin C.
1. i cng
- Vitamin l nhng hp cht hu c m t bo ngi v ng vt khng th t tng hp
(tr vitamin D), c mt trong thc n vi s lng nh, cu trc hon ton khc vi
glucid, protid v lipid nhng rt cn thit cho mt s phn ng chuyn ha gip duy tr s
pht trin v s sng bnh thng, khi thiu ht s gy nn bnh l c hiu.
- Tu theo gii v giai on pht trin ca c th, nhu cu vitamin rt khc nhau.
C th gp tha hoc thiu vitamin. S thiu ht vitamin d o nhiu nguyn nhn v ng
thi c th thiu nhiu loi vitamin. Do vy, trong iu tr cn phi tm nguyn nhn v
phi hp nhiu loi vitamin khc nhau. Thc t c th gp tha vitamin , c bit l cc
vitamin tan trong du.
Da vo tnh cht ha tan t rong nc hay du cc vitamin c xp thnh 2 nhm:
- Cc vitamin tan trong du: vitamin A, D, E, K thi tr chm, tha s gy nn bnh l
tha vitamin.
- Cc vitamin tan trong nc: vitamin nhm B ( B 1, B2, B3, B5, B6, B8, B9, B12 )v vitamin C
thi tr nhanh ra khi c th, nhng nu dng liu cao cng gy nn ng c.
2. Cc vitamin tan trong du
2.1. Vitamin A
2.1.1. Ngun gc- cu trc v tnh cht
Vitamin A c 3 dng: retinol, retinal v acid retionic. Retinol l mt ru di dng ester
c nhiu trong gan, b, ph omat, sa, lng trng. Retinal dng aldehyd ca vitamin A.
C 3 tin vitamin A: , , - caroten. - caroten c nhiu trong c, qu c mu nh gc,
c rt hoc rau xanh, vo c th, ch c 1/6 lng - caroten chuyn thnh retinol.
1E.R = 6 g - caroten = 3,3 IU vitamin A; (E.R l equivalent Retinal).
* Trn th gic:
Vitamin A ch yu l retinol v retinal ng vai tr quan trng trong hot ng ca th
gic. Thiu vitamin A s gy ra bnh qung g, kh mt, lot gic mc. Acid r etinoic
khng c tc dng trn th gic.
C ch: trong mu vitamin A c chuyn thnh trans - retinol v sau thnh 11 - cis-
retinol v 11- cis- retinal. Trong bng ti 11 - cis- retinal kt hp vi opsin to thnh
Rhodopsin. Rhodopsin l mt sc t nhy cm vi nh sng t bo hnh nn ca vng
mc gip cho vng mc nhn c cc hnh nh khi thiu nh sng.
Khi ra nh sng Rhodopsin b phn hu thnh opsin v trans - retinal. Trans- retinal c th
c chuyn thnh cis - retinol hoc trans- retinol i vo mu tip tc chu k ca s nhn.
* Trn biu m v t chc da:
c bit acid retinoic kch thch bit ha t bo biu m, sinh tit nhy, c ch s sng
ha t bo biu m.
Ngi thiu vitamin A d b mn cm vi cc cht gy ung th v cc t bo nn c a biu
m nhng vng khc nhau tng sn r rt v gim kh nng bit ha. C ch tc dng
chng ung th ca vitamin A vn cha c gii thch y . C th vitamin A iu ha
s sinh tng hp protein c bit cn thit cho s bit ha t bo ca t ch c biu m v
c ch s nhn ln ca t bo ung th.
* Trn chc nng min dch:
- Vitamin A tng sc khng ca c th. Thiu vitamin A kch thc ca t chc
lympho thay i. -caroten lm tng hot ng ca t bo dit (Killer cell), tng s nhn
ln ca t bo lympho B v T.
* -caroten c tc dng chng oxy ha mnh c s dng trong phng v chng lo ha.
Tham gia cu to ht vi th dng chp (Chylomicron).
2.1.3. Du hiu thiu ht vitamin A
Nhu cu hng ngy ngi ln cn 4000 - 5000 n v/ ngy, tr em t 400- 1000 n
v/ ngy.
Khi thiu vitamin A c cc triu chng: tng sng ha biu m, da kh, thoi ha tuyn
m hi, nhim trng da, qung g, kh mng tip hp, kh gic mc c th gp vim lot
gic mc d dn n m lo v c th d b nhim trng h hp, tit niu, sinh dc v
chm ln, chn n.
2.1.4. Du hiu tha vitamin A
Ung liu cao ko di d gy tha vitamin A, biu hin: da kh, trc vy, nga, vim da,
rng tc, au xng, tng p lc ni s, au u, chn n, mt mi, d b kch thch v c
th gp xut huyt.
2.1.5. Dc ng hc
Trn 90% retinol trong khu phn n di dng retinolpalmitat. Nh enzym lipase ca ty
ester ny b thu phn gii phng retinol hp thu. Retinol c hp thu hon ton
rut nh protein mang retinol CRBP (cellular retinol binding protein). Trong mu retinol
gn vo protein i vo cc t chc v c d tr gan, gii phng ra protein mang
retinol. Vitamin A thi qua mt di dng lin hp vi acid glucuronic v c chu k gan -
rut. Khng thy dng cha chuyn ha trong nc tiu.
2.1.6. Ch nh v liu dng
* Ch nh:
- Bnh kh mt, qung g, tr chm ln d mc cc bnh nhim trng, suy dinh dng,
bnh Kwashiorkor.
- Bnh trng c, da, tc, mng kh, bnh sng, bnh vy nn, cc vt thng, vt bang.
- H tr trong iu tr ung th da, c t cung, i trng, phi v phng -chng lo ho .
* Ch phm v liu dng:
- Vin nang, vin nn 5000 ; 50000 n v.
- Vin nang du c cha lng v itamin A khc nhau tu tng ch phm v thng dao
ng t 200-800 n v.
- Ung 5000 n v mi ngy hoc cch 10 - 15 ngy ung 50.000 n v.
- Ph n c thai ung di 2500 n v/ ngy.
2.2. Vitamin D
2.2.1. Ngun gc- cu trc- tnh cht
- Vitamin D 1 l hn hp chng ci xng, tn mang tnh cht lch s.
- Ergocalciferol (D 2) c ngun gc tng hp thng c dng trong iu tr.
- Cholecalciferol (D 3) c ngun gc t nhin c th chit xut t du gan c v mt s cy
h c (Solanaceae) hoc c th t tng h p di tc dng ca tia cc tm.
- Vitamin D c coi nh mt hormon v:
. c tng hp di da i vo mu n c quan ch to nn tc dng thng qua
receptor c hiu.
. Hot tnh enzym hydroxylase xc tc cho qu trnh chuyn ha vitamin D to thnh cht
c hot tnh c iu ha theo c ch iu khin ngc thng qua nng ion calci
trong mu.
- Vitamin D 2 v D3 d b phn hu bi nh sng, oxy, acid.
- Tng hp thu calci rut v ti hp thu calci ng thn do kch thch tng si nh cc
carrier vn chuyn calci. Phi hp vi hormon cn gip iu ha nng calci trong mu.
- Tng tch t calci trong xng, gim bi tit phosphat v gip chuyn phosphat hu c
thnh phosphat v c.
- Oxy ha citrat gip cho s ha tan phc hp calc i v iu ha nng calci.
2.2.3. Du hiu thiu vitamin D
Thiu Vitamin D c th do gim hp thu rut, suy cn gip, dng thuc c ch enzym
gan, ngi t tip xc vi nng. Thiu vitamin D c du hiu gim calci v phosphat trong
mu, c th gp cn h calc i mu. Thiu lu di dn n ci cng tr em v nhuyn
xng ngi ln.
2.2.4. Du hiu tha vitamin
Tr di 1 tui dng lin tc 400 n v/ ngy. Tr trn 1 tui dng lin tc trn 1000 n
v / ngy c th gy ng c. Liu trn 50.000n v / ngy c t h gy ng c c tr em
v ngi ln. Khi ng c c biu hin tng calci mu, chn n, mt mi, i nhiu, kht
nc, nn, a chy, ri lon tm thn. Tng calci mu ko di gy calci ha cc tng v
c th gp suy thn. Gp ng c phi ngng ung vita min D, c ch n t calci, dng
glucocorticoid v truyn dch.
2.2.5. Dc ng hc
Vitamin D c hp thu rut non; D 3 hp thu tt hn D 2. Trong mu vitamin D c
gn vo - globulin v c tch lu gan v t chc m. to thnh cht c tc dng,
vitamin D c hydroxyl ha qua 2 giai on. gan c chuyn thnh 25 -
hydroxycalciferol hay calcifediol sau i vo mu n thn b hydroxyl ha ln th 2
to thnh 1 , 25 dihydroxylcalciferol hay calcitrol c hot tnh. Enzym tham gia phn ng
hydroxyl ha vitamin D gan v thn c th gy cm ng hoc tng hot tnh bi s thiu
vitamin D, calci, phosphat, hormon cn gip, prolactin v estrogen.
Thi tr ch yu qua mt, phn nh thi qua nc tiu. Thuc ha c chu k gan rut.
2.2.6. Ch nh- ch phm v liu dng
* Ch nh:
- Phng v chng ci xng tr em, phng v chng long xng, nhuyn xng
ngi ln, ngi gy xng lu lnh.
- Phng v chng co git trong suy cn gip.
- Hi chng Fanconi.
* Ch phm v liu dng
Mt n v quc t vitamin D bng 25 nanogam ergocalciferol hoc colecalciferol. Hin
nay c nhiu ch phm dng vin nang, vin nn, dung dch ung hoc tim bp cha
ergocalciferol, colecalciferol, alfacalcidol, calcitriol, hoc dihydrotachysterol hm lng
khc nhau.
- Phng bnh (tr em): ung 500- 1000 n v/ ngy hoc cch 6 thng ung liu duy nht
200.000 n v.
- iu tr ci xng: ung 10.000 - 20.000 n v (chia 3 ln/ ngy). Ngi ln ung 400 -
800 n v/ ngy.
- Chng co git do suy cn gip: ung hoc tim bp 50. 000- 200.000 n v/ ngy. Tun
dng 2 ln.
2.3. Vitamin E
2.3.1. Ngun gc- cu trc- tnh cht
Vitamin E gm 3 dng: , v - tocopherol c cu trc v tc dng dc l tng t

nhau. Ring - tocopherol chim 90% lng tocopherol trong t chc v c tc dng sinh
hc cao nht nn c s dng nhiu trn lm sng.
D - - tocopherol c hot tnh mnh hn L - tocopherol, 1 mg d- - tocopherol = 1,5
n v vitamin E.
Vitamin E c nhiu trong cc ht ng cc, la m, ng, u, gi , du lc, du olive, rau
xanh, gan, m, b, lng trng, b t t mt tc dng trong khng kh, tia cc tm, nhit
cao, FeCl 3 v peroxid.
- Tng sn xut tinh trng v kh nng th thai, lm t ca trng th thai.
- Ngn cn s to thnh gc t do, lm vng bn mng t bo c bit khi c mt vitamin
C v cc cht c cha nhm SH.
- Tng hp thu v d tr vitamin A, nhng li lm gim mt s triu chng ca s tha
vitamin A.
2.3.3. Du hiu thiu ht
Nhu cu hng ngy ca ngi ln l 10 - 30 mg. Thiu ht ko di s gp m t s triu
chng sau: gim phn x, tht iu, gim nhy cm xc gic, yu c, teo c ph i, gim
sn xut tinh trng, gim kh nng th thai, do xy thai, non, tn thng c tim ,
thiu mu, tan mu v rung git nhn cu.
2.3.4. Du hiu tha vitamin
Dng liu cao trn 300 n v/ ngy c th gy bun nn, nn, y hi, i lng, vim rut
hoi t. Tim tnh mch c th gy ri lon chc nng gan - thn, do hin nay khng
dng.
2.3.5. Dc ng hc
Sau khi thu phn rut non, thng qua cc ht vi dng chp i vo dng bch huyt
vo mu. Trong mu gn vo -lipoprotein v c phn phi vo hu ht cc t chc. D
tr nhiu trong gan v t chc m. i qua hng ro rau thai km.
* Ch nh:
- Do xy thai, ph n b xy thai lin tip,v s inh
- Teo c ; thiu mu, tan mu, bnh x cng b tr em v lipid mu cao.
- Chng lo ha: vitamin E c phi hp vi coenzym Q, acid amin cha lu hunh
hoc - caroten, vitamin C v selen.
- Cn th tin trin do gim s oxy ho ca - caroten.
- Chng i dm sau hoc ri lon kinh nguyt.
* Ch phm v liu dng:
- Ch phm :
Vin nang: 200, 400, v 600 mg;vin nn hoc vin bao ng: 10, 50, 100 v 200 mg;
ng tim : 30, 50, 100 hoc 300 mg/mL
- Liu lng: Thuc c th ung hoc tim bp. Liu thng dng cho ngi c biu hin
thiu ht cao gp 4- 5 ln nhu cu hoc 40 -50 mg/ngy.
2.4. Vitamin K (xem bi "thuc tc dng trn qu trnh ng mu")
3. Cc vitamin tan trong nc
3.1. Vitamin B 1 (thiamin, Aneurin)
3.1.1. Ngun gc, cu trc v tnh cht
C nhiu trong men bia (6- 10 mg/ 100g), cm go, u tng. Ngoi ra c lng nh
vitamin B 1 trong sa, trng, tht nc, gan, thn.
Khng n nh vi nh sng v m. Mt hot tnh trong mi trng trung tnh v base.
n nh tnh cht pH = 4.
Enzym diphosphatkinase xc tc cho s chuyn ha thiamin thnh thiamin pyrophosphat
b c ch bi cc cht khng thiamin: neopyrithiamin v oxythiamin.
3.1.2 . Vai tr sinh l
- Dng hot tnh ca thiamin l thiaminpyrophosphat c vai tr mt coenzym ca
decarboxylase, transketolase gip cho qu trnh chuyn ha pyrurat, - ketoglutarat thnh
cc aldehyd v acid carboxylic v chuyn ha pentose trong chu trnh
hexosemonophosphat. Khi thiu thiamin nng pyrurat trong mu tng cao v
transketolase trong hng cu gim r rt.
- Tham gia tng hp acetylcholin v kh carboxyl ca valin, leucin v isoleucin.
3.1.3.Du hiu thiu ht
Khi thiu vitamin B1 c th lm cho c th mt mi, chn n, gim tr nh, au, vim
dy thn kinh, gim trng lc c.
Nu thiu nng v ko di c th dn n bnh t ph Beri -Beri v suy tim, ngy nay t
gp.
3.1.4.Dc ng hc
Hp thu rut nh qu trnh vn chuyn tch cc, liu cao c th khuch tn th ng qua
nim mc rut. Bo ha ngng hp thu vi liu 8 - 15 mg nhng chia nh li u v ung ri
rc cng vi thc n s tng s hp thu.
Thiamin c tp trung cao nht gan, no, thn, tim. Khi cc m qu nhu cu thiamin
s b thi tr qua nc tiu di dng cha chuyn ha, hoc dng pyrimidin.
3.1.5.Ch nh v liu dng
* Ch nh:
- Bnh t ph Beri- Beri
- Vim au dy thn kinh, c bit ngi nghin ru, ph n c thai.
- Ri lon tiu ha: chn n, kh tiu, a chy ko di, vim lot i trng.
- Bnh tim mch, ngi c ch nui dng nhn to v nhc c.
* Liu dng:
- Trung bnh ngi ln ung 0,04 - 0,1g/ ngy hoc tim bp 0,05 g/ ngy.
- Liu cao 0,1- 1,0g/ ngy (chia 2- 3 ln) dng iu t vim dy thn kinh, au khp,
au mnh my.
- Khi nhu cu s dng glucid tng th cn tng liu lng thiamin. C 1000 calo c ngun
t glucid cn 0,5 mg thiamin.
* Khng tim trc tip vitamin B 1 vo tnh mch gy shock c th dn n t vong. C th
pha 100 mg thiamin trong 1 lt dung dch glucose nh git tnh mch.
3.2. Vitamin B 2 (Riboflavin) v vitamin B 6 (Pyridoxin)
- Vitamin B 2: c mu vng v c mt trong hu ht cc thc phm, vi khun rut c
kh nng tng hp vitamin B 2. t tan trong nc hn cc vitamin nhm B khc v d b
phn hu trong mi trng nc v base, l thnh phn cu to nn Flavomononucleotid
(FMN) v Flavoadenindinucleotid (FAD). FMN v FAD l cofactor ca cyt - c- reductase,
oxydase v dehydrogenase gip tng cng chuyn ha glucid, lipid, protid v vn
chuyn in t trong chui h hp t bo.
t gp thiu ht ring r vitamin B 2. nhng ngi nui dng nhn to, vim da, nim
mc, thiu mu v ri lon th gic c th ung vitamin B 2 (5- 10 mg/ ngy).
- Vitamin B 6: c mt trong nhiu loi thc phm ging vitamin B 1 v rt d phn hu
nhit cao hoc tip xc vi cht oxy ha hay tia cc tm. Di s xc tc ca
pyridoxalkinase, vitamin B 6 chuyn thnh pyridoxalphosphat mt coenzym ca
transaminase, decarboxylase v desaminase. Ngoi ra, vitamin B 6 cn tham gia tng hp
GABA v chuyn ha acid oxalic, vitamin B 12, acid folic.
C th gp thiu vitamin B 6 ngi suy dinh dng hoc dng INH, hydralazin,
pencilamin
Thuc c dng ng ung, tim bp hoc di da 0,05 - 0,1g/ ngy cho nhng ngi
c vim dy thn kinh ngoi vi, thn kinh th gic, x va ng mch, ng kinh, chng
ma vn tr em, ngi say tu xe, vim nim mc ming, thiu mu, gim bch cu ht
hoc khi dng km 1 s thuc.
3.3. Vitamin B 3 (acid nicotinic, Niacin, vitamin PP): Xin xem bi thuc h lipoprotein
mu.
3.4. Vitamin B 5 v B8
t gp thiu ht 2vitamin ny ring r
Vitamin B5 (acid panthothenic) :
C mt trong hu ht cc loi thc phm, l thnh phn rt quan trng cu to nn
coenzym A, gip cho s chuyn ha glucid, lipid, tng hp cc sterol trong c hormon
steroid v porphyrin. Thuc c ch nh trong ri lon chuyn ha do cc nguyn nhn
khc nhau, bnh ngoi da, chng mt do khng sinh aminoglycosid gy ra, phng v
chng sc sau m v vim nhim ng h hp.
Vitamin B 8 (vitamin H, Biotin):
C nhiu trong cc ph tng, lng trng, c, cc loi ht v l cofactor ca enzym
carboxylase tham gia phn ng kh carboxyl ca 4 c cht: Pyrurat - CoA, acetyl- CoA,
Propionyl- CoA v - methylcrotonyl- CoA gip cho s chuyn ha glucid v lipid. Tuy
nhin, vitamin B8 thng c ch nh trong bnh da tng t it b nhn, bnh nhn c
ch n nhn to v thiu ht enzym ph thuc biotin c tnh di truyn.
3.5. Vitamin C (acid ascorbic)
3.5.1. Ngun gc- tnh cht
- C trong hu ht rau, qu c bit trong rau ci xoong, cam, qut, chanh, bi, c chua.
Tan mnh trong nc nhng d b phn hu bi nhit , cc cht oxy ha v trong mi
trng base.
Trong c th, acid ascorbic b oxy ha to thnh acid dehydroascorbic vn cn y
hot tnh v 2 in t. y l phn ng thun nghch.
Nh c nhm endiol trong phn t nn vitamin C l cofactor ca nhiu phn ng oxy ha
kh quan trng trong s tng hp collagen, carnitin, chuyn acid folic thnh acid folinic,
c ch hyaluronidase lm vng bn thnh mch.
- Chuyn dopamin thnh noradrenalin , tng hp serotonin t tryptrophan, tng hp
hormon thng thn v s tng hp collagen, proteoglycan v cc thnh phn hu c khc
rng, xng, ni m mao mch.
- Gip chuyn Fe +3 thnh Fe +2 lm tng s hp thu st rut.
- Ngoi ra, vitamin C cn c tc dng hip ng vi vitamin E, - caroten, selen lm ngn
cn s to gc t do gy c t, bo tng tng hp interferon, gim nhy cm ca t bo
vi histamin.
3.5.3. Du hiu thiu ht
- Thiu trm trng vitamin C gy bnh Scorbut - ngy nay t gp, in hnh c du hiu:
chy mu di da, rng ming, rng rng, tng sng ha nang lng, vim li . - Thiu va
phi biu hin: mt mi, vim li, ming, thiu mu, gim sc khng d b nhim
trng.
3.5.4. Du hiu tha vitamin C
Tuy t tch lu, nhng khi dng liu cao trn 1g/ ngy v di ngy c th gp tha vitamin
C, biu hin: mt ng, kch ng, i lng, vim lot d dy - rut, gim sc bn hng cu
c th gy tan mu c bit ngi thiu G 6PD. Ph n mang thai dng liu cao di ngy
c th gy bnh Scorbut cho con. C th gp si thn oxalat do dehydroascorbic chuyn
thnh acid oxalic v tng huyt p.
* Ch nh:
- Phng v iu tr bnh Scorbut, chy mu do thiu vitamin C.
- Tng sc khng trong nhim trng, nhi m c, thai nghn.
- Thiu mu, d ng v ngi nghin ru, nghin thuc l.
* Liu dng:
- Ung trung bnh 0,2- 0,5g/ ngy, nn chia liu nh ung nhiu ln trong ngy.
- Tim di da hoc tnh mch khng vt qu 1g/ ngy. Ch c th gp schock khi
tim, c bit khi tim tnh mch.
- Tr em dng mt na liu ngi ln.
Cu hi t lng gi
1. Trnh by vai tr sinh l v p dng iu tr ca vitamin A.
2. Trnh by vai tr sinh l v p dng iu tr ca vitamin D.
3. Trnh by vai tr sinh l v p dng iu tr ca vitamin E.
4. Trnh by vai tr sinh l v p dng iu tr ca vitamin B 1.
5. Trnh by vai tr sinh l v p dng iu tr ca vitamin B 2 v vitamin B 6.
6. Trnh by vai tr sinh l v p dng iu tr ca vitamin C.
Bi 35: Hormon v thuc khng hormon

1. Trnh by c c ch tc dng v p dng iu tr ca hormon gip trng v
khng gip trng tng hp.
2. Trnh by c tc dng v c ch tc dng ca i nsulin
3. Trnh by c c ch tc dng, p dng lm sng ca glucocorticoid.
4. Phn tch c tc dng khng mong mun ca corticoid, cch theo di v d
phng.
5. Nu c tc dng v p dng iu tr ca androgen v thuc khng androgen.
6. Nu c tc dng v p dng iu tr ca estrogen v thuc khng estrogen.
7. Trnh by c tc dng v p dng iu tr ca progesteron v thuc khng
progesteron.
8. Trnh by c tc dng v p dng iu tr ca cc thuc chng th thai.
1. hormon tuyn gip

Tuyn gip sn xut 2 loi hormon khc nhau:
- Thyroxin v triiodothyronin c vai tr quan trng trong s pht trin bnh thng ca c
th v chuyn ha nng lng.
- Calcitonin (thyrocalcitonin) l hormon iu ha chuyn ha calci v phospho.
1.1.Thyroxin v triiodothy ronin (T4 v T3)
- iu ha pht trin c th: kim tra hu ht cc qu trnh tng hp protein v s pht
trin ca h thn kinh. Rt nhiu enzym chuyn ha lipid, protid v glucid chu nh
hng ca thyroxin. Thiu thyroxin th enzym gi m hot ng.
- Lm tng qu trnh chuyn ha ca c th, c bit l chuyn ha ca cc t chc tim,
gan, thn. C vai tr quan trng trong to nhit v iu ho thn nhit ca ng vt ng
nhit.
Khi chc phn tuyn gip km th gy ph nim dch, chuyn ha c s gim, thn nhit
h, rng tc, mch chm, rut gim nhu ng, km n, sc kho v tr khn gim ( tr
em, gi l chng n n). Ngoi cc triu chng trn, tr chm ln, tuyn gip to ra v
tuyn yn vn bi tit thm cc cht kch thch tuyn gip. Trong tuyn y cht dng
keo, nhng rt km v s lng hormon. vi vng ni, nc ung t iod cng gy bu

c a phng. Bnh thng mi ngy ta cn 0,075 g iod.
Khi cng tuyn th gy Basedow: bu c, mt li, tay run, mch nhanh, cholester ol-
mu gim, chuyn ha c s tng (vt trn 20%). Thyroxin mu tng, nhng v c ri
lon tin yn- gip, nn tuyn gip vn to ra (cng c trng hp khng to).
T bo tuyn c thyreoglobulin, khi b thu phn s cho thyroxin (3,5 diiodothyrozin - T4)
v 3, 5, 3' triiodotyronin (T 3). T l T 4/ T3 trong thyreoglobulin l 5/1, ngha l phn ln
hormon c gii phng l thyroxin, cn phn ln T 3 tun hon trong mu li l t
chuyn ha ngoi bin ca T 4. Tc dng ca T 3 mnh hn T 4 3- 4 ln. trong huyt tng,
T3 v T4 gn vo thyroxin- binding globulin (TBG), dng t do ca T 4 ch bng khong
0,04% tng lng v T 3 l khong 0,4%.
I
5' 6' 5 6
HO O CH 2CHCOOH
3' 2' 3 2
NH 2
I I
3 ,5 ,3 ' triiodothryronin (T3)
I I
6'
HO O CH2CHCOOH
I I NH2
Thyroxin (T4)
S kh iod ca T 4 c th xy ra vng trong, to ra 3, 3, 5 triodotyronin, c gi l T 3

ngc (reverse T3 hoc r T 3), khng c hot tnh. Thuc chn , corticoid, i lu ngy,
c ch enzym chuyn T 4 thnh T 3, lm gim lng T 3 v lm tng r T 3 trong huyt tng.
Hormon TSH iu ha s thu phn thyreoglobulin v s nhp iod vo tuyn gip. Ngc
li m thyroxyn v 3, 5, 3' triod tironin trong huy t tng iu ha s tit TSH.
Trong huyt tng, c mt gama globulin tng hp trong lympho tc ng cng tng t
nh TSH, nhng thi gian lu hn, l yu t L.A.T.S. (long - acting thyroid stimulator).
1.1.2. Ch nh v ch phm
Hai ch nh chnh l suy tuyn gip (hay myxoedme) v bu c a phng.
- Thyreoidin; bt tuyn gip kh ca ng vt (c 0,17 - 0,23% iod), ung 0,1- 0,2g mi
ln, mi ngy ung 2- 3 ln. Liu ti a mt ln 0,3g, mt ngy 1,0g.
- Thyroxin: vin 0,1 mg; dung dch ung 1 gi t = 5 g. Ung liu u 0,1 mg. Sau tng
dn tng 0,025 mg.
- Kali iodid: trn 1 mg vo 100 g mui n thng gi l mui iod d phng bu c
a phng.
- Levothyroxin (Levothyrox, Thyrax, Berithyrox) vin nn 25 - 50- 100- 150 g.
L ch phm tng hp c nhiu u im nn l thuc c chn la trong iu tr: thuc
c tnh n nh cao, thun nht, khng c protein ngoi lai nn khng gy d ng, d xc
nh nng trong huyt tng, thi gian bn thi di (7 ngy), gi thnh h.
Liu lng: i t liu thp, tng dn tng 25 g tu theo tnh trng bnh v tui bnh
nhn.
1.2. Calcitonin
L hormon lm h calci mu, c tc dng ngc vi hormon cn gip trng, do "t bo C"
ca tuyn gip bi tit. L mt chui a peptid hoc gm 32 acid amin c trng lng
phn t l 3600. Tc dng chnh ba ni:
- Xng: c ch tiu xng bng c ch hot tnh ca cc hu ct bo (ostoclaste), ng
thi lm tng to xng do kch thch to ct bo (ostoblaste).
- Thn: gy tng thi tr calci v phosphat qua nc tiu do tc dng trc tip. Tuy nhin,
do c ch tiu xng nn calcitonin lm gim bi tit Ca 2+, Mg2+ v hydroxyprolin qua
nc tiu.
- ng tiu ha: lm tng hp thu calci
Tm li, calcitonin nh mt hormon d tr, hormon tit kim calci v n lm ngng s
hu xng v lm tng hp thu calci qua tiu ha.
1.2.2. Ch nh
- Calcitonin c tc dng lm h calci - mu v phosphat- mu trong cc trng hp cng
cn gip trng, tng calci mu khng r nguyn nhn tr em, nhim c vitamin D, di
cn ung th gy tiu xng, bnh Paget (c ng ha v d ha ca xng u tng rt
mnh).
- Cc bnh long xng: sau mn kinh, tui cao, dng corticoid ko di.
- Ngoi ra, calcitonin cn c tc dng gim au xng, c dng trong cc di cn ung

th.
- Triu chng tiu ha: bun nn, nn, tiu chy, au bng
- Triu chng v mch mu: nng mt, mt, nng chi v c cm gic kin b.
- Thn: i tiu nhiu ln, a niu
1.2.4. Ch phm
- Calcitonin: 100 UI/ ngy u, sau gim xung 50 UI mi tun 3 ln.
- Calcitonin ca c hi (salmon): Miacalcic
ng 1 mL cha 50 UI- chai xt nh liu 50 v 200 UI.
Tim di da hoc xt vo mi 50 - 100 UI mi ngy hoc cch ngy.
Calcitonin ca c hi mnh hn calcitonin ca ngi v ln t 10 - 40 ln v tc dng lu
hn 10 ln.
1.3. Thuc khng gip trng tng hp
Qu trnh tng hp thyroxin c 4 giai on:
- Gn iodid v c vo tuyn (iodid l iod dng ion I -)
- Oxy ha iodid thnh iod t do
- To mono- v diiodotyrosin (MIT- DIT)
- Ghp 2 iodotyrozin thnh L - thyroxin- tetraiodotyrosin T 4 (TIT) (xem hnh )
Thuc khng gip trng c dng cha cng gip (bnh Basedow). C th chia
thnh 4 nhm:
Hnh 35.1.V tr tc dng ca thuc khng gip trng

MIT: monoiodotyrosin, DIT: diiodo - tyrosin
(1): Thiocyanat, perclorat
(2): Nhm thiamid carbimazol, benzylthiouracil, propylthiouracil, methimazol
(3): Lithium
1.3.1. Thuc c ch gn iodid vo tuyn

c ch qu trnh vn chuyn iod nh thiocyanat (SCN -), perclorat (ClO 4-), nitrat. c v
thng gy mt bch cu ht, khng c dng trong lm sng.
1.3.2. Thuc c ch trc tip tng hp thyroxin: Thioamid
S

N C R
1.3.2.1. C ch
Loi ny khng c ch gn iod vo tuyn gip, nhng c ch to thnh cc phc hp hu
c ca iod do c ch mt s enzym nh iod per oxydase, cc enzym oxy ha iod. V vy
tuyn khng tng hp c mono - v diiodotyrosin.
1.3.2.2. c tnh
Dng thuc c ch tng hp thyroxin ko di, lng thyroxin gim, lm tuyn yn tng
tit TSH. TSH tng, kch thch tuyn gip nhp iod, lm tng sinh, dn n chng ph
nim (tuyn gip cha nhiu cht dng keo, nhng t hormon)
Nhm thuc ny t gy tai bin. Tai bin nng nht l gim bch cu ht (0,3 - 0,6%)
thng xy ra sau vi thng iu tr. V vy cn kim tra s lng bch cu c nh k v
nn dng thuc ngt qung.
Cc tai bin khc: pht ban, st, au khp, nhc u, bun nn, vim gan, vim thn.
Thng ngng thuc hoc i thuc khc s ht.
1.3.2.3. Ch phm
Cc loi thuc ny thng c dng lm sng cha cng tuyn gip, gm:
- Aminothiazol: mi ngy 0,6- 0,8g. Gim dn, ri dng liu duy tr 0,2g. Hin nay t
dng v c.
- Thio- uracil: mi ln 0,5g. Mi ngy 2- 3 ln, tai bin 5,8%.
R = CH3 metyl thiouracil (MTU)

R = C 3H7 propyl thiouracil (PTU)
R = CH2 - C6H5 benzyl thiouracil (Basden)
- Thiamazol (Basolan): mi ngy ung 15 - 60 mg. Tai bin 3,4%.

- Carbimazol (Neomecazol): mi ngy ung 15 - 60 mg. Vo c th chuyn thnh
methiazol, cht ny mnh gp 10 ln PTU nn a dng hn.
1.3.2.4. Cch dng
Ung thuc lm 3 giai on:
- Tn cng: 3- 6 tun vi liu 150- 200 mg
- Duy tr: 3- 6 thng vi liu 100 mg
- Cng c: hng thng. Liu hng ngy bng 1/4 liu tn cng.
1.3.3. Iod
Nhu cu hng ngy l 150 g. Khi thc n khng cung cp iod, s gy bu c n
thun. Tri li, khi lng iod trong mu qu cao s lm gim tc dng ca TSH trn
AMPv. Lm gim gii phng thyroxin.
- Ch nh: chun b bnh nhn trc khi m ct tuyn gip.
- Dng cng vi thuc khng gip trng v thuc phong to adrenergic trong iu tr
tng nng tuyn gip.
- Ch phm: dung dch Lugol (iod 1g, kali iodid 2g, nc va 20mL), ung XXX git
mi ngy (XX git cha 10mg iod).
- c tnh: thng t v hi phc khi ngng dng: trng c, sng tuyn nc bt, lot
nim mc, chy mi... (tng t nh nhim c brom)
1.3.4. Ph hu t chc tuyn: iod phng x

1.3.5. Thuc phong to h adrenergic
Nhiu triu chng ca cng gip l cng giao cm. V vy dng guanethidin, reserpin.
Nhng tt hn c l thuc chn propranolol. Nhm thuc ny ch c tc dng cha triu
chng, khng tc dng vo tuyn.
2. Hormon tuyn ty
o Langerhans ca tuyn ty c 4 loi t bo bi tit:
- T bo A () chim 20%, tit glucagon v proglucagon
- T bo B () chim 75%, tit insulin, proinsulin v C peptid
- T bo C ( ) chim 3%, tit somatostatin
- T bo F (PP) chim < 2%, tit pancreatic polypeptid (PP)
Bi ny ch trnh by 2 hormon quan trng l insulin l glucagon.
2.1. Insulin
Insulin l mt protein c trng lng phn t l 5800 Da, gm 2 chui peptid A (21
acid amin) v B (30 acid amin) ni vi nhau bng 2 cu disulfid. Ton b tuyn ty ca
ngi c 8 mg insulin, tng ng 200 n v sinh hc. Khi i, tuyn ty tit khong
40 g (1 n v) insulin vo tnh mc h ca. Glucose l tc nhn ch yu gy tit insulin,
thi gian bn thi trong huyt tng l 5 - 6 pht vi insulin v khong 17 pht vi
proinsulin. Insulin b ging ha ch yu gan v thn do b ct ng ni disulfid gia
chui A v B bi insulinase.
Insulin iu ha ng huyt ti cc m ch ch yu l gan, c v m. Insulin l hormon
ch yu kim tra s thu hi, s dng v d tr cc cht dinh dng cho t bo. Insulin
kch thch cc qu trnh ng ha ca t bo (s dng v d tr glucose, acid amin, acid
bo), ng thi c ch cc qu trnh d ha (phn hu glycogen, m v protein). Tc dng
chung l kch thch vn chuyn cc c cht v ion vo trong t bo, hot ha v bt hot
cc enzym c hiu.
Glucose nhp vo t bo bng s khuch tn thun li nh vo cc cht vn chuyn
glucose (glucose transporters - GLUT):
GLUT 1 c mi m, c bit l hng cu v no
GLUT 2 c t bo ca ty, gan, thn, rut
GLUT 3 c no, thn, rau thai
GLUT 4 c c v m m
GLUT 5 c rut v thn
Glucose c s dng l nh vo h thng enzym hexokinase chuyn thnh glucose -

6- phosphat (GGP). Sau G6P s chuyn thnh glycogen d tr hoc b oxy ha
cung cp nng lng cho m. Hexokinase IV l mt glucokinase c thy k t hp vi
GLUT 2 trong gan v t bo ca ty; hexokinase II li c thy kt hp vi GLUT 4
trong t bo c vn, c tim v m m. C 2 hexokinase ny u c iu ha bi insulin
ngay mc phin m di truyn.
2.1.1.1. Tc dng ca insulin ti gan
- c ch hy glycogen (c ch phosphorylase)
- c ch chuyn acid bo v acid amin thnh keto acid
- c ch chuyn acid amin thnh glucose
- Thc y d tr glucose di dng glycogen (gy cm ng glucokinase v glycogen
synthetase)
- Lm tng tng hp trigly cerid v VLDL.
2.1.1.2. Tc dng ca insulin ti c vn
- Lm tng tng hp protein, tng nhp acid amin vo t bo
- Lm tng tng hp glycogen, tng nhp glucose vo t bo
2.1.1.3. Tc dng ca insulin ti m m
- Lm tng d tr triglycerid v lm gi m acid bo t do trong tun hon theo 3 c ch:
. Gy cm ng lipoproteinlipase tun hon nn lm tng thu phn triglycerid t
lipoprotein tun hon.
. Este ha cc acid bo t thu phn lipoprotein
. c ch trc tip lipase trong t bo nn lm gim lipo lyse ca triglycerid d tr.
2.1.2. Receptor ca insulin
Hu nh mi t bo ca ng vt c v u c receptor vi insulin, nhng s lng rt
khc nhau: mng t bo hng cu ch c 40 receptor trong khi mng t bo m, t bo gan
c ti 300.000. Khi insul in gn vo receptor, n s hot ha cc tyrosin kinase trong t
bo (ngi truyn tin th 2) v thc y cc qu trnh phosphoryl ha gy ra s chuyn v
ca cc cht vn chuyn glucose (GLUT) v pha mng t bo nhp glucose vo trong
t bo. Khi thiu insulin, t bo s khng s dng c glucose, glucose huyt s tng gi
l bnh i tho ng. C 2 loi (typ) i tho ng. (Xin xem thm bi Thuc h
glucose mu).
- i tho ng typ I, do tn thng t bo ca ty, ty khng bi tit insul in nn
phi iu tr b bng insulin ngoi lai, gi l bnh i tho ng ph thuc vo insulin.
Bnh thng gp ngi tr, th gy.
- i tho ng typ II, do tn thng ti receptor (gim s lng hoc gim tnh cm th
ca receptor vi insulin), ins ulin mu vn bnh thng hoc c khi cn tng nn gi l
bnh i tho ng khng ph thuc vo insulin. Bnh thng gp ngi trn 40 tui,
bo bu.
2.1.3. p dng iu tr
- Bnh i tho ng v cc bin chng ca n (xin xem thm bi "Thuc h glu cose
mu")
- Nn, tr gy yu, km n: dng insulin vi glucose
2.1.4. Cc ch phm chnh
Cc ch phm thng c ngun gc t b, ln hoc bng k thut ti t hp DNA ca
insulin ngi. Insulin b mang tnh khng nguyn nhiu hn ln.
Cc loi ch phm: xin xem bi Thuc h glucose mu.
2.2. Glucagon
Do t bo alpha ca o Langerhans tit ra, glucagon c tc dng tng glucose mu, tng
acid lactic mu, tng acid pyruvic mu, tng acid bo t do huyt tng.
Vi liu cao, glucagon kch thch thng thn bi tit catecholamin.
Glucagon lm tng sc co bp ca c tim, nhp tim v cung lng tim, h huyt p, tng
t nh isoprenalin (thuc c tc dng cng adrenergic).
Liu cao lm gin c trn ca rut khng thng qua AMPv.
2.2.1. C ch tc dng
Glucagon hot ha adenylcyclase, lm tng m 3', 5' AMP vng, 3', 5' AMP vng
hot ha phosphorylase gan, chuyn glycogen thnh glucose. C vn khng c receptor
vi glucagon.
C ch ny cng ging nh c ch v tc dng ca catecholamin hot ha cc recepto r
adrenergic.
2.2.2. Ch nh
- H glucose- mu do dng qu liu insulin (kt hp vi glucose tim tnh mch), hoc
cn sc insulin ko di.
- Sc (glucagon c dng thay isoprenalin).
- nh gi d tr glycogen trong gan, phn loi cc th bnh v g lycogen.
2.2.3. Ch phm
Glucagon: 1 mL = 1mg. Tim di da, tim bp hoc tnh mch. Tc dng xut hin
nhanh. Cng tc dng ph thuc vo d tr glycogen ca gan.
3. hormon v thng thn: glucocorticoid
V thng thn c 3 vng sn xut hormon:

- Vng cun pha ngoi, sn xut hormon iu ha thng bng in gii
(mineralocorticoid), i din l aldosteron, chu s kim tra chnh ca h renin -
angiotensin.
- Vng b v vng li pha trong, sn xut hormon iu ha glucose (glucocorticoid -
hydrocortison hay cortisol) v androgen, chu s kim tra chnh ca ACTH tuyn yn.
Trong lm sng thng dng glucocorticoid nn y ch trnh by nhm thuc ny.
Corticoid iu ha glucose: CORTISOL (hydrocortison )
3.1. Tc dng sinh l v tai bin
Mi tc dng sinh l ca corticoid u l ngun gc ca cc tai bin khi dng ko di.
3.1.1. Trn chuyn ha
- Chuyn ha glucid: corticoid thc y to glucose t protid, tp trung thm glycogen
gan, lm gim s dng glucose ca cc m, nn lm tng glucose mu . V th c khuynh
hng gy ra hoc lm nng thm bnh i tho ng.
- Chuyn ha protid: corticoid lm gim nhp acid amin vo trong t bo, tng acid amin
tun hon, dn n teo c, thng bng nit ( -). Do tng d ha protid, nhiu m b nh
hng: m lin kt km bn vng (gy nhng vch rn di da), m lympho b teo (tuyn
hung, lch, hch lympho), xng b tha do lm teo cc thm m lin kt, ni lng ng
cc cht v c to nn khung xng (do xng di d b gy, t sng b ln, hoi
t v khun c xng i).
- Chuyn ha lipid: corticoid va c tc dng hu lipid trong cc t bo m, lm tng acid
bo t do; va c tc dng phn b li lipid trong c th, lm m ng nhiu mt
(khun mt mt trng), c, na thn trn (nh dng Cushing) , trong khi cc chi v na
thn di th teo li. C gi thit gii thch rng t bo m ca na thn trn p ng ch
yu vi tng insulin do glucocorticoid gy tng ng huyt, trong khi cc t bo m
khc li km nhy cm vi insulin v p ng vi t c dng hu lipid.
- Chuyn ha nc v in gii:
. Na+: lm tng ti hp thu Na + v nc ti ng thn, d gy ph v tng huyt p.
. K+: lm tng thi K + (v c H +), d gy base mu gim K + (v c base mu gim Cl -).
. Ca2+; lm tng thi Ca 2+ qua thn, gim hp thu Ca 2+ rut do i khng vi vitamin D.
Khuynh hng lm gim Ca - mu ny dn ti cng cn gip trng phn ng ko Ca 2+
t xng ra, cng lm xng b tha, lm tr em chm ln.
. Nc: nc thng i theo cc ion. Khi ph do aldosteron t ng th corticoid gy i
nhiu (nh trong x gan) v n i khng vi aldosteron ti thn.
3.1.2. Trn cc c quan, m
- Kch thch thn kinh trung ng, gy lc quan, c th l do ci thin nhanh c tnh
trng bnh l. V sau lm bt rt, bn chn, lo u, kh ng (c th l do ri lon trao i
ion Na+, K+ trong dch no tu). Gy thm n, do tc dng trn vng i.
- Lm tng ng mu, tng s lng hng cu, bch cu, tiu cu, nhng lm gim s
lng t bo lympho do hu cc c quan lympho.
- Trn ng tiu ha: corticoid va c tc dng gin tip, va c tc dng trc tip lm tng
tit dch v acid v pepsin, lm gim sn xut cht nhy, gim tng hp prostaglandin E 1,
E2 c vai tr trong vic bo v nim mc d dy. V vy, corticoid c th gy vim lot d
dy. Tai bin ny thng gp khi dng thuc ko di hoc dng liu cao.
- Do c ch cu to nguyn bo si, c ch cc m ht, corticoid lm chm ln so cc vt
thng.
3.2. Cc tc dng c dng trong iu tr
Ba tc dng chnh c dng trong iu tr l chng vim, chng d ng v c ch min
dch. Tuy nhin, cc tc dng ny ch t c khi nng cortisol trong mu cao hn
nng sinh l, l nguyn nhn d dn n cc tai bin trong iu tr. V vy, trong
trng hp c th, nn dng th uc ti ch trnh tc dng ton thn v nng cao hiu
qu iu tr n ti a. C ch tc dng ca corticoid rt phc tp v c nhiu tc dng
trn mt t bo ch, v li c nhiu t bo ch.
3.2.1. Tc dng chng vim
Glucocorticoid tc dng trn nh iu giai on khc nhau ca qu trnh vim, khng ph
thuc vo nguyn nhn gy vim:
- c ch mnh s di chuyn bch cu v vim.
- Lm gim sn xut v gim hot tnh ca nhiu cht trung gian ha hc ca vim nh
histamin, serotonin, bradykinin, cc d n xut ca acid arachidonic (s 1).
Glucocorticoid c ch phospholipase A 2, lm gim tng hp v gii phng leucotrien,
prostaglandin. Tc dng ny l gin tip v glucocorticoid lm tng sn xut lipocortin, l
protein c mt trong t bo, c tc dng c ch phospholipase A 2. Khi phospholipase A 2
b c ch, phospholipid khng chuyn c thnh acid arachidonic.
- c ch gii phng cc men tiu th, cc ion superoxyd (cc gc t do), lm gim hot
tnh ca cc yu t ha hng ng, cc cht hot ha c a plasminogen, collagenase,
elastase...
- Lm gim hot ng thc bo ca i thc bo, bch cu a nhn, gim sn xut cc
cytokin.
Phospholipid mng Glucocorticoid
(-)
Phospholipase A 2 Lipocortin
Acid arachidonic Thuc chng vim

Khng steroid
Lipo- Cyclo- (-)

oxygenase oxygenase
Leucotrien Prostaglandin
Hnh 35.2. v tr tc dng ca

glucocorticoid v thuc chng vim phi steroid
trong tng hp cc prostaglandin
3.2.2. Tc dng chng d ng

Cc phn ng d ng xy ra do s gn ca cc IgE hot ha trn cc receptor c hiu
dng bo (mastocyte) v bch cu base tnh di tc dng ca d nguyn. S gn hot
ha phospholipase C, cht ny t ch phosphatidyl- inositol diphosphat mng t bo thnh
diacylglycerol v inositoltriphosphat. Hai cht ny ng vai tr "ngi truyn tin th
hai", lm cc ht bo tng ca t bo gii phng cc cht trung gian ha hc ca phn
ng d ng: histamin, serotonin... (hnh 7.2).
Phosphatidyl- inositol KN + KT
diphosphat Glucocorticoid
(-)
Phospholipase C
Diacylglycerol Inositol triphosphat
Hot ha
"ngi truyn tin th hai"
HISTAMIN
SEROTONIN
Hnh 35.3. Tc dng chng d ng ca glucocorticoid
Bng cch c ch phospholipase C, glucocorticoid phong to gii phng trung gian ha

hc ca phn ng d ng. Nh vy, IgE gn trn dng bo nhng khng hot ha c
nhng t bo . Glucocorticoid l nhng cht chng d ng mnh.
3.2.3. Tc dng c ch min dch

Glucocorticoid tc dng ch yu trn min dch t bo, t nh hng n min dch th
dch.
Tc dng c ch min dch biu hin nhiu khu:
- c ch tng sinh cc t b o lympho T do lm gim sn xut interleukin 1 (t i thc
bo) v interleukin 2 (t T 4).
- Gim hot tnh gy c t bo ca cc lympho T (T 8) v cc t bo NK (natural killer: t
bo dit t nhin) do c ch sn xut interleukin 2 v interferon gamma.
- Do c ch sn xut TNF (yu t hoi t u) v c interferon, glucocorticoid lm suy gim
hot tnh dit khun, gy c t bo v nhn dng khng nguyn ca i thc bo.
Mt s tc dng ny cng ng thi l tc dng chng vim.
Do c ch tng sinh, glucoc orticoid c tc dng tt trong iu tr bnh bch cu lympho
cp, bnh Hodgkin.
3.3. Ch nh
3.3.1. Ch nh bt buc: thay th s thiu ht hormon
3.3.1.1. Suy thng thn cp
- B th tch tun hon v mui: NaCl 0,9% 1lt (5% trng lng c th tro ng 24
gi).
- Glucocorticoid liu cao: Hydrocortison 100 mg t/m. Sau 50 - 100 mg 8h/ ln trong
ngy u. Sau 24 n 72 gi thay bng tim bp hoc ung 25 mg 8h/ ln.
3.3.1.2. Suy thng thn mn tnh (bnh Addison)
Hydrocortison 20 mg ung vo bui sng v 10 mg vo bui tra.
3.3.2. Ch nh thng thng trong chng vim v c ch min dch
3.3.2.1. Vim khp, vim khp dng thp
- Mt khi dng corticoid th phi dng hng nm ! V th rt d c tai bin.
- Liu u tin thng l pred nison 10 mg (hoc tng ng)
- Khi au qu: triamcinolon acetonid 5 - 20 mg tim khp (ch lm ti bnh vin, tht v
khun)
3.3.2.2. Bnh thp tim
- Ch dng corticoid khi salicylat khng c tc dng
- Bnh nng, corticoid c hiu qu nhanh. Liu predn ison 40mg/ngy
- Khi ngng corticoid, bnh c th tr li. Nn phi hp vi salicylat
3.3.2.3. Cc bnh thn
Hi chng thn h v lupus ban : prednison 60 mg/ ngy (tr em 2mg/ kg) 3- 4 tun.
Liu duy tr 3 ngy/ tun, ko di ti hng nm .
3.3.2.4. Cc bnh dy h (collagenose)
- Nm da cng (sclerodermia): khng chu thuc
- Vim nhiu c, vim nt quanh mch, vim au nhiu c do thp: prednison 1mg/ kg/
ngy. Gim dn
- Lupus ban ton thn bt pht: prednison 1 mg/ kg/ ngy. Sau 48 gi nu khn g gim
bnh, tng mi ngy 20 mg cho n khi c p ng. Sau dng liu duy tr 5 mg/
tun. C th dng thm salicylat, azathioprin, cyclophosphamid.
3.3.2.5. Bnh d ng
- Dng thuc chng d ng: khng histamin, adrenalin trong cc biu hin c p tnh.
- Corticoid c tc dng chm
3.3.2.6. Hen
- Dng corticoid dng kh dung, cng vi cc thuc gin ph qun (thuc cng 2
adrenergic, theophylin...).
phng tai bin nm candida ng mi hng
3.3.2.7. Bnh ngoi da
- Ngoi tc dng chung, khi bi ngoi, corticoid c ch ti ch s phn bo, v vy c tc
dng tt trong iu tr bnh vy nn v cc bnh da c tng sinh t bo.
- Trn da bnh thng, khong 1% liu hydrocortison c hp thu. Nu bng p, c th
lm tng hp thu n 10 ln. S h p thu tu thuc tng vng da bi thuc, tng cao
vng da vim, nht l vng trc vy.
* Tc dng khng mong mun
- Bi thuc trn din rng, ko di, nht l cho tr em, thuc c th c hp thu, gy tai
bin ton thn, tr chm ln.
- Tc dng ti ch: teo da, xut hin cc im gin mao mch, chm xut huyt, ban ,
sn, mn m, trng c, mt sc t da, tng p lc nhn cu...
* Mt s ch phm
Flucinolon acetonid (Synalar) 0,01% - 0,025%- 0,2%
Triamcinolon acetonid (Aristocor, Kenalog) 0,025% - 0,1%
Betametason dipropionat (Diproson) 0,05% - 0,1% (tc dng mnh)
Cc ch phm trn thng c bo ch di cc dng khc nhau nh thuc m (thch
hp vi da kh), kem (da mm, tn thng c dch r, cc hc ca c th nh m o...),
dng gel (dng cho vng da u, nch, bn).
Khi bi thuc, cn xoa u thnh lp mng, 1 - 2 ln/ ngy, theo ng ch dn, nht l
thuc c tc dng mnh.
3.4. Chng ch nh
- Mi nhim khun hoc nm cha c iu tr c hiu.
- Lot d dy- hnh t trng, long xng.
- Vim gan siu vi A v B, v khng A khng B.
- Ch nh thn trng trong i tho ng, tng huyt p.
3.5. Nhng im cn ch khi dng thuc
- Khi dng corticoid thin nhin (cortisol, hydrocortison) phi n nht. i vi thuc tng
hp, n tng i nht.
- Lun cho mt liu duy nht vo 8 gi sng. Nu dng liu cao th 2/3 liu ung vo bui
sng, 1/3 cn li ung vo bui chiu.
- Tm liu ti thiu c tc dng.
- Kim tra nh k nc tiu, huyt p, in quang d dy ct sng, ng mu, kali mu,
thm d chc phn trc h khu no - tuyn yn- thng thn.
- Dng thuc phi hp: tng liu insulin i vi bnh nhn i tho ng, phi hp
khng sinh nu c nhim khun.
- Ch n: nhiu protein, calci v kali; t mui, ng v lipid. C th dng th m
vitamin D nh Dedrogyl 5 git/ ngy (mi git cha 0,005mg 25 - OH vitamin D 3)
- Tuyt i v khun khi dng corticoid tim vo khp.
- Sau mt t dng ko di (trn hai tun) vi liu cao khi ngng thuc t ngt bnh
nhn c th cht do suy thng thn cp: cc triu chng tiu ha, mt nc, gim Na,
gim K mu, suy nhc, ng lm, tt huyt p. V th khng ngng thuc t ngt.
Hin c xu hng dng liu cch nht, gim dn, c v "an ton" cho tuyn thng thn
hn. Mt s th d:
. ang ung prednison 40 mg/ ngy: c th dng 80 mg/ ngy, cch nht; gim dn 5 mg
mi tun (hoc gim 10% tng 10 ngy)
. ang dng 5- 10 mg/ ngy: gim 1 mg/ tun
. ang dng 5 mg/ ngy: gim 1 mg/ thng
. Mt phc in hnh cho bnh nhn dng liu prednison duy tr 50 mg/ ngy c th
thay nh sau:
Ngy 1: 50 mg Ngy 7: 75 mg

Ngy 5: 70 mg Ngy 11: 65 mg
v.v...
Mi corticoid dng trong iu tr u l dn xut ca cortisol hay hydrocortison (hormon
thin nhin c OH v tr 11). Bng cch thay i cu trc ca cortisol, ta c th lm tng
rt nhiu tc dng chng vim v thi gian bn thi tr ca thuc, ng thi lm gim kh
nng gi mui v nc.
Cu trc steroid c 4 vng:
- Vng A: khi c thm ng ni kp gia v tr 1 - 2, tc dng chng vim tng v gi

mui gim (prednison, prednisolon).
- Vng B: thm -CH3 v tr 6 (methylprednisolon), ho c F 9 , hoc c 2 v tr 9-
6 (fludrocortison, flucinonid), tc dng chng vim cng mnh v ko di t 1/2. Nhng F
v tr 9 li lm tng tc dng gi Na +
- Vng D: thm -CH3 hay -OH v tr 16 , lm gim mnh kh nng gi mui ca hp
cht 9 F (triamcinolon, dexametason betametason).
V th hin nay c rt nhiu ch phm corticoid mnh v tc dng di. Liu lng v thi
gian dng rt khc nhau. Thy thuc cn lu trnh tai bin cho bnh nhn.
3.7. Dc ng hc
Glucocorticoid hp thu d dng qua ng tiu ha, t 1/2 huyt tng khong t 90 - 300
pht. Trong huyt tng, cortisol gn vi transcortin (90%) v vi albumin (6%). Cortisol
b chuyn ha ch yu gan bng kh ng ni 4 - 5 v kh ceton v tr 3. Thi tr qua
thn di dng sulfo- v glycuro- hp. Tc dng sinh hc (t 1/2 sinh hc) ln hn rt nhiu
so vi t1/2 huyt tng.
Bng 35.1: Lit k mt s corticoid thng dng

Tn thuc Tc dng Tc dng Chuyn t1/2 sinh Liu
chng vim gi Na ha hc tng
ng ng
Tc dng ngn (12h)
Cortison 0,8 0,8 0,8 8- 12 h 25 mg
Hydrocortison 1 1 1 8- 12 h 20 mg
Tc dng trung bnh
(12- 36h)
Prednison 4 0,8 4 12- 36 5
Prednisolon 4 0,8 4 12- 36 5
Metylprednisolon 5 0,5 5 12- 36 4
Triamcinolon 5 0 5 12- 36 4
Tc dng di (36-54 h)
Betametason 25- 30 0 25 36- 54 0,75
Dexametason 25- 30 0 25 36- 54 0,75
Mt s ch phm dng tim c t dc l polyetylen glycol, glysorbat... lm thuc thi tr
rt chm, tu theo bnh v liu lng, c th ch tim 1 tun, 2 tun ho c 1 thng 1 ln,
nh Depomedrol (cha metylprednisolon acetat 40 mg trong 1 mL ), Rotexmedica,
Kenacort (cha triamcinolon acetonid 40 - 80 mg/ mL). Tuy nhin, loi ny thng c
nhiu tc dng ph nh teo da, teo c, xp xng v ri lon ni tit.
4. hormon tuyn sinh dc
4.1. Androgen (testosteron)
Ging nh bung trng, tinh hon va c chc nng sn xut tinh trng (t tinh nguyn
bo v t bo Sertoli, di nh hng ca FSH tuyn yn), va c chc nng ni tit (t
bo Leydig bi tit androgen di nh hng ca LH tuyn yn).
ngi, androgen quan trng nht do tinh hon tit ra l testosteron. Cc androgen khc
l androstenedion, dehydroepiandrosteron u c tc dng yu. Mi ngy c th sn xut
khong 8 mg testosteron. Trong , 95% l do t b o Leydig, cn 5% l do thng thn.
Nng testosteron trong mu ca nam khong 0,6 g/ dL vo sau tui dy th; sau tui
55, nng gim dn. Huyt tng ph n c nng testosteron khong 0,03 g/ dL do
ngun gc t bung trng v thng thn. Khong 65% testosteron trong mu gn vo
sex hormone- binding globulin (TeBG), phn ln s cn li gn vo albumin, ch khong
2% dng t do c kh nng nhp vo t bo gn vo receptor ni bo.
4.1.1. Tc dng
- Lm pht trin tuyn tin lit, ti tinh, c quan sinh dc nam v c tnh sinh dc th
yu.
- i khng vi oestrogen
- Lm tng tng hp protein, pht trin xng, lm cho c th pht trin nhanh khi dy th
(c bp n nang, xng di ra). Sau sn ni b ct ha.
- Kch thch to hng cu, lm tng tng hp heme v globin.
Testosteron khng phi l dng c hot tnh mnh. Ti t bo ch, di tc dng ca 5 -
reductase, n chuyn thnh dihydrotestosteron c hot tnh. C 2 cng gn vo receptor
trong bo tng pht huy tc dng. Trong bnh lng tnh gi, tuy c th vn tit
testosteron bnh thng, nhng t bo ch thiu 5 - reductase hoc thiu protein
receptor vi testosteron v dihydrotestosteron (Griffin, 1982), nn testosteron khng pht
huy c tc dng.
Di tc dng ca aromatase mt s m (m, gan, h khu no), testosteron c th
chuyn thnh estradiol, c vai tr iu ha chc phn sinh dc.
4.1.2. Ch nh
Testosteron v cc mui c sp xp vo bng B
- Chm pht trin c quan sinh dc nam, dy th mun.
- Ri lon kinh nguyt (kinh nhiu, ko di, hnh kinh au, ung th v, tc dng i
khng vi oestrogen.
- Suy nhc c nng, gy yu,.
- Long xng. Dng ring hoc cng vi estrogen.
- Ngi cao tui, nh mt liu php thay th.
Testosteron tim l dung dch tan trong du, c hp thu, chuyn ha v thi tr nhanh
nn km tc dng. Loi ung cng c hp thu nhanh, nhng cng km tc dng v b
chuyn ha nhiu khi qua gan ln u. Cc este ca testosteron (testosteron propionat,
cypionat v enantat) u t phn cc hn, c hp thu t t nn duy tr c tc dng di.
Nhiu androgen tng hp b chuyn ha chm nn c thi gian bn thi di.
* Loi c tc dng hormon:
- Testosteron propionat (hoc acetat): mi ngy tim bp 10 - 25 mg, hoc cch 2- 3 ngy
tim 1 ln 50 mg. Liu ti a mi ngy: 50 mg.
- Metyl- 17 testosteron: 2- 3 ln yu hn testosteron. C th ung. Tt hn l t di li
thm qua nim mc. Liu 5 - 25 mg. Liu ti a 50 mg mt ln, 100 mg mt ngy.
- Testosteron chm:
Dung dch du testosteron onantat: 1 mL = 0,25g. Mi ln tim bp 1 mL.
Hn dch tinh th testosteron isobutyrat: tim bp, di da 50 mg, 15 ngy 1 ln. Vin
testosteron acetat: 0,1g testosteron acetat cy trong c, 1 - 2 thng 1 ln.
* Loi c tc dng ng ha:
Loi ny u l dn cht ca testosteron v methyl - 17- testosteron khng c tc dng

hormon (khng lm nam tnh ha), nhng cn tc dng ng ha mnh: tng ng ha
protid, gi nit v cc mui K +, Na+, phospho... nn lm pht trin c xng, t ng cn (tt
nhin l ch n phi gi c cn i v cc thnh phn, nht l v acid amin)
V cu trc ha hc, cc androgen ng ha khc vi methyl testosteron l hoc mt

methyl C 17, hoc mt ceton C 3, hoc thay i v tr ng ni kp C 4- C5. Th d (xem
cng thc):
Androgen ng ha Liu (gam) Cng thc

Androtanolon 0,01- 0,05 Mt ng kp
Nortestosteron 0,01- 0,025 Thay CH 3 bng C2H5
Metandienon 0,005- 0,02 Thm ni kp 1- 2
Stanozolol 0,004- 0,08 Mt ceton C 3
Ch nh: gy st, tha xng, km n, mi m dy, sau m v cc thuc trn vn cn rt
t tc dng hormon, cho nn khng dng cho tr em di 15 tui.
Thuc cn b lm dng dng cho cc vn ng vin th thao vi liu rt cao, thuc loi
doping, b cm.
4.1.4. Tai bin ca androgen
Liu cao v ko di : gy nam tnh, qu sn tuyn tin lit
mt gan: ngng thuc th ht.
4.1.5. Chng ch nh
- Tr di 15 tui
- Ph n c thai
- Ung th tuyn tin lit (phi dng estrogen)
4.1.6. Tthuc khng androgen
Thuc khng androgen do c ch tng hp hoc i khng tc dng ca androgen ti

receptor. Thuc thng c dng iu tr qu sn hoc carcinom tuyn tin lit, trng
c, hi u ca nam, chng nhiu lng ca n, dy th sm.
4.1.6.1. Thuc c ch 5 reductase: Finasterid
mt s m (tuyn tin lit, nang lng), di tc dng ca 5 reductase, testosteron
mi c chuyn thnh dng hot tnh l dihydrotestosteron. V vy, thuc c ch 5
reductase s c ch chn lc tc dng androgen trn nhng m ny, nhng khng lm
gim nng testosteron v LH huyt tng.
Finasterid c dng iu tr qu sn v u tin lit tuyn vi liu 5 mg/ ngy. Tc dng
sau ung 8 ting v ko di 24 ting. Cn c ch nh cho hi u.
4.1.6.2. Thuc i khng ti receptor
- Cyproteron v cyproteron acetat
Tranh chp vi dihydrotestosteron gn vo receptor ca m ch. Dng acetat cn c
tc dng progesteron, c ch tng tit LH v FSH theo c ch iu ha ngc nn tc
dng khng androgen cng mnh.
Ch nh trong chng rm lng n, trng c. Vi nam, dng iu tr hi, u tuyn tin
lit, dy th sm.
Thuc cn ang c theo di, nh gi.
- Flutamid:
Flutamid l thuc khng androgen khng mang nhn steroid nn trnh c hot tnh
hormon khc. Vo c th, c chuyn thnh 2 hyd roxyflutamid, gn tranh chp vi
dihydrotestosteron ti receptor.
Ch nh trong u tin lit tuyn. Vin nang, 750 mg/ ngy.
4.2. Estrogen
ph n, cc estrogen c sn xut l estradiol (E 2- 17 estradiol), estron (E 1) v
estriol (E 3). Estradiol l sn phm ni tit chnh ca bung trng. Phn ln estron v
estriol u l cht chuyn ha ca estradiol gan hoc m ngoi bin t androstenediol
v cc androgen khc.
ph n bnh thng, nng E 2 trong huyt tng thay i theo chu k kinh nguyt:
giai on u l 50 pg/ mL v thi k tin phng non l 350 - 850 pg/ mL. Trong mu,
E2 gn ch yu vo 2 globulin (SHBG- sex hormone- binding globulin) v mt phn vo
albumin. Ti m ch, n c gii phng ra dng t do, vt qua mng t bo gn vo
receptor ni bo.
4.2.1. Tc dng
- L nguyn nhn chnh ca cc thay i xy ra trong tui dy th con gi v cc c
tnh sinh dc ca ph n (vai tr th yu l androgen; pht trin xng, lng, trng c...).
- C tc dng trc tip lm pht trin v trng thnh m o, t cung, vi trng. Ngoi
tc dng lm pht trin c t cung E 2 cn c vai tr quan trng lm pht trin ni mc t
cung.
- Trn chuyn ha:
. E2 c vai tr c bit duy tr cu trc bnh thng ca da v thnh mch ph n.
. Lm gim tc tiu xng do c tc dng i khng vi PTH ti xng, nhng khng
kch thch to xng.
. Trn chuyn ha lipid: lm tng HDL, lm gim nh LDL, gim cholesterol, nhng lm
tng nh triglycerid.
- Trn ng mu: estrogen lm tng ng mu , do lm tng yu t II, VII, IX v X, lm
gim antithrombin III. Ngoi ra cn lm tng hm lng plasminogen v lm gim s kt
dnh tiu cu.
- Cc tc dng khc: estrogen lm d thot dch t lng mch ra khong gian bo, gy
ph. Khi th tch mu gim, thn s gi Na + v nc, thc y tng hp receptor ca
progesteron.
- Trn nam gii, estrogen liu cao lm teo tinh hon, lm ngng to tinh trng v lm
ngng pht trin, lm teo c quan sinh dc ngoi.
4.2.2. Ch nh
4.2.2.1. L thnh phn ca thuc t rnh thai theo ng ung (xem bi "Thuc trnh
thai").
4.2.2.2. Thay th hormon sau thi k mn kinh
Bung trng gim bi tit estrogen dn dn, ko di vi nm sau khi mn kinh. Nhng
khi ct b bung trng th s c ri lon t ngt, cn dng hormon thay th ngay. Trong
iu tr ri lon sau mn kinh, estrogen c ch nh trong d phng cc biu hin sau:
- Chng long xng: long xng l do mt hydroxyapatit (phc hp calci - phosphat) v
cht c bn protein hoc cht keo (to khung xng), lm x ng mng, yu, d gy t
nhin (ct sng, c xng i, c tay). Estrogen lm gim tiu xng, c tc dng d
phng nhiu hn iu tr chng long xng. Thng dng phi hp vi calci, vitamin D,
biphosphonat.
- Triu chng ri lon vn mch: cn nng b ng, bc ha vi cm gic n lnh, v m
hi, d cm. Estrogen rt c hiu qu.
- D phng bnh tim mch: khi thiu estrogen, d dn n tng cholesterol mu, tng
LDL, s lng receptor LDL ca t bo gim. Tuy nhin, nng HDL, VLDL v
triglycerid t chu nh hng. Nhiu thng k cho thy sau tui mn kinh, bnh tim mch
v nhi mu c tim thng tng nhanh v l nguyn nhn gy t vong. Tuy nhin, dng
estrogen iu tr thay th ch nn mc liu thp, thi gian ngn, trnh nguy c ung
th v.
4.2.2.3. Cc ch nh khc
- Chm pht trin, suy gim bung trng tui dy th
- Tc dng i khng vi androgen: trng c, rm lng n, vim tinh hon do quai b, u
tin lit tuyn. Hin c xu hng dng cc cht tng t GnRH (Leuprolid) c tc dng
c ch tng hp andrrogen.
Estrogen c hiu qu rt tt cho phn ln cc ch nh iu tr. Tuy nhin, mi khi quyt
nh cn cn nhc gia li ch v nguy c cho tng bnh nhn. Nhng nguy c thng
c coi l do estrogen gm ; ung th (v, ni mc t cung), vim tc mch, thay i
chuyn ha ng v lipid, tng huyt p, bnh ti mt (do tng cholesterol trong mt),
bun nn, thay i tnh tnh.
4.2.4. Chng ch nh
- Tuyt i khng dng cho trc tui dy th, khi c thai
- Khi u ph thuc vo estrogen nh carcinom ni mc t cung, v.
- Chy mu ng sinh dc, bnh gan ang trong giai on chn on, c tin s vim tc
mch.
Cc estrogen ch khc nhau v cng tc dng v ng dng do b chuyn ha nhiu
gan. Estradiol l estrogen thin nhin mnh nht sau l estron v estriol. Khi ung, b
chuyn ho qua gan ln th nht nn mt tc dng nhanh. Mt khc, mt cht chuyn ha
quan trng ca n l 2 - hydroxyestron (catechol estrogen) c tc dng nh mt cht dn
truyn thn kinh no. V vy cc ch phm ca estradiol v estron c th gy tc dng
ph trn thn kinh trung ng nhiu hn cc ch phm tng hp.
C 2 nhm ch phm tng hp: nhm c nhn steroid ging estrogen t nhin nh ethinyl
estradiol, mestranol, quinestrol; nhm khng c nhn steroid nh diethylstilbestrol (DES),
mnh ngang estradiol nhng t/2 di), clorotrianisen, methallenestril. Trong mt s cy v
nm, trong mt s thuc tr su tng hp (p p' - DDT) cng c nhiu estrogen khng
mang nhn steroid c hot tnh ging estrogen hoc ngc li, khng estrogen v c cha
vng phenol ging vi vng A ca estrogen l v tr gn vo receptor ca estrogen.
Cc ch phm tng hp c th dng di dng ung, tim, hp thu qua da, bi ti ch. C
dng tc dng ngay, c dng tc dng ko di vi ngy hoc dng gii phng lin tc.
- Estradiol (Estrace)
Ung: vin nn 0,5- 1- 2 mg
Kem bi m o: 0,1 mg/ g
- Estradiol valerat
Dung dch du 10- 20- 40 mg/ ml tim bp
- Estradiol qua da (Estraderm)

Cao dn gii phng hot cht chm thm qua da vi cc tc khc nhau 0,05 -
0,075- 0,1 mg/ ngy.
- Ethinyl estradiol (Estinyl)
Ung: vin nn 0,02- 0,05- 0,5 mg
4.2.6. Cc thuc khng estrogen
Cc thuc khng oestrogen l cc thuc c tc dng i khng vi tc dng sinh hc ca
estrogen. C 2 thuc c dng lm sng:
4.2.6.1. Clomifen (Clomid)
Clomifen citrat l mt cht khng mang nhn steroid.
C ch
Clomifen tranh chp vi oestrogen ni sinh ti cc receptor vng di i v tuyn yn,
i lp vi c ch c ch ngc chiu, v vy lm tng bi tit LHRH ca vng di i
v tng bi tit FSH, LH ca tuyn yn. kt qu l lm tng gii phng oestrogen ca
bung trng. Nu iu tr vo trc giai on phng non, s gy c p hng non.
Ch nh
- Dng chn on d tr gonadotrophin ca tuyn yn
- Dng trong iu tr v sinh do khng phng non.
Cch dng
Clomid vin 50 mg. Liu u tin ung 1 vin/ ngy, ung 5 ngy lin k t ngy th 5
ca chu k kinh.
Nu khng thnh cng, phi i 30 ngy, trc khi bt u t iu tr th hai bng ung
1 hoc 2 vin/ ngy.
4.2.6.2. Tamoxifen (Nolvadex)
Tamoxifen l dn xut ca triphenyl ethylen khng mang nhn steroid.
C ch
Cc thuc ny ngn cn phc hp oestrogen - receptor gn vo v tr tc dng trn ADN
ca t bo ch. V vy, ngn cn s pht trin ca cc khi u ph thuc vo estrogen.
Ch nh
Ung th v ph thuc vo hormon trn ph n mn kinh
Cch dng
- Nolvadex, vin nn 10 v 20 mg
- Liu trung bnh t 20- 40 mg, ung lm 2 ln.
4.3. Progestin
Cc progestin bao gm hormon thin nhin progesteron t c dng trong iu tr,v cc
ch phm tng hp c hot tnh ging progesteron.
Progesteron l progestin quan trng nht ngi. Ngoi tc dng hormon, n cn l cht
tin thn tng hp estrogen, androgen v steroid v thng thn. Progesteron c
tng hp t cholesterol ch yu l vt th vng ca bung trng, sau l tinh hon v
v thng thn. Khi c thai, rau thai tng hp mt s lng ln. na u ca chu k
kinh, mi ngy ch vi mg progesteron c bi tit, sang na sau ca chu k s lng bi
tit tng ti 10- 20 mg/ ngy v vo cui thi k mang thai l vi trm mg. nam l
khong 1- 5 mg/ ngy.
4.3.1. Tc dng
- Trn t cung: progesteron c bi tit nhiu na sau ca chu k kinh (giai on
hong th) s lm chm giai on tng sinh ca ni mc t cung ca estrogen na u
ca chu k v lm pht trin ni mc xut tit, to iu kin cho trng lm t. Cui chu
k kinh, hong th t ngt gim gii phng progesteron l yu t chnh khi pht kinh
nguyt. Khi c thai, progesteron c ch to vng kinh v c ch co bp t cung, c tc
dng gi thai.
- Trn tuyn v: na sau ca chu k kinh v nht l khi c thai, cng vi estrogen,
progesteron lm tng sinh chm nang tuyn v chun b cho vic tit sa. Tri vi
tuyn v, s tng sinh ni mc t cung li xy ra mnh nht l di nh hng ca
estrogen. Cn ghi nh s khc bit ny s dng trong iu tr v nhn nh v tc dng
khng mong mun.
- Trn thn nhit: gia chu k kinh, khi phng non, thn nhit thng tng 0,56 0C v
duy tr cho n ngy thy kinh. C ch chnh xc cn cha r, nhng c vai tr ca
progesteron v h khu no.
- Trn chuyn ha: progesteron kch thch hot t nh ca lipoproteinlipase v lm tng
ng m, lm gim LDH v lm gim tc dng c li ca estrogen trn chuyn ha m.
Tuy nhin, tc dng cn ph thuc vo ch phm, liu lng v ng dng. Progesteron
cng c th lm gim tc dng ca aldosteron trn ng thn, lm gim ti hp thu natri,
do d lm tng bi tit b aldosteron.
4.3.2. Ch nh
Hai ch nh rt thng dng l:
- Phi hp vi estrogen hoc dng ring trong "vin trnh thai" (xem bi "thuc trnh
thai")
- Liu php thay th hormon sau th i k mn kinh. Thng phi hp vi estrogen lm
gim nguy c gy ung th v, t cung.
Ngoi ra, cn dng trong mt s trng hp sau:
- c ch bung trng trong cc triu chng au kinh, chy mu t cung, rm lng, bnh
lc mng trong t cung: dng li u cao theo ng tim (th d medroxyprogesteron acetat
150 mg tim bp cch 90 ngy/ ln)
Trc y, cn dng chng da xy thai do tc dng c ch co bp t cung. Hin khng
dng v c nhiu thuc gin t cung khc tt hn (thuc cng 2, thuc c ch tng hp
prostaglandin ) v prgesteron d c nguy c cho thai ( gy nam ha v d dng sinh dc)
4.3.3. Thn trng v chng ch nh
- C thai
- Tng lipid mu. Progestin trong thuc trnh thai hoc dng mt mnh c th gy tng
huyt p trn mt s bnh nhn.
4.3.4. Cc ch phm
Progesteron thin nhin t dng trong iu tr v b chuyn ha nhanh. Cc progestin tng
hp c chia lm 2 nhm:
- Nhm c 21 carbon c tc dng chn lc cao v ph hot tnh ging vi hormon ni
sinh. Thng c dng phi hp vi estrogen trong iu tr thay th hormon ph n
sau mn kinh.
- Nhm dn xut t 19- nortestosteron (th h 3), khng c C 19, C20 v C 21 do c hot
tnh progestin mnh nhng cn cc tc dng estrogen, androgen v chuyn ha, tuy y u
(lin quan n tc dng khng mong mun) v ung c.
Bng 35.2: Mt s ch phm thng dng

ng Thi gian Hot tnh
dng tc dng Estrogen Androgen Chuyn
ha
Progesteron v dx
- Progesteron tb 1 ngy - - -
-Hydroxyprogesteron
caproat tb 8- 14 ngy -
- Medroxyprogesteron 4 - 12 tun
acetat tb 1- 3 ngy - + -
dx 19- Nortestosteron
- Desogestrel ung 1- 3 ngy - - -
- Norethynadrel ung 1- 3 ngy + - -
- Lynestrenol ung 1- 3 ngy + + +
- L- Norgestrel ung 1- 3 ngy - + +
Ghi ch: tb: tim bp (-): khng c hot tnh
(+): c hot tnh (): hot tnh yu
4.4. Thuc khng progestin
Mifepriston
c dng u tin Php vo nm 1988
Mifepriston l dn xut ca 19 - norprogestin, gn mnh vo receptor ca progesteron.
Nu c mt progestin, mifepriston tc dng nh mt cht i khng tranh chp ti
receptor, nu tc dng mt mnh th mifepriston li c tc dng nh progestin, nhng yu
(ng vn mt phn- partial agonist)
Dng vo giai on sm ca thai k, mifepriston lm bong mng rng do phong ta cc
receptor progesteron ca t cung, dn n bong ti mm (blastocyst), lm gim sn xut
choriogonadotropin (CG). Chnh nhng tc dng ny s lm hong th gim tit
progesteron, cng lm bong thm mng rng. Progesteron gim lm tng sn xut
prostaglandin ti t cung, gy co bp t cung v sy thai.
Mifepriston cng c dng trnh th thai sau giao hp do ngn cn trng lm t. Tc
dng c th cn hn c thuc phi hp estrogen proge stin liu cao.
Ngoi ra mifepriston cn c dng y thai cht lu trong t cung, bnh lc mng
trong t cung. Ung th v, u c trn (leiomyomas)
Cc thuc loi ny c dng t khong 1998 - 2000 v cn cn theo di lm sng.
Gy sy thai trong qu u bng cho ung ung 400 - 600 mg/ ngy 4 ngy; hoc 800
mg/ ngy 2 ngy. Kt qu ti 85%. Nu ung 1 liu 600 mg mifepriston, sau 48h cho
ung hoc t m o misoprostol (tng t PGE 1), kt qu sy thai c th ti 95%.
5. Thuc trnh thai
5.1.C s sinh l
Trong na u chu k kinh nguyt, di tc dng ca hormon gii phng FSH (FSH - RH)
ca vng di i, tuyn yn bi tit FSH, lm cho nang trng trng thnh, tit foliculin
(oestrogen). Sau , vng di i tit hormon gii phng LH (LH - RH), lm tuyn yn
bi tit LH, n ngy th 14, khi FSH/LH t c t l thch hp th bung trng s

phng non. Nu gp tinh trng, trng s th tinh v lm t.
5.2. Cc loi thuc chnh
5.2.1. Thuc trnh thai phi hp
Phi hp oestrogen v progesteron t ng hp. Cc loi thuc ny u dng estrogen l
ethinylestradiol. Nhng thuc c cha 50 g ethinyl estradiol u c gi l chun
(standard) phn bit vi loi liu thp (minidosage) ch cha 30 - 40 g ethinyl
estradiol. Hm lng v bn cht ca progesteron phi hp th thay i theo tng loi,
phn ln l 19 nortestosteron.
Ngoi ra cn phn bit loi 1 pha (monophasic pills) l loi c hm lng hormon khng
i trong sut chu k kinh, loi 2 v 3 pha (diphasic, triphasic pills) c hm lng
progesteron tng dn trong khi hm lng estrogen khng thay i hoc hi tng vo gia
chu k kinh. Loi 2 hoc 3 pha c tng lng progesteron thp hn loi 1 pha.
- Tc dng trung ng: theo c ch iu ha ngc chiu, estroge n c ch bi tit FSH-
RH v LH- RH, tuyn yn s gim tit FSH v LH, do khng t c nng v t l
thch hp cho s phng non, cc nang bo km pht trin.
- Tc dng ngoi bin: lm thay i dch nhy ca c t cung, tinh trng kh hot ng,
ng thi lm nim mc ni mc t cung km pht trin, trng khng lm t c.
+ Tc dng ca estrogen vi nhng liu t 50 - 100 g cho t ngy th 5 ca chu l kinh
l c ch phng non. Trn bung trng, lm ngng pht trin nang trng: trn ni
mc t cung, lm qu sn nim mc cho nn l nguyn nhn ca rong kinh: trn t cung,
lm tng tit cc tuyn: trn m o, lm dy thnh v trc vy. Nhng thay i ny lm
d nhim candida v trichomonas.
+ Tc dng ca progesteron: trn bung trng lm n gng pht trin, gim th tch: trn
ni mc t cung, lm teo: t cung mm, c t cung t bi tit, lm dch tit nhy hn, tinh
trng kh chuyn ng. Gy mc lng, tng cn.
Do nhng bt li ca tng hormon, nn thng dng phi hp hai th cng mt lc, hoc
ni tip nhau, c hai u c gim liu. S phi hp m bo cho t cung, m o t thay
i so vi bnh thng.
Sau ngng thuc, chu k bnh thng tr li ti 98% trng hp.
5.2.1.2. Cc tc dng dc l
Trn bung trng: c ch chc phn ca bu ng trng, nang trng khng pht trin v khi
dng lu, bung trng nh dn.
Sau khi ngng thuc, khong 75% s li phng non trong chu k u v 97% trong chu
k th 3, khong 2% vn gi v kinh sau vi nm.
Trn t cung: sau thi gian di dng thuc c t h c qu sn t cung v hnh thnh polyp.
Cc thuc c cha 19 nor progestin v t estrogen s lm teo tuyn nhiu hn v thng

t chy mu.
Trn v: thuc cha estrogen thng gy kch thch, n v.
Trn mu: xy ra huyt khi tc mch. C th l d o tng cc yu t ng mu II, VII,
IX, X v lm gim antithrombin III.
Nhiu ngi b thiu acid folic.
Trn chuyn ha lipid: estrogen lm tng triglycerid, tng cholesterol este ha v
cholesterol t do, tng phospholipid, tng HDL. Cn LDL li thng gim.
Chuyn ha ng: ging nh ngi mang thai, gim hp thu ng qua tiu ha.
Progesteron lm tng mc insulin c s.
Da: lm tng sc t da i khi tng b nhn, trng c (do progestin). Tuy nhin, v
androgen ca bung trng gim nn nhiu ngi c gim b nhn, trng c v pht trin
tc.
Loi nh:
- Bun nn, au v, kinh nhiu, ph do estrogen trong thuc. Thay thuc c t estrogen
hn hoc nhiu progesteron.
- Nhc u nh, thong qua. i khi c migren. Thay th uc.
- V kinh i khi xy ra, lm nhm vi c thai. Thay thuc.
Loi trung bnh:
Cn ngng thuc.
- Kinh nhiu: thay bng loi 2 - 3 pha, lng hormon t hn.
- Tng cn
- Da sm mu: khong 5% sau mt nm v 40% sau 8 nm dng thuc.
- Thiu vitamin B cng lm tng mu da. Phc hi chm khi ngng thuc.
- Trng c: vi ch phm cha nhiu androgen.
- Rm lng: ch phm c 19 nortestosteron.
- Nhim khun m o: thng gp v kh iu tr.
- V kinh: t gp, 95% phc hi sau ngng thuc.
Loi nng:
- Huyt khi tc mch, vim tc tnh mch: khong 1/1000
- Nhi mu c tim: d gp ngi bo c tin s tin sn git tng huyt p, tng lipid
mu, i tho ng, ht thuc. Tai bin thng gim i nhng ngi dng thuc
khng lin tc.
- Bnh mch no: d gp ngi trn 35 tui vi t l 37 ca/ 100.000 ngi/ nm.
- Trm cm, i hi phi ngng thuc khong 6%.
- Ung th: cha c mi lin quan vi dng thuc.
5.2.1.4. Chng ch nh
Cao huyt p, cc bnh v mch mu (nh vim tc mch) vim gan, ung th v- t cung,
i tho ng, bo bu, ph n trn 40 tui (v d c tai bin v mch u).
Lm gim tc dng chng th thai
- Cc thuc gy cm ng enzym chuyn ha thuc gan, lm tng ging ha oestrogen
v progesteron: Rifampici n, phenytoin, phenobarbital.
- Cc thuc lm thay i vi khun ng rut, tng thi tr oestrogen -progesteron qua
phn: ampicilin, neomycin, tetracyclin, penicilin, cloramphenicol, nitrofuratoin.
Lm tng c tnh i vi gan ca thuc chng th thai
Cc thuc chng trm cm loi 3 vng, IMAO, troleandromycin
5.2.1.6. Ch phm
C rt nhiu loi. Th d:
- Marvelon 21: vin c Desogestrel 150 mcg + Ethinylestradiol 30 mcg.
Mi v c 21 vin thuc + 7 vin khng thuc
- Nordette: mi vin c Levonorgestrel 1 50 mcg + Ethinylestradiol 30 mcg.
- Rigevidon 21 + 7 v Rigevidon 21 + 7 Fe (st: Fe fumarat 25 mg): mi vin c
Levonnorgestrel 150 mcg + Ethinylestradiol 30 mcg.
- Tri- regol:
Hot cht 6 vin vng 5 vin m chn 10 vin trng
Levonorgestrel 0,05 mg 0,075 mg 0,125 mg
Ethinylestradiol 0,03 mg 0,04 mg 0,03 mg
T ngy th 5 sau kinh, vin vng ung trc, sau n vin mu m chn ri vin trng.
Nu khong cch gia hai vin trn 36 gi th khng an ton.
Thuc thng ng thnh v 21 vin c hot cht + 7 vin khng c hot cht ung
theo th t, mi ngy ung 1 vin vo bui chiu sau ba n. Ngy bt u thy kinh, tnh
l ngy th nht, nu vng kinh l 28 ngy.
Nu hm trc qun, th hm sau ung b. Nu gin on qu 36 gi, tc dng khng

m bo.
5.2.2. Thuc trnh thai c progesteron n thun
5.2.2.1 C ch
Do ch c progesteron, nn tc dng ch yu l ngoi bin: thay i dch nhy c t
cung v lm km pht trin nim mc ni mc t cung. Hiu qu trnh thai khng bng
thuc phi hp.
Hiu lc ch c sau 15 ngy dng thuc, v ch m bo nu ung u, khng qun.
Thng dng cho ph n c bnh gan, tng huyt p, c vim tc mch. Chm kinh,
bnh tm thn.
5.2.2.2. Tai bin
- Do khng c oestrogen nn khng c tai bin tim mch
- Ri lon kinh nguyt. Thng xy ra trong nm u, l nguyn nhn gy b thuc. Dn
dn kinh nguyt s tr v bnh thng sau 1 nm.
- Nhc u, chng mt, ph, tng cn.
5.2.2.3. Chng ch nh
Do thuc c tc dng lm kh nim mc dch m o, cho nn khng dng cho ph n
di 40 tui.
5.2.2.4. Ch phm v cch dng
Tt c u l loi norsteroid
Loi liu cao:
Dng khng lin tc, ung t ngy th 5 n ngy th 25 ca chu k, c dng cho
nhng ph n c tai bin mch, hoc ph n trn 50 tui, tai b in v mch thng cao.
- Khng dng cho ngi c cao huyt p, i tho ng hoc c lipid mu cao.
- Cc ch phm: Lynesterol, Orgametrin vin 5 mg, ung 2 vin/ ngy.
Loi liu thp
Dng lin tc hng ngy, ngay c khi thy kinh. Ch nh cho nhng ng i khng dng
c oestrogen, hoc c chng ch nh vi thuc trnh thai loi phi hp.
Cc ch phm
. Norgesstrel (Microval) vin 0,03 mg. Ung 1 vin/ ngy
. Lynestrenol (Exluton) vin 0,5 mg. Ngy u thy kinh bt u ung, ung lin tc 28
ngy.
Cc thuc khc
- Cc polyme tng hp, cc vi nang silastic c mang thuc chng th thai c cy, ghp
vo c th, c th gii phng mt lng thuc n nh vo mu sut trong 6 thng.
- Cc loi kem v thuc si bt c tc dng ti ch, dng bi vo cc mng ngn hoc
bm vo m o trc khi giao hp dit tinh trng.
- Ortho- crem; c acid ricinoleic, acid boric v lauryl natri sulfat.
- Nonoxynol- 9: cha nonylphenoxy- polytoxyetanol.
Thuc trnh thai dng cho nam gii
Thuc c ch sn xut tinh trng: t uy c nhiu hng nghin cu, nhng cho ti nay cha
c mt thuc no c hiu qu v an ton.
5.2.3. Thuc trnh thai sau giao hp. Cn gi l vin trnh thai khn cp
Dng thuc phi hp hoc mt mnh estrogen trong vng 72 gi c hiu qu ti 99%.
Ethinyl estradiol 2,5 mg 2 ln/ ngy 5 ngy; Diethylstilbestrol 50 mg/ ngy 5 ngy:
Norgestrel 0,5 mg ethinyl estradiol 0,05 mg 2 vin 2 ln/ 2 gi.
Thuc c th tc dng theo nhiu c ch: c ch hoc lm chm phng non; lm ni mc
t cung khng tip nhn c trng; sn xut dch nhy c t cung, lm gim s xm
nhp ca tinh trng; cn tr s di chuyn ca tinh trng, trng trong vi t cung.
Tc dng ph 40% bun nn v nn (dng km thuc chng nn) nhc u, chngmt,
cng v, au bng, chut rt . V phi dng liu cao nn c nhiu tc dng ph, trnh s
dng rng ri (FDA ca M khng cho dng).
. Postinor (thuc c dng Vit nam). Mi vin cha Levononorgestrel (progesteron)
0,75 mg. Dng cho ph n giao hp khng c k hoch. Nu c giao h p thng xuyn,
nn dng loi thuc phi hp.
Liu dng: ung 1 vin trong vng 1 gi sau giao hp. Nu c giao hp li, ung thm 1
vin sau vin u 8 gi. Ni chung, hng thng ung khng qu 4 vin.
Chng ch nh: ang c thai hoc nghi ng c thai, chy mu m o cha r nguyn
nhn, bnh gan- thn, c tin s carxinom v, bung trng hoc t cung.
Li ch khng lin quan n tc dng trnh thai
Sau hng chc nm dng thuc trnh thai phi hp, ngoi hiu qu trnh thai cao (ti 98 -
99%), ngi ta cn nhn thy 1 s li ch sau ca thuc:
- Lm gim nguy c u nang bung trng, ung th bung trng v ni mc t cung sau 6
thng dng thuc. Sau 2 nm dng thuc t l mi mc gim ti 50%.
- Lm gim u lnh tnh tuyn v.
- Lm gim cc bnh vim nhim vng h chu.
- iu ha c kinh nguyt, lm gim mt mu khi thy kinh, do gim c t l
thiu mu thiu st.
- Gim c t l lot tiu ha, vim khp dng thp, ci thin c trng c, rm lng.
cu hi t lng gi
1. Trnh by tc dng sinh l ca T3- T4 v p dng iu tr.
2. Trnh by c ch tc dng v p dng iu tr ca thuc khng gip trng tng
hp.
3. Trnh by tc dng v c ch tc dng ca insulin
4. Phn tch cc tc dng sinh l, tai bin, cch theo di v phng tai bin ca
glucocorticoid.
5. Phn tch v so snh tc dng chng vim ca steroid (glucocorticoid) v thuc
chng vim khng phi steroid.
6. Trnh by c ch tc dng chng d ng v c ch min dch ca glucocorticoid.
7. Gii thch v cc ch nh v chng ch nh ca glucocortico id.
8. Trnh by v nhng im cn ch khi dng glucocorticoid.
9. Trnh by ch nh v chng ch nh ca testosteron.
10. Da vo tc dng sinh l ca estrogen, phn tch ch nh v chng ch nh ca
estrogen.
11. Phn tch c ch tc dng v p dng lm sng ca thuc khng estrogen clomifen
v tamoxifen.
12. Da vo tc dng sinh l, phn tch ch nh v chng ch nh ca progesteron.
13. Trnh by c ch tc dng v p dng lm sng ca thuc khng progesteron:
mifepriston.
14. Trnh by c ch tc dng ca thuc trnh t hai phi hp. Cc loi thuc phihp?
15. Phn tch c ch tc dng, u nhc im ca thuc trnh thai c progesteron n
thun.
Bi 36: iu tr ng c thuc cp tnh

1. Trnh by c nguyn tc loi tr cht c ra khi c th
2. Gii thch c nguyn tc trung ha cht c trong c th
3. Trnh by c nguyn tc iu tr triu chng v hi sc trong ng c thuc
Ng c thuc thng l do nhm ln (ca thy thuc, ca ngi bnh) hoc do c (t

t, u c). Nhng trng hp nhm ln thng khng nng lm, v c chn on
ng v sm nn x l kp thi. Cn nhn g trng hp c th thng rt nng v nn
nhn che giu tn thuc dng, liu thuc nhim c li qu ln v lc a n iu tr
thng mun, cho nn chn on kh khn, x tr nhiu khi phi m mm.
Ch c rt t thuc c triu chng ng c c hiu v cch iu tr c hiu. V vy, cc
x tr ng c thuc ni chung l loi tr nhanh chng cht c ra khi c th, trung ha
phn thuc c hp thu v iu tr cc triu chng nhm hi sc cho nn nhn.
1. Loi tr cht c ra khi c th
1.1. Qua ng tiu ha
- Gy nn: Apomorphin hin khng dng v nhiu tc dng ph
- Ipeca: Dng di dng siro t 15 - 20 ml, pha long trong 250 ml nc. Nu sau 15 pht
khng nn, c th dng li. Thng dng cho tr em trn 1 tui.
Trong trng hp khng c thuc, nn nhn cn tnh, c th ngoy hng hoc dng mn
tht cho ung.
- Ra d dy bng nc m hoc thuc tm (KMnO 4) dung dch mt phn nghn (1: 1000
)cho n khi nc ra tr thnh trong.
Vi cc thuc hp thu nhanh nh aspirin, cloroquin, meprobamat, bar bituric, colchicin,
thuc chng rung tim, ra d dy v gy nn ch c tc dng trong 6 gi u, khi cht
trng c cn d dy. i vi loi benzodiazepin, thuc chng rung tim, hoc nhim
c hn hp, hoc nhng cht khng r, c th ra trong vng 24 g i.
Dng thn trng khi nn nhn hn m v d a nhm ng cao su vo kh qun, hoc
cht nn quay ngc ng v ph. Tuyt i trnh ra d dy cho nhng ngi b trng
c cc cht n mn nh acid mnh, base, v ng cao su c th lm rch thc qun.
Sau ra d dy, cho than hot, v c nhiu u im: Hon ton khng c, ngn cn c
chu k gan- rut i vi cc thuc thi theo ng mt, do tng thi theo phn.
Liu 50- 100g. Mt trm gam than hot c th hp ph c 4 g thuc chng trm cm
loi tricyclic. Thng cho 30- 40 g, cch 4 gi 1 ln.
1.2. Qua ng h hp
Ng c cc thuc thi qua ng h hp nh cc thuc m bay hi, ru, kh t, xng,
aceton..., cn lm tng h hp bng cc thuc kch thch nh cardiazol (tim tnh mch
ng 5 ml, dung dch 10%), lobelin (tim tnh mch ng 1 ml, dung dch 1%), hoc h hp
nhn to.
1.3. Qua ng tit niu
1.3.1. Thng dng cc thuc li niu thm thu
Nh manitol (10%; 25%), glucose u trng (10%; 30%), dung dch Ringer. Phi chc
chn rng chc phn thn cn tt. Khng c dng khi c suy thn, suy tim, ph phi
cp, huyt p cao, try tim mch nng.
Khi dng cc thuc li niu ny th cc khng sinh cng b tng thi, cho nn cn phi
nng liu cao hn.
1.3.2. Kim ho nc tiu
Trong trng hp ng c cc acid n h (barbituric, salicylat, dn xut pyrazolol).
Thngdng hai th:
- Natri bicarbonat (NaHCO 3): Dung dch 14%0, truyn nh git tnh mch 2 - 3 lt mt
ngy. Nhng c nhc im l a thm Na + vo c th, v vy khi chc phn thn khng
c tt, d gy tai bin ph no.
- T.H.A.M. (trihydroxymetylaminmetan), truyn tnh mch 300 - 500 ml.
HO- H2C HO- H2C

+
HO- H2C C NH2 + H HO- H2C C- + NH3
HO- H2C HO- H2C
THAM c u im l khng mang Na + v d thm vo c trong t bo.

1.3.3. Acid ha nc tiu
lm tng thi cc base hu c nh cloroquin, dn xut quinolein, imipramin,
mecamylamin, dn xut acridin, nicotin, procain, quinin, phenothiazin.
Cc thuc lm acid ha nc tiu thng dng l amoni alorid ung 3,0 - 6,0g hoc acid
phosphoric 15- 100 git mt ngy.
Acid ha kh thc hin hn kim ha v c th chu ng tnh trng toan km hn trng
thi nhim kim, cho nn cng d gy nguy him.
2. Trung ha cht c
Thng dng cc cht tng k ngn cn hp thu cht c, lm mt hot tnh hoc i
khng vi tc dng ca cht c.
2.1. Cc cht tng k ha hc ti d dy
ngn cn hp th cht c, thng dng ra d dy bng cc dung dch:

- Tanin 1- 2%: 100- 200 ml (c th thay th bng nc ch c), c tc dng lm kt ta
mt s alcaloid v kim loi nh strychnin, calcaloid ca cy quinquina, apomorphin,
cocain, mui km, coban, ng, thu ngn, ch...
- Sa, lng trng trng (6 qu cho 1 lt nc) ngn cn hp thu cc mui thy ngn,
phenol.
- Than hot (nh dch 2%), hoc bt go r ang chy, kaolin c tc dng hp ph cc cht
c nh HgCl 2 (sublim), strycnin, morphin... Than hot cn hp ph mnh c cc cht
mang in tch dng cng nh m, cho nn c th dng c trong hu ht cc trng
hp nhim c ng tiu ha.
2.2. Cc cht tng k ha hc dng ng ton thn
- To methemoglobin (bng natri nitrit 3% - 10ml) khi b ng c acid cyanhydric (thng
gp trong ng c sn). Acid cyanhydric rt c i lc vi cytocrom oxydase (c Fe +++) l
cc enzym h hp ca m. Khi b ng c, c c enzym ny b c ch. Nhng acid
cyanhydric li c i lc mnh hn vi Fe +++ ca methemoglobin, nn khi gy c
methemoglobin, acid cyanhydric s hp vi methemoglobin to thnh
cyanomethemoglobin v gii phng cytochrom - oxydase.
- Dng B.A.L. khi b ng c cc kim loi nng nh Hg, As, Pb.
- Dng EDTA hoc mui Na v calci ca acid ny khi b ng c cc ion ha tr 2: Ch,
st, mangan, crm, ng v digitalis ( thi tr calci).
2.3. S dng cc thuc i khng dc l c hiu
Dng naloxon tim tnh mch khi b ng c morphin v cc opiat khc; dng vitamin K
liu cao khi ng c dicumarol; truyn tnh mch dung dch glucose khi b ng c
insulin... Phng php ny dng iu tr c hiu qu nhanh v tt, nhng ch c rt t
thuc c tc dng i khng d c l c hiu, cho nn phn ln phi iu tr theo triu
chng.
3. iu tr triu chng v hi sc cho ngi bnh
3.1. p dng i khng sinh l

Dng thuc kch thch thn kinh khi ng c cc thuc c ch (dng bemegrid,
amphetamin khi ng c barbiturat), dng thuc lm mm c khi ng c cc thuc co
git (dng cura khi ng c strrynin)..., hoc ngc li, dng barbiturat khi ng c
amphetamin, long no, cardiazol.
Phng php ny khng tt lm v thuc i khng cng phi dng vi liu cao, thng l
liu c, cho nn c hi i vi nn nhn.
3.2. Hi sc cho ngi bnh
- Tr tim, gi huyt p, chng try tim mch: Dng cc thuc tr tim thng thng,
noradrenalin 1- 4 mg ha trong 500- 1000ml dung dch glucose ng trng, truyn nh
git tnh mch. C th dng D.O.C dung dch du 1- 5 mg tim bp.
- Tr h hp: Cc thuc kch thch h hp (cardiazol, cafein), h hp nhn to, th oxy.
- Thm phn phc mc hoc thn nhn to: Ch dng trong trng hp nhim c nng,
thn suy, cc phng php iu tr thng th ng khng mang li kt qu, hoc cc
trng hp chng ch nh dng cc thuc li niu thm thu. Thng gp ng c kim
loi nng, sulfonamid liu cao, barbiturat liu cao.
- Thay mu c ch nh trong cc trng hp:
. Nhim c phospho trng: Phi l m trc 8 gi mi c kh nng cu c nn nhn.
. Nhim c vi liu cht: Cc thuc chng st rt, cht c t bo, isoniazid, dn xut
salicylat (nht l vi tr em).
. Cc cht lm tan mu: Saponin, sulfon...
. Cc cht gy methemoglobin: Phenacetin, anilin, nitrit, cloroquin... C th iu tr bng
xanh methylen ng 1%- 10 ml ha trong 500 ml dung dch glucose ng trng truyn
nh git tnh mch; hoc tim tnh mch vitamin C 4,0 - 6,0g trong 24 gi. Khi khng c
kt qu th thay mu.
Cn phi sm v khi lng mu thay th phi c nhiu (t nht l 7 lt). Nu hm sau
mu cn cha nhiu hemoglobin ha tan th c th phi truyn li.
3.3. Cng tc chm sc ngi bnh
- Ch dinh dng: Cho n cc thuc n nh, d tiu, calo, hoc truyn hu mn n u
c tn thng thc qun (nhim c acid). Cn cho thm nhiu vitamin, c bit l
vitamin B, C; cho thm insulin khi phi truyn nhiu ng (ose):
- Cc khng sinh phng nhim khun th pht.
- Lm tt cng tc h l: Ht m, ri, v sinh chng lot ...
3.4. Bng k mt s thuc trng c thng gp v cch iu tr
Trong bng ny ch k mt s thuc thng gy c v cc thuc c tc dng iu tr c
hiu. Ngoi nhng thuc iu tr ny cn phi hp thm cc thuc v phng php hi
sinh tng hp tu theo tnh trng trng c.
Nhng thuc khng k trong bng ny, khi trng c phn nhiu l ch iu tr triu
chng kt hp vi hi sc.
Thuc ng c Thuc gii c chnh Trnh by Liu lng v cch dng

Aspirin (Nhm - Na bicarbonat Dung dch 12,5%o - Truyn nh git t/m 1,5- 3,0g mt ngy,
salicylat) nu c toan huyt.
- Vitamin K ng 1ml = 0,05g - Tim t/m hoc tim bp 4 ng/ ngy
- Cc dung dch b - B nc, Na +, K+, glucose tu theo tnh
nc Na, K +, glucose trng bnh.
Barbiturat - Natri bicarbonat - Dung dch 12,5%o Truyn nh git tnh mch 1,5 - 3,0 lt /
- Cc thuc v phng ngy
php hi sinh tng hp.
Benzodiazepin Flumazenil (Anexate) ng 5 ml = 0,5 mg Tim t/m liu u 0,3 mg nu cha tnh,
sau mi pht tim nhc li liu ti a l 2
mg.
Cloroquin - Adrenalin ng 1ml= 1 mg - Tim t/m 0,25 mcg/ kg/ pht.
Nivaquin - Diazepam ng 2ml= 10 mg - Truyn t/m 2mg/ kg trong 30 pht, sau
(Amino 4 1- 2 mg/ kg/ ngy trong 48 gi...
quinolein)
Curare loi - Prostigmin v cc loi ng 0,5 mg Tim t/m tng liu 0,5 mg, khng vt qu
tranh chp vi phong to 3,0 mg (c th tim trc 1mg atropin
acetylcholin cholinesterase ngn cn tc dng ca prostigmin trn h
M)
C c dc - Pilocarpin ng bt 0,1g - Tim di da 10 mg mt ln cho ti khi
(belladon) v c nc bt
cc ch phm - Tanin 1- 2% - Ung 100 ml
c atropin
Ch EDTA calci ng 10 ml = 0,5g - 1,0g ha trong 500 ml dung dch glucose
ng trng truyn nh git tnh mch.
Cht sinh Xanh methylen ng 1% = 10 ml - Pha 1 ng trong 500 ml dung dch
methemoglobin glucose ng trng truyn nh git tnh
mch
Vitamin C ng 0,1g - Tim t/m 4,0- 6,0g/ 24 gi
Thuc ng c Thuc gii c chnh Trnh by Liu lng v cch dng

Cht phong ta Contrathion (P.A.M) L 200 mg - Truyn t/m dung dch c 400 mg
cholinesterase contrathion ha trong 25 ml NaCL 9%o
mi pht 1 ml
Atropin ng 1 mg - Tim t/m tng mg.
Digitalin EDTA natri ng 10 ml = 0,2g - 3,0g ha trong 250 ml dung dch glucose
ng trng truyn tnh mch trong 30
pht.
KCl - Truyn nh git tnh mch 20 - 40 mEq/
gi
Tng liu 120 mEq.
Isoniazid v - Vitamin B 6 ng 2ml = 0,05g - Tim bp hoc t/m mi ngy 50 - 500 mg.
IMAO C th ti vi gam.
- Diazepam ng 2ml= 10 mg - Tim chm t/m 1- 2 ng nu c co git
Khng filic Acid folic ng 1 ml= 2,5g - Tim bp 3- 6 mg mt ngy
Khng Vitamin K 1 ng 1 ml = 0,5g - Tim tnh mch hoc tim bp 4 - 6 ng
protrombin mt ngy.
Kim loi nng B.A.L ng 2 ml = 200 mg - 2- 3 mg/ kg cho mt ln tim bp. Ngy
(As, Au, Hg) th nht v 2, cch 4 gi tim mt ln;
ngy th 3, cch 6 gi; nhng ngy sau, 2
ln trong 1 ngy.
Morphin v cc - Naloxon 0,4 mg - Tim bp 0,4- 0,6 mg
opiat khc - Naltrexon
- Tanin Dung dch 1- 2% - Ung 100ml
- Thuc tm Dung dch 1%o - Ra d dy
Muscarin (nm Atropin ng1/4 mg hoc 1 - Tim di da hoc tnh mch tng liu
c) mg 0,5- 1,0 mg
Phong ta - Atropin ng 1 mg - Tim tnh mch 1- 2 ng

adrenergic - Glucagon ng 1 mg - Tim bp hoc tnh mch 1 - 2 ng duy
tr co bp tim
Phospho - Thuc tm Dung dch 1%o - Ra d dy
- ng sulfat Dung dch 0,5% - Ra d dy 500 ml
- Nc oxy gi Dung dch 1% - Ung nhiu ln trong ngy
Quinidin - Natri lactat L 250- 500 ml Truyn t/m 250 ml trong 30 pht
Nhc li nu cn
Strychnin - Barbiturat - Barbital - Dng cho ti khi xut hin ng
phenobarbital
- Nesdonal
- Curare - Remyolan ng 5 - Tim t/m tng liu 50 - 100 mg ti khi
ml = 0,1g khng cn co git
Cyanur (acid - Natri nitrit - Dung dch 2% - Tim chm t/m 10- 20 ml
cyanhydric) - Natri hyposulfit - ng 10 ml = 1,0g - Tim chm t/m 30- 50 ml
4. Mt s thuc c hiu dng trong nhim c

4.1. Dimercaprol
Trong chin tranh th gii th hai, Anh nghin cu cc cht chng li cht c ha
hc cha hi asen, tm ra dimercaprol. Do dimercaprol cn gi l British- anti-
Lewisite (vit tt l B.A.L).
4.1.1. Cu trc ha hc v l ha tnh
Dimercaprol l 2, 3- dimercaptopropanol:
L cht lng snh, khng mu, mi kh chu, tan trong du thc vt, trong ru v cc
cht ha tan hu c khc.
Dimercaprol ngn nga c tnh ca nhng phc hp thiol - kim loi, bng cch phn ng
vi kim loi hnh thnh phc hp dimercaprol - kim loi, ng thi gii phng h
enzym c thiol; nh trong ng c asen, dimercaprol tc dng vi asen theo cch sau:
S _ Pr HS _ CH2
R _ As S _
CH2
_
S Pr _
HS CH R As _

S _
CH + 2Pr _ SH
_
HO CH2
_
HO CH2 Enym cha SH
B.A.L
Dng kt hp cht asen Phc hp dimercaprol v hp cht
vi enzym cha - SH asen tan trong nc, thi
theo nc tiu
Kh nng to chelat ca dimercaprol thay i tu tng kim loi, mnh nht vi thu ngn,
mui vng v na kim loi nh asen.
Ngoi tc dng ln h enzym cha nhm - SH, dimercaprol cn tc dng trc tip ln cc
enzym c hot ha bi cc ion kim loi nh: Catalase, anhydrase carbonic, peroxydase.
4.1.3. Tc dng ph ca dimercaprol
- Nhc u, bun nn, nn, au bng
- Tng huyt p, tim p nhanh.
- Bong tm thi cc nim mc, vim kt mc, chy nc mi, tng tit nc bt.
- au c v vng sau xng c
- Kh chu im tim, i khi p xe.
- tr em, st, gim bch cu, i khi co git
- c ch chc nng ca tuyn gip trong trng h p dng ko di.
- Thiu mu tan mu trong trng hp thiu G 6PD.
4.1.4. Ch nh, liu lng
Dng trong iu tr ng c asen, thu ngn, mui vng. N cng c gi tr nh mt cht
b tr cho CaNa 2 EDTA trong ng c ch v cho penicilamin trong bnh Wilson. t hiu
lc trong nhim c bismuth, tali, ng, crm v nicken.
- Tm tnh cm th ca ngi bnh: Ln tim u tin 50 mg.
- Ng c cp: cch 4 gi tim 4 mg/ kg cho 48 gi u, ri 3 mg/ kg 2 ln mt ngy
trong 8 ngy (liu ti a 5 mg/ kg/ ngy).
- Ng c mn: cch 4 gi tim 2,5 mg/ kg cho 48 gi u, ri 2,5 mg/ kg 1 ln mt ngy
trong 10- 15 ngy.
- Tim bp su, mi ln tim, chuyn ch tim; dng bm tim bng thu tinh.
- Kim ha nc tiu trong thi gian iu tr ( bo v thn i vi tc dng c ca
nhng kim loi c gii phng).
4.2. EDTA calci dinatri v EDTA dinatri
4.2.1. EDTA dinatri (Na 2 EDTA)
4.2.1.1. Tc dng
Tc nhn chelat khng c calci, khi vo c th to phc d dng vi calci. Thi qua thn
di dng chelat ca calci: 72% thi qua nc tiu trong 2 4 gi.
4.2.1.2. Ch nh: Dng iu tr nhng trng hp qu ti calci:
- Da: Bnh cng b, hi chng Thibierge - Weissenbach.
- Mu: Tng calci- mu.
4.2.1.3. Chng ch nh: Suy thn nng

4.2.1.4. Cch dng v liu lng:
ng tim 10 ml, dung dch tim 5%.
Ch dng trong nhng trng hp cp, 1- 2 ng tim c ha long trong dung dch
huyt thanh mn hay ngt ng trng, truyn nh git tnh mch rt chm trong ngy
( trnh him ha bnh tetani). Mt t iu tr trong 5 ngy v gia nhng ngy phi
c theo di, c thi gian ngh 7 ngy.
Vin bc ng: 0,25g
Dng cho iu tr ngoi tr v liu duy tr t 6 - 8 vin bc ng/ ngy.
Liu dng: 5 ngy/ tun l.
4.2.2. EDTA calci dinatri
4.2.2.1. Tc dng
EDTA l ethylendiamin tetra acetic acid. Thng dng mui dinatra (Na 2EDTA, dinatri
edetat) lm tan nc, c kh nng gp (chelate) calci. Nhng Na 2EDTA gy tetani
do h calci mu, nn khi ng c kim loi ha tr 2 hoc 3 (ch, ng, st, coban, cadimi,
cht phng x) th dng dinatri calci edetat (CaNa 2EDTA) s to thnh nhng ph c bn,
mt ton b hot tnh ion v c tnh ca n v khng b tai bin h calci mu: c thi
qua thn: trong 24 gi, 72% thuc c tm thy di dng chelat trong nc tiu, thi
gian na thi tr huyt tng l 40 pht. Khng khuch tn qua dch n o- ty.
4.2.2.2. Ch nh
- Ng c ch
- Ng c kim loi nng: Crm (eczma ca ximang), st (chng nhim hemosiderin),
coban, ng, cht phng x...
4.2.2.3. Chng ch nh
Suy thn nng
4.2.2.4. Tc dng ph
- c tnh vi thn: Thng tn ng thn, al bumin- niu, gim niu, suy thn (thng
thng c hi phc).
- Bun nn, i lng, chut rt c, st, au c.
- Ko di thi gian prothrombin.
- iu tr ko di c th gy mt magnesi (ngng iu tr v dng mt mui magnesi).
- Vim tnh mch huyt khi t rong trng hp dng nhng dung dch qu c c.
4.2.2.5. Cch dng v liu lng
ng tim 10 ml, c 0,50g.
- ng tnh mch: 15 - 25 mg/ kg c th, truyn nh git tnh mch trong 250 - 500 ml
dung dch huyt thanh ngt ng trng trong 1 - 2 gi, 2 ln/ ngy; liu ti a 50 mg/ kg/
ngy; chu k iu tr trong 5 ngy lin, vi khong cch ti thiu 2 ngy gia nhng chu
k iu tr. Kim tra nc tiu hng ngy v ngng iu tr trong trng hp bt thng.
- ng tim bp (dung dch 20%): c ch nh tr ong bnh no do ng c ch, vi
tng p lc ca dch no tu; 4 - 6 gi tim 12,5 mg/ kg (ti a 50 mg/ kg/ ngy). Dung
dch c ha thm vi procain 1% tim.
4.3. Penicilamin
Penicilamin (D- bta, bta- dimethylcystein) l cht thu phn ca penicilin, c th tng
hp.
To chelat vi kim loi nng, hp vi nhng cht ny thnh nhng phc ha tan v c
thi qua nc tiu. Trong cystein niu, penicilamin hp thnh vi cystein mt phc hp
ho tan.
Hp thu tt qua ng tiu ha; thi gian na thi tr l 2 - 3 gi, thi qua nc tiu di
dng disulfid.
- Bnh Wilson: 500 mg/ ngy vi 25 mg/ pyridoxin; iu tr cn c theo ui sut i.
- Ng c ch v thu ngn: 500 mg - 1,5g/ ngy trong 1- 2 thng. Tr em 30- 40 mg/ kg
cn nng.
- Cystein- niu mn ( phng bnh si): 250 mg/ ngy, liu c tng dn ti 500 mg, 4
ln/ ngy tu theo s chu thuc.
- Vim nhiu khp mn tin trin: Thng u 300 mg/ ngy; thng th hai, th ba: 600
mg/ ngy, nu sau 3 thng iu tr khng thy c kt qu th ngng thuc.
- Ung thuc lc i, 2 gi trc hoc 3 gi sau khi n.
4.3.2. Chng ch nh
- C thai, bnh mu, bnh thn, chng nhc c
- D ng vi penicilin.
4.3.3. Tc dng ph
- D ng, protein niu, mt v gic, khu gic.
- Vim nhiu dy thn kinh
- Vng da mt
- c ch tu xng: Thiu mu, gim bch cu, tiu cu.
4.4. Pralidoxim (2- PAM)
Xin xem bi Thuc tc dng trn h cholinergic, phn iu tr ng c hp cht

phospho hu c.
cu hi t lng gi
1. Nu 3 nguyn tc trong iu tr ng c thuc cp tnh
2. Trnh by nguyn tc loi tr cht c qua ng tiu ha.
3. Trnh by nguyn tc loi tr cht c qua ng tit niu
4. Trnh by v phn tch c ch ca nguyn tc trung ha cht c trong c th.
5. Trnh by c ch tc dng v cch dng EDTA, penic ilamin.
6. Trnh by cc phng php iu tr triu chng v hi chng trong nhim c
thuc cp tnh.

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dc l hc 2007 - i hc Y H ni

(sch dng cho sinh vin h bc s a khoa)

Mc tiu hc tp: Sau khi hc xong bi ny, sinh vin c kh nng:

Dc ng hc (Pharmacokinetics) nghin cu cc qu trnh chuyn vn ca thuc t lc c

Hnh 1.1. S chuyn vn ca thuc trong c th

1. Cc cch vn chuyn thuc qua mng sinh hc

K l hng s phn ly ca 1 acid; pKa = - logKa

Hnh 1.2: S khuch tn qua mng

Bng 1.2: nh hng ca pH n s ion ha ca salicylic acid

Hnh 1.3. Cc cch vn chuyn thuc qua mng sinh hc

C quan c ti Huyt C quan c ti

Hnh 1.4. H phn phi thuc 3 gian

2.2.1. S gn thuc vo protein huyt tng

Bng 1.3: T l gn thuc vo protein huyt tng

T l gn thuc vi protein huyt tng

Thuc l acid yu Thuc l base yu

cc base yu). T no, thuc ra theo c ch khuch tn th ng, ph thuc ch yu vo tan

cha t c mc m, iu gii thch v sao b m ng m li c th ra a con vn cn

2.3.1. Mc ch ca chuyn ha thuc:

Hp thu Sinh chuyn ha Thi tr

Hnh 1.5. Cc phn ng chuyn ha thuc c ph n lm 2 pha

Cc phn ng chnh pha ny gm:

C cht C cht (R- OH)

Phn ng c thc hin theo nhiu bc:

Hnh 1.6: S oxy ha thuc ca cytocrom P 450

Bng 1.4: Cc phn ng chnh trong chuyn ha thuc pha I

- Azo- kh RN=NR1RNH- NHR1RNH2+R1NH2

- Carbonyl- kh R- CR' R- CHR'

3. Phn ng thy Procain,

2.4.1.2. ngha lm sng

Lng thuc c thi tr theo t/2

S ln t 1/2 Lng thuc c thi tr (%)

(sch dng cho sinh vin h bc s a khoa)

Mc tiu hc tp: Sau khi hc xong bi ny, sinh vin c kh nng:

Dc lc hc nghin cu tc dng ca thuc ln c th sng, gii thch c ch ca cc tc dng

(sch dng cho sinh vin h bc s a khoa)

Cc lc lin kt trn u l thun nghch.

Hnh 2.1. Phc hp acetylcholin - receptor M

2) Chuyn tc dng tng h gia ligand v receptor thnh mt tn hiu gy ra c p ng

(sch dng cho sinh vin h bc s a khoa)

(sch dng cho sinh vin h bc s a khoa)

(sch dng cho sinh vin h bc s a khoa)

(sch dng cho sinh vin h bc s a khoa)

Sulfanilamid PABA (para amino benzoic acid)

(sch dng cho sinh vin h bc s a khoa)

Dng thuc Gii phng dc Dc cht ti ni Hiu qu

(sch dng cho sinh vin h bc s a khoa)

- Thuc c sinh kh dng cao.

1. Cng thc ca Young: dng cho tr t 2- 12 tui

2. Cng thc ca Cowling: Dng cho tr em t 2 - 12 tui

Th d: liu cho ngi ln l 2,0. Liu cho tr 4 tui l

4. Cng thc ca Clark

(sch dng cho sinh vin h bc s a khoa)

BSA: Body Surface Area -Din tch c th (tra monogram)

(sch dng cho sinh vin h bc s a khoa)

Rt nhiu thuc khi dng cho ngi m s thi tr qua sa v nh vy c th gy c hi c ho con.

(sch dng cho sinh vin h bc s a khoa)

bo ca h tun hon. Th d: thiu mu tan mu do penicilin, thiu mu tan mu t min do

(sch dng cho sinh vin h bc s a khoa)

4.4.1. Quen thuc nhanh (tAChyphylaxis)

(sch dng cho sinh vin h bc s a khoa)

1. Trnh by cc c ch tc dng ca thuc.

Mc tiu hc tp: Sau khi hc xong bi ny, sinh vin c kh nng: