Hoa Duoc Tri Lieu

HA DC TR LIU
ThS. BS. Trn Trung Ngha

1. NGUYN TC TR LIU HA DC TRONG TM THN........................................3
1.1. Phn loi:...................................................................................................................... 3
1.2. Tc ng dc l:......................................................................................................... 3
1.3. C ch:......................................................................................................................... 3
1.4. Tc dng ph:............................................................................................................... 4
1.5. Nhng yu t lin quan n bnh nhn:.......................................................................4
2. THUC CHNG LON THN..................................................................................... 8
2.1. Thuc chng lon thn in hnh:.................................................................................8
2.2. Thuc chng lon thn khng in hnh:.....................................................................16
2.3. Tc dng ph ngoi thp do thuc chng lon thn....................................................23
3. THUC CHNG TRM CM SSRIs..........................................................................31
3.2. Chi jnh trj liu:........................................................................................................... 34
3.3. Thn trong v tc dng ph:.......................................................................................38
3.4. Tng tc thuc:......................................................................................................... 41
3.5. Liu lng v hng dn s dng:............................................................................43
4. THUC CHNG TRM CM TCAs:.........................................................................45
4.1. Dc luc hoc:............................................................................................................. 45
4.2. Chi jnh trj liu:........................................................................................................... 46
4.3. Thn trong v tc dng ph:.......................................................................................47
4.4. Tng tc thuc:......................................................................................................... 48
4.5. Liu lng v hng dn lm sng:...........................................................................49
5. CC THUC BENZODIAZEPINE (BZD) V CC THUC TC QNG LN THU
THE BENZODIAZEPINE:.......................................................................................................... 51
5.1. Tc ng dc l:....................................................................................................... 52
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5.2. Chi jnh trj liu:........................................................................................................... 53
5.3. Flumazenil trong trng hp qu liu BZD:................................................................55
5.4. Thn trong v cc tc dng ph ca BZD:..................................................................56
5.5. Dung np l thuc v cai nghin:.............................................................................57
5.6. Tng tc thuc:......................................................................................................... 58
5.7. Giao thoa gia BZD zolpidem v zaleplon:..............................................................58
5.8. Liu lng v hng dn lm sng:...........................................................................58
6. THUC IU HA KH SC.....................................................................................60
6.1. i cng v thuc iu hoa kh sc:.........................................................................60
6.2. Lithium:....................................................................................................................... 62
6.3. Valproate:.................................................................................................................... 68
6.4. Carbamazepine v Oxcarbamazepine:.......................................................................72
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1. NGUYN TC TR LIU HA DC TRONG TM THN
1.1. Phn Ioai:
Thuc dng trj liu cho cc ri lon tm thn c goi chung l thuc hng thn
(psychotropic drug). Nhng thuc ny c m t theo p dng lm sng chnh yu ca thuc;
VD: thuc chng trm cm, thuc chng lon thn, thuc n jnh kh sc, thuc ng, thuc lm
tng nhn thc, thuc kch thch. C mt kh khn vi cch tip cn ny l c nhiu thuc c
nhiu chi jnh khc. VD: thuc nhm SSR c c tc dng chng trm cm v gii lo u, thuc
i khng serotonine dopamine c tc dng chng lon thn v n jnh kh sc.
Thuc hng thn cn c sp xp theo cu trc ha hoc (VD: thuc 3 vng), rtheo
c ch (VD: c ch MAO), theo ljch s (VD: thuc theo qui c, thuc th h u tin), tnh l
thng (VD: thuc khng in hnh), theo chi jnh (VD: thuc chng trm cm). Kh khn nhiu
hn na l c nhiu thuc c dng iu trj cho cc bnh l thn kinh, v ni khoa cng c
dng iu trj cho c cc ri lon tm thn.
Thm vo , cc thut ng thuc hng thn cng m m. Cc thuc u tin thng
dng iu trj tm thn phn lit c goi l thuc bnh thn. Khi c nhng thuc mi hn
dng iu trj lo u, li phn bit thnh thuc bnh thn chnh v ph. Lc ban u, thuc chng
trm cm l thuc chng trm cm 3 vng (TCAs) hoc MAOs. Trong nhng nm 70, 80,
nhng thuc chng trm cm mi hn xut hin th c goi l thuc chng trm cm th h
th 2, th 3. Hin nay, nhng thuc c hn iu trj lon thn c goi l thuc an thn kinh
(neuroleptics) qui c, in hnh, truyn thng. Thuc mi hn goi l thuc an thn kinh khng
in hnh. Trong bi ny, hn ch su m m nay, cc thuc c sp xp thep c ch tc
ng hoc cu trc tng tu nhau thng nht, d tham kho v d hiu.
1.2. Tc dng duc I:
C yu t mi trng v di truyn u nh hng n p ng c tnh c nhn, v tnh
dung np i vi thuc hng thn. Do , mt thuc c th khng chng minh c tnh hiu
qu trn nhiu bnh nhn c bnh l trong vic ci thin triu chng. nhiu trng hp, nhn
ra nhng yu t tin lng v kh nng ca thuc tr nn quan trong hn, nhng thng kh
thuc hin c. Ngay c trong cng mt nhm thuc, cc thuc cng kh phn bit vi thuc
khc do c nhng khc bit tinh vi hn, v mt cu trc phn t, kiu tng tc vi h thng
cht dn truyn thn kinh, khc bit v dc luc hoc, c hay khng c chuyn ha cht hot
ng, tnh kt ni vi protein. Nhng khc bit ny cng vi sinh ha ca tng bnh nhn to
nn mt hnh nh tng i v hiu qu thuc, dung np, tnh an ton v t l gia nguy c
li ch i vi tng bnh nhn. Tnh a bin ny, m nhiu yu t vn cha hiu r c, gy
kh khn cho vic tin on hiu qu thuc. Tuy nhin, hiu bit v bn cht ca tng loi
thuc lm tng kh nng thnh cng trong iu trj.
1.3. Co ch:
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C ch tc ng ca cc thuc hng thn vn cha c hiu r. Cch gii thch
chun muc nht l cch thc thuc lm thay i tp trung ca cc th th dopamine,
serotonine, norepinephrine, histamine gamma-aminobutyric acid (GABA). Nhng thay i
c cho l do kt qu ca cc cht ng vn, i vn tc ng n ti hp thu cht dn truyn
thn kinh, lm thun li cho su ch tit hoc c ch men chuyn ha. V d, mt thuc c th
l cht ng vn, do kch thch hot ng sinh hoc ca th th; hoc mt cht i vn s c
ch hot ng sinh hoc. Mt s thuc c c tnh ng vn tng phn v chng khng c kh
nng tc ng ton ven n mt th th chuyn bit no . Mt s thuc hng thn cng c
hiu qu lm sng thng qua c ch khc ch khng thng qua tng tc vi th th. V d:
lithium tc ng bng cch c ch truc tip ln men inositol 1 phosphatase. Mt s hiu qu
kt ni chc chn vi tc ng ca khe thn kinh (synaptic) chuyn bit. V d: hu ht cc
thuc trj lon thn c kh nng phong ta th th dopamine type 2 (D2). Tng tu, cc cht
ng vn benzodiazepine kt ni vi phc hp th th gia th th benzodiazepine v th th
GABA.
1.4. Tc dng ph:
Tc dng ph l nguy c khng th trnh khi khi iu trj bng thuc. Mc d khng th
c kin thc bao qut v tt c nhng tc dng ph c th c ca thuc, nh lm sng khi k
toa nn bit r nhng tc dng ph thng gp hn, cng nh nhng hu qu nguy him.
Khng c mt ti liu no, k c nhng thng tin v sn phm, c tt c nhng tc dng ph
nguy him phi iu trj c th c.
Vic cn nhc nhng tc dng ph bao gm kh nng chc chn c th xut hin, nh
hng ca tc dng ph n cht lng cuc sng, thi gian xut hin ca thuc, v nguyn
nhn xut hin. Nh vy, phi bit rng, khng c thuc no chc chn lm ci thin v mt
lm sng cho tt c bnh nhn; khng c tc dng ph no, lhng c vn no thng gp
xut hin trn tt c bnh nhn. Khi c bnh l y khoa no cng xut hin hoc tin s c phn
ng tri ngc tng tu t bnh nhn vo nguy c cao bj tc dng ph, vic lm hp l l
phi xem xt li cht/thuc c k toa khng qui c xem c lin quan n tc dng ph
khng.
Cc tc dng ph c th do nhng tc ng dc l tng tu vi tnh trj liu hoc do
nhng c tnh khng thng gp. V d, tc dng ph thng gp ca TCAs l gy phong ta
th th muscarinic acetylcholine hoc th th H2. Nu bnh nhn nhy cm vi nhng tc dng
ny, nhng thuc thay th m khng gy ra tc dng ny c th c chi jnh s dng. Nu
tc dng ph l biu hin ca c ch tc ng c tin on ca mt thuc, th tc dng ph
khi iu trj l iu khng th trnh khi. Do , tnh phong ta ti hp thu serotonine ca SSRs
c th gy nn, gy suy gim tnh dc. Tc dng phong ta D2 ca cc thuc iu trj lon thn
c th gy tc dng ph ngoi thp. Tc dng ng vn th th benzodiazepine c th gy tht
iu, gy ng ngy. Trong nhng trng hp ny, cc thuc thm vo thng phi gip nhng
thuc iu trj u tin c dung np tt hn.
1.5. Nhng yu t Iin quan dn bnh nhn:
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1.5.1. Tnh p ng vi thuc, v tnh nhy cm vi tc dng ph ca thuc c lin
quan vi nhng yu t lin quan n bnh nhn. y chnh l l do ti sao m
khng c mt cch trj liu no ph hp vi tt c moi ngi. Nhng yu t lin
quan n bnh nhn l: chn on bnh, yu t di truyn, cch sng, tnh trng
sc khe tng th, bnh l ng thi v tin s p ng thuc.
1.5.2. Chn on: Khng chn on chnh xc lm gim kh nng chon lua mt loi
thuc ti u. Chn on sai khng chi c th b mt c hi, m cn lm cho triu
chng nng hn. Chn on v cho bnh nhn ang trong giai on trm cm
ca ri lon lng cuc thnh chn on trm cm n cuc, c th gy ra cn
hng cm hoc gy chu ky nhanh khi dng thuc chng trm cm. Khi iu trj
khng thnh cng hoc lm cho triu chng nng hn, nh lm sng cn nh gi
li chn on.
1.5.3. p ng vi trj liu trong qu kh: mt thuc chuyn bit c chon ty theo
p ng vi thuc trong qu kh ca bnh nhn (su tun th, hiu qu trj liu, tc
dng ph), tnh p ng thuc trong gia nh bnh nhn, ph tc dng ph vi
nhm bnh nhn c bit, chi jnh trj liu trong thuc hnh lm sng. Nu thuc
tng c hiu qu trj liu cho bnh nhn hoc ngi thn trong gia nh bnh nhn,
nn dng tr li loi thuc v thuc cng nhm. Tuy nhin, vn c mt s bnh
nhn li khng p ng vi loi thuc m trc ho p ng rt tt, khi dng tr
li. Tin s c tc dng ph t mt thuc no cng l du chi im cho bit
bnh nhn s khng tun th vi loi thuc .
S c ch nu bnh nhn nh c chi tit nhng thuc hng thn c dng: chi
jnh loi thuc, liu lng, thi gian dng, thuc kt hp. Tuy nhin, do vn bnh l tm
thn m nhiu bnh nhn li c tr nh rt km. Gia nh ca bnh nhn l ngun luc gip tm
hiu thm nhng thng tin ny.
1.5.4. p ng vi trj liu trong gia nh: thuc p ng c tnh ging nhau trong gia
nh. Do , p ng thuc tt mt ngi thn no cng l iu c ch cho
vic chon lua thuc cho bnh nhn.
1.5.5. Bnh l phi hp: trong mt s trng hp, cc bnh l y khoa c th gy ra cc
triu chng tm thn. Bnh nhn bnh tuyn gip cha c iu trj ng s c
cc triu chng trm cm. Chng ngng th lc ng cng gy trm cm v suy
gim nhn thc. Thuc c chon phi hn ch gy nng n mc ti thiu nhng
bnh l y khoa c trc.
Dng thuc gii tr (thuc lc .), ung qu nhiu ru, thng s dng nc ung
c caffein s lm phc tp va thm ch cn lm gim hiu qu trj liu bng thuc hng thn.
Nhng cht ny c th c nhng nh hng tm thn quan trong v trong mt s trng hp,
c th l nguyn nhn gy xut hin triu chng.
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1.5.6. Tha thun v gio dc bnh nhn: bnh nhn nn c thng tin v k hoch
trj liu, tc dng ph c th c, v li ch ca mi cch trj liu. Nu khuyn bnh
nhn dng loi thuc c bit no, nn gii thch r rng l do ca li khuyn .
Bnh nhn hu nh s tip tc dng thuc nu ho hiu c y l do ho phi
dng thuc, l do thuc c chi jnh cho ho.
Mi lin minh trj liu gia bc s v bnh nhn lun lun hu ch. Cung cp cho bnh
nhn bit v nhng iu khng mong i khi dng thuc, tc dng ph thng gp ca thuc,
s gip ci thin su tun th iu trj. Nu bnh nhn tin tng vo kin thc ca bc s, vo
kh nng phn on ca bc s, ho s chp nhn dng th loi thuc no ch i hiu
qu sp n.
Nghin cu cho thy, nu bnh nhn c thng tin v tc dng ph ca thuc, th t l
xut hin tc dng ph cao hn nhng t l ngng iu trj li gim hn. Mt s bnh nhn cho
rng iu trj bng thuc l thn dc, mt s khc li xem thuc nh k th. Do , khi lm
tha thun trj liu vi bnh nhn, ngi than v bc s nn nu r l do iu trj, cng nh li
ch ca vic iu trj v nguy c c th c khi iu trj.
1.5.7. Liu lng thi gian iu trj v theo di:
Liu iu trj c hiu qu ty theo c tnh ca thuc v cc yu t ca bnh nhn, nh
tnh nhy cm v kh nng chuyn ha thuc, bnh kt hp v thuc ang dng ng thi, tin
s dung loi thuc no. Nng thuc huyt tng ca nhiu thuc hng thn c th tng
ln gp 10 ln. Do , liu hiu qu nht ca tng bnh nhn cn phi c th thch, cn c
hng dn v kinh nghim trj liu vi khong liu iu trj. Mt s thuc c lin h r rt gia
vic tng liu v p ng trj liu.
Kh nng ca mt thuc c cho l liu tng ng cn c t c kt qu hin
ti, ch khng phi l t c hiu luc ca thuc. V d: haloperidol c mnh nhiu hn so
vi chlorpromazine, khong 5mg haloperidol c kh nng trj liu tng ng 100mg
chlorpromazine. Tuy nhin, nhng thuc ny c hiu luc lm sng tng ng nhau.
Thuc phi c s dng vi liu t c hiu luc trong mt thi gian cn thit. Mc
d tnh dung np v tnh an ton ca thuc lun cn c xem xt, nhng cn trnh vic dng
liu thp hn liu iu trj v th nghim tnh trj liu khng y . Dng liu khng thch hp s
lm bnh nhn c nguy c bj tc dng ph m khng gip bnh nhn c c li ch trj liu.
Thi gian dng thuc thng c dua vo thi gian bn hy ca thuc trong huyt
tng v ph tc dng ph ca thuc. Thuc c tnh an thn nn c dng bui ti, hoc liu
ban ngy thp hn liu bui ti. Ngc li vi nhng thuc c tnh kch thch. Hu ht ch
dng thuc hng thn u dua vo su jnh chun nng thuc trong huyt tng hn l
dua vo kh nng chim ngu ca thuc no. C nhiu bng chng cho rng c su phn ly
ng k gia ng luc hoc trong huyt tng v no. Dua vo ng luc hoc ca thuc trong
huyt tng lp nn ch dng thuc s dn n hiu sai v ch dung thuc hp l.
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Thng thng thuc hng thn nn c dng lin tc, ngoi tr trng hp dng
thuc trong mt ng, kch ng cp tnh, lo u d di theo tnh hung. Sai lm thng gp khi
dng thuc benzodiazepine hot luc cao, nh alprazolam (anax), clonazepam (Rivotril) l chi
dng sau khi cn hong lon xut hin. Nhng thuc ny nn s dng trong ch u n
ngn nga cn hong lon.
Mt s bnh nhn tng bj ri lon tnh dc trong iu trj vi SSRs khi dng thuc
trong cc k nghi, nn thinh thong ho ngng thuc thuc hin hnh vi tnh dc tron ven. Vic
s dng thuc SSR ngt qung cng c hiu qu iu trj chng lon kh sc trc k kinh.
Thuc nn c s dng 2 tun trc giai on hong th ca chu ky kinh nguyt.
1.5.8. Thi gian iu trj:
Cu hi m bnh nhn thng xuyn t ra l: ti cn dng thuc trong bao lu. Cu
tr li ty thuc vo nhiu yu t: bn cht ca bnh l, thi gian ca triu chng, tin s gia
nh v cn i mc bnh nhn dung np thuc vi li ch ca vic iu trj. C th gii thch
hp l vi bnh nhn v nhng kh nng c th nhng trc ht, phi cho bnh nhn thy
rng thuc gip ch cho ho vi iu kin nhng tc dng ph c th chp nhn c. Khi vic
tho lun ng tin cy v thi gian iu trj c thuc hin th thnh cng trong trj liu chc
chn s t c. Hu ht cc bnh l tm thn u tin trin mn tnh v ti pht, nn iu trj
lu di l iu cn thit ngn nga bnh l ti din. Tuy nhin, cc thuc hng thn khng
c cho l iu trj khi c cc bnh l tm thn nhng c th gip kim sot c bnh.
Vic iu trj c chia thnh 3 giai on: iu trj th nghim u tin, iu trj tip din
v iu trj duy tr. Giai on u nn ko di t nht vi tun, chm p ng trj liu l c im
ca hu ht cc thuc hng thn. Thi gian cn thit cho giai on th nghim thuc cng
nn c a ra tho lun ngay t khi bt u iu trj bnh nhn khng mong i qu mc
v su ci thin ngay lp tc cc triu chng. Hu ht bnh nhn u bj tc dng ph sm trong
qu trnh iu trj bng ha dc trc khi ht triu chng. Trong mt s trng hp, thuc cn
lm cho cc triu chng nng hn. Bnh nhn v vy nn c t vn trc rng nhng phn
ng xu ban u khng phi l iu tin on cho kt qu iu trj sau ny. V d: nhiu bnh
nhn bj ri lon hong lon thng s bj run git ht hong, hoc tng cn hong lon sau khi
bt u iu trj bng thuc chng trm cm 3 vng hay SSRs. Thuc ng vn
benzodiazepine l mt ngoi l gip hn ch triu chng lm sng ny. Vi thuc ng v chng
lo u li c hiu qu ngay tc th.
Tuy nhin, vic bt u dng thuc khng gip bo v hon ton chng li ti pht. iu
trj tip tc s gip vic bo v chng ti pht c n jnh hn. Thi gian ti u nht cho giai
on iu trj tip tc v iu trj duy tr thay i v ty thuc vo tin s bnh ca bnh nhn. V
d: trm cm nng mn tnh khi pht sm c tin trin nng hn so vi trm cm nng mn
tnh khi pht mun. Cng vi tnh khi pht sm ca bnh, tin s bnh din qua nhiu giai
on, mc nng v di ca cc giai on ti din cng cn vic iu trj di hn, kh
on trc c.
1.5.9. t nghim cn lm sng v theo di c tnh trj liu qua mu:
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L xt nghim c bn xc jnh bnh l v theo di iu trj.
t nghim cn lm sng khng gip chn on xc jnh bnh l tm thn nhng l yu
t nhm loi tr cc bnh l y khoa tim n c th gy ra triu chng tm thn hoc nh
gi bin chng do iu trj thuc.
Cc xt nghim thng thuc hin l: CG, chc nng h to mu, chc nng gan,
thn, tuyn gip, nht l vi cc loi thuc nh lithium, clozapine .
Cc xt nghim khc cn c theo di l ng huyt, lipid mu, nht l khi iu trj
bng cc thuc chng lon thn khng in hnh.
Cng cn theo di nng huyt tng ca thuc iu trj vi nhng loi c gii hn trj
liu hep nh lithium. Vi lithium, nng huyt tng thp khng gip ci thin c triu
chng; nng huyt tng cao hn gii hn li gy ra ng c nng.
t nghim cn lm sng cn gip sng loc nng cht gy nghin hoc thuc bj lm
dng.
1.5.10. Kt hp thuc:
Theo hng dn thuc hnh ca Hip Hi Tm Thn Hoa Ky, nn trnh vic kt hp
thuc trong iu trj tm thn. Mc d n trj liu l l tng nht nhng trj liu phi hp cng
thng thy trong tm thn t rt lu (khong u nhng nm 50). Vic kt hp thuc, thuc
hnh tt vic tng liu hoc kt hp thuc n nay vn cn c tho lun rt nhiu trong y
vn v ti cc hi tho khoa hoc. S lng trung bnh ca cc thuc dng cng lc ngy cng
tng cho n hin ti. Vi bnh nhn tm thn ni tr, s lng thuc trung bnh dng phi hp
thng l 3 loi. Tuy nhin, vn hin nay l khi kt hp thuc, cc bc s li t linh ng
trong vic gia gim liu thuc kt hp, hoc kt hp thuc nhng chi c 1 loi c hiu qu iu
trj.
Fluoxetine olanzapine l kt hp thuc thng nht cho iu trj ri lon lng cuc.
Hu ht cc bnh nhn ri lon lng cuc thng c kt hp nhiu thuc hng thn.
Thuc i vn th th dopamine hoc thuc i vn th th serotonine dopamine thng
c kt hp trong iu trj trm cm lon thn. Tng tu, bnh nhn OCD chi p ng phn
no vi SSRs, nn thng c dng phi hp vi thuc i vn th th serotonine
dopamine.
Cc thuc c kt hp cn nhm i khng li cc tc dng ph, iu trj cc triu
chng chuyn bit v c th chuyn i t thuc ny sang thuc khc. Vic kt hp thuc
nh vy gip duy tr tnh trng p ng tt ca bnh vi iu trj.
2. THUC CHNG LON THN
2.1. Thuc chng Ioan thn din hnh:
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Thuc u tin c tm ra l Chlorpromazine, t nhng nm 50. C tc dng i vn
vi th th D2, nn c goi l nhm thuc i vn th th dopamine (DRA dopamine
receptor antagonist), cn c goi l thuc chng lon thn th h 1, thuc chng lon thn
in hnh, thuc chng lon thn qui c.
Hin nay, nhm thuc ny khng cn l thuc chnh iu trj bnh tm thn phn lit
hay cc bnh l c cc triu chng lon thn. Cc nhm thuc mi ngy cng thay th nhm
DRA cng nhiu, nh thuc i vn serotonine dopamine (SDA serotonine-dopamine
antagonist), thuc i vn tng phn dopamine (PDA partital dopamine antagonist) trong vai
tr l thuc chon lua hng u vi cc bnh l tng tu. Khng chi do cc thuc mi ny t gy
cc triu chng ngoi thp m cn iu trj triu chng m tnh trong tm thn phn lit, suy
gim nhn thc, trm cm lon thn.
c chia nhm ty theo cu trc phn t ha hoc. C cc nhm thuc sau:
phenothiazine (chlorpromazine, promazine, triflupromazine), piperazine (acetophenazine,
fluphenazine, trifluophenazine, perphenazine, thioridazine), thioxanthene (chlorprothixene),
dibenzoxazepine (loxapine), digydroindole (molindone), butyrophenone (droperidol,
haloperidol), diphenylbutylpiperidine (pimozide), raualfa alcaloid (reserpine).
Tt c cc thuc u hp thu qua ng ung, nhng dng djch hp thu tt hn so vi
dng vin nn hay vin nang. Nng inh huyt thanh t c sau 1 4 gi ung hoc 30
60 pht sau khi dng ng tim. Ht thuc, ung caf, thuc khng acid, thc n lm cho nh
hng n hp thu ca cc thuc. Sau 3 5 ngy dng thuc th t c nng iu trj.
Thi gian bn hy ca a s thuc l khong 24 gi. Nu bnh nhn dung np thuc tt, vi tt
c cc loi thuc, chi nn dng 1 ln trong ngy, ng ung khi bnh n jnh. Hu ht cc
thuc DRA u gn kt cao vi protein. Dng ng tim truyn s khi pht tc ng nhanh
hn v ng tin cy hn. Tnh kh dng sinh hoc ca dng thuc ng tim cng cao hn
gp 10 ln ng ung. Hu ht cc thuc DRA c men CP 2D6 v CP 3A chuyn ha.
Nhng yu t nh hung dn duc dng hc ca thuc chng Ioan thn
Tui thanh thi ca thuc gim ngi gi.
Bnh l ni khoa Gim lng mu qua gan cng lm gim thanh thi thuc.
Bnh gan cng lm gim thanh thi.
u t gy thoi trin Carbamazepine, phenytoin, ethambutol, barbiturate
Cht c ch thanh thi SSR, TCA, cimetidine, beta-bloquant, ciprofloxacine, ketoconazole.
Thay i tnh kt dnh vi protein Gim albumine huyt tng do suy dinh dng, suy gan.
Ha dc tr liu Page 9
Dng tim tc dng ko di ca haloperidol v fluphenazine c dng 1 ln mi 1 4
tun ty theo liu ca mi bnh nhn. C th phi dng u n n 6 thng mi t c
nng c hiu qu, nn cn phi tip tc dng thuc ng ung trong thng u khi
dng dng tc dng chm.
Tc ng ca thuc chng lon thn do kh nng c ch cht dn thuyn thn kinh h
dopamine. Cc thuc DRA tc ng n khong 60 th th D2 trong no. Thuc DRA cng
phong ta th th h noradrenergic, cholinergic, histaminergic ty theo tng loi thuc.
Mt s tnh nng chung ca DRA l ty vo tim luc ca mi thuc. Tim luc ca thuc
l s lng thuc cn dng t c tc dng trj liu. Thuc c tim luc thp nh
chlorpromazine, thioridazine c dng vi liu hnh trm miligram/ngy, c th gy tng cn,
gy an thn nhiu hn thuc c tim luc cao nh haloperidol, fluphenazine, nhm ny chi cn
dng t hn 10mg/ngy. Thuc c tim luc cao hu nh gy tc dng ph ngoi thp nhiu
hn.
2.1.1. Chi d[nh tr[ Iiu:
Cc chi d[nh tr[ Iiu ca DRA
Giai on lon thn cp tnh trong tm thn phn lit v ri lon cm xc phn lit.
iu trj duy tr trong tm thn phn lit v ri lon cm xc phn lit
Hng cm
Trm cm lon thn
Ri lon hoang tng
Ri lon nhn cch ranh gii
Ri lon lon thn do s dng cht
Sng v sa st tm thn
Ri lon tm thn do bnh l c th
Tm thn phn lit tr em
Ri lon pht trin lan ta
Hi chng Tourette
Bnh Hungtington
Ha dc tr liu Page 10
Tm thn phn lit v ri lon cm xc phn lit: cc thuc DRA u c tc dng iu trj
ngn hn v di hn kim sot tm thn phn lit v ri lon cm xc phn lit. Thuc c
hiu qu iu trj triu chng cp tnh v ngn nga ti pht. Thuc c hiu qu ng kinh ngc
vi cc triu chng dng tnh ca tm thn phn lit (nh: o gic, hoang tng, kch ng).
Cc triu chng m tnh li hu nh t ci thin v c th nng hn v thuc gy hn ch din t
bng nt mt, gy mt vn ng, cc tc dng ph ging triu chng m tnh.
Tm thn phn lit v ri lon cm xc phn lit c c im l giai on thuyn gim
v ti pht. Thuc DRA lm gim nguy c ti nng ca triu chng lon thn sau khi c
iu trj n jnh bng thuc trong giai on cp tnh. Do , sau giai on lon thn u tin,
bnh nhn phi iu trj duy tr t 1 2 nm; nu ti pht nhiu giai on lon thn, thi gian
duy tr l 2 5 nm. Thm ch c mt s nh lm sng khuyn dng n sut i.
Hng cm: thuc DRA c hiu qu iu trj triu chng lon thn ca cn hng cm. V
cc thuc chng hng cm (nh lithium) c khi pht hiu qu chm hn so vi thuc chng
lon thn trong vic iu trj triu chng cp tnh, nn cch iu trj chun cho cn hng cm l
kt hp thuc DRA hoc SDA vi lithium, lamotrigine, carbamazepine, valproate v sau dn
dn b thuc chng lon thn.
Trm cm c triu chng lon thn: iu trj kt hp thuc chng lon thn v mt thuc
chng trm cm l cch iu trj cho trm cm nng c lon thn. Ngoi cch ny, cn c th
dng chong in (CT electroconvulsive therapy).
Ri lon hoang tng: ri lon ny cng p ng tt vi iu trj bng thuc DRA.
Kch ng trm trong v hnh vi bo luc: vi nhng bnh nhn ny, ty theo chn on,
c th iu trj bng DRA. Cc triu chng nh: cu kinh qu mc, mt kim sot xung ng,
gy hn nhiu, tng ng qu mc, kch ng, p ng vi iu trj ngn hn bng cc thuc
DRA. Tr khuyt tt v tm thn, c bit l chm pht trin tm thn nng, ri lon tu k,
thng c giai on bo luc, gy hn, kch ng, cng p ng vi iu trj bng thuc chng
lon thn. Tuy nhin, iu trj lp li thuc chng lon thn kim sot hnh vi xung ng tr
em vn cn l iu ang bn ci.
Hi chng Tourette: thuc DRA cn c dng iu trj ri lon Tourette, bnh l thn
kinh c biu hin bng nhng tic vn ng v pht m. Haloperidol v pimozide (Orap) l thuc
thng c dng nht nhng nhng thuc DRA khc cng c hiu qu. Mt s nh lm sng
li a dng clonidine iu trj bnh l ny v t c nguy c bj tc dng ph v thn kinh.
Pimozide cng t c dng hn v tc dng ph v tim mch.
Ri lon nhn cch ranh gii: nhng bnh nhn ny c nhng tri nghim v cc triu
chng lon thn thong qua, nh: ri lon tri gic, tnh nghi ng, tng lin h, hung hng, c
th cn phi c iu trj bng DRA. Bnh l ny cng cn iu trj bng thuc n jnh kh sc.
Sng v sa st tm thn: khong 2/3 bnh nhn kch ng p ng vi iu trj bng
DRA. Thuc c tim luc cao thng dng liu thp (VD: haloperidol 0.5 1mg/ngy). Cc
thuc DRA cng c dng iu trj triu chng lon thn v kch ng trong sng. Tuy
nhin, cn phi xc jnh nguyn nhn gy sng, v sng do ng c cc thuc khng
cholinergic c th tr nng nu dng cc thuc DRA c tim luc thp do c tc dng khng
muscarinic ng k.
Ri lon lon thn c lin quan n cht: ng c cocain, amphetamine, phencyclidine
hay nhng cht khc c th gy triu chng lon thn. V cc triu chng ny thng tu gii
hn theo thi gian nn cng cn trnh dng cc thuc DRA tr phi bnh nhn kch ng, gy
hn d di. Thng chi dng benzodiazepine bnh nhn m dju. Benzodiazepine nn c
dng thay th DRA trong trng hp ng c phencyclidine trnh tc dng anticholinergic
ca DRA. Nu bnh nhn c hoang tng, o gic nh trong cai ru, cc thuc DRA c th
lm tng nguy c gy co git.
Tm thn phn lit tr em: bnh nhi cn c iu trj bng thuc chng lon thn
mc d vn cn t nghin cu v iu ny. Cc nghin cu hin nay cn nghj iu trj vi
nhng triu chng ri lon sm tr em c nguy c bj tm thn phn lit nhm ngn nga cc
triu chng bc pht. Cn xem xt k lng cc tc dng ph, c bit cc triu chng nhn
thc v tnh trng thc tinh.
Cc chi jnh khc v tm thn v bnh l khng phi tm thn: thuc DRA cn lm gim
run git ca bnh l Huntington. Bnh nhn ny c th c triu chng o gic, hoang tng,
hng cm, hng cm nhe. Nhng triu chng ny p ng c vi thuc DRA v nn s
dng thuc DRA c tim luc cao. Tuy nhin, cc nh lm sng nn ch n th cng trng
luc ca bnh l ny c th l triu chng ca hi chng ngoi thp.
Thuc DRA cn dng iu trj ri lon kim sot xung ng nu cc can thip khc
tht bi. Bnh nhn bj ri lon pht trin lan ta cng c th tng ng qu mc, go tht, kch
ng tn cng. Mt s triu chng ny c th p ng vi thuc DRA tim luc cao, nhng hin
c t nghin cu cho thy li ch ca vic iu trj ny.
Cc bnh l thn kinh him gp nh: chng ma vung (ballismus) v chng ma vung
na ngi (hemiballismus) vi biu hin vn ng y ti ca cc chi, cng p ng vi iu
trj bng thuc chng lon thn. Chi jnh khc ca DRA l bun nn, nn, nc v nga khng trj.
Cc bnh l ni tit v ng kinh thy thi dng c biu hin lon thn c th p ng vi
thuc chng lon thn.
2.1.2. Tc dng ph:
Hu ht cc tc dng ph ca DRA l tc dng ph thn kinh. Cc thuc c tim luc
thp thng c nhiu tc dng ph khng phi thn kinh hn cc thuc c tim luc cao. Ri
lon vn ng do thuc l tc dng ph thng gp ca DRA (xem bi ring).
Hi chng c tnh do thuc chng lon thn: y l tc dng ph nguy him cht ngi
ca DRA, c th xut hin bt k lc no trong qu trnh iu trj. Bao gm: st cao, cng c
nng, lon trng luc c, mt vn ng, chng khng ni, l ln, kch ng, tng nhjp tim v
tng huyt p dn n suy tim mch. V cn lm sng, c tng bch cu, tng CPK (creatinine
phosphokinase), tng men gan, tng myoglobin huyt tng v myoglobin niu, thng dn
n suy thn. Cc triu chng thng tin trin trong vng 24 72 gi, v hi chng thng
ko di 10 14 ngy nu khng iu trj. Chn on thng bj b l trong nhng ngy u, do
tnh trng thu rt v kch ng c th bj nhm l phn ng nng ca tnh trng lon thn. Nam
thng gp nhiu hn n, ngi tr thng gp nhiu hn ngi gi. T l t vong c th n
20 30 hoc cao hn nu dng loi thuc chch trc . Thng gp do cc thuc c tim
luc cao.
Nu nghi ng c hi chng ny, nn ngng ngay DRA v x l nh sau: trj liu nng
, lm mt thn nhit, theo di sinh hiu, cn bng nc v in gii, lng nc tiu. Thuc
chng parkinson c dng lm gin tnh trng cng c. Dantrolene (thuc dn c
xng) dng liu 0.8 2.5mg/kg mi 6 gi, ng tim truyn, tng liu ti a 10mg/ngy, c
th iu trj c. Khi bnh nhn c th ung, dng dantrolene 100 200mg/ngy.
Bromocriptine (20 30mg/ngy chia lm 4 ln) hoc amantadine c th kt hp iu trj. iu trj
tip tc khong 5 10 ngy. Cng nn tip tc iu trj lon thn bng cch i sang cc thuc
DRA tim luc thp hoc thuc SDR, d cc thuc ny, k c clozapine cng c th gy ra hi
chng c tnh.
Ngng ng kinh: thuc DRA c th lm gim ngng ng kinh. Chlorpromazine,
thioridazine v cc thuc tim luc thp khc c cho l gy ra ng kinh nhiu hn thuc c
tim luc cao. Molindone l thuc t gy ng kinh nht trong s cc thuc DRA. Nguy c cao bj
co git l nhng bnh nhn c ng kinh hoc c tn thng no.
An thn: do phong ta th th histamine H1, nn DRA thng gy an thn.
Chlorpromazine l thuc DRA gy an thn nhiu nht. Nn cho ton b liu thuc c ngy vo
bui ti trc khi ng hn ch tc dng ph an thn ny, sau , bnh nhn s dung np
dn tc dng ph ny.
Tc dng anticholinergic trung ng: triu chng anticholinergic trung ng gm: kch
ng d di, mt jnh hng thi gian, con ngi, ni chn, o gic, co git, st cao v dn
ng t. Sng s v hn m c th xy ra. iu trj anticholinergic trung ng: ngng ngay
thuc gy hi chng ny, theo di st v y khoa, v dng physostigmine 2mg truyn tnh mch
chm, lp li sau 1 gi nu cn. Nu dng qu nhiu physostigmine s gy nguy him vi triu
chng ng c: tng tit nc bot, tot m hi. Atropine c th i khng li tc dng ng c
physostigmine.
Tc dng ph tim: DRA lm gim co bp tim, hy emzyme gy co bp trong t bo c
tim, tng tc lu hnh catecholamine v ko di thi gian dn truyn nh tht, ko di thi
gian tr ca t bo c tim. Thuc DRA tim luc thp gy ng c tim nhiu hn thuc tim luc
cao . Chlorpromazine gy ko di khong T v PR, gy vi sng T v suy gim khong ST.
Thioridazine v mesoridazine c bit cn gy ko di nng n khong T, c nguy c gy
xon inh. Nhng thuc ny chi c dng khi nhng thuc khc khng c hiu qu.
t t: c nhiu bo co cho thy c nhiu trng hp t t do tim mch khi dng
DRA, c th do lon nhjp tim. Nhng nguyn nhn khc c th gy t t l: co git, ngt, st
c tnh, sc tim, hi chng c tnh.
H huyt p t th: h huyt p t th thng xut hin khi dng thuc c tim luc
thp, c bit l chlorpromazine, thioridazine, chlorprothixene. Khi tim bp thuc c tim luc
thp, nn theo di huyt p (khi nm v ng) trc v sau khi dng liu u tin v trong
nhng ngy u iu trj.
H huyt p t th do phong ta h adrenergic v thng chi xut hin trong nhng
ngy u. Sau , thng bnh nhn s dung np vi tc dng ph ny. Do , chi nn dng
liu khi u thp i vi nhng thuc ny. Chng mt, t ng d khng thng gp nhng c
th gy chn thng cho bnh nhn. Nn thng bo cho bnh nhn bit v tc dng ph ny,
v hng dn ho ng ln t t sau khi nm hoc dua lng. Bnh nhn nn trnh dng
caffein, ru; v nu khng phi ang iu trj h p, nn cho bnh nhn n nhiu mui. Mang
bt tt cht c th hu ch.
H huyt p c th c iu trj bng cch cho bnh nhn nm di, chn gc cao hn
u, p hai chn nh i xe p. Dng nhng thuc tng th tch tun hon hay tng huyt p,
nh norepinephrine, c th c chi jnh trong nhng trng hp nng. Ngoi h huyt p do
thuc phong ta -adrenergic, thuc cn phong ta tnh kch thch -adrenergic ca
epinephrine, nhng li khng kch thch h -adrenergic. Do , dng epinephrine lm tr nng
tnh trng h huyt p nn bj chng chi jnh dng trong h huyt p do thuc chng lon thn.
Trong trng hp h huyt p ny, nhng thuc kch thch duy nht -adrenergic nh
metaraminol, norepinephrine l nhng thuc c lua chon dng iu trj.
Tc dng ph huyt hoc: gim bch cu tm thi khong 3500 cng thng gp nhng
khng nng. Gim bch cu ht l mt tc dng ph nguy him e doa tnh mng, gp
1/10.000 bnh nhn iu trj bng DRA. Gim tiu cu hoc ban xut huyt khng do gim tiu
cu, thiu mu tn huyt, gim ton th cc dng t bo mu cng xut hin nhng him. Mc
d chi jnh m cng thc mu khng phi thng quy, nhng nu bnh nhn bj au hong v
st, cn phi thuc hin ngay cng thc mu kim tra nhng tc dng ph v huyt hoc. Nu
cc chi s v mu thp, nn ngng ngay DRA v nn chuyn bnh nhn n chuyn khoa
huyt hoc. T l t vong do bin chng ny cao, khong 30.
Tc dng ph anticholinergic ngoi bin: tc dng ph ny c cc biu hin: kh ming,
mi, nhn m, to bn, b tiu, gin ng t thng gp, c bit l vi thuc c tim luc thp
nh chlorpromazine, thioridazine, mesoridazine. Mt s bnh nhn c th bj nn, bun nn.
To bn c th iu trj bng cc cht x thng dng, nhng nu to bn nng c th
do lit rut. Cn gim liu DRA hoc thay i thuc khc t tc dng ph anticholinergic.
Pilocarpine c th dng iu trj lit rut mc d tc dng ph ny c cho l chi thong
qua. Bethanechol (recholine) (liu 20 40mg/ngy) c th dng iu trj b tiu.
Tng cn c lin quan n tng tn sut t vong, mc bnh v tnh trng khng p
ng vi thuc. DRA tim luc thp gy tng cn ng k nhng khng nhiu nh SDA nh
olanzapine, clozapine. Molindone v loxapine t gy tng cn nht.
Tc dng ph ni tit: phong ta th th dopamine ti rnh c phu s gy ra tng tit
prolactine, lm v to, tit sa, mt kinh, c cht khoi cm n v gy bt luc nam. Thuc
SDA, ngoi tr risperidone, khng lin quan n tng prolactine v l thuc chon lua iu trj khi
bnh nhn mc phi tc dng ph do tng prolactine.
Tc dng ph tnh dc: c nam v n khi dng DRA u bj gim khoi cm, gim ham
mun tnh dc. Khong 50 bnh nhn nam dng thuc chng lon thn cho bit bj ri lon
phng tinh v cng cng. Sildenafil (Viagra), vardenafil (Livitra) hay tadalafil (Cialis) thng
c dng iu trj ri lon cuc khoi do thuc chng lon thn, nhng hin nay cha c
nghin cu no v kt hp gia cc thuc ny v DRA. c bit, thioridazine gy ra gim ham
mun tnh dc v phng tinh ngc nam. Chng cng cng v au khi khoi cm cng
c c ghi nhn, c th do tc ng i vn th th -adrenergic.
Tc dng ph v da v mt: vim da dj ng v nhy cm vi nh sng c th gp, c
bit l vi nhng thuc tim luc thp. Ni mn nga, ni ban sn, m xut huyt v mn nc
c th xut hin sm trong nhng tun u, v hi phc dn. Phn ng nhy cm vi nh sng
ging nh l tnh trng rm nng nng cng xut hin nhng bnh nhn dng
chlorpromazine. Nhng bnh nhn ny nn c cnh bo v tc dng ph , v khng phi
nng qu 30 60 pht, v phi dng thuc chng nng. Dng chlorpromazine lu di c th
xut hin mng da i mu xanh xm nhng vng phi nng. Thay i da thng bt u
bng mu nu hoc nu vng v tin trin thnh cc mu: xm en, xanh kim loi, mu ta.
Nhng mng i mu ny hi ph dn khi bnh nhn c i sang dng thuc khc.
Nhim sc t vng mc bt hi phc c lin quan n s dng thioridazine vi liu trn
1000mg/ngy. Nhng triu chng sm ca tc dng ph ny thinh thong c th gy l ln v
m do gp kh khn v thj gic vo bui ti. Nhim sc t c th vn tin trin sau khi
ngng dng thioridazine, v cui cng l gy m. V l do ny m chi khuyn dng thioridazine
vi liu ti a 800mg/ngy.
Bnh nhn dng chlorpromazine c th bj nhim sc t lnh tnh mt, c trng bng
nhng ht trm tch nu trng mt trc thy tinh th v mt sau gic mc, chi pht hin khi
khm bng rch thy tinh th. Trm tch c th tin trin thnh ht trng v vng nu, thng
thnh hnh sao. Thng kt mc i mu thnh mu nu. Khng gy nguy hi cho vng mc
v thj gic vn khng bao gi bj suy gim. Bnh l ny thng hi phc dn khi ngng
chlorpromazine.
Vng da: tng men gan trong qu trnh iu trj bng DRA thng thong qua v khng
ng k v mt lm sng. Khi ln u tin dng chlorpromazine, vng da do thuyn tc hoc do
mt trong gan c th gp. Thng xut hin trong thng u tin khi iu trj v c du bo
trc bng tnh trng au bng trn, bun nn, nn. Sau thng c st, ban , tng bch
cu i toan, bilirunin niu, tng bilirunin huyt thanh, tng phosphatase kim, tng men gan.
Hin nay nhng trng hp ny cuc ky him gp nhng nu xut hin vng da, nn ngng
ngay thuc.
Tim Ic v tc dng ph ca DRA
Tn thuc Phn Ioai ha hc Liu ung tuong
duong (mg)
Tc dng ph
An thn T dng Ngoai thp
Pimozide Diphenylbutylpiperidine 1.5
Fluphenazine Phenothiazine 2
Haloperidol Butyrophenone 2
Thiothixene Thioxanthene 4
Trifluoperazine Phenothiazine 5
Perphenazine Phenthiazine 8 /
Molindone Didydroindolone 10
Loxapine Dibenzoxazepine 10 / /
Prochlorperazine Phenothiazine 15
Acetophenazine Phenothiazine 20 /
Triflupromazine Phenothiazine 25 /
Mesoridazine Phenothiazine 50
Chlorpromazine Phenothiazine 100
Chlorprothixene Thioxanthene 100 /
Thioridazine Phenothiazine 100
2.2. Thuc chng Ioan thn khng din hnh:
Cc thuc i vn serotonine dopamine (SDA serotonine dopamine antagonist) cn
c goi l thuc chng lon thn th h 2, hoc khng in hnh. Bao gm: risperidone,
olanzapine, quetiapine, clozapine, ziprasidone. Thuc phong ta th th serotonine type 5-HT2
v th th D2 lm c s cho vic iu trj bnh. SDA cng tc ng chuyn bit hn ln h
dopamine mesolimbic nhiu hn th vn, lin quan n vic phn ly nhanh chng khi th
th D2.
Tt c cc thuc SDA c cng c tnh sau: (1) phong ta t th th D2 hn so vi DRA;
(2) t c nguy c mc phi hi chng ngoi thp hn so vi DRA, nht l ri lon vn ng
mun; (3) c hiu qu r rt trong iu trj tm thn phn lit v (4) c hiu qu r rt trong iu
trj cn hng cm. Cc thuc SDA u c cu trc phn t khc nhau, c i luc th th khc
nhau. Tng tc gia th th vi hiu luc trj liu cng khng r.
Aripiprazole li c mt cc tc ng mi hn: i vn tng phn ln th th dopamine.
y l mt tin b xa hn so vi thuc chng lon thn th h th 2 trong vic iu trj lon
thn.
Mc d t nhng cc thuc SDA vn c tc dng ph ngoi thp, thuc SDA cn gy
tng cn ng k, v lm tng nguy c mc phi bnh tiu ng Theo FDA ca Hoa Ky, tt c
cc thuc SDA u phi gn nhn cnh bo cn c theo di st xao v nguy c gy bt
thng ng huyt.
Trong s nhng thuc SDA, clozapine c c tnh ring bit. y khng c xem l
thuc chon lua hng u v cc tc dng ph v cn phi kim tra huyt hoc mi tun. Mc d
thuc ny c hiu qu cao trong iu trj hng cm, trm cm, nhng vn khng c FDA xp
vo chi jnh iu trj cc tnh trng bnh l . Olanzapine c chi jnh l thuc iu trj cc
giai on hng cm cp, mn tnh trong ri lon lng cuc , nhng li chi dng cho nhng
trng hp tht bi trj liu vi nhng can thip khc (thuc).
2.2.1. Chi d[nh tr[ Iiu:
Mc d c chng minh l c hiu qu iu trj cn hng cm, nhng cc thuc
ny thng c t nh trj liu thm vo vi trm cm khng trj, PTSD (posttraumatic stress
disorder), ri lon hnh vi trong sa st tm thn. Nhng thuc SDA cn c xem l thuc chon
lua hng u, ngoi tr clozapine do thuc ny gy ra tc dng ph huyt hoc nn cn theo
di huyt hoc mi tun
Tm thn phn lit v ri lon cm xc phn lit: cc SDA c hiu qu trong iu trj cc
chng lon thn cp v mn, nh tm thn phn lit v ri lon cm xc phn lit, c ngi
trng thnh v tr vj thnh nin. Cc thuc SDA c hiu qu, thm ch cn tt hn, nh cc
thuc chng lon thn in hnh (DRA) trong iu trj cc triu chng dng tnh ca tm thn
phn lit v c hiu qu cao hn r rt so vi DRA trong iu trj triu chng m tnh. BN dng
thuc SDA t bj ti pht hn, t phi nhp vin hn, t phi cn cp cu tm thn, t phi t vn
in thoi v tm thn, v s ngy iu trj ngn hn so vi dng DRA.
V clozapine c nhng tc dng ph gy nguy him n tnh mng nn ni gn nh chi
dng bnh nhn tm thn phn lit khng vi tt c cc thuc chng lon thn khc. Nhng
chi jnh khc ca clozapine bao gm: ri lon vn ng mun nng, nhng bnh nhn c
ngng d bj triu chng ngoi thp. Nhng bnh nhn dung np tt vi clozapine c th s
dng lu di. Tc dng ca clozapine c th tng ln do risperidone, aripiprazole do cc thuc
ny lm tng nng ca clozapine v thinh thong c th gy ci thin v lm sng mt cch
ngon mc.
Ri lon kh sc: tt c cc thuc SDA c FDA chng thuc cho iu trj cn hng
cm. Olanzapine cng c chng minh l iu trj duy tr trong ri lon lng cuc. Tuy nhin,
ni chung, thuc chng lon thn in hnh v benzodiazepine c hiu qu lm m dju cn
hng cm nhanh hn cc thuc SDA. Cc thuc SDA cn c hiu qu triu chng trm cm
trong tm thn phn lit, tng tc dng chng trm cm trong iu trj cn trm cm. Do , kt
hp thuc SDA v thuc chng trm cm thng dng iu trj trm cm khng trj. Kt hp
fluoxetine v olanzapine l kt hp c FDA khuyn dng.
Cc chi jnh khc: c khong 10 bnh nhn tm thn phn lit c hnh vi gy hn v
bo luc. Thuc SDA cng c hiu qu iu trj tnh trng gy hn. Cc chi jnh khc cn bao
gm: hi chng suy gim min djch mc phi (ADS), ri lon kiu tu k, ri lon Tourette, bnh
Huntington, hi chng Lesch-Nyhan. Risperidone v olanzapine cn c dng kim sot
tnh trng gy hn v tu gy thng tch tr em. Nhng thuc ny cn c chi jnh cng
vi thuc kch thch giao cm, nh methylphenidate hay dextroamphetamine iu trj chng
tng ng gim ch tr em (ADHD), l nhng bnh nhn thng c kt hp c ri lon
ng x, ri lon chng i (opposition-defiant disorder). Cc thuc SDA, c bit l olanzapine,
clozapine, quetiapine, cn c ch cho nhng bnh nhn bj ri lon vn ng mun. Thuc c
ngn chn nhng vn ng bt thng trong ri lon vn ng mun. Thuc cn iu trj trm
cm lon thn, lon thn th pht sau chn thng u, sa st tm thn, lon thn do thuc.
iu trj bng SDA cn lm gim nguy c tu st, ng c nc bnh nhn tm thn
phn lit. Bnh nhn OCD khng trj c th p ng vi SDA, nhng cng c mt s bnh nhn
c triu chng cp cu ca OCD khi iu trj bng SDA. Mt s bnh nhn ri lon nhn cch
ranh gii c th ci thin khi iu trj bng SDA.
2.2.2. Tc dng ph: cc thuc SDA c cng ph tc dng ph, nhng khc nhau
mc thng xuyn v mc nng ca tc dng ph. Tc dng ph thng
gp c th xem bng Tc dng ph SDA. Cc tc dng ph chuyn bit,
thng gp ca mi SDA c nhn mnh trong gii thiu tng thuc.
2.2.3. Risperidone: l mt thuc nhm benzisoxazole. Risperidone c chuyn ha
rt nhiu gan thnh 9 hydroxyrisperidone, mt chuyn ha cht c hot ng
lon thn tng ng risperidone. Nng huyt tng ca risperidone t
inh sau 1 gi v ca cht chuyn ha u tin l sau 3 gi (sau khi ung).
Risperidone hot ng sinh hoc n 70. Thi gian bn hy kt hp ca
risperidone v 9 hydroxyrisperidone l khong 20 gi, nn c hiu qu chi
bng liu duy nht trong ngy. L mt cht i vn ca th th 5-HT2A v th th
dopamine D2, th th 1 2 adrenergic v th th histamine H1. Thuc cng c i
luc thp vi th th adrenergic v th th muscarinic cholinergic. Mc d thuc
c tim luc i vn th th D2 nh haloperidol nhng thuc t gy tc dng ph
ngoi thp nh haloperidol.
Tc dng ph ca risperidone: ty thuc vo liu lng v c khuynh hng xut hin
nhiu khi dng liu thp hn liu khi u cn thit. Tng cn, bun nn v nn, gy lo u, gy
nghet mi, ri lon cng, ri lon cuc khoi, v gy sm da l cc tc dng ph thng gp
ca risperidone. Nhng l do thng gy ngng risperidone li l tc dng ph ngoi thp,
chong vng, tng ng, bun ng, bun nn. Tng r rt prolactin c th xut hin v gy v
to, tit sa. Tng cn li thng gp tr em hn ngi trng thnh.
Liu lng: liu khi u thng l 1 2mg/m., v sau c th tng n 4mg mi
ngy. Khi kho st bng PT (positron emission tomography) cho thy: vi liu 1 4mg/ngy
s gy phong ta th th D2 cn cho tc dng trj liu. Vi liu cao hn 6mg/ngy th s gy ra
nguy c bj tc dng ph, nht l tc dng ph ngoi thp. Khng c tng quan gia nng
huyt tng v hiu qu iu trj. Risperidone l dng thuc SDA c dng tc dng chm, c
tim bp su mi 2 tun. Liu lng tim bp c th thay i 25 50 75mg. Nn dng
risperidone liu ung cng vi liu tc dng chm trong 3 tun u tin trc khi ngng liu
ung. VN, risperidone c trnh by di dng vin nn: 1mg, 2mg (Risperdal, Respidon,
Resdep, Risperidone, Repadon .)
Nhng thuc c ch men CP 2D6 nh paroxetine, fluoxetine c th c ch cc
chuyn ha cht hot ng ca risperidone. Risperidone l cht c ch yu men CP 2D6 nn
t gy nh hng ln cc thuc khc. Kt hp risperidone v cc thuc SSR c th gy tng
ng k prolactine, gy tit sa, v to.
2.2.4. OIanzapine: gn 85 olanzapine c hp thu qua ng tiu ha v c n
40 liu bj bt hot khi chuyn ha u tin gan. Nng inh t c sau
5 gi v thi gian bn hy l 31 gi, do chi nn dng 1 ln/ngy. Cng vi tc
ng i vn 5-HT2A v D2, olanzapine cn i vn th th D1, D4, 1, 5-HT1A v
th th muscarinic M1 M5, H1.
Tc dng ph ca olanzapine: khc vi clozapine, olanzapine chi gy tng cn nhiu v
thng xuyn hn cc thuc chng lon thn khng in hnh khc, v n jnh li sau khong
10 thng. Tc dng ny khng lin quan n liu lng v khng tin trin tip theo thi gian.
Cc d kin lm sng cho thy inh im ca tc dng ph ny l khong 9 thng, sau c
th tng tip nhng chm hn. Bun ng, kh ming, chong vng, to bn, kh tiu, tng
ngon ming, bn chn khng yn, run, c th do s dng olanzapine. Mt s bnh nhn
(khong 2) c th phi ngng olanzapine v tng men gan. Tc dng ph ngoi thp c th
lin quan vi liu, tc: liu cng cao th cng c th bj hi chng ngoi thp. Chnh nhng tc
dng ph ny m cn theo di ng huyt v men gan trong qu trnh iu trj bng
olanzapine. FDA (t chc thuc v thuc phm ca M) khuyn co nguy c bj sc bnh nhn
sa st tm thn khi iu trj bng olanzapine hay nhng thuc SDA khc nhng vi t l thp;
vi tnh trng tng cn, c th ci thin bng luyn tp th luc.
Liu lng olanzapine: VN, olanzapine c trnh by di dng vin nn: 5mg,
10mg (Zyprexa, Oleanz rapitab, Ozapine, Olanzapine .). Liu khi u ca olanzapine iu
trj lon thn thng l 5 10mg; iu trj hng cm cp thng l liu 10 15mg, dng 1
ln trong ngy. Vi liu 10mg tim bp/tnh mch, c th dng iu trj cn kch ng ca
tm thn phn lit, ri lon lng cuc.
Vi liu khi u 5 10mg/ngy, sau 1 tun, c th tng liu n 10mg/ngy. Liu s
dng trong lm sng thng l 5 20mg/ngy nhng nu cn thit c th tng n 30
40mg/ngy vi trng hp khng trj. Tuy nhin vi liu cao s c nguy c bj tc dng ph
ngoi thp v nhng tc dng ph khc.
Tng tc thuc ca olanzapine: fluvoxamine v cimetidine lm tng nng
olanzapine; carbamazepine, phenytoin lm gim nng ca olanzapine. Ru ethanol lm
tng hp thu olanzapine n hn 25, dn n tnh trng an thn, bun ng tng. Olanzapine
t gy nh hng n chuyn ha ca cc thuc khc.
2.2.5. Quetiapine: l mt cht thuc nhm dibenzothiazepine, c cu trc gn ging
clozapine, nhng khc bit r rt vi clozapine v tc ng sinh hoc. Thuc
c hp thu nhanh chng qua ng tiu ha, t nng inh sau khong 1
2 gi. Thi gian bn hy khong 7 gi, v nng ti u nht l sau 1 2
ngy. Cng vi kh nng i vn vi D2 v 5-HT2, quetiapine cn phong ta th
th 5-HT6, D1, H1, 1, 2. Thuc li khng phong ta th th muscarinic, hay th
th benzodiazepine. Tnh i vn th th ca quetiapine thng thp hn so vi
cc thuc chng lon thn khc, v thuc thng khng gy ra hi chng ngoi
thp.
Tc dng ph ca quetiapine: an thn, h huyt p t th, chong vng l nhng tc
dng ph thng gp nht ca quetiapine, nhng thng thong qua v c th kim sot dn
khi tng dn liu t t. uetiapine l thuc SDA t gy hi chng ngoi thp nht, bt k liu
lng. Do , y l thuc c ch nht iu trj bnh nhn bj Parkinson c triu chng lon
thn khi dng thuc ng vn dopamine. Tng prolactine him gp khi dng quetiapine, v
thng bj nhe v thong qua nu c. Thuc c th gy tng cn nhe mt s ngi, nhng
mt s khc li bj tng cn r rt. Tng nhe nhjp tim, to bn, tng nhe men gan cng c th
xut hin. C th c lin quan n tnh trng c thy tinh th trong nhng nghin cu trn
ng vt, nhng li khng ghi nhn thy trong lm sng. Tuy nhin, li ghi nhn thy c nhng
bt thng trn thy tinh th trong giai on u iu trj.
Liu lng ca quetiapine: trong tm thn phn lit, thng dng vi liu 400mg; trong
giai on hng cm v ri lon lng cuc, thng dng vi liu 800mg v 300mg. Tuy vy, vn
c nhng bnh nhn cn n liu 1200 1600mg/ngy. Mc d c thi gian bn hy ngn,
cng chi nn dng quetiapine 1 ln/ngy. Liu que6tiapine 25 300mg vo bui ti cn gip
gy ng trong mt ng.
Tng tc thuc ca quetiapine: vn cn ang nghin cu. Phenytoin lm tng
thanh thi ca quetiapine gp 5 ln.
2.2.6. Ziprasidone: thuc nhm benzothiazolyl piperazine. t nng inh sau 2 6
gi. Sau t 1 3 ngy s dng th c t c nng iu trj. Thi gian bn
hy l 5 10 gi, nn cn dng 2 ln/ngy. Hot tnh sinh hoc ca ziprasidone
tng gp 2 nu dng chung vi thc n. Nng inh ca ziprasidone dng
ng tim bp t c sau 1 gi.
Ziprasidone cng nh cc thuc SDA khc, phong ta th th D2 v 5-HT2A, v cng i
vn th th 5-HT1D, 5-HT2C, D3, D4, 1, H1. Thuc cn c i luc thp vi th th D, M v 2.
Ziprasidone cn ng vn th th serotonine 5-HT1A, c ch ti hp thu serotonine, c ch ti
hp thu norepinephrine. Do , c nhng bo co lm sng v tc dng ging nh chng trm
cm ca ziprasidone nhng bnh nhn khng phi tm thn phn lit.
Tc dng ph ca ziprasidone: bun ng, au u, chong vng, bun nn, m sng l
nhng tc dng ph thng gp khi dng ziprasidone. Thuc hu nh khng c tc dng ph
ng k bn ngoi h thn kinh trung ng, hu nh khng gy tng cn v khng gy ta8g
prolactine. Thuc c lin quan n tnh trng ko di khong TC nn mt s nh lm sng
khng chon ziprasidone l thuc chon lua hng u. Ko di khong TC n 1.4 milisecond
gp khong 4.7 bnh nhn dng ziprasidone liu 40 120mg/ngy, nn chng chi jnh
dng ziprasidone phi hp vi nhng thuc ko di khong TC, nh dofetilide, sotalol,
quinidine, thuc chng lon nhjp nhm a, , mesoridazine, thioridazine, chlorpromazine,
droperidol, pimozide, sparfloxacine, gatifloxacine, moxifloxacine, halofantrine, mefloquine,
pentamidine, arsenic trioxide, levomethadyl acetate, dolasetron mesylate, probucol, tacrolimus.
Ziprasidone nn trnh dng bnh nhn bj hi chng T ko di bm sinh, bnh nhn c tin
s lon nhjp tim.
Liu lng ca ziprasidone: nn bt u bng liu 40mg/ngy, chia lm 2 ln. Thuc
thng c hiu qu liu 80 160mg/ngy (cng chia 2 ln/ngy). Tuy nhin, trong lm sng,
nn dng liu cao 240mg/ngy. Liu tim bp nn dng khong 10 20mg, mi 2 gi vi liu
10mg, v mi 4 gi vi liu 20mg. Tng liu tim bp khng nn vt qu 40mg.
Tng tc thuc ch yu vi tc dng ph ko di khong TC. Ngoi ra, ziprasidone t
tng tc thuc ng k khc trong lm sng.
2.2.7. CIozapine: thuc nhm dibenzodiazepine. c hp thu nhanh v t nng
inh trong khong 2 gi. t c nng iu trj, cn t nht 1 tun vi
liu dng 2 ln/ngy. Thi gian bn hy l 12 gi. Clozapine c 2 chuyn ha
cht chnh, trong c N-dimethyl clozapine c th c tc ng ha dc.
Clozapine l mt cht i vn th th 5-HT2A, D1, D3, D4, v (c bit l th th
1). Thuc c tim luc i vn tng i thp vi th th D2. Trn hnh nh PT
cho thy 10mg haloperidol phong ta 80 th th D2 th vn, th clozapine vi
liu tng ng chi phong ta 40 50. Su khc bit ny chc chn l l do
cho thy clozapine khng gy ra tc ng ngoi thp.
Nhng chi jnh c bit ca clozapine: ngoi hiu qu iu trj c bit cho cc bnh
nhn khng trj, clozapine cn dng iu trj ri lon vn ng mun nng. Thuc cn khng
ch triu chng ri lon vn ng, nhng cc bt thng vn ng s tr li nu ngng
clozapine. Trong mt s him trng hp, clozapine c th gy ri lon vn ng mun.
Clozapine cn dng iu trj triu chng lon thn nhng bnh nhn khng dung np vi
triu chng ngoi thp do cc thuc khc, hng cm khng trj, trm cm lon thn nng, bnh
Parkinson lnh tnh, bnh Huntington, bnh nhn tu st trong tm thn phn lit, cm xc phn
lit. Nhng bnh l khng trj khc cho thy c p ng vi clozapine, bao gm: ri lon pht
trin lan ta, tu k thi nin thiu, OCD (dng n c clozapine hoc kt hp vi SSR). Tuy
nhin, cng c mt s trng hp him bj triu chng OCD khi dng clozapine.
Tc dng ph ca clozapine: thng gp nht l bun ng, chong vng, ngt, nhjp
nhanh, h huyt p, thay i CG, bun nn, nn. Nhng tc dng ph thng gp khc l:
mt mi, tng cn, triu chng tiu ha khc (thng gp nht l to bn), triu chng
anticholinergic, cm gic yu c. Tng tit nc bot, chy nc bot nhiu l tc dng ph xut
hin sm trong qu trnh iu trj, nht l vo ban m. Tc dng ph ny do suy gim kh nng
nut nc bot. C nhiu bo co cho rng clonidine, amtriptyline c th lm gim chng tng
tit nc bot, nhng cch hiu qu nht li l t khn chn 2 bn mp khi ng.
Nguy c bj co git khong 4 vi liu trn 600mg/ngy. Gim bch cu, gim bch cu
ht, st thng gp 1 bnh nhn. Trong nm u tin iu trj, c khong 0.73 BN bj gim
bch cu khng ht. n nm th 2, nguy c ny l 0.07. Gim bch cu trung tnh gp
khong 2.32 trong nm th nht, v 0.69 nm th hai. Chng chi jnh dng clozapine khi
m bch cu di 3500 t bo/mm
3
, bnh l ty xng trc y, tin s bj gim bch cu
ht do clozapine, dng loi thuc c tc dng c ch ty xng nh carbamazepine.
Trong 6 thng u iu trj bng clozapine, m bch cu mi tun l chi jnh bt buc
theo di gim bch cu. Nu bch cu vn bnh thng, vic kim tra c th gim mi 2
tun. Nu bch cu gim di 3000 t bo/mm
3
, hoc nu bch cu ht gim di 1500 t
bo/mm
3
, phi ngng ngay clozapine. Khi , cn khm v c kin ca chuyn khoa huyt
hoc. Nhng bnh nhn bj gim bch cu ht th khng nn s dng li clozapine.
Vim c tim cng l mt nguy c nng khi dng clozapine.
Liu lng ca clozapine: clozapine c trnh by di dng vin nn 25mg v
100mg. Liu khi u thng l 25mg dng t 1 2 ln/ngy, mc d c th khi u bng
liu thp hn l 12.5mg x 2 ln/ngy Sau , c th tng liu t t (25mg mi 2 3 ngy) n
300mg/ngy chia lm 2 3 ln/ngy. Liu ti a c th dng l 900mg/ngy. C th phi o
nng clozapine trong mu nu bnh nhn khng p ng trj liu. Nng trong mu tt nht
ca clozapine l 350mg/mL, s c p ng tt nht.
Tng tc thuc ca clozapine: khng nn dng chung clozapine vi nhng thuc c
th gy gim bch cu ht, suy ty xng, nh carbamazepine, phenytoin, propylthiouracil,
sulfonamides, captopril. Khi kt hp lithium vi clozapine, c th c nguy c bj co git, l ln,
ri lon vn ng, do khng nn kt hp nhng bnh nhn tng bj hi chng c tnh
do thuc chng lon thn. Clomipramine c th lm tng nguy c co git do lm gim ngng
co git v lm tng nng ca clozapine huyt tng. Risperidone v fluoxetine, paroxetine,
fluvoxamine lm tng nng ca clozapine huyt thanh. Kt hp clozapine paroxetine c
th gy thc y tnh trng gim bch cu do clozapine.
So snh tc dng ph ca SDA v DRA
DRA CIozapine Risperidone OIanzapine Quetiapine Ziprasidone
HC ngoi thp n 0 0 n 0 0
Lon vn ng mun 0 ()
Co git n 0 0 0
An thn n
HC c tnh
H huyt p t th n n 0 0
TC n 0 n 0 0 n 0 n
Tng men gan 0 n 0 n 0 n 0 n 0 n 0 n
Anticholinergic n 0 0 0
Gim BC ht 0 0 0 0 0
Tng prolactine n 0 n 0 0 0
Gim phng tinh n 0 0 0 0 0
Tng cn n 0
Nghet mi n n n n 0 n 0
2.2.8. Hung dn Im sng:
Tt c cc SDA (ngoi tr clozapine) u dng iu trj giai on lon thn u tin,
trong khi clozapine chi dnh cho bnh nhn khng trj vi tt c cc thuc chng lon thn
khc. Nu bnh nhn khng p ng vi thuc SDA u tin, nn th dng cc thuc SDA
khc. Chon lua thuc nn dua vo tnh trng lm sng v tin s p ng vi thuc. Thuc
SDA thng cn 4 6 tun t c hiu qu hon ton v c th cn n 8 tun nh
gi thuc SDA c th t c hiu qu iu trj hon ton hay khng. Do , ci thin u tin
trn lm sng l tnh trng an thn (bun ng). Dua trn cch nh gi ny, olanzapine v
quetiapine l thuc a thch iu trj ban u tnh trng kch ng, bo luc, lo u cao . Tuy
vy, vn chp nhn iu trj kt hp SDA vi thuc DRA hoc benzodiazepine trong vi tun u
iu trj. Lorazepam c th dng liu 1 2mg ung hoc tim bp iu trj kch ng. Khi c
hiu qu, nn gim liu dn lorazepam. Vi bnh nhn khng trj, c th cn n 6 thng
nh gi ci thin lm sng khi dng SDA.
Vic s dng SDA nn bt u bng liu thp, tng dn liu t liu iu trj. Vic
tng dn liu l cn thit nh gi nhng tc dng ph c th c. Nu ngng thuc trn 36
gi, nn dng tr li bng liu ban u (v tng dn). Khi quyt jnh ngng dng olanzapine
hoc clozapine, nn gim liu t t (nu c th) trnh triu chng cholinergic di ngc,
nh tot m hi, bng, tiu chy, tng ng.
Khi mun dng SDA, nn gii thch cho bnh nhn v thn nhn v nhng nguy c v
li ch ca SDA. Khi dng clozapine, nn lp bng tha thun vi bnh nhn.
Khi tm hiu bnh s, cn tm hiu cc yu t: bnh l huyt hoc, ng kinh, bnh tim
mch, bnh l gan thn v lm dng cht. Nu c bnh l gan thn, cn khi u dng liu
thp. Khm lm sng cn kim tra huyt p lc nm nghi v lc ng sng loc tnh trng h
huyt t th. Cc xt nghim cn thuc hin gm: CG, cng thc mu, chc nng agn, thn.
Nn theo di ng huyt, lipid mu v cn nng theo chu ky.
Mc d vic i t DRA sang SDA c th t ngt nhng cng nn gim dn DRA khi
bt u th nghim dn bng SDA. Clozapine v olanzapine c tc dng ph anticholinergic,
v khi chuyn t 1 trong 2 thuc ny bng mt thuc khc hn, cn ch n triu chng
cholinergic di ngc. Chuyn i t risperidone sang olanzapine cn thuc hin t vic gim
dn risperidone trong 3 tun, v cng lc vi dng olanzapine 10mg/ngy. Risperidone,
quetiapine, ziprasidone khng c tc dng ph anticholinergic, nn khi ngng t ngt thuc
DRA, clozapine, olanzapine sang 1 trong cc thuc trn c th gy xut hin tnh trng di
ngc cholinergic: tit nhiu nc bot, bun nn, nn, tiu chy. C th gim nhe tnh trng di
ngc ny bng cch tng nhanh risperidone, quetiapine, ziprasidone kt hp vi mt thuc
anticholinergic (v sau gim dn thuc anticholinergic ny). Bt k vic bt u dng hoc
ngng dng mt thuc SDA no cng nn thuc hin t t.
Khi BN bj mt bch cu ht khi dng clozapine, nn i sang olanzapine mc d dng
olanzapine khi ang bj mt bch cu ht do clozapine c th lm ko di thi gian hi phc
t khong 3 4 ngy n khong 11 12 ngy. cn thn nn i tnh trng mt bch cu
ht n jnh hon ton ri mi s dng olanzapine.
S dng SDA thai ph cha c nghin cu, nhng nn bit rng risperidone gy
tng prolactin (c th tng gp 3 4 ln so vi bnh thng). V bi v thuc SDA c th c
tit qua sa nn khng c dng cho ph n ang cho con b.
2.3. Tc dng ph ngoai thp do thuc chng Ioan thn:
2.3.1. L[ch s:
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Gloan van ong muonH( ac nghie+n cu &9ch te< ho'c "a%u tie+n cuoi
na1. 1960 cho tha6 tI -e -oa'n $an "ong .uon tha6 "o<i t 0(5EJ65E( Kan
"a%u ng0i ta cho raLng ngu6e+n nha+n &o to<n th0ng th'c the< 05 na#o hoa;c
&o MT8 nhng ,au "o gia5 thu6et na6 *9 *ac *o5 $a ngu6e+n nha+n "0'c
=ac "9nh -a tac &u'ng phu' cu5a thuoc !T( )g0i ta nhan tha6 *enh
nha+n -0n tuo<i $a phu' n# thN &eF .aOc -oa'n $an "ong .uon h0n(
2.3.2. Loan trng lc c cap:
>uat hien trong $ong t $ai gi0 ha6 $ai nga6 "a%u 31 C 4 nga64 khi
&ung thuoc chong -oa'n tha%n(
Dhi &ung thuoc chong -oa'n tha%n chung $0i -ithiu.8 co the< -a.
ta1ng nha'6 ca5. $0i pha5n ng -oa'n tr0ng -'c c0 cap(
Th0ng ga;p nhat -a tNnh tra'ng ca1ng "en .c kho+ng kie<. ,oat
"0'c c0 05 co< $a .a;tP hoa;c co thaOt8 $a;n $e'o "a%u hoa;c -ng( o the<
a5nh h05ng "en c0 $an nha#n -a. =uat hien c0n =oa6 nha#n ca%u -a.
.aOt nhNn ng0'c -e+n $a *9 GkhoaH 05 $9 trQ "o( )eu *9 05 thanh Rua5n ,e#
ga+6 kho th05(
S0i nh#ng K) -a%n "a%u tie+n *9 tNnh tra'ng na6 ,e# -a. cho ho' co
ca5. giac na;ng ne% h0n8 -a. .at -ong tin $ao K2 "ie%u tr9(
o the< "ie%u tr9 nhanh chong tNnh tra'ng na6 *aLng cac thuoc khang
cho-inergic nhT *en/tropine8 *iperi&en 3Ukineton48 &iphenh6&ra.ine 3Par,i&o-48
trihe=6pheni&6- 3Urtane4( Thuoc cu#ng co tac &u'ng phong nga tac &u'ng
phu' na6 trong $ai gi0 ,au( Va;c &u raLng tac &u'ng phu' na6 cu#ng co
the< nhanh chong *ien .at tr0c khi ,5 &u'ng thuoc( Thuoc co the< "0'c
chI "9nh trong $ai nga6 ke tiep ,au khi -oa'n tr0ng -'c c0 cap =uat hien(
Tieu chuan chan oan loan trng lc c cap theo DSM IV:
!"
U( Vot 3ha6 nhie%u h0n4 cac &au hieu ha6 trieu chng ,au =uat hien
-ie+n Ruan "en $iec &ung thuoc an tha%n kinh
T the *at th0ng cu5a "a%u $a co< ,o $0i c0 the< 3nh $e'o co<4(
o thaOt cac c0 ha. 3cng ha.8 nha1n .a;t8 ha .ieng to4(
2u6 gia5. kha5 na1ng nuot 3kho nuot48 ,u6 gia5. kha5 na1ng noi8
,u6 gia5. kha5 na1ng th05 3co thaOt $ung ha%u th'c Rua5n8 roi -oa'n
phat a+.4(
!0i noi kho+ng ro# rang8 noi -aOp &o *05i cng -0#i ha6 phN "a'i
-0#i 3noi kho8 -0#i to4(
The -0#i8 roi -oa'n chc na1ng -0#i(
VaOt -iec -e+n8 =uong8 ha6 ,ang *e+n 3ocu-og6ric cri,i,4(
T the *at th0ng cu5a chi =a ha6 tha+n(
K( ac &au hieu ha6 trieu chng trong tie+u chua<n U =uat hien trong
$ong 7 nga6 t khi *aOt "a%u ha6 khi ta1ng nhanh -ie%u thuoc an tha%n
kinh ha6 khi gia5. -ie%u thuoc "ie%u tr9 3ha6 phong nga4 cac trieu
chng ngoa'i thap cap 3nh thuoc anticho-inergic4(
( ac trieu chng trong tie+u chua<n U kho+ng gia5i thQch thQch "ang $0i
.ot roi -oa'n ta+. tha%n 3nh cac trieu chng ca1ng tr0ng -'c cu5a
ta+. tha%n pha+n -iet4( ac trieu chng na6 &o *05i .ot roi -oa'n
ta+. tha%n khiT cac trieu chng co tr0c khi &ung thuoc an tha%n kinh
ha6 kho+ng phu h0'p $0i hNnh thc can thiep &0'c -6 3nh -a kho+ng
ca5i thien ,au khi gia5. -ie%u thuoc an tha%n kinh ha6 ,au khi &ung thuoc
anticho-inergic4(
7( ac trieu chng trong tie+u chua<n U kho+ng &o *05i cac chat kho+ng
pha5i thuoc an tha%n kinh ha6 cac *enh -6 tha%n kinh ha6 noi khoa to<ng
Ruat khac( ac trieu chng na6 &o *05i *enh -6 noi khoa to<ng
Ruat khiT cac trieu chc =uat hien tr0c khi &ung thuoc an tha%n
kinh ha6 co ,' hien &ien cac &au hieu tha%n kinh khu tru .a kho+ng
gia5i thQch "0'c ha6 cac trieu chng tien trie<n trong khi kho+ng tha6
"o<i thuoc(
2.3.3. Trang thai #o$n cho$n %hong &en:
?0'c phat hien $a .o+ ta5 ,0.8 chI ,au -oa'n tr0ng -'c c0 cap(
Kenh nha+n co ca5. giac *t rt8 *o%n cho%n8 kho+ng the< ngo%i 6e+n8 ca%n
pha5i "i -ui "i t0i "e< gia5. *0t ,' kho ch9u( Tra'ng thai *o%n cho%n kho+ng
6e+n cu#ng -a .ot trong cac roi -oa'n ngoa'i thap &o thuoc chong -oa'n
tha%n(
o tac gia5 con "e% ngh9 raLngT tra'ng thai *o%n cho%n kho+ng 6e+n
go%. ca5 roi -oa'n $an "ong $a roi -oa'n $e% ta+. tha%n 32tah-8 19854( 7o
"o8 tNnh tra'ng na6 co the< *9 cho .ot trieu chng -oa'n tha%n8 hoa;c -o a+u8
hoa;c tra%. ca5.( o tr0ng h0'p8 K) tr05 ne+n kQch "ong8 *'c tc $N kho+ng
the< kie<. ,oat "0'c ca5. giac $e% tNnh tra'ng na6(
Th0ng =uat hien ,au khi &ung thuoc .ot th0i gian ngaOn( S0i
ha-operi&o- -ie%u 5.g8 co "en 40E K) co tNnh tra'ng na6P $0i -ie%u 10.g8 co
"en 75E co tNnh tra'ng na6( )h $a68 khi ta1ng -ie%u thuoc ,e# -a. tNnh
tra'ng na6 cang na;ng h0nP $a khi gia5. -ie%u8 tNnh tra'ng na6 ,e# "0'c ca5i
thien(
?a+6 -a -oa'i tac &u'ng phu' ha6 ga;p nhat khi &ung thuoc !T co<
"ie<n8 th0ng ga+6 ra ,' kho+ng tua+n thu5 "ie%u tr9 nhie%u nhat ,o $0i cac
tac &u'ng phu' ngoa'i thap khac8 $a &o "o -a. ta1ng ngu6 c0 tai phat
*enh ta+. tha%n(
Tr0c "a+68 nhie%u tac gia5 "e% ngh9 ,5 &u'ng thuoc khang cho-inergic
"e< "ie%u tr9 nhng kho+ng hieu Rua58 ngoa'i tr tr0ng h0'p co ket h0'p $0i
cac trieu chng ngoa'i thap khac8 nhT cng c0(
Thuoc "e% ngh9 -a cac *en/o&ia/epine nhT &ia/epa. 3Sa-iu.8 2e&u=en
5.g8 10.g48 -ora/epa. 3Uti$an8 Te.e,ta 0(5.g8 1.g8 2.g4(
Tu6 nhie+n8 thuoc cho'n -'a hang "a%u -a'i -a thuoc c che *eta 3*eta
*-oRuant,48 nhat -a proprano-o- 3co the< ta1ng -ie%u "en 120.gWnga64( ac
thuoc *etaJ*-oRuant, tan trong &a%u th0ng "a't hieu Rua5 cao h0n cac *etaJ
*-oRuant, tan trong n0c(
Tieu chuan chan oan trang thai #o$n cho$n %hong &en
theo DSM IV!":
U( >uat hien cac than phie%n chu5 Ruan $e% tNnh tra'ng kho+ng 6e+n ,au khi
,5 &u'ng thuoc an tha%n kinh( Xt nhat .ot trong cac trieu chng ,au
"0'c ghi nhan
5 "ong *o%n cho%n8 "ung "a 2 cha+n(
)hun nha56 2 cha+n khi "ng(
?i t0i -ui "e< gia5. *o%n cho%n(
Dho+ng the< ngo%i ha6 "ng 6e+n trong $ai phut
K( Dh05i "a%u trieu chng cu5a tie+u chua<n U $a K =uat hien trong $ong
4 tua%n ,au khi *aOt "a%u hoa;c ta1ng -ie%u an tha%n kinh hoa;c gia5. -ie%u
thuoc "ie%u tr9 3hoa;c phong nga4 cac trieu chng ngoa'i thap cap
3nh -a thuoc anticho-inergic4
( Trieu chng 05 tie+u chua<n U kho+ng "0'c gia5i thQch thQch "ang *05i
.ot roi -oa'n ta+. tha%n 3nh ta+. tha%n pha+n -iet8 cai nghien chat8
kQch "ong &o c0n tra%. ca5. hoa;c &o c0n hng ca5.8 gia ta1ng hanh $i
trong roi -oa'n gia5. ,ut chu 6W gia ta1ng hanh $i4( ac trieu chng
na6 &o *05i .ot roi -oa'n ta+. tha%n khiT cac trieu chng =uat hien
tr0c khi &ung thuoc8 kho+ng tha6 gia ta1ng tNnh tra'ng kho+ng 6e+n -ie+n
Ruan $0i ta1ng -ie%u thuoc an tha%n kinh8 kho+ng tha6 gia5. tNnh tra'ng
na6 -ie+n Ruan $0i can thiep &0'c -6 3nhT kho+ng ca5i thien khi gia5.
-ie%u thuoc an tha%n kinh hoa;c khi "ie%u tr9 $0i cac thuoc "0'c "e%
ngh9 "ie%u tr9 tNnh tra'ng "ng ngo%i kho+ng 6e+n4(
7( ac trieu chng trong tie+u chua<n U kho+ng pha5i &o cac thuoc kho+ng
pha5i an tha%n kinh hoa;c cac tNnh tra'ng *enh -6 to<ng Ruat khac( ac
trieu chng na6 &o *05i *enh -6 noi khoa to<ng Ruat khi cac trieu
chng =uat hien tr0c khi ,5 &u'ng an tha%n kinh hoa;c cac trieu
chng nga6 cang na;ng .a;c &u kho+ng tha6 "o<i che "o thuoc(
2.3.4. 'o(i chng )ar%in*on:
Yoi chng na6 .ang nhie%u "a;c "ie<. "ie<n hNnh cu5a *enh Parkin,on
ngu6e+n phatT gia5. &ieFn ta5 *aLng net .a;t 3.a;t na'48 &au *anh =e ra1ng
ca8 gia5. $an "ong8 cha56 n0c &a#i8 $iet ch# nho58 run kie<u $e+ thuoc8
run khi nghI8 cng c0 toan tha+n( Yoi chng na6 th0ng =uat hien t t
,au khi cho thuoc chong -oa'n tha%n(
?ie%u tr9 cu#ng *aLng cac thuoc khang cho-inergic8 hoa;c cac thuoc
"o%ng $an &opa.ine nh a.anta&ine 326..etre-48 *ro.ocriptine 3Par-o&e-4(
)goai ra con ga;p tNnh tra'ng .at $an "ong 3akine,ia4T "a;c trng *05i
tNnh tra'ng gia5. tQnh t' phat nhT $an "ong kho+ng t' chu58 noi kho+ng t'
chu58 -a#nh "a'.8 kho *aOt "a%u cac hoa't "ong trong ,inh hoa't( u#ng =uat
hien ,au $ai tua%n "ie%u tr9 *aLng thuoc !T( Tu6 nhie+n8 tNnh tra'ng akine,ia
con co the< *ie<u hien nh trieu chng a+. tQnh trong ta+. tha%n pha+n
-iet( ?ie%u tr9 cu#ng *aLng cac thuoc khang cho-inergic8 $a cu#ng co the<
-a. ca5i thien cac Gtrieu chng am tnh na6(
Yoi chng tho5 3ra**it ,6n&ro.e4T -a nh#ng c5 "ong nhanh8 .9n
3nho54 05 .o+i nh c5 "ong nhai cu5a tho5( o the< -aFn -on $0i -oa'n $an
"ong .uon 05 .ieng C -0#i( o the< ga;p 05 khoa5ng 4E K) &ung thuoc
!T( ?ie%u tr9 nhanh chong $a &eF &ang *aLng thuoc khang cho-inergic(
o the< "ie%u tr9 phong nga -oa'n tr0ng -'c c0 cap8 hoi chng
parkin,on8 hoi chng tho58 .at $an "ong8 *aLng cac thuoc khang
cho-inergic cung -uc $0i thuoc !T(
Tieu chuan chan oan ho(i chng )ar%in*on theo DSM IV: !"
U( Vot 3ha6 nhie%u h0n4 &au hieu ha6 trieu chng ,au =uat hien -ie+n
Ruan "en $iec &ung thuoc chong -oa'n tha%n(
Zun kie<u Parkin,on 3nhT run khi nghI ng0i8 nh9p nhang8 ro# ret8 $0i
ta%n ,o 3J6 chu k6Wgia+68 =a56 ra 05 chi8 "a%u8 .ieng ha6 -0#i 4(
ng c0 kie<u Parkin,on 3nhT co cng kie<u ra1ng ca ha6 co cng8 co
cng kie<u ong chN keo &ai4(
Vat $an "ong 3nhT gia5. ,' *ie<u -o net .a;t .ot cach t' nhie+n8
t the8 -0i noi8 $an "ong c0 the<4
K( ac trieu chng 05 tie+u chua<n U =uat hien trong $ong $ai tua%n khi
*aOt "a%u &ung ha6 ta1ng -ie%u thuoc chong -oa'n tha%n8 ha6 gia5. cac
thuoc "ie%u tr9 3ha6 phong nga4 cac trieu chng ngoa'i thap 3nh -a
thuoc anticho-inergic4
( ac trieu chng trong tie+u chua<n U kho+ng "0'c gia5i thQch thQch "ang
*05i .ot roi -oa'n ta+. tha%n 3nh T cac trieu chng a+. tQnh ha6 ca1ng
tr0ng -'c cu5a ta+. tha%n pha+n -iet8 cha. cha'p ta+. tha%n $an "ong
trong giai "oa'n tra%. ca5. chu5 6eu4( KaLng c0 .a cac trieu chng
"0'c gia5i thQch thQch "ang *05i .ot roi -oa'n ta+. tha%n co the< *ao
go%. theo ,auT ac trieu chng co tr0c khi &ung thuoc an tha%n kinh
ha6 kho+ng phu h0'p $0i hNnh thc can thiep &0'c -6 3nh -a kho+ng
ca5i thien ,au khi gia5. -ie%u thuoc an tha%n kinh ha6 ,au khi &ung thuoc
anticho-inergic4(
7( ac trieu chng trong tie+u chua<n U kho+ng &o *05i cac chat kho+ng
pha5i thuoc an tha%n kinh ha6 cac *enh -6 tha%n kinh ha6 noi khoa to<ng
Ruat khac 3nh -a *enh Parkin,on ha6 *enh [i-,on4( ac trieu chng
&o *05i *enh -6 noi khoa to<ng Ruat khiT cac trieu chng =uat hien
tr0c khi &ung thuoc an tha%n kinh ha6 co ,' hien &ien cac &au
hieu tha%n kinh khu tru .a kho+ng gia5i thQch "0'c ha6 cac trieu
chng tien trie<n .a;c &u kho+ng tha6 "o<i che "o thuoc 4(
2.3.5. Loan +a(n o(ng ,uo(n tar-i+e -&*%ine*ia TD":
Th0ng ga;p 05 *enh nha+n &ung thuoc !T -a+u &ai8 nhat -a thuoc
!T co< "ie<n( Kie<u hien cu5a roi -oa'n na6 -a cac c5 "ong *at th0ng
cu5a .ieng8 .a;t8 -0#i $a c5 "ong .ua giat8 .ua $0n cu5a ta68 cha+n8
c0 the<( Dho+ng giong nh cac tac &u'ng phu' ke< tre+n8 *enh nha+n *9 !S?V
th0ng kho+ng 6 thc "0'c raLng ho' co nh#ng c5 "ong *at th0ng(
!S?V "ap ng ke. $0i "ie%u tr9(
!a nh#ng c5 "ong kho+ng chu5 6 05 .a;t8 tha+n .Nnh8 hoa;c 05 chi(
\o%.T tra'ng thai *o%n cho%n kho+ng 6e+n .uon8 -oa'n tr0ng -'c c0 .uon
3th0ng 05 c0 co<8 c0 $ai48 tic, .uon(
Th0ng co -ie+n Ruan "en $iec &ung keo &ai cac thuoc phong to5a
thu' the< &opa.ine8 .a th0ng ga;p nhat -a thuoc !T8 nhng cu#ng co
the< ga;p 05 K) &ung thuoc chong tra%. ca5. a.o=apine8 thuoc chong
no+n nh .etoc-opra.ine8 proch-orpera/ine ]
0 che "e% ngh9T cac thu' the< ,au ,6nap ta1ng nha'6 ca5. $0i
&opa.ine ,au .ot th0i gian &ung thuoc phong to5a thu' the< &opa.ine( o
nh#ng c0 che "0'c "e% ngh9 khac nhT ta1ng hoa't "ong nora&rena-ineP hoa;c
"ie%u tr9 *aLng thuoc chong -oa'n tha%n -a. ,inh ra cac goc t' &o -a. to<n
th0ng cac co<ng catecho-a.ineP hoa;c -ie+n Ruan "en he \UKUP hoa;c ,u6
thoai na#o toan *o(
Ta%n ,uat tha6 "o<i tu6 theo nho. &a+n c "0'c nghie+n cu8 tuo<i (((
Tu6 nhie+n8 co the< =ac "9nh trong khoa5ng 15 C 20E K) &ung thuoc !T keo
&ai(
^eu to ngu6 c0T ngu6 c0 *9 T7 ta1ng theo tuo<i cu5a K)( Phu' n# th0ng
co ngu6 c0 cao h0n na.( Ta1ng theo -ie%u thuoc !T "0'c ,5 &u'ng8 th0i gian
,5 &u'ng $a tie%n ,5 *9 tac &u'ng phu' ngoa'i thap ,0. trong Rua trNnh
"ie%u tr9( T7 con =uat hien cao 05 nh#ng K) co to<n th0ng na#o8 cac
*enh $e% ca5. =uc 3hng ca5.8 tra%. ca5. ]4
?ie%u tr9T th0ng $0i nh#ng *ie<u hien nhe'8 K) th0ng kho+ng nhan
*iet "0'c( )h#ng tr0ng h0'p na;ng a5nh h05ng "en a1n uong8 nghI ng0i
thN ca%n "ie%u tr9(
)ga1n nga =uat hien T7 -a Ruan tro'ng( 7o "o ca%n "anh gia -ie%u
-0'ng thuoc !T toi thie<u thQch h0'p "oi $0i tng giai "oa'n *enh8 ne+n ca%n
pha5i co chien -0'c gia5. -ie%u thuoc !T( Dhi gia5. -ie%u thuoc !T8 T7
cu#ng co the< gia5. &a%n t t( ac trieu chng T7 cu#ng co the< *ien
.at ta'. th0i khi ta1ng -ie%u thuoc !T8 nh#ng cu#ng co the< na;ng h0n khi
ta1ng -ie%u thuoc !T(
?oi $0i K) co T7 .a kho+ng the< ngng thuoc !T8 thuoc !T "0'c
"e% ngh9 -a c-o/apine( Thuoc na6 co the< -a. ca5i thien cac trieu chng
T7 3ga%n 50E tr0ng h0'p8 nhat -a cac tr0ng h0'p -oa'n tr0ng -'c c0 .uon
na;ng4(
Thuoc khang cho-inergic co the< -a. =au h0n trieu chng T7(
ac thuoc khac "0'c "e% ngh9 nhT re,erpine 31 C 6.gWnga648
tetra*ena/ine 350 C 200.gWnga648 o=6pertine J cac thuoc na6 -a. ,u6 gia5.
cac catecho-a.ine( ac thuoc "oi $an nora&renergic nh proprano-o-8
c-oni&ineP cac thuoc he \UKUergic nh *en/o&ia/epine8 *ac-o_en8 $a-proate8
ga..a C $in6- \UKUP thuoc "o%ng $an &opa.ine &ung -ie%u thap nh
-e$o&opa8 a.anta&ineP cac thuoc phong to5a ke+nh ca-ci nh $erapa.i-8
&i-tia/e. cu#ng "0'c ,5 &u'ng( Zie+ng $ita.ine M "0'c ghi nhan -a. ca5i
thien trieu chng8 &o co "a;c tQnh chong o=i hoa ne+n *a5o $e te *ao
tha%n kinh "oi $0i cac goc t' &oP -ie%u ,5 &u'ng co the< t 400 C 1200
A`Wnga6(
Tieu chuan chan oan roi loan +a(n o(ng ,uo(n theo DSM
IV: !"
U( )h#ng c5 "ong *at th0ng cu5a -0#i8 ha.8 tha+n8 chi =uat hien -ie+n
Ruan $0i $iec &ung thuoc chong -oa'n tha%n
K( )h#ng c5 "ong *at th0ng hien &ien toi thie<u 4 tua%n $a *ie<u
hien *at c cac &a'ng ,auT
)h#ng c5 "ong .ua giat
)h#ng c5 "ong .ua $0n
)h#ng c5 "ong "e%u "a;n(
( )h#ng &au hieu ha6 trieu chng trong tie+u chua<n U $a K =uat hien
trong th0i gian &ung thuoc an tha%n kinh ha6 trong $ong 4 tua%n ngng
ha6 gia5. thuoc uong 3ha6 trong 8 tua%n gia5. ha6 ngng thuoc &a'ng
tac &u'ng keo &ai4
7( o th0i gian &ung thuoc an tha%n kinh toi thie<u 3 thang 31 thang
neu h0n 60 tuo<i4(
M( ac trieu chng kho+ng &o cac *enh -6 noi khoa ha6 tha%n kinh 3nh
-aT *enh Yuntington8 .ua $0n 26n&enha.8 roi -oa'n $an "ong t'
phat8 c0ng giap8 *enh [i-,on4 ra1ng gia5 kho+ng phu h0'p8 &ung cac
thuoc khac ga+6 roi -oa'n $an "ong cap co the< ho%i phu'c 3nh -aT !J
&opa8 *ro.ocriptine4( o *aLng c0 cac trieu chng &o cac ngu6e+n
nha+n na6T cac trieu chng =uat hien tr0c ha6 *ie<u hien cac &au
tha%n kinh "9nh $9 kho+ng gia5i thQch "0'c( ac trieu chng kho+ng "0'c
-6 gia5i thQch h0'p *05i cac roi -oa'n $an "ong cap -ie+n Ruan thuoc an
tha%n kinh 3nh -aT -oa'n tr0ng -'c c0 cap8 tNnh tra'ng "ng ngo%i kho+ng
6e+n cap4(
2.3.6. 'o(i chng ac t.nh -o thuoc /LT:
Yie. ga;p8 nhng co the< ga+6 ngu6 hie<. "en tQnh .a'ng K)( Kie<u
hienT tNnh tra'ng cng c0 na;ng ne% h0n8 tha6 "o<i tNnh tra'ng ta+. tha%n 3,a5ng8
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3. THUC CHNG TRM CM SSRIs
Thuc c ch ti hp thu chon loc serotonine (serotonine selective reuptake inhibitor
SSR) u tin c pht hin nm 1987 l fluoxetine lm thay i thi v iu trj ho dc
vi trm cm. L do u tin l do tc dng ph ca fluoxetine thng c dung np tt hn
nhng thuc iu trj trc y, nh thuc chng trm cm ba vng (TCA) v thuc c ch
MAO (MAO) v tnh n gin trong liu dng fluoxetine.
Sau , nhng thuc SSR khc c pht hin, c cng c tnh c bn ca
fluoxetine. T 1990, danh sch cc chi jnh iu trj c chng thuc cho nhng thuc xp
trong nhm ny m rng thm, khng chi l trm cm, nh: ri lon m nh cng ch (OCD),
ri lon hong lon, ri lon lo u lan to, ri lon lon cm trc k kinh, ri lon lo u x hi
v ri lon n ung. Tt c cc thuc SSR c hiu qu tng ng iu trj cc ri lon
ny.
SSRIs dng cho ngui trung thnh v tr em
CitaIopram EscitaIopram Fuoxetine FIuvoxamine Paroxetine SertraIine
Trm cm
nng
Ngi trng
thnh
Ngi trng Ngi trng
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tr em
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thnh
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tm
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thnh
Ri lon lon
kh sc
trc k
kinh
Ngi trng
thnh
Ngi trng
thnh
Ngi trng
thnh
3.1. Ha hc:
Cc thuc SSR c cu trc ho hoc khc bit nhau, nhng escitalopram l ngoi l, l
dng ng phn ca citalopram. Tnh a dng v phn t gii thch c ti sao c c nhn
p ng v dung np vi cc thuc SSR khc nhau.
3.1.1. Duc dng hc:
Su khc bit quan trong nht gia cc SSR l thi gian bn hu trong huyt tng c
thay i rng. Fluoxetine c thi gian bn hu di nht 4 6 ngy; cc chuyn ho cht hot
ng ca thuc c thi gian bn hu 7 9 ngy. Thi gian bn hu ca sertraline khong 26
gi, v thuc c mt t chuyn ho cht hot ng c thi gian bn hu 3 5 ngy. Thi gian
bn hu ca thuc cn li (khng c chuyn ho cht hot ng no ng k) l: citalopram 35
gi, escitalopram l 27 32 gi, paroxetine l 21 gi, fluvoxamine l 15 gi. V c bn, SSR
hp thu tt bng ng ung, t nng inh sau khong 3 8 gi. Su hp thu sertraline
thay i nhe nu c thc n.
T l gn kt vi protein ca sertraline, fluoxetine, paroxetine cao nht; escitalopram
gn kt t nht.
Tt c cc SSR c chuyn ho gan do men cytocrome P450 (CP). Nhng do cc
SSR c chi s trj liu rng nn him khi nhng thuc khc gy tng vn nng ca cc
SSR. Tng tc thuc quan trong nht vi SSR l lm c ch chuyn ho SSR nu dng
ng thi. Cc SSR u c kh nng gy c ch chuyn ho ca kh nhiu thuc.
Fluvoxamine l thuc gp nhiu kh khn nht lin quan n tng tc thuc.
Fuvoxamine nh hng r rt n vi men CP. V d v tng tc quan trong l gia
fluvoxamine v theophylline do tng tc qua men CP 1A2; fluvoxamine v clozapine qua c
ch men CP 1A2; fluvoxamine vi clonazepam v alprazolam do c ch men CP 3A4.
Fluoxetine v paroxetine c tc ng ng k n men CP 2D6, gy nh hng n hiu qu
ca cc cht ging opiate, nh: codein, hydrocodone, do phong to su chuyn i cc thuc
ny thnh dng hot ng. Do , dng ng thi fluoxetine, paroxetine vi mt thuc opiate
lm nh hng n hiu qu gy m ca thuc opiate. Sertraline, citalopram, escitalopram hu
nh t gy cc bin chng iu trj do tng tc thuc.
Kh nng c ch men cytocrom P450 (CYP) ca cc thuc chng trm cm thung dng
Xp Ioai tuong di CYP 1A2 CYP 2C CYP 2D6 CYP 3A
Cao Fluvoxamine Fluoxetine Bupropion Fluvoxamine
Fluvoxamine Fluoxetine Nefazodone
Paroxetine TCAs
Trung bnh TCAs hng th 3 Sertraline TCAs hng th 2 Fluoxetine
Fluoxetine Citalopram Sertraline
scitalopram
Sertraline
Thp (ti thiu) Bupropion Paroxetine Fluvoxamine Citalopram
Mirtazapine Venlafaxine Mirtazapine scitalopram
Nefazodone Nefazodone Mirtazapine
Paroxetine Venlafaxine Paroxetine
Sertraline Venlafaxine
Venlafaxine
3.1.2. Duc Ic hc:
Cc thuc SSR c cho l c hiu qu trj liu thng qua c ch ti hp thu 5-HT.
Thuc cng t nh hng n ti hp thu norepinephrine hay dopamine. Thng thng tc
ng lm sng thch hp, su bo ho cht vn chuyn 5-HT u t c ngay t liu khi
u. V nguyn tc, liu cao cng khng lm tng hiu qu iu trj chng trm cm nhng c
th lm tng nguy c bj tc dng ph.
Citalopram v escitalopram l cht c ch chon loc nht n su ti hp thu serotonine,
v t gy c ch ti hp thu norepinephrine hay dopamine, v t c i luc vi th th histamine
H1, GABA, hay benzodiazepine. Cc SSR khc c c tnh tng tu, ngoi tr fluoxetine c
ch ti hp thu norepinephrine v gn kt vi th th 5-HT2C, sertraline c ch ti hp thu
norepinephrine, dopamine, paroxetine c hiu qu khng cholinergic ng k khi dng liu cao,
v gn kt vi men tng hp nitric oxide. Tng tc dc luc hoc xut hin tim n bn di
hiu qu chng trm cm khi kt hp s dng fluoxetine v olanzapine, l khi dng chung
gy tng tp trung norepinephrine no. S dng ng thi SSR v thuc nhm triptane
(sumatriptan, naratriptan, rizatriptan, zolmitriptan) c th gy tng tc dc luc hoc nng n,
gy ra hi chng serotonine. Tuy nhin, nhiu ngi, vic dng thuc nhm triptan vi liu
thp SSR phng nga cn au u nhng khng c tc dng ph. Phn ng tng tu c
th xut hin khi dng SSR vi tramadol (ltram).
3.2. Chi d[nh tr[ Iiu:
3.2.1. Trm cm:
Ngoi tr fluvoxamine cha c FDA chp nhn, cc thuc SSR khc u c chp
nhn iu trj trm cm. Mt s nghin cu cho thy cc thuc chng trm cm c tc ng ln
serotonine hoc/v norepinephrine, nh MAO, TCA, venlafaxine, mirtazapine t hiu qu hi
phc bnh cao hn so vi SSR trong cc nghin cu i u (so snh). SSR c chon l
thuc u tay trong iu trj chi v s dng n gin, an ton v ph hot ng rng.
So snh truc tip, n c th mt thuc SSR khng bc l bt c u im no so vi
thuc SSR khc. Tuy nhin, tnh a dng r rng l do kh nng p ng ca bnh nhn vi
cc SSR khc nhau. V d: hn 50 p ng km vi mt thuc SSR c th p ng tt vi
mt thuc SSR khc. Do , trc khi thay i bng mt thuc chng trm cm khng phi
SSR, nn th tt c cc thuc SSR khc khi bnh nhn khng p ng vi thuc SSR s
dng u tin. Mt s bc s lm sng c gng chon mt thuc SSR c bit cho nhng bnh
nhn chuyn bit dua trn danh sch tc dng ph ca ring tng thuc. V d: fluoxetine l
mt thuc SSR c tc ng kch thch, mt s bc s s tha nhn rng chon s dng
fluoxetine s c hiu qu tt hn vi bnh nhn bj mt ch, hn l dng SSR c tc dng an
thn. Tuy nhin su khc bit ny thng thay i tuy theo bnh nhn.
3.2.2. T st:
Nhng nm cui thp nin 80 th k , mt s bo co c pht hnh rng ri
nghj v mi lin h gia vic dng fluoxetine v hnh vi kch ng, k c tu st, nhng nhiu
xem xt sau khng xc nhn mi lin h ny. Mi y nht, cc nghin cu iu trj bng
SSR cho trm cm tr em v tr vj thnh nin pht hin tnh trng tng nhe tng hoc xung
ng tu st. Nhng trn thuc t, vn khng r rng v nguyn nhn v tc ng gia vic dng
SSR v tng nguy c tu st. Tuy nhin, mt s bnh nhn tr nn lo u, bi ri mt cch c
bit khi bt u dng SSR. Su xut hin cc triu chng ny c hnh dung l c th gi ra
hoc lm trm trong hn tng tu st. Do , tt c bnh nhn trm cm nn c theo di
st sut thi gian c nguy c cao c tng/hnh vi tu st, nhng ngy u, tun u khi s
dng SSR. iu quan trong phi nh l cc SSR l thuc chng trm cm c hiu qu u
tin l ngn nga tu st, rt ngn v phng nga giai on trm cm.
3.2.3. Trm cm trong thai k v sau sanh:
T l ti pht trm cm nng trong thai ky khi bnh nhn ngng thuc hoc th ngng
thuc, hoc gim liu thuc l rt cao. T l ny thay i t 68 100 bnh nhn. Do , nhiu
ph n cn tip tc dng thuc trong sut thai ky v sau sanh. nh hng ca tnh trng trm
cm ngi me ln qu trnh pht trin ca tr vn cha r rng. Khng c tnh trng tng
nguy c gy qui thai bm sinh khi phi s dng SSR trong thai k. Do , nguy c ti pht
trm cm thai ph ngng SSR cao gp nhiu ln so vi nguy c ca thai vi tc ng ca
SSR. C mt s bng chng nghj rng c tnh trng tng nguy c phi chm sc nhi c
bit sau sanh nhng thai ph dng SSR. Tuy nhin cng tn ti bng chng tng tu khi
ngng iu trj paroxetine. Khng mi lin h no gia vic s dng SSR v bin chng s
sinh (neonatal) ng k. Cc nghin cu theo di tr trong nhng nm hoc u tin cng khng
pht hin bin chng quanh giai on chu sinh (perinatal), bt thng bo thai, gim im ,
chm ni/ngn ng, hay nhng ri lon hnh vi chuyn bit no c th do s dng fluoxetine
trong thai k.
Trm cm sau sanh (c hay khng c lon thn) nh hng mt t n cc b me. Mt
s bc s lm sng bt u chi jnh dng SSR nu c tnh trng bun sau sanh (postpartum
blues) ko di vi tun sau sanh, hoc nu thai ph bt u trm bun trong thai k. C th chi
jnh trc SSR trong thai k nu thai ph c nguy c mc phi trng thi bun sau sanh v c
th gip bo v tr s sinh, nht l nhng thai ph c th c suy ngh nguy him sau khi sinh.
Cc thuc SSR tit qua sa me nhng huyt tng ca nhng tr c nui bng sa ca b
me ang s dng SSR c nng SSR rt thp. Tuy nhin, trong mt s trng hp, nng
thuc trong mu tr ny cao hn trung bnh. Do , cn ch n vic thng tin v nguy c
tim tng cho nhng bnh nhn ang c iu trj.
3.2.4. Trm cm ngui gi v ngui c bnh co th:
Cc thuc SSR an ton v dung np tt vi ngi gi v ngi c bnh thuc th. Nh
cch phn loi, thuc SSR c t hoc khng gy c cho tim, tc dng ph khng cholinergic,
khng histamine hoc tc dng ph inotropic adrenergic. Ring paroxetine c hot tnh khng
cholinergic, nn c th gy to bn, lm suy gim nhn thc. Cc SSR c th gy suy gim
nhn thc rt nhe, ko di thi gian tun hon mu, gim natri mu v iu ny c th nh
hng n sc kho nhng bnh nhn iu trj bng SSR. Cc SSR cn c hiu qu n trm
cm sau t qu v lm gim kjch tnh tnh trng hay khc lc.
3.2.5. Trm cm tr em:
Cc nghin cu v SSR tr em v tr vj thnh nin thng khng tm c hiu qu
ca SSR. Chi c fluoxetine c FDA chp nhn l thuc chng trm cm dnh cho la tui
ny. Trn thuc t, tr em cng bj trm cm v can thip bng ho trj liu cng cn thit cho
nhiu trng hp bnh, nn cc bc s lm sng cng phi chi jnh thuc SSR cho nhng
trng hp ny. Cc nghin cu nghj rng thuc SSR c th lm tng ngh hoc hnh vi
tu st, ngh hoc hnh vi bo luc tr em/tr vj thnh nin trm cm. V vy, khi iu trj trm
cm bnh nhn ny, cn thit theo di st tc dng v hnh vi khng mong mun ny.
3.2.6. Ri Ioan Io u:
Ri lon m nh cng ch (OCD! fluvoxamine, paroxetine, sertraline v fluoxetine
nn chi jnh cho nhng bnh nhn trn 18 tui. Fluvoxamine v sertraline c chp nhn l
thuc iu trj OCD tr em/tr vj thnh nin (6 17 tui). Khong 50 bnh nhn OCD c
triu chng OCD t thi nin thiu/tui vj thnh nin, hn s bnh nhn ny p ng tt vi
thuc. p ng trj liu c th rt kjch tnh. Nhng s liu lu nm cho thy kiu bnh l OCD l
dng bnh c tnh di truyn v ko di sut i p ng tt nht vi iu trj duy tr bng thuc
v trj liu nhn thc hnh vi, ngay t khi khi pht bnh t thi nin thiu cho n cui i.
Liu thuc SSR cho bnh l OCD cn duy tr cao hn trong iu trj trm cm. Mc d
p ng vi thuc c th xut hin trong vi tun u tin iu trj nhng cng cn nhiu thng
iu trj mi t hiu qu trj liu ti a. Nhng bnh nhn khng p ng vi thuc SSR c th
s p ng tt hn vi phi hp bng risperidone. Bn cnh vic phi theo di tc dng ph
ngoi thp do risperidone, cn theo di tc dng ph do tng prolactine trong nhng trng
hp phi hp trj liu. Trn lm sng, tnh trng tng nng prolactine c th biu hin bng
tnh trng v to, hoc chng tit sa (c nam v n) v chng mt kinh.
Hin nay, mt s ri lon khc cng c xem l bin th ca OCD. l cc bnh l
vi cc triu chng c trng l hnh vi tu ct c th nhng khng c tu st, v d: chng nh
(lng) tc, xm lng my, xung ng xm vng da d bn, xung ng ct (c th). Cc bnh
nhn c hnh vi ny c th p ng vi thuc SSR. Nhng bnh l bin th khc gm c:
xung ng nh bc, xung ng mua sm, chng nghi bnh, ri lon s bin dng c th.
Ri lon hong lon! Paroxetine v sertraline c chi jnh s dng iu trj ri lon
hong lon, c hay khng km theo chng m s khong rng. Nhng thuc ny c hiu qu
chm hn so vi alprazolam (anax) hay clonazepam (Rivotril), nhng c hiu qu lu di tt
hn so vi benzodiazepine trong iu trj ri lon hong lon c km trm cm. Citalopram,
fluvoxamine, fluoxetine cng c th lm gim triu chng cn trm cm nguyn pht hoc th
pht. Do fluoxetine c kh nng gy ra cc triu chng lo u, bnh nhn bj cn hong lon phi
c chi jnh bt u s dng liu thp (5mg/ngy) v tng dn liu chm chp. Dng
benzodiazepine liu thp c th c s dng nhm kim sot tc dng ph lo u ca
fluoxetine.
Ri lon lo "u #$ h%i! thuc SSR c hiu qu iu trj m s x hi. Thuc lm gim c
triu chng bnh v tnh trng mt nng luc (do bnh gy ra). T l p ng vi thuc SSR
tng ng vi MAO phenelzine (Nardil), trc y l mt thuc iu trj tiu chun. Thuc
SSR an ton hn so vi MAO hoc benzodiazepine.
Ri lon &'r(&& &au &ang ch)n (*TSD! ho dc trj liu vi PTSD nhm vo cc triu
chng c bit ca 3 nhm: ti tri nghim, n trnh v tng gi nh. Trong iu trj lu di,
thuc SSR c ph trj liu cc triu chng c trng ca PTSD rng hn so vi TCA v MAO.
Tng liu benzodiazepine c ch i vi cn cp tnh. Thuc SSR gy ci thin r rt c triu
chng xm ln v triu chng n trnh.
Ri lon lo "u lan 'o! Thuc SSR c ch iu trj cc m s chuyn bit, ri lon lo
u lan to v ri lon lo u chia ly. Vic nh gi mang tnh c nhn v k lng l cc tip cn
u tin, ch c bit v vic pht hin loi bnh l p ng tt vi trj liu bng thuc. Km
theo , trj liu nhn thc hnh vi hay trj liu tm l khc cng nn kt hp t hiu qu
cao hn.
Ch+ng ,n ung -. /% '"m l0 -1 cc ri lon ,n ung 2hc! fluoxetine c chi jnh
iu trj cho chng n ung v , nhng php trj liu tt nht cho bnh l ny vn l tm l trj
liu. Liu fluoxetine nn l 60mg/ngy th tt hn liu 20mg/ngy. Trong mt s nghin cu
kim sot tt, fluoxetine vi liu 60mg/ngy tt hn nhiu so vi gi dc nhm lm gim tnh
trng n ung khng ngng v gim nn. Mt s chuyn gia nghj rng chi nn trj liu nhn
thc hnh vi n thun (m khng km iu trj ho dc); v nu khng c p ng sau 3
6 tun th mi kt hp vi fluoxetine. Thi gian thch hp iu trj bng fluoxetine v tm l trj
liu khng c gii hn.
Fluvoxamine khng hiu qu ng k iu trj chng n ung v trong nghin cu
m i, c so snh vi gi dc.
Ch+ng chn ,n '"m 'hn! fluoxetine c dng iu trj bnh nhn chn n tm thn
ni tr nhm kim sot ri lon kh sc kt hp v triu chng m nh cng ch. C t nht 2
nghin cu cn thn, mt nghin cu trong 7 thng, 1 nghin cu trong 24 thng nhng u
khng pht hin fluoxetine c hiu qu ln kt qu ton b v ln vic duy tr cn trong. Vic
iu trj c hiu qu chng chn n tm thn l php trj liu nhn thc hnh vi, trj liu ni tm,
trj liu ng nng tm thn, trj liu gia nh kt hp vi thuc SSR.
Ch+ng 34o 5h6! fluoxetine kt hp vi chin lc v hnh vi cho thy c hiu qu gim
cn tt nht. C t l ng k bnh nhn dng SSR, k c fluoxetine, gim cn trong giai on
u, nhng sau c th tng cn tr li. Tuy vy, cng cn bit rng, tt c cc thuc SSR
u c th gy tng cn.
Ri lon lon cm 'r7c 26 2inh ngu89'! ri lon lon cm trc k kinh nguyt c
trng bi kh sc suy sp v thay i hnh vi vo tun trc khi c kinh, thay i r rt so vi
lc bnh thng. Sertraline, paroxetine, fluoxetine, v fluvoxamine c tc dng lm gim triu
chng ri lon cm trc k kinh. Nghin cu th nghim c so snh s dng fluoxetine,
sertraline trong c chu ky, hoc chi trong giai on hong th (2 tun gia lc rng trng v khi
c kinh nguyt) cho thy u c hiu qu nh nhau.
Mt nghin cu quan st khng r rng cho thy fluoxetine lm thay i thi gian chu k
kinh nguyt, nhiu hn 4 ngy, ko di hn hoc thu ngn li. Tc ng ca SSR ln thi gian
chu k kinh hu nh cha c bit r, v i hi phi theo di cn thn khi dng SSR ph
n trong tui sinh .
3.2.7. Nhng chi d[nh khng chnh thng:
:u)' 'inh &7m! hiu qu chng co tht ca SSR c li dng iu trj cho nam gii
bj chng xut tinh sm. Thuc SSR cho php ko di thi gian giao hp v ci thin su tho
mn tnh dc cho nhng cp v chng m ngi chng bj xut tinh sm. Fluoxetine v
sertraline c ch cho vic s dng nhm mc ch ny.
*ara5hilia& ('6nh ;<c /=i 'r<8! thuc SSR gim hnh vi m nh cng ch nhng
bnh nhn bj paraphilias. SSR lm gim thi gian trung bnh trong ngy cho hnh vi tho mn,
thi thc tnh dc khng thch hp. Nhng bng chng cho thy, thuc c tc ng tt ln m
nh tnh dc hn l hnh vi ph by.
Ch+ng '> 2?! hnh vi m nh cng ch, tnh trng km giao tip x hi, tnh trng
hung hng c trng cho chng tu k p ng vi nhng thuc tc ng ln h serotonine nh
SSR v clomipramine. Sertraline, fluovoxamine cho thy gip ci thin tnh hung hng, hnh vi
tu gy thng tch, hnh vi lp li, mt s mc v tnh trng tr hon v ngn ng, v him
hn l tc ng n tnh thiu lin h x hi ngi trng thnh c ri lon kiu tu k.
Fluoxetine cng c hiu qu n chng tu k tr em, tr vj thnh nin, v ngi trng
thnh.
3.3. Thn trng v tc dng ph:
Tc dng ph ca SSR thng c xem xt tuy theo cch khi pht, thi gian ko di
v mc nng. V d: bun nn v tnh trng bn chn lo u thng l tc dng ph xut hin
sm, nhe, v tu gii hn theo thi gian.
3.3.1. Ri lon ch+c n,ng '6nh ;<c! tt c cc thuc SSR u gy ri lon chc
nng tnh dc v l tc dng ph thng gp nht ca SSR khi s dng lu di.
Tn sut mi mc ca tc dng ph ny khong 50 80. Than phin thng
nht l gim cuc khoi, c ch tnh trng cuc khoi, gim ham mun tnh dc.
Mt s nghin cu nghj rng ri lon chc nng tnh dc c lin quan n liu
s dng, nhng mi lin quan ny cng khng r rng lm. Khng ging nh
hu ht cc tc dng ph khc do SSR, c ch tnh dc him khi hi phc sau
vi tun u iu trj, nhng thng ko di cng vi thi gian s dng thuc.
mt s trng hp, tnh trng ny c th ci thin theo thi gian.
Chin lc chng li ri lon tnh dc do SSR c cp n rt nhiu nhng khng
chin lc no chng mnh c hiu qu. Mt s nghin cu nghj gim liu SSR v thm
bupropion vo. Cc nghin cu cng m t nhng thnh cng trong iu trj ri lon tnh dc do
SSR bng sildenafil (Viagra), c hiu qu iu trj ri lon chc nng cng. Cui cng th
bnh nhn cng phi i sang thuc chng trm cm khc khng nh hng n chc nng
tnh dc, nh: mirtazapine, bupropion.
3.3.2. Tc ;<ng 5h< -@ ; ;18 ru%'! tc dng ph ny rt thng gp, c lin quan
n tc dng ln th th serotonin 5HT3. Than phin thng nht l: bun nn,
tiu chy, chn n, nn, y hi, kh tiu. Sertraline v fluvoxamine thng gy
ra tc dng ph ny nht. Paroxetine phng thch chm so vi paroxetine phng
thch ngay lp tc, cng t gy tc dng ph d dy rut hn. Tuy nhin, vi
paroxetine, do tc ng khng cholinergic, nn thng gy to bn. Bun nn v
tiu lng thng lin quan vi liu s dng v thng chi thong qua, hi phc
trong vi tun. Tuy nhin, tnh trng y hi v tiu chy vn tn ti, c bit l
khi s dng sertraline. Chn n lc khi u iu trj cng thng xut hin v
thng gp khi s dng fluoxetine. Chn n v gim cn do SSR thng bt
u khi dng thuc v gp nhiu nht khong 20 tun; sau , cn trong thng
tr v mc bnh thng. C n khong 1/3 bnh nhn bj tng cn, thinh
thong tng n 9kg. Tc dng ph ny do tc ng n qu trnh chuyn ho,
hoc lm tng ngon ming, hoc do c 2. Tnh trng ny thng din ra t t v
thng khng p ng vi ch n king hoc luyn tp th dc. Paroxetine
thng gy tng cn hn so vi cc SSR khc, nht l ph n tr.
3.3.3. Aau /u! tn sut mi mc ca tnh trng au u khi s dng SSR khong 18
20, chi cao hn 1 so vi gi dc. Fluoxetine l thuc d gy au u nht
so vi cc SSR khc. Tuy nhin, tt c cc thuc SSR u c hiu qu iu trj
phng nga cn au u migrain v au u cng c nhiu BN.
3.3.4. Tc ;<ng 5h< lBn h9 TCTD!
Eo "u! Fluoxetine c th gy ra lo u, nht l nhng tun u iu trj. Tuy nhin, tc
dng u tin ny s gim hon ton sau vi tun. Tnh trng lo u c th c gim hn nu
iu trj bng paroxetine, escitalopram, nht l nu mong mun c tc dng an thn, bun ng.
F)' ngG -1 an 'hn! tc ng chnh ca SSR ln gic ng l gip ci thin gic ng
nn SSR iu trj c trm cm v lo u. Tuy nhin, c n bnh nhn dng SSR gp vn
v gic ng hoc ng qu mc, hoc cm thy mt mi. Fluoxetine l thuc thng gy mt
ng nht trong s cc SSR, nn n thng chi dng vo bui sng. Sertraline, fluvoxamine
cng gy mt ng tng ng vi gy tnh trng ng nhiu; citalopram, v nht l paroxetine
cng thng gy ng nhiu. scitalopram gy cn tr gic ng nhiu hn so vi citalopram (t
ng hn). Mt s bnh nhn li dng tc dng ph ca SSR ng nn dng bui ti trc
khi ng, trong khi s khc li dng thuc vo ban ngy gip gim ng. Mt ng do SSR c
th iu trj bng benzodiazepine, trazodone (nhng phi gii thch tc dng ph gy cng
cng dng vt ca trazodone), hoc nhng thuc gy ng khc. Ring tnh trng ng nhiu
do SSR th cn phi i sang thuc SSR khc, hoc i bupropion.
Tc /%ng 2hc lBn gi)c ngG! c nhiu BN dng SSR than phin cm gic ng nh
ang thc, hoc thy c mng. Mt s khc li m t tnh trng nghin rng khi ng, tnh trng
chn khng yn, git c lc ng, tot m hi lc ng.
T6nh 'rng cHn mIn cm #Jc! cn mn cm xc l tnh trng thng thy khi s dng
SSR ko di. Cc BN m t tnh trng khng c kh nng khc, hay phn ng vi mt tnh
hung cm xc no , cm thy v cm, th , khng vi thay i cm xc. Tc dng ph
ny thng lm cho BN ngng iu trj ngay c khi thuc gip thot khi trng thi trm cm, lo
u.
K"8 ng5! cc quan st lm sng tch cuc nhn thy BN dng SSR c biu hin tng
ngp. Tc dng ph ny khng phi do thuc gy mt mi, hay do gic ng m km, m l do
SSR tc ng ln vng h i.
Co giL'! co git chim khong 0.1 0.2 BN iu trj bng SSR. T l ny tng tu
nh cc thuc chng trm cm khc v khng khc bit so vi gi dc. Co git thng xut
hin khi dng liu cao (VD: fluoxetine liu 100mg/ngy hoc cao hn).
Tri9u ch+ng ngoi 'h5! SSR him khi gy tnh trng bn chn khng yn, run, tng
trng luc c kiu bnh xe rng ca, lon trng luc c cp (veo c, trn mt, ri lon dng
i), i ng chm. Mt s him trng hp bj ri lon vn ng mun. BN bj bnh Parkinson
c iu trj tt cng c th bj nng hn khi s dng SSR.
Tc ;<ng an'icholin(rgic! paroxetine gy tnh trng anticholinergic nhe nh: kh
ming, to bn, an thn, lin quan n liu. Tuy nhin, a s bnh nhn dng paroxetine vn
khng thy c tc dng ph ny. Cc thuc SSR khc thng gy kh ming, nhng tnh trng
kh ming ny li gin tip do tc ng muscarinic.
3.3.5. Tc ;<ng 5h< hu8' hMc! cc SSR c th gy suy gim chc nng kt tp tiu
cu nhng khng lm gim s lng tiu cu. Tnh trng ny c th biu hin
bng d bj bm tm di da, hoc chy mu nhiu, ko di. Khi xut hin tnh
trng ny, nn thuc hin xt nghim mu. Theo di k lng khi bnh nhn s
dng kt hp SSR v thuc chng ng, hoc aspirin.
3.3.6. Ri lon /i9n gii -1 gluco&(! cc SSR gy gim cp tnh ng huyt, do
, bnh nhn tiu ng nn c theo di st ng huyt. Mt s him
trng hp c tnh trng h natri mu do SSR v tnh trng tit hormon bi niu
khng ph hp c th gp nhng bnh nhn dng km thuc li tiu.
3.3.7. *hn +ng n%i 'i' -1 ;N +ng! cc SSR gy gim nng SSR v gy pht
trin m tuyn v (mammoplasia), chng tit sa c nam v n. Tuyn v c
th v bnh thng khi ngng thuc, nhng phi ko di n vi thng sau.
Cc hnh thc pht ban khc nhau c th xut hin trong khong 4 bnh nhn s
dng SSR; trong mt s nh bnh nhn ny, phn ng dj ng c th lan ton c th v nh
hng n h h hp, him hn cn c th gy x ho phi v gy ngng th. Vic s dng
SSR do cn phi ngng ngay lp tc bnh nhn bj pht ban.
3.3.8. O%i ch+ng &(ro'onin(! vic s dng ng thi SSR v mt thuc MAO, L-
tryptophan, hay lithium c th lm tng nng serotonine huyt tng v t
n nng ng c, gy ra mt lot cc triu chng c goi tn l hi chng
serotonine. Hi chng ny nng n v c th gy t vong do kch thch qu mc
serotonine, gm c cc triu chng c sp xp theo th tu xut hin khi bnh
cng lc cng xu dn i:
tiu chy,
bn chn khng yn,
kch ng d di, tng phn x, mt n jnh thn kinh thuc vt vi cc du hiu
sinh tn dao ng nhanh chng,
rung git c, co git, tng thn nhit, rung ry khng kim sot, cng ,
sng, hn m, trng thi ng kinh, suy tun hon v cht.
iu trj hi chng serotonine cn phi loi b nhng thuc gy ra tnh trng ny, chc
chn phi thnh lp h thng nng thch hp: nitroglycerine, cyproheptadine, methysergide
(Sansert), chn lnh, chlorpromazine, dantrolene (Dantrium), benzodiazepine, chng ng kinh,
thng kh h tr, thuc gy t.
3.3.9. T6nh 'rng 'o' m= h.i! mt s bnh nhn mc phi tnh trng tot m hi khi
s dng SSR. Tnh trng tot m hi ny khng lin quan g n nhit mi
trng. Tot m hi m c th gy t m chn mn v bt buc bnh nhn
phi thay i qun o ng. Dng terazosin 1 2mg/ngy c th c hiu qu
ng kinh ngc n vic lm mt tc dng ph gy tot m hi.
3.3.10. O%i ch+ng cai SSRP!
Ngng t ngt SSR, nht l vi cc SSR c thi gian bn hu ngn (VD: paroxetine,
fluvoxamine) c th gy ra hi chng cai vi biu hin: tnh trng chng mt, run, bun nn,
au u, trm cm di ngc, lo u, mt ng, km tp trung ch , th nhanh, dj cm, triu
chng ging migrain. Tnh trng ny thng khng xut hin nu iu trj SSR cha n 6
tun, v thng hi phc dn trong 3 tun. Nhng bnh nhn c tc dng ph thong qua
trong nhng tun u khi bt u dng SSR thng hay bj hi chng ngng SSR.
Fluoxetine l loi SSR t gy hi chng ny nht v thi gian bn hu ca cc chuyn
ho cht ko di hn 1 tun v thuc tu gim dn hiu qu. Do , fluoxetine thng c s
dng iu trj cho nhng trng hp bj hi chng cai SSR khc. Tuy nhin, hi chng cai cng
xut hin vi fluoxetine nhng nhe hn v chm hn.
3.4. Tuong tc thuc:
Cc thuc SSR hu nh khng tc ng n hu ht cc thuc khc. Hi chng
serotonine c th xut hin nu dng chung MAO, tryptophan, lithium hoc thuc chng trm
cm khc c tc dng c ch ti hp thu serotonin. Fluoxetine, sertraline, paroxetine c th lm
tng nng huyt tng ca chng trm cm TCA v gy ng c TCA trn lm sng. Mt s
tng tc dc ng hoc c th xut hin, c nhn ra trong cc phn tch th nghim men
CP nhng him thy tng tc trong lm sng.
Kt hp lithium v cc thuc tc ng ln h serotonine cn phi thn trong v c th
gy co git. Thuc SSR v nht l fluvoxamine, khng nn dng chung vi clozapine v lm
tng nng clozapine v gy co git. Thuc SSR c th lm tng thi gian tn ti v mc
nng ca tnh trng o gic do zolpidem.
3.4.1. Qluo#('in(!
Fluoxetine c th c chi jnh dng chung vi thuc TCA, nhng chi nn dng liu
thp TCA. V fluoxetine c h men CP ca gan chuyn ho, nn thuc c th lm tc ng
n chuyn ho ca cc thuc khc, c th gp 7 dn s c dng ng phn khng hot
ng ca h men ny, cn c goi l nhng ngi c chuyn ho km. Fluoxetine c th lm
gim chuyn ho ca carbamazepine, thuc chng seo (antineoplastic), diazepam v
phenytoin. Tng tc thuc do fluoxetine l lm nh hng n nng huyt tng ca
benzodiazepine, thuc chng lon thn v lithium. Fluoxetine khng tng tc vi arfarin
(Coumadin), tolbutamide, chlorothiazide.
3.4.2. S(r'ralin(!
Sertraline c th thay th arfarin trong gn kt vi protein huyt tng v c th gy
tng thi gian prothrombin. Cc s liu v tng tc thuc gia sertraline tng tu vi
fluoxetine mc d sertraline khng tng tc mnh m vi enzyme CP 2D6.
3.4.3. *aro#('in(!
Paroxetine c nguy c gy tng tc thuc nhiu hn so vi fluoxetine v sertraline v
thuc ny c kh nng c ch mnh n enzyme CP 2D6. Cimetidine c th lm tng nng
sertraline v paroxetine. Phenobarbital v phenytoin c th lm gim nng ca
paroxetine. V thuc c kh nng tc ng n men CP 2D6, nn vic s dng ng thi
paroxetine vi thuc chng trm cm khc, phenothiazines v thuc chng lon nhjp phi c
thn trong cao . Paroxetine c th lm tng hiu qu chng ng ca arfarin. Dng ng
thi paroxetine v tramadol (ltram) c th thc y xut hin hi chng serotonine ngi
gi.
3.4.4. Qlu-o#amin(!
Trong s cc thuc SSR, fluvoxamine c nguy c cao nht gy tng tc thuc.
Fluvoxamine c chuyn ho bng men CP 3A4, m h men ny bj ketoconazole c ch
hot ng. Fluvoxamine c th lm tng thi gian bn hu ca alprazolam (anax), triazolam
(Halcion) v diazepam, nn fluvoxamine khng nn s dng ng thi vi cc thuc ny.
Fluvoxamine c th lm tng nng theophylline gp 3 ln v tng nng arfarin gp 2
ln, nn c th gy nhng h qu ng k trong lm sng; do , nng huyt thanh ca
theophylline v arfarin nn c theo di st sao v nn iu chinh liu tuy theo nng
thuc trong huyt thanh. Fluvoxamine lm tng nng v lm tng tc ng ca clozapine,
carbamazepine, methadone (Dolophine, Methadose), propranolol, diltiazem. Fluvoxamine
tng tc khng ng k vi lorazepam hay digoxin.
3.4.5. Ci'alo5ram!
Citalopram khng c ch ng k bt c h men CP no. Vic s dng ng thi
cimetidine lm tng nng citalopram khong 40. Citalopram khng tc ng ng k
chuyn ho ca cc thuc sau, cng nh chuyn ho ca thuc citalopram cng khng bj cc
thuc sau nh hng: digoxin, lithium, arfarin, carbamazepine, imipramine. Citalopram lm
tng nng ca metoprolol gp 2 ln, nhng iu ny thng khng nh hng n huyt p
cng nh nhjp tim. Nhng s liu thng k v vic s dng ng thi citalopram v thuc c
ch CP 3A4, CP 2D6, tuy vy, cng cha nhiu.
3.4.6. R&ci'alo5ram!
scitalopram c kh nng c ch tng i n men CP 2D6 v c th lm tng ng
k nng desipramine, metoprolol.
3.5. Liu Iung v hung dn s dng:
3.5.1. Qluo#('in(!
Fluoxetine c trnh by di dng vin bao phim 10- v 20-mg, hay vin nn 10mg,
hoc vin bao phim c mng 90mg dng 1 ln/tun, hoc dng dung djch ung (20mg/5mL).
Liu ban u thng dng l 10 20mg ung/ngy, thng c cho vo bui sng, v
tc dng ph gy mt ng. Fluoxetine nn c dng cng vi thuc phm gim thiu tc
dng ph bun nn. Thi gian bn hu di v c chuyn ho cht hot ng lm thuc cn n
4 tun mi t nng sn sng c hiu qu.
Liu 20mg thng l liu c hiu qu cao iu trj trm cm. Liu ti a c khuyn
dng l liu 80mg/ngy. gim thiu tc dng ph lo u v bn chn khi bt u s dng, cc
bc s lm sng nn bt u bng liu 5- hoc 10-mg/ngy (vin nn hoc dng dung djch). V
sau , c th tng liu u mi ngy. Liu iu trj ca fluoxetine, cng nh cc SSR khc,
t hiu qu vi cc ri lon khc u cao hn so vi iu trj trm cm.
3.5.2. S(r'ralin(!
Sertraline c trnh by vi dng vin nn 25-, 50-, 100mg. iu trj ban u tnh trng
trm cm vi sertraline nn bt u vi liu 50mg/ngy. hn ch tc dng ph tiu ho, cc
bc s lm sng nn bt u bng liu 25mg/ngy v tng ln 50mg/ngy sau 3 tun. Nu bnh
nhn khng p ng sau 1 3 tun, c th tng liu sertraline 50mg mi tun, v c th t ti
a 200mg dng 1 ln trong ngy.
Sertraline c th dng bui sng hoc ti. Nn s dng ngay sau n nhm lm gim tc
dng ph tiu ho. Dng dung djch ung sertraline (1mL 20mg) cha 12 cn v phi c
pha vi nc khi s dng.
Trong iu trj ri lon hong lon, sertraline nn c bt u bng liu 25mg nhm
gim nguy c kch thch gy cn hong lon.
3.5.3. *aro#('in(!
Dng paroxetine phng thch tc th c dng trnh by vin nn 20mg, hoc vin bao
phim 10-, 30- v 40-mg, hoc dung djch sa hng cam 10mg/5mL. Paroxetine dng iu trj
trm cm nn bt u bng liu 10 hoc 20mg/ngy. Tng liu nu khng p ng thch hp
sau 1 3 tun. Liu ti a chi l 50mg/ngy. Nu bnh nhn cm thy kh chju v tiu ho, nn
s dng thuc cng vi thuc phm. Paroxetine c th bt u bng liu duy nht vo bui ti,
liu cao c th chia thnh 2 ln trong ngy.
Dng phng thch chm paroxetine (Paxil CR) c dng trnh by vin nn 12.5-, 25- v
37.5-mg. Liu khi u iu trj trm cm l 25mg/ngy, v iu trj ri lon hong lon th
liu iu trj l 12.5mg/ngy.
Paroxetine l thuc SSR hu nh lun gy hi chng ngng thuc, do nng thuc
trong huyt tng gim nhanh chng nu ngng s dng. hn ch tnh trng ny khi ngng
thuc t ngt, paroxetine nn gim tng bc, v mi ln thay i liu phi cch nhau 2 3
tun.
3.5.4. Qlu-o#amin(!
Fluvoxamine c th c dng trnh by l vin nn 25mg v thng gp vin nn 50-,
100-mg. Liu mi ngy c hiu qu l 50 300mg. Liu bt u iu trj thng l 50mg dng 1
ln trong ngy trc khi ng, trong tun u tin; sau c th iu chinh liu tuy theo tc
dng ph v p ng lm sng. Liu trn 100mg/ngy nn c chia lm 2 ln ung. Gim liu
tm thi hoc tng liu chm c th thuc hin khi tnh trng bun nn xut hin trong 2 tun
u iu trj.
Fluovoxamine c th c chi jnh dng liu duy nht vo bui ti nhm gim thiu tc
dng ph. Vin thuc nn c nut cng vi thc n, nhng khng c nhai. Ngng t
ngt fluvoxamine c th gy hi chng ngng thuc.
3.5.5. Ci'alo5ram!
Citalopram c dng trnh by thng l vin nn 20-, 40-mg v dng dung djch
(10mg/5mL). Liu khi u thng l 20mg/ngy trong tun u tin, sau thng tng liu
n 40mg/ngy. ngi gi hoc bnh nhn suy gan, nn s dng liu 20mg/ngy, v chi nn
tng liu n 40mg/ngy khi khng p ng vi liu 20mg/ngy. Vin thuc chi nn dng 1 ln
trong ngy, hoc sng hoc ti, c th dng cng thc n hoc khng.
3.5.6. R&ci'alo5ram!
scitalopram c th c cc dng trnh by l vin nn 10-, 20-mg, cng nh dng dung
djch 5mg/5mL. Liu c khuyn s dng l liu 10mg/ngy. Trong nhiu nghin cu th
nghim lm sng, liu 20mg/ngy cng khng t hiu qu no nhiu hn.
3.6. Hiu qu km:
Mt s bnh nhn p ng km vi SSR vi biu hin ti din triu chng trm cm
sau mt thi gian iu trj (thng l 4 6 thng). C ch chnh xc ca tnh trng ny vn
cha c bit r rng. Bin php hn ch tnh trng ny nhm ci thin tnh trng p ng vi
SSR l tng hoc gim liu; gim dn liu ri sau th nghim vi loi thuc chng trm cm
khc cng nhm hoc khc nhm; tng vic s dng bupropion hoc thuc khc.
4. THUC CHNG TRM CM TCAs:
Thuc chng trm cm 3 vng v 4 vng (TCAs tri/tetracyclic antidepressants) c ljch
s lu i trong tm thn, c nhn ra kh nng t gia nhng nm 50. D c gii thiu l
thuc chng trm cm, chi jnh trj liu ca thuc hin nay bao gm c ri lon hong lon,
ri lon lo u ton th, ri lon sau sang chn tm l (PTSD), ri lon m nh cng ch, hi
chng au. T khi gii thiu nhng thuc th h mi hn, nh SSRs, bupropion (ellbutrin),
venlafaxin (ffexor) v mirtazapine (Remeron), chi jnh TCAs gim r rt, tuy chng vn cn
cuc k hu dng.
4.1. Duc Ic hc:
Hp thu TCAs ng tiu ha c hon ton v chuyn ha ng k ngay t khi c
hiu qu u tin. Nng inh ca thuc trong huyt tng trong vng 2 8 gi v thi gian
bn hy thay i t 10 70 gi; ring nortriptyline, maprotiline, nht l protriptyline c thi gian
bn hy di hn. Do thi gian bn hy di, nn c th dng thuc 1 ln/ngy. 5 7 ngy l thi
gian cn thit t nng n jnh trong huyt thanh. mipramine pamoate (Tofanil) l dng
thuc du tr tim trong c, chi jnh dng thuc loi ny hn ch nhiu.
TCAs tri qua chuyn ha gan do h men CP P450. Tng tc thuc c th xut
hin do cnh tranh chuyn ha men CP 2D6 gia TCAs v quinidine, cimetidine, fluoxetine
(Prozac), sertraline (Zoloft), paroxetine (Paxil), cc thuc nhm phenothiazine, carbamazepine
(Tegretol), thuc chng lon nhjp nhm C nh propafenone, flecainide. Khi dng chung vi cc
thuc trn c th lm tng nng ca TCAs trong huyt tng. Ngoi ra, nhng dng thay i
khc trong hot ng ca men CP 2D6 c gy tng nng huyt tng ca TCA ln n 40
ln ty ngi bnh. Liu lng TCA do cn iu chinh chnh xc vi nhng thay i ca
chuyn ha TCA gan.
TCAs gy kha cc vj tr vn chuyn ca norepinephrine v serotonine nn lm tng
tp trung ca cc cht dn truyn TK ny. Mi thuc hp dn khc nhau vi mi loi cht dn
truyn, vi clomipramine (Anafranil) hu ht tc ng ln serotonine; vi desipramine
(Norpramin Pertofrane) tc ng chon loc ln hu nh l norepinephrine. Tc dng ph ca
TCAs do tc dng i vn ln th th muscarinic acetylcholine, histamine H1, adrenergic 1 2.
Thuc c kh nng gy tc dng ph do tc ng cc th th khc nhau lm hnh thnh nn
bng tc dng ph khc nhau theo tng thuc. Amoxepine (Asendin), nortriptyline, desipramine
v maprotiline t gy tc dng ph anticholinergic; doxepin (Adapin, Sinequan) li ch yu tc
dng ph antihistamine. Mc d TCAs hu nh u gy to bn, an thn, kh ming, m sng
nhiu hn so vi SSRs, nhng t gy ri lon tnh dc, tng cn, ri lon gic ng hn so vi
SSRs. Thi gian bn hy v thanh thi huyt tng ca hu ht TCA u tng tu nhau.
Mi chi jnh sau cng l chi jnh ca cc thuc SSRs, nhng c p dng rng ri
hn trong vic s dng TCAs trong lm sng. Tuy nhin, cc thuc TCAs cho thy l mt thay
i ph hp vi nhng bnh nhn khng dung np vi cc tc dng ph ca thuc SSRs.
Ri Ioan trm cm nng: iu trj giai on trm cm nng v iu trj phng nga ri
lon trm cm ch yu l chi jnh chnh ca cc thuc TCAs. Cc thuc TCAs cng c hiu qu
iu trj trm cm BN ri lon lng cuc , nhng hu nh chng cng gy ra cn hng cm,
hng cm nhe hoc ri lon kh sc chu ky nhiu hn so vi cc thuc chng trm cm mi
hn, nht l khi so vi cc thuc SSRs v bupropion. Do , thuc TCAs khng c khuyn
dng thng qui iu trj trm cm trong ri lon lng cuc hoc .
Cc triu chng su ut (melancholia), giai on trm cm nng trc , v c tin s
gia nh c ri lon trm cm lm tng kh nng p ng vi iu trj. Tt c cc thuc TCAs c
th dng c hiu qu tng ng nhau trong iu trj ri lon trm cm. Tuy nhin, tng c
th, vn c p ng vi mt thuc TCA ny nhiu hn so vi nhng thuc TCA khc. iu trj
trm cm c nt lon thn lun lun cn phi dng km mt thuc chng lon thn vi thuc
chng trm cm.
Mc d hin nay c dng rng ri nh mt thuc chng trm cm nhng
clomipramine chi c Hoa Ky chp nhn cho iu trj OCD (ri lon m nh cng ch).
Ri Ioan hong Ioan c m s khong rng: imipramine l TCA c nghin cu
nhiu nht i vi iu trj ri lon hong lon c m s khong rng, nhng cc thuc TCAs
khc vn c hiu qu khi dng vi liu thng dng iu trj chng trm cm. Bi v c kh
nng gy lo u vo giai on u, nn liu khi u ca TCA nn l liu thp v nn tng dn
liu tht chm. Liu thp BZD cng nn s dng trong giai on u hn ch nhng tc
dng ph khng mong mun ny.
Ri Ioan Io u ton th: dng doxepin iu trj ri lon lo u cng c FDA ca
M chp nhn. Cc d liu nghin cu cho thy imipramine cng hu hiu. Mc d him khi
c dng, nhng chlordiazepoxide kt hp amitriptyline (Limbitrol) cng c kh nng iu trj
ri lon lo u trm cm hn hp.
Ri Ioan m nh cung ch: ri lon m nh cng ch cho thy p ng c bit tt
vi clomipramine, cng nh vi cc thuc SSR. Mt s ci thin bnh c th thy sau 2 4
tun, nhng cc triu chng gim nhiu hn c th chi tip tc sau 4 5 thng iu trj. Khng
mt thuc TCA no c hiu qu gn nh clomipramine trong iu trj ri lon ny. Clomipramine
cng l thuc chon lua cho nhng bnh nhn trm cm c triu chng m nh ni bt.
Chng dau: cc thuc TCAs c dng rng ri iu trj chng au mn tnh ca
bnh l thn kinh v phng nga chng au u migrain. Amitriptyline l thuc TCA thng
dng nht vi chi jnh ny. Khi iu trj au, liu thuc thng dng thp hn so vi liu iu trj
trm cm, VD: 75mg amitriptyline thng t hiu qu. Hiu qu iu trj thng t c
nhanh chng.
Cc ri Ioan khc: chng i dm tr em c th c iu trj vi imipramine. Bnh
l lot d dy c th iu trj vi doxepin do c tc dng anticholinergic r rt. Nhng chi jnh
khc ca TCA l chng ng r, c mng v PTSD. Cc thuc cng thng c s dng tr
em v tr vj thnh nin bj ADHD ri lon tng ng gim ch (attention-deficit/hyperactivity
disorder), chng i li trong lc ng, ri lon lo u chia ly v ri lon hong s trong m.
Clomipramine thng c dng iu trj chng phng tinh sm, ri lon vn ng v hnh
vi xung ng tr em tu k; tuy nhin, v cc thuc TCAs c th gy t t mt s tr em, tr
vj thnh nin nn trnh vic s dng rng ri.
4.3. Thn trng v tc dng ph:
Tm thn: gy chuyn kh sc thnh hng cm/hng cm nhe. Cng c th gy ri
lon lon thn. Vi liu cao, gy l ln, sng, nht l BN sa st tm thn.
Khng choIinergic: thng BN s dung np c vi liu thp khi c tc dng ph
ny, hoc khi tip tc dng, BN dn dn c th dung np c thuc. Bao gm: kh ming, to
bn, nhn m, sng, tiu kh. C th nhai keo cao su, st ming bng nc flor c th lm
gim kh ming. Bethanechol 25 50mg x 3 4 ln/ngy c th lm gim tnh trng tiu kh v
ci thin cc ri lon phng tinh khi dng trc khi quan h tnh dc khong 30 pht. Glaucome
gc ng c th bj nng hn khi dng thuc, v khi xut hin glaucome cn phi dng ngay lp
tc thuc co ng t. Thuc TCAs phi trnh dng BN glaucome gc ng v thay th bng
thuc SSR. Khi kt hp vi thuc i vn th th dopamine, hoc thuc anticholinergic th tc
dng ph anticholinergic nghim trong c th dn n hi chng anticholinergic trung ng
nh sng, l ln. Khi , c th phi s dng tim bp hoc tnh mch physostigmine chn
on v iu trj.
Tc dng ph tim mach: dng vi liu iu trj thng thng, cc thuc TCA c th gy
nhjp tim nhanh, sng T thp, khong T ko di v gy suy phc b ST trong ghi in tim.
mipramine l thuc c hiu luc ging quinidine vi nng huyt tng c tnh trj liu v c
th lm co tm tht sm. V thuc cn ko di thi gian dn truyn in tim, nn phi chng chi
jnh vi BN bj khim khuyt dn truyn in tim. nhng BN c tin s bj bt k bnh l tim
mch no, cc thuc TCAs chi nn dng sau khi cc thuc SSR hoc cc thuc chng trm
cm mi khng c hiu qu; v nu c dng, chi nn bt u vi liu thp, tng t t v
theo di st chc nng tim. Tt c cc thuc TCAs u c th gy tng nhjp tim tn ti trong
nhiu thng nn y cng l mt trong cc l do thng gp nht ngng s dng thuc,
nht l ngi tr. Vi liu cao, cng nh khi dng qu liu, c th gy lon nhjp tim.
Ha huyt p tu th cng thng gp v i hi phi ngng TCAs. Nortriptyline t gy
tc dng ph ny nht. trnh h huyt p t th, khng nn dng caffein, ung t nht 2 lt
nc/ngy, n thm mui. Khi dng km vi thuc h p, nn gim liu thuc trnh nguy c
h huyt p t th.
Cc tc dng ph ca h thn kinh t dng cn k n l: tot m hi, hi hp, nh
trng nguc, tng huyt p. Thuc TCA phi c ngng vi ngy trc m chng trnh v c
th gy xut hin giai on tng huyt p trong khi m.
An thn: tnh an thn l hiu qu thng gp ca cc thuc TCAs v c ng h nu
mt ng l than phin ca BN. Tc dng an thn ca TCAs l do tc dng anticholinergic v
khng histamine. Amitriptyline, trimipramine v doxepin l cc thuc gy an thn nhiu nht;
imipramine, amoxepine, nortriptyline v maprotiline l thuc t gy an thn hn; desipramine v
protriptyline l thuc t gy an thn nht.
Tc dng v thn kinh: run nhanh v mjn c th xut hin. Run git c v run li, run
chi trn thng gp. Tc dng ph him gp bao gm: mt ngn ng, dj cm, lit c mc v
tht iu.
Amoxepine l thuc duy nht gy hi chng parkinson, trng thi bn chn khng yn,
v ngay c lon trng luc c do tc ng phong ta h dopaminergic ca mt trong s cc
chuyn ha cht ca thuc. Amoxepine cng c th gy hi chng c tnh trong nhiu trg
hp hp him. Maprotiline c th gy co git khi tng liu qu nhanh hoc gi liu cao qu lu
di. Clomipramine v amoxepine c th lm gim ngng ng kinh nhiu hn so vi cc
thuc khc cng nhm. Tuy nhin, trong cng mt nhm, cc thuc TCAs t c nguy c gy co
git, ngoi tr nhng bnh nhn c nguy c co git (VD: BN ng kinh, BN c tn thng no).
Mc d cc thuc TCAs vn c th dng cc BN trn, nhng liu khi u nn thp hn so
vi bnh thng v nn tng liu t t.
Dj ng v tc dng ph huyt hoc: ban c th gp trong 4 5 BN dng maprotiline.
Him gp vng da. Mt bch cu ht, mt lympho bo, chng gim bch cu tng bch cu i
toan cng l nhng tc dng ph him gp khi iu trj bng TCA. Tuy nhin nu mt BN bj au
hong hoc st trong nhng thng u iu trj bng TCA nn c thuc hin ton b cng thc
mu ngay lp tc.
Tc dng ph gan: tng men gan nhe v tu gii hn c th xut hin v nn c
theo di. Cc thuc TCAs c th gy ra vim gan cp tnh t pht trong khong 0.1 1 BN.
Tc dng ph ny c th e doa tnh mng v cn phi ngng ngay thuc chng trm
cm.
Cc tc dng ph khc: tng cn nhe cng thng gp. Amoxepine cng c tc dng
i vn th th dopamine v c th gy tng tit prolactine, lit dng, chng tit sa, tt kinh.
ut tit bt thng hormon khng li niu cng c gp cc thuc TCAs. Cc tc dng
ph khc l: bun nn, nn v vim gan.
Thn trng: cc thuc TCAs cn c th gy hi chng cai tr s sinh, nhjp nhanh dai
dng, x gan, cu kinh v gim phn x b. Thuc cng i qua sa, nhng nng thng
mc khng pht hin c trong huyt tng ca tr. Thuc cng thng phi dng thn trong
BN bnh gan, thn. Cc thuc TCAs khng nn dng trong sut giai on iu trj bng CT,
trc tin l do nguy c bj tc dng nghim trong v tim.
4.4. Tuong tc thuc:
Monoamine oxidase inhibitors (thuc c ch MAO): cc thuc TCA khng nn dng
trong vng 14 ngy khi bt u chi jnh s dng MAOs.
Thuc h huyt p: cc thuc TCAs phong ta ti hp thu guanethidine (simil, smelin),
l cht cn thit cho hiu qu h p. Hiu qu h p qua i khng th th adrenergic (nh
propranolol, clonidine) cng c th bj cc thuc TCAs phong ta. Dng ng thi TCA v -
methyldopa (Aldomet) c th gy ra kch ng hnh vi.
Thuc chng lon nhjp: c tnh chng lon nhjp ca cc thuc TCAs c th cng hp
vi tnh chng lon nhjp ca quinidine, v hiu qu ny cn tng mnh do TCA c ch chuyn
ha ca quinidine.
Thuc khng th th dopamine (DRA): dng ng thi TCA v DRA lm tng nng
huyt tng ca c 2 nhm thuc. Nng huyt tng ca desipramine c th tng gp 2
ln khi dng ng thi vi perphenazine (Trilafon). Cc thuc DRA cng kt hp vi hiu qu
khng histamine v an thn ca cc thuc TCAs.
Cc cht gy trm cm h TKT: cc cht opioids, gii lo u, thuc ng v thuc cm
khng cn k toa c hiu qu gy nghin do tc ng gy suy nhc h TKT, khi dng ng
thi vi cc TCAs. BN nn c khuyn trnh li xe hoc s dng cc dng c nguy him.
Cc cht kch thch giao cm: dng cc thuc 3 vng vi cc thuc kch thch giao cm
c th gy hiu qu tim mch nng n.
Cc thuc trnh thai ng ung: cc thuc ny lm gim nng huyt tng ca
TCA do cm ng men gan.
Cc tng tc thuc khc: Nicotine c th gy gim nng TCA. Nng huyt tng
ca TCA cng c th gim bi acid ascorbid (vitamin C), ammonium chloride, barbiturates, ht
thuc l, carbamazepine, chloral hydrate, lithium v primidone (Mysoline). Nng huyt tng
ca TCA c th tng do dng ng thi vi acetazolamide (Diamox), Na carbonate, acid
acetylsalicylic, cimetidine, li tiu thiazide, fluoxetine, paroxetine, fluvoxamine. Nng huyt
tng ca TCA c th tng gp 3 4 ln nu dng ng thi vi fluoxetine, fluvoxamine,
paroxetine.
4.5. Liu Iung v hung dn Im sng:
Nhng BN du kin dng thuc TCA nn c khm thng qui v c th v cn lm
sng, bao gm: cng thc mu (ch bch cu), ion , chc nng gan. CG nn lm tt c
BN, c bit l ph n trn 40 tui v nam trn 30 tui. Cc thuc TCA c chng chi jnh BN
c TC trn 450 milli giy. Liu ban u thp v tng dn liu. V c nhiu thuc thay th c
hiu qu cao thay cho TCA, cho nn, nn dng cc thuc mi hn nu c bt k bnh l y khoa
m c th tng tc khng mong mun vi thuc TCA.
Ngi gi v tr em nhy cm hn vi tc dng ph ca TCA hn so vi ngi trng
thnh tr. tr em, CG phi c theo di thng k trong sut qu trnh dng TCA.
Liu dng v nng trj liu trong mu thay i ty tng thuc. Ngoi tr protriptyline,
tt c cc thuc TCAs khc c th b1t u bng liu 25mg/ngy v tng n liu dung np.
Chia liu khi bt u c tc dng nng, mc d hu ht liu dng cng nn dng bui ti
nhm gy ng, nu l thuc c tnh an thn nh amitriptyline. Cui cng, ton b liu trong
ngy nn cho vo trc khi ng. Sai lm thng gp trong lm sng l: ngng tng liu khi BN
dung np vi thuc nhng liu dng thp hn liu trj liu ti a v khng cho thy ci thin
trong lm sng. Nh lm sng phi nh gi thng qui mch v thay i huyt p t th khi
tng liu.
Nortriptyline nn dng liu khi u 25ng/ngy. Hu ht BN chi cn liu 75mg/ngy th
c th t c nng thuc trong mu l 100mg/nL. Tuy nhin, c th tng liu n
150mg/ngy nu cn.
Amoxepine bt u bng liu 150mg/ngy v tng n 400mg/ngy.
Protriptyline thng bt u bng liu 15mg/ngy v tng n 60mg/ngy.
Maprotyline c lin quan n tng tn sut co git nu tng liu qu nhanh hoc duy tr
liu qu cao. Maprotyline thng nn bt u bng liu 25mg/ngy v tng trong 4 tun tr ln,
n 225mg/ngy. Nn duy duy tr liu cao ny chi trong 6 tun v gim cn 175 200mg/ngy.
BN bj au mn tnh c th c bit nhy cm vi tc dng ph ca cc thuc TCAs khi
bt u s dng thuc. Do , vic iu trj nn bt u bng liu thp v tng liu chm. Tuy
nhin, nhng BN au mn tnh c th c giai on gim nhe vi trj liu liu thp ko di, nh
amitriptyline hoc nortriptyline liu 10 75mg/ngy.
Cc thuc TCAs nn trnh dng tr em, ngoi tr khng cn cch no khc. Liu
hng dn lm sng cho tr em: imipramine bt u vi liu 1.5mg/kg/ngy. Liu c th c
chun khng qu 5mg/kg/ngy. Vi chng i dm, liu thng dng l 50 100mg/ngy
vo trc gi i ng. Clomipramine c th c liu khi u 50mg/ngy v tng khng qu
3mg/kg/ngy hoc 200mg/ngy.
Khi ngng iu trj TCA, nn gim liu n khong liu ti a trong vng 1 thng. Khi
, nu triu chng khng xut hin tr li, gim khong 25mg (hoc 5mg protriptyline) mi 4
7 ngy. Gim liu chm trnh hi chng bng pht cholinergic nh: bun nn, tng ng d
dy, tot m hi, au u, au c, nn. Hi chng ny c th c iu trj bng dung li liu
nh thuc trc v gim dn chm hn trc. C nhng trng hp nng nh: ti pht
triu chng hng cm, hoc hng cm nhe sau khi ngng t ngt thuc TCA.
Nng d huyt tuong v theo di tr[ Iiu: jnh chun t nng huyt tng c
ngha lm sng chi nn lm sau 5 7 ngy vi cng mt liu, v sau 8 12 gi sau liu cui
cng. V c thay i trong tnh hp thu v chuyn ha, nng huyt tng c th thay i n
30 50 ln gia cc bnh nhn dng cng mt liu TCA. Nortriptyline l thuc duy nht c ca
s trj liu, theo nu liu di 50mg/mL hoc trn 150mg/mL th gim hiu qu.
Nng huyt tng c th c ch xc jnh p ng, nh gi l do tht bi trj liu,
hoc tham kho nng huyt tng c hiu qu cho vic trj liu trong tng lai. Mt s bnh
nhn c p ng trj liu vi nng huyt tng thp hn l thuyt v mt s khc li p ng
vi nng huyt tng cao l thuyt nhng khng bj tc dng ph. Tuy nhin, vi trng hp
c nng huyt tng cao hn l thuyt, nh lm sang nn cnh gic v theo di st, nh:
theo di CG hng lot.
Qu Iiu: qu liu TCA rt nguy him v c th gy t vong. S dng TCA do khng
nn dung liu ti a v khng nn cho thuc qu 1 tun vi bnh nhn c nguy c tu st.
Amoxapine l thuc TCA c nguy c t vong cao nht so vi cc TCA khc khi dung qu liu.
Cc thuc chng trm cm th h mi an ton hn khi dung qu liu.
Triu chng qu liu TCA gm: kch ng, sang, tng phn x gn su, lit rut v lit
bang quang, mt kim sot huyt p, than nhit v gin ng t. Tnh trng c th tin trin n
hn m, suy h hp. Lon nhjp tim c th khng p ng vi iu trj. V thi gian bn hy ca
TCA ko di, bnh nhn c nguy c lon nhjp tim ko di n 3 4 ngy sau khi qu liu, do
ho nn c theo di st ti n vj chm sc tch cuc (C).
Thng tin v TCA
Tn thuc Liu thung dng ngui
trung thnh (mgngy)
Nng d tr[ Iiu trong
huyt tuong (gmL)
mipramine 150 300 150 300
Desipramine 150 300 150 300
Trimipramine 150 300
Amitriptyline 150 300 100 250
Nortriptyline 50 150 50 150
Protriptyline 15 60 75 250
Amoxapine 150 400
Doxepine 150 300 100 250
Maprotiline 150 230 150 300
Clomipramine 130 250
5. CC THUC BENZODIAZEPINE (BZD) V CC THUC TC QNG LN THU THE
BENZODIAZEPINE:
Cc thuc benzdiazepine c tn gn ging nhau do c cng cu trc phn t. Thuc
cng c cng tc ng ln cc th th, nn cc th th ny c goi l th th benzodiazepine,
c tc ng iu chinh ln hot ng ca GABA (gamma aminobutyric acid). Cc thuc ng
vn khng phi benzodiazepine, nh zolpidem (ambien), zaleplon (Sonata) v eszopiclone
(Lunesta), cng c cp bi ny do c hiu qu lm sng dua trn tng tc vi phc
hp th th GABA bng cch kt ni kho cht hay kt hp v th th benzodiazepine.
Flumazenil (Romazicon), mt cht i vn th th benzodiazepine, c dng o nghjch
tc dng an thn do benzodiazepine trong cp cu qu liu benzodiazepine, cng c cp
bi ny. Do benzodiazepine c hiu qu gii lo u nhanh chng nn thuc rt thng c
s dng iu trj ngay lp tc tnh trng mt ng, kch ng hoc lo u trong cc ri lon tm
thn. Thm vo , cc thuc benzodiazepine cng c tc dng gy m, chng co git v gin
c. Tuy nhin, v nguy c l thuc v tm thn v sinh l, vic s dng lu di benzodiazepine
trong kt hp iu trj tm thn, nn c cn nhc.
Mt s BZD chnh yu:
Alprazolam (anax)
Clonazepam (Klonopin)
Diazepam (Valium)
Chlordiazepoxide (Librium)
Lorazepam (Ativan)
Oxazepam (Serax)
Prazepam (Centrex)
Clorazepate (Tranxene)
Triazolam (Halcion)
Temazepam (Restoril)
Flurazepam (Dalmane)
Midazolam (Versed)
uazepam (Doral)
Flumazenil (Romazicon)
Mitrazepam
Lormetazolam
Loprazolam
Clobazam
Flunitrazepam
Brotizolam
5.1. Tc dng duc I:
Ngoi tr clorazepate (Tranxene), tt c cc benzodiazepine c hp thu hon ton
m khng thay i cu trc qua ng tiu ho. hp thu v t nng inh, thi gian khi
pht tc ng nhanh nht l diazepam (Valium, Seduxen), lorazepam (Ativan, Temesta),
alprazolam (anax), triazolam (Halcion) v estazolam (ProSom). Vic khi pht tc ng nhanh
quan trong vi nhng bnh nhn s dng n c benzodiazepine m dju trong giai on lo
u cp tnh, hoc ng nhanh. Mt s benzodiazepine c hiu qu khi dng ng tim tnh
mch, trong khi chi c lorazepam v midazolam (Versed) c hp thu nhanh v nng ng
tin cy khi dng ng tim bp.
Diazepam, chlordiazepoxide, clonazepam (Klonopin, Rivotril), clorazepate, flurazepam
(Dalmane), prazepam (Centrax), quazepam (Doral) v halazepam (Paxipam) c thi gian bn
hu trong huyt tng thay i t 30 100 gi, v v vy c goi l cc benzodiazepine tc
dng di. Thi gian bn hu ca cc cht ny c th n 200 gi nhng bnh nhn c di
truyn tnh trng chuyn ho chm. Bi v t nng thuc n jnh trong huyt tng c
th cn n 2 tun, nn nhng bnh nhn tng c triu chng ng c thuc sau 7 10
ngy nn c nh gi li liu iu trj.
Thi gian bn hu ca lorazepam, oxazepam (Serax), temazepam (Restoril) v
estazolam khong 8 10 gi. Alprazolam c thi gian bn hu khong 10 15 gi. Triazolam
c thi gian bn hu ngn nht (khong 2 3 gi). Vic nh gi ny c xem xt khi s
dng thuc ng ung.
u im ca thuc tc dng di so vi thuc c tc dng ngn l s ln s dng t hn,
t thay i nng huyt tng, t gy hin tng cai nghin. Bt tin ca thuc tc dng di l
su tch lu thuc, tng nguy c suy gim chc nng tm thn vn ng vo ban ngy. Thun li
ca thuc tc dng ngn so vi thuc tc dng di l khng tch lu thuc v t gy an thn vo
ban ngy. Bt tin ca thuc tc dng ngn l s dng nhiu ln, gy tnh trng nghin nhanh
chng v nng n. Tnh trng mt ng ny ngc v qun thun chiu c cho l do thuc
tc dng ngn nhiu hn so vi thuc tc dng di.
Zaleplon, zolpidem v eszopiclone c cu trc khc hn v khc vic kt hp vi tiu
n vj ca th th GABA. Cc benzodiazepine hot ho tt c 3 vj tr kt ni chuyn bit
GABAA benzodiazepine, gy m knh clor v lm gim kch thch t bo c, t bo thn kinh.
Zolpidem, zaleplon v eszopiclon c tnh chon loc trn mt s cc tiu n vj ca th th
GABA. Do iu ny nn hiu qu an thn chon loc hn, v tng i khng gy gin c, khng
c hiu qu chng ng kinh.
Zolpidem, zaleplon, eszopiclon c hp thu nhanh v tt hn qua ng ung, mc
d su hp thu thuc c th tm hon ti a 1 gi nu c dng chung vi thc n. Zaleplon
t nng inh trong huyt tng trong 1 gi v thi gian bn hu khong 1 gi. Nu c
dng ngay sau ba n c nhiu du m, n ung thjnh son, t nng inh chm hn
khong 1 gi, lm gim hiu qu khi pht gic ng. Thi gian bi tit hon ton khong 6 gi
ngi trng thnh kho mnh. szopiclone kt ni km vi protein huyt tng (52 59).
Chuyn ho nhanh v khng c cht chuyn ho hot ng ca cc thuc zolpidem, zaleplon,
eszopiclone gip trnh tch t thuc trong huyt tng so vi cc thuc benzodiazepine tc
dng di.
FGHGIGMt ng:
Mt ng l triu chng thng gp trong cc bnh l tm thn hay thuc th, nn cc
thuc ng khng nn dng lin tip qu 7 10 ngy m khng tm hiu nguyn nhn gy mt
ng. Thuc ra, nhiu bnh nhn gp tnh trng kh duy tr gic ng v s dng ko di tc dng
gy ng ca thuc. Temazepam, flurazepam, v triazolam l nhng benzodiazepam c chi jnh
duy nht cho tnh trng mt ng. Zolpidem, zaleplon v eszopiclone cng chi c chi jnh duy
nht vi tnh trng mt ng. Trong khi nhng thuc ny thng khng gy ra tnh trng mt ng
ny ngc sau khi ngng vic s dng thuc trong mt thi gian, nhng mt s bnh nhn vn
gp tnh trng kh ng tng dn trong nhng m u tin sau khi ngng thuc. Vic s dng
zolpidem, zaleplon v eszopiclone ko di hn mt thng cng khng nh hng n nhng
kh chju khi ngng thuc t ngt. Khng c bt k su dung np thuc (khi o bng cc thang
gic ng) khi th nghim eszopiclone trong 6 thng.
Flurazepam, temazepam, quazepam, estazolam v triazolam l nhng benzodiazepine
c chng minh cho tc dng gy ng. V nguyn tc cc thuc ng benzodiazepam khc
nhau thi gian bn hu; benzodiazepine c thi gian bn hu di nht, triazolam ngn nht.
Flurazepam c th gy ra suy gim nhe tnh trng nhn thc ngay sau khi s dng; triazolam
c th gy ny ngc tnh trng lo u nhe v qun thun chiu. uazepam gy bun ng ban
ngy khi dng lu. Temazepam hay estazolam c th thch hp vi a s ngi trng thnh.
stazola gy khi pht gic ng nhanh chng v hiu qu trong khong 6 8 gi.
FGHGHGCc ri Ioan Io u:
Ri Ioan Io u Ian to: Cc thuc benzodiazepine c hiu qu cao trong vic gim nhe
tnh trng lo u do ri lon lo u lan to. Hu ht bnh nhn c iu trj thuc ny trong mt
thi gian ngn chuyn bit v jnh r gii hn. V ri lon lo u lan to l mt bnh l mn tnh
c t l ti din cao nn mt s bnh nhn bj ri lon ny thng c cho iu trj duy tr ko
di bng benzodiazepine.
Ri Ioan hong Ioan: Alprazolam v clonazepam, hai thuc benzodiazepine c tim luc
cao, thng c dng iu trj ri lon hong lon, c km hoc khng m s m ng. Mc
d cc thuc SSR (serotonine selective reuptake inhibitor nhm thuc chng trm cm c
ch ti hp thu chon loc serotonine) cng c chi jnh iu trj ri lon ny, nhng cc
thuc benzodiazepine c u th gy hiu qu nhanh chng v khng gy ri lon hot ng
tnh dc ng k v khng gy tng cn. Tuy nhin, SSR vn thng c chon lua iu trj
hn v chng c hiu qu ln c cc bnh km theo, v d: ri lon m nh cng ch (OCD).
Cc thuc benzodiazepine v SSR c th c dng phi hp t u cho cc triu chng
hong lon cp; sau benzodiazepine c gim dn sau 3 4 tun khi SSR c hiu qu
iu trj.
m s x hi: Clonazepam c hiu qu iu trj cho m s x hi. Cc benzodiazepine
khc (nh diazepam) cng c dng nh thuc h tr cho iu trj m s x hi.
Cc ri Ioan Io u khc: Cc benzodiazepine c dng phi hp iu trj ri lon
thch ng c triu chng lo u, lo u bnh l vi cc tnh hung x hi (v d: sau tai nn), ri
lon m nh cng ch (OCD) v ri lon sau sang chn tm l (PTSD).
Ri lon trm cm lo u hn hp: Alprazolam c chi jnh iu trj lo u phi hp
trm cm. Mt s thuc chng trm cm c nhiu c tnh an ton hn, c a thch hn
lm alprazolam ri xung chon lua hng th hai, nhng c mt s bnh nhn p ng km vi
cc thuc chng trm cm li p ng tt vi alprazolam.
FGHGJGRi Ioan Iung cc type I:
Clonazepam, lorazepam v alprazolam c hiu qu trong iu trj cn hng cm v l
thuc h tr thay th thuc chng lon thn trong iu trj duy tr. Khi kt hp vi lithium hay
lamotrigine, clonazepam c th tng thi gian n jnh bnh gia cc cn chu ky v cc giai
on trm cm.
FGHGKGTrang thi bn chn khng yn (akathisia):
Thuc chon lua hng u trong iu trj trng thi bn chn thng l cht i vn th
th 2 adrenergic. Tuy nhin, cc thuc benzodiazepine cng c hiu qu iu trj cho mt s
bnh nhn bj trng thi bn chn.
FGHGFGBnh Parkinson:
Mt s bnh nhn bnh Parkinson nguyn pht c th p ng vi vic s dng
zolpidem lu di nhm lm gim tnh trng vn ng chm chp v tnh trng cng .
Zolpidem c dng vi liu 10mg x 4 ln/ngy trong nhiu nm c th c bnh nhn dung
np tt m khng gy bun ng.
FGHGLGCc chi d[nh khc trong tm thn:
Chlordiazepoxide (Librium) c dng iu trj cc triu chng cai ru. Cc thuc
benzodiazepine khc (nht l lorazepam dng ng tnh mch) cng c dng kim sot
triu chng kch ng do s dng cht (nh lm dng amphetamine) v kch ng do lon
thn, trong lc cp cu. Cc thuc benzodiazepine cn c dng thay th amobarbital
(Amytal) trong nhng cuc phng vn c h tr thuc. Cc thuc benzodiazepine cn c
dng iu trj trng thi cng trng luc. Mt s bnh nhn bj ri lon hoang tng c triu
chng lo u hay hong lon cng p ng vi thuc benzodiazepine.
5.3. FIumazeniI trong trung hp qu Iiu BZD:
Flumazenil c s dng nhm mc ch o nghjch tc dng ph an thn, qun, triu
chng tm thn vn ng do cht ng vn th th benzodiazepine, nh cc thuc
benzodiazepine, zolpidem, zaleplon. Flumazenil c dng ng tnh mch, c thi gian bn
hu 7 15 pht. Cc tc dng ph thng gp nht ca flumazenil l bun nn, nn, chong
vng, kch ng, cm xc dao ng, dn mch da, au vj tr tim (thuc), mt mi, nhn km,
au u. Tc dng ph nguy kjch thng gp nht do flumazenil l thc y cn co git, nht
l cc bnh nhn bj ng kinh, nhng bnh nhn l thuc sinh l vi benzodiazepine, nhng
bnh nhn ung s lng ln benzodiazepine. Dng flumazenil n c cng c th gy gim
su hi phc tr nh.
Trong trng hp qu liu nhiu loi thuc, tc ng do ng c (nh: co git, lon nhjp
tim) nhiu loi thuc (nh: thuc 3 vng) c th xut hin r rng hn khi c hiu qu o
nghjch ca flumazenil vi hiu qu ca benzodiazepine. V d: co git do qu liu thuc 3 vng
c th c gim nhe phn no khi bnh nhn cng dng qu liu benzodiazepine. Nhng khi
dng flumazenil, tnh trng co git, lon nhjp tim do ng c thuc 3 vng c th xut hin v
gy ra tnh trng nguy kjch. Flumazenil khng gy o nghjch tc ng ca ru ethanol, cc
thuc nhm barbiturate, cc cht gc opiate. iu trj ban u cc trng hp qu liu hay nghi
ng qu liu benzodiazepine nn dng liu flumazenil u tin l 0.2mg (2mL) tim tnh mch
trong 30 giy. Nu tnh trng thc khng phc hi sau 30 giy, dng liu k tip l 0.3mg
(3mL) tim trong 30 giy. Liu sau l 0.5mg (5mL) nu sau 30 giy vn cha hi phc
thc. Trong 1 pht, tng liu flumazenil khng c qu 3mg. Tuy nhin, bc s lm sng
khng nn vi v chi jnh s dng flumazenil. Trc khi s dng flumazenil, nn thit lp
ng truyn tnh mch v ng th h tr m bo chc chn. Bnh nhn nn c hi tinh
dn.
Hu ht cc bnh nhn qu liu benzodiazepine p ng vi liu tch lu flumazenil 1
3mg. Vi liu trn 3mg khng chc s c hiu qu cao hn. Nu bnh nhn khng p ng sau
5 pht nhn liu tch lu flumazenil 5mg, nguyn nhn chnh ca tinh trng an thn chc chn
khng do cht ng vn th th benzodiazepine v vic tng thm liu flumazenil cng khng
c hiu qu g thm.
Tnh trng an thn c th xut hin tr li 1 3 bnh nhn c iu trj vi
flumazenil. C th ngn nga hoc iu trj tnh trng ny bng cch dng liu lp li flumazenil
trong khong 20 pht. Khi iu trj lp li, khng dng qu 1mg (0.5mg trong 1 pht) bt ky
thi im no, v khng khng dng qu 3mg trong 1 gi.
5.4. Thn trng v cc tc dng ph ca BZD:
Tc dng ph thng gp nht ca benzodiazepine l tnh trng l , gp 10 bnh
nhn dng thuc. Do tc dng ph ny, nn khuyn bnh nhn dng thuc cn thn khi li xe
hoc vn hnh my mc nguy him. Tnh trng l c th ko di sut ngy sau khi dng
thuc benzodiazepine nhm iu trj mt ng trong m trc, nn cn goi l tnh an thn cn
tha vo !an ngy. Mt s bnh nhn cn bj tnh trng tht iu ( 2) v chong vng (
1). Cc triu chng ny c th gy ra tnh trng suy sp tinh thn, gy u phin, nht l
ngi gi. Hu ht cc tc dng ph nguy him ca cc thuc benzodiazepine xut hin khi
dng chung vi cc cht gy an thn nh ru ethanol. Kt hp ny c th gy tnh trng l
r rt, mt c ch, hay gy c tnh trng c ch h hp. Him hn, cht ng vn th th
benzodiazepine c th gy suy gim nhn thc nhe.
Cc thuc benzodiazepine tim luc cao, c bit l triazolam, zolpidem, c th gy qun
thun chiu. Tng tnh trng gy hn ngc c th gp nhng ngi s dng
benzodiazepine, mc d tc dng ny thng gp nhng ngi bj sang chn no trc .
Phn ng dj ng vi thuc him khi gp, nhng c mt s nghin cu ghi nhn tnh trng ni
sn hng ban, nga ton thn. Cc triu chng ng c benzodiazepine gm c: l ln, ni lu
ru, mt iu ho ng tc, l , kh th, gim phn x.
Triazolam c ch nhiu nht do nhng ghi nhn v biu hin gy hn hnh vi d
di khi dng triazolam. Do vy, nh sn xut khuyn co khng nn dng thuc qu 10 ngy khi
iu trj mt ng, v cc bc s nn nh gi cn thn nhng bt thng khi c thay i ni bt
v t duy, hnh vi cc bnh nhn dng triazolam, nh gi thch hp tt c cc nguyn nhn
c th c. Triazolam chnh thc bj cm Anh nm 1991. Nhng bnh nhn bnh gan, ngi
gi hu nh chc chn c tc dng ph hoc triu chng ng c khi dng benzodiazepine,
nh: hn m gan, c bit khi dng lp li hoc dng liu cao. Cc thuc benzodiazepine c
th gy gim h hp r rt cc bnh nhn bnh phi tc nghn mn tnh, gy ngng th lc
ng. Alprazolam cn gy kch thch n ung v gy tng cn. Cc thuc benzodiazepine nn
c dng mt cch thn trong nhng ngi c tin cn lm dng cht, ri lon nhn thc
hay nhc c nng.
Mt s d liu cho thy cc thuc benzodiazepine gy qui thai. Do , khng nn dng
thuc trong thai k. Ngoi ra, vic s dng benzodiazepine tam c nguyt th 3 c th gy ra
hi chng cai tr s sinh. Thuc c tit qua sa vi nng gy nh hng ln tr s
sinh. Cc thuc benzodiazepine c th gy kh th, chm nhjp tim v l tr dng nhi.
Zolpidem v zaleplon thng c dung np tt. Vi liu 10mg zolpidem/ngy v liu
10mg zaleplon/ngy, mt s t bnh nhn cm thy chong vng, l , kh tiu hay tiu chy.
Zolpidem v zaleplon cng tit qua sa nn bj chng chi jnh cho nhng b me ang cho con
b. Liu zolpidem v zaleplon nn gim ngi gi, ngi bj suy gan.
Mt mt s him trng hp, zolpidem gy ra o gic v thay i hnh vi. Kt hp
zolpidem v SSR c th ko di thi gian tn ti o gic cc bnh nhn nhy cm.
szopiclone dng ngi gi c lin quan gia liu lng v tc dng ph gy au,
kh ming v ngi thy mi kh chju, nht l tnh trng ngi thy mi kh chju.
5.5. Dung nap I thuc v cai nghin:
Khi dng cc thuc benzodiazepine trong mt thi gian ngn (1 2 tun) vi liu trung
bnh, thuc khng gy dung np, l thuc hoc tnh trng cai nghin r rt. Cc thuc
benzodiazepine tc ng nhanh (nh triazolam) c th c ngoi l, v mt s bnh nhn c
ghi nhn c tnh trng lo u tng dn sau khi dng liu duy nht benzodiazepine. Mt s bnh
nhn dung np vi tc dng gii lo u ca benzodiazepine v cn phi tng liu duy tr tc
dng gim lo u.
Hi chng cai nghin, hay cn goi l hi chng ngng thuc, xut hin tuy thuc vo
thi gian dng thuc, liu s dng, tc gim liu v thi gian bn hu ca loi thuc s
dng. Hi chng cai benzodiazepine c biu hin bng tnh trng lo u, bn chn khng yn,
ht hong, tot m hi, cu kinh, mt mi, m sng, run, mt ng, cm gic yu t. Ngng t
ngt benzodiazepine, c bit l cc loi thuc c thi gian bn hu ngn, s gy ra hi chng
cai nng n, gm cc biu hin: trm ut, hoang tng, sng, co git. Cc triu chng nng
hu nh xut hin khi s dng flumazenil nhm mc ch o nghjch nhanh chng cc hiu
qu ca cc cht ng vn th th benzodiazepine. Mt s c im ca hi chng cai c th
gp trong 90 cc trng hp s dng benzodiazepine. Tin trin thnh hi chng cai nng
chi gp nhng bnh nhn dng benzodiazepine liu cao v ko di. Su xut hin hi chng
cai c th tm hon trong 1 2 tun khi c iu trj bng benzodiazepine thi gian bn hu
di. c bit alprazolam c th gy ra hi chng cai nng ngay lp tc khi ngng thuc, nn
cn phi gim thuc t t.
Khi ngng thuc, cn gim liu t t (25 trong 1 tun), nu khng, hu nh s xut
hin tnh trng ti din hoc di ngc cc triu chng (ang/va mi iu trj bng
benzodiazepine). Theo di cc triu chng (c th nh gi bng cc thang chun ho) v
nng tm l rt c ch ngng benzodiazepine thnh cng. S dng ng thi
carbamazepine (Tegretol) khi ang ngng/gim benzodiazepine c cho l bin php cai
benzodiazepine nhanh hn, dung np tt hn so vi vic gim liu benzodiazepine n thun.
Liu carbamazepine h tr cai benzodiazepine thay i trong khong 400 500mg/ngy.
Mt s bc s lm sng ghi nhn tnh trng c bit kh khn khi cai alprazolam, nht l vi
nhng bnh nhn s dng alprazolam liu cao, ko di. c mt s nghin cu bo co iu
trj cai alprazolam thnh cng bng clonazepam, bng cch gim liu t t. Zolpidem v
zaleplon c th gy ra hi chng cai nhe, ko di khong 1 ngy, khi trc iu trj bng liu
cao. Him hn, mt s bnh nhn dng zolpidem vi liu 300 400mg/ngy, khi ngng t
ngt s gy ra triu chng cai ko di n 4 ngy hoc hn. Tnh trng dung np vi tc dng
an thn khng xy ra vi vic s dng zolpidem v zaleplon.
5.6. Tuong tc thuc:
Tng tc ca cc thuc ng vn th th benzodiazepine mnh v thng dng nht
thng gy ra tnh trng an thn (bun ng) v suy h hp, khi s dng ng thi
benzodiazepine, zolpidem, zaleplon cc cht gy c ch thn kinh trung ng, nh ru, cc
thuc barbiturate, thuc chng trm cm TCA, thuc i vn th th dopamine (DRA
dopamine receptor antagonist), cc cht opioid, cc thuc khng histamine. Mt iu ho,
chng mt vn ngn hu nh lun xut hin khi kt hp lithium, thuc chng lon thn,
clonazepam vi nhau. Kt hp thuc benzodiazepine vi clozapine c th gy sng, v do ,
nn trnh su kt hp ny. Cimetidine, disulfiram, isoniazide, estrogen v thuc trnh thai ng
ung lm tng nng huyt tng ca diazepam, clorazepate, chlordiazepoxide, flurazepam,
prazepam v halazepam. Cimetidine lm tng nng huyt tng ca zaleplon. Nefazodone,
fluvoxamine c th lm tng nng huyt tng ca triazolam, alprazolam n nng ng
c. V vy, nh sn xut nefazodone khuyn co liu triazolam nn gim 75, liu alprazolam
gim 50 khi kt hp vi nefazodone. Nhng thuc khng cn toa thuc ho h tiu, c
qung co c tc dng gii lo u, c th c kh nng tc ng nh cht ng vn th th
benzodiazepine thng qua hip ng qu mc ln th th GABA. Carbamazepine c th lm
gim nng huyt tng ca alprazolam. Thuc phm v cht khng acid c th lm gim
nng huyt tng ca cc thuc benzodiazepine. Ht thuc c th lm tng chuyn ho cc
thuc benzodiazepine. Rifampin (Rifadin), phenytoin (Dilantin), carbamazepine, phenobarbital
lm tng ng k qu trnh chuyn ho ca zaleplon. Cc thuc benzodiazepine c th lm
tng nng huyt thanh ca phenytoin, digoxin. Cc thuc SSR c th ko di v lm nng
hn tnh trng o gic do zolpidem.
5.7. Giao thoa gia BZD zoIpidem v zaIepIon:
Cha pht hin c su giao thoa trong phng th nghim gia vic s dng cc thuc
benzodiazepine, zolpidem v zaleplon.
5.8. Liu Iung v hung dn Im sng:
Trong lm sng, quyt jnh iu trj bng benzodiazepine cho cc bnh nhn lo u nn
c cn nhc cn thn. Cc nguyn nhn bnh l thuc th gy lo u (nh: suy gip, nghin
cafein, thuc ang s dng .) phi c loi b hn. Vic dng benzodiazepine nn c bt
u bng liu thp v nn ch n c tnh gy an thn ca thuc, kh nng lm dng thuc.
Thi gian trj liu nn c thit lp t l bt u trj liu, tnh cn thit ca vic tip tc trj liu
phi c nh gi li mi thng do nhng vn lin quan n vic s dng thuc
benzodiazepine lu di. Tuy nhin, c mt s bnh nhn bj ri lon lo u khng p ng vi bt
k trj liu no ngoi tr thuc benzodiazepine dng ko di.
Cc thuc benzodiazepine c nhiu dng trnh by khc nhau. Clonazepam c dng
trnh by di dng dung djch nc, nn d dng cho cc bnh nhn gp kh khn khi nut
thuc vin. Alprazolam c trnh by di dng phng thch ko di, lm gim s ln s
dng. Mt s thuc benzodiazepine c hiu luc cao hn thuc BZD khc nn c th chi cn
dng liu tng i thp hn so vi mt s thuc khc m vn c hiu qu tng ng. V
d: clonazepam l mt BZD c hiu luc cao, liu 0.25mg tng ng liu 5mg ca diazepam;
v tng ng 15mg oxazepam, nn oxazepam goi l thuc BZD c hiu luc thp.
Zaleplon c dng trnh by l vin nang 5 v 10mg. Liu 10mg zaleplon l liu thng
s dng cho mt ngi trng thnh, nhng liu ti a n 20mg. Liu duy nht zaleplon c
th gy ng 4 gi, t gy tnh trng kh chju sau . Vi mt ngi 65 tui, hay bj suy gan, chi
nn dng liu 5mg.
xzopiclone c dng trnh by l vin nn 1 2 3mg. Liu khi u khng nn vt
qu 1mg vi nhng bnh nhn suy gan nng, hay nhng bnh nhn ang s dng thuc c
ch men CP 3A4. Liu c khuyn s dng nhm d i vo gic ng, duy tr gic ng
khong 2 3mg cho mt ngi trng thnh (18 64 tui) v l 2mg cho ngi gi (t 65 tui
tr ln). Liu 1mg gip i vo gic ng tt dng cho ngi gi ln u tin bj kh ng.
Thuc Tn thuong mai Liu tuong
duong
(mg)
Liu s
dng
(mg)
Dang trnh by
Diazepam Valium, Seduxen 5 2.5 40 2.6 2-, 5-, 10- vin nn, vin 15mg bi
tit chm
Clonazepam Klonopin, Rivotril 0.5 0.5 4 0.5-, 1-, 2- vin nn
Alprazolam anax 0.25 0.5 6 0.125-, 0.25-, 0.5-, 2- vin nn tan,
vin nn 1.5- phng thch chm.
Lorazepam Ativan, Temesta 1 0.5 6 0.5-, 1-, 2- vin nn, v ng 4mg/mL
dng ngoi rut
Oxazepam Serax 10 15 120 7.5-, 10-, 30- vin nang v vin nn
15mg
Chlordiazepoxide Librium 15 10 100 Vin nn, vin nang 5-, 10-, v 25-
Clorazepate Tranxene 7.5 15 60 Vin nn 3.75-, 7.5-, 15- v vin nn
phng thch chm 11.5-, 22.5-
Halazepam Paxipam 20 60 160 Vin nn 20-, 40-
Midazolam Versed 0.25 1 50 5mg/mL dng ngoi rut, lo 1-, 2-, 5-
v 10mL
Flurazepam Dalmane 5 15 30 Vin nang 15-, 30-mg
Temazepam Restoril 5 7.5 30 Vin nang 7.5-, 15-, 30-mg
Triazolam Halcion 0.125 0.125 0.25 Vin nn 0.125 v 0.25mg
stazolam ProSom 0.33 1 2 Vin nn 1-, 2-mg
uazepam Doral 5 7.5 15 Vin nn 7.5- v 15mg
Zolpidem Ambien 2.5 5 10 Vin nn 5- v 10mg
Zaleplon Sonata 2 5 20 Vin nang 5- v 10mg
Flumazenil Romazicon 0.05 0.2
0.5mg/p
ht
0.1mg/mL, ng cha 5- v 10mL
6. THUC IU HA KH SC
6.1. ai cuong v thuc diu hoa kh sc:
Ta'i V6#8 hien na68 =u h0ng "ie%u tr9 roi -oa'n -0#ng c'c co tha6 "o<i(
Theo Khangoo ZD $a c, 3200348 trong .ot kha5o ,at cac tre5 e. roi -oa'n
-0#ng c'c8 cac thuoc "0'c ,5 &u'ng $0i trat t' nh ,auT $a-proate 379E48
-ithiu. 351E48 ga*apentin 329E4(
!ithiu.8 car*a.a/epine8 $a-proate $a $erapa.i- co hieu Rua5 t0ng
"0ng nhau trong "ie%u tr9 c0n hng ca5.P t65 -e "ap ng tha6 "o<i t 60 C
78E 3U.erican P,6chiatric U,,ociation8 1994P Ko@&en 1995P Ko@&en $a c, 1994P
7e-ga&o $a \e-en*erg 1995P 7u*o$,k6 19948 1995P 7u*o$,k6 $a Ku/an 19974(
Tu6 nhie+n $aFn co .ot thang th *ac trong $iec cho'n -'a thuoc "ie%u tr9(
Th t' cho'n -'a thuoc "ie%u hoa khQ ,aOc "0'c gi0i thieuT -ithiu.8 $a-proate8
car*a.a/epine8 -a.otrigine( Theo Ko@&en 3200448 $a-proate co hieu Rua5 h0n
trong "ie%u tr9 c0n cap8 &u6 trN roi -oa'n -0#ng c'c ,o $0i -ithiu.8 $a -a'i Qt
ngu6 hie<. h0n(
Kenh nha+n $0i 2 the< *enhT giai "oa'n ho<n h0'p $a chu k6 nhanh8 co
the< chI "ap ng $0i $a-proate hoa;c car*a.a/epine 3Bree.an $a c,8 1992P
Po,t8 1992P 2@ann $a c,8 19974( Sa-proate co tac &u'ng t0ng "0ng $0i roi
-oa'n khQ ,aOc chu kN nhanh $a &a'ng kho+ng co chu k6 nhanh 3Ko@&en $a c,8
19944( 7o "o nho. "o%ng thuan .0i "a+6 "a# "e% ngh9 raLng $a-proate -a
cho'n -'a "a%u tie+n cho $iec "ie%u tr9 chu k6 nhanh8 ke "o -a car*a.a/epine
$a cuoi cung -a -ithiu. 3Ka5ng ?o%ng Thuan hu6e+n Vo+n8 19974( Trong
.ot hoi ngh9 "o%ng thuan khac 3199648 -ithiu. $a Sa-proate "0'c khu6e+n
-a cho'n -'a "a%u tie+n $0i c0n hng ca5. "ie<n hNnhP $0i c0n ho<n h0'p8
thuoc cho'n -'a -a'i -a Sa-proate(
ab V6#8 -a.otrigine $a ga*apentin "a# "0'c &ung trong -a+. ,ang "oi
$0i cac tr0ng h0'p roi -oa'n -0#ng c'c khang tr9 3a-a*re,e $a c, 1996P
[a-&en $a Ye,,-inger 19954( Thuoc chong "ong kinh .0i -a /oni,a.i&e
cu#ng co tac &u'ng "ie%u tr9 hng ca5. trong .ot th5 nghie. .05 3Dan*a
$a c, 19944( ac tac &u'ng phu' th0ng ga;p nhat cu5a ga*apentin $a
-a.otrigine -a choang $ang8 "au "a%u8 chng nhNn "o+i8 that "ie%u $an
"ong8 *uo%n no+n $a no+n8 gia5. th9 -'c8 *uo%n ngu58 .et .o5i8 phat *an
"o58 ta1ng ca+n 3Ke6&oun $a c, 1995P Vat,ou $a c, 1996P V(c( Vc!ean 1995P
Ve,,enhei.er 1995P \(!( Vorri, 19954( \a*apentin co -ie+n Ruan "en tNnh tra'ng
ga+6 han8 ta1ng "ong $a c0n th9nh no 05 .ot ,o tre5 e. .a ha%u het
trong nho. tre5 na6 co roi -oa'n ta1ng "ong gia5. chu 6 3!ee $a c, 1996P
Ta--ian $a c, 19964(
Thuoc c che ke+nh ca-ci nh $erapa.i- "a# co nghie+n cu th5
nghie. co .u "o+i tre+n cac *enh nha+n hng ca5. $a hng ca5. nhe'
37o,e $a c, 1986P 7u*o$,k6 $a c, 1986P \ar/a C Tre$ino $a c, 1992P \iannini
$a c, 19848 19858 1987P Yo,ch- $a Do/e.6 1989P Pa//ag-ia $a c, 19934( S0i
$erapa.i- ,o ,anh co hieu Rua5 t0ng "0ng -ithiu. trong 4 C 5 tua%n nghie+n
cu( Serapa.i- $a ni.onipine cu#ng "0'c ghi nhan co tac &u'ng "ie%u hoa
khQ ,aOc tre+n .ot ,o K) hng ca5. $a co chu k6 nhanh 3Karton $a \it-in
1987P \iannini $a c, 1987P \oo&nick 1985P Vanna 1991P Pa//ag-ia $a c, 1993P
[ehr $a c, 19884P nghie+n cu th5 nghie. .u $0i ni.o&ipine tre+n 11
*enh nha+n chu k6 nhanh 3\ar/a C Tre$ino $a c, 1992P Yo,ch- $a Do/e.6
19894( Tu6 nhie+n8 co nghie+n cu -a'i nhan tha6 $erapa.i- -a'i ke. hieu
Rua5 h0n -ithiu. trong "ie%u tr9 hng ca5. 3[a-ton $a c, 19964(
ac thuoc chong -oa'n tha%n nh c-orpro.a/ine8 ha-operi&o-8 pi.o/i&e8
thio=anthene $a thiori&a/ine &ung "0n "oc hoa;c phoi h0'p $0i -ithiu. cu#ng
co hieu Rua5 trong c0n cap hoa;c "ie%u tr9 &u6 trN 3Uh-_or, $a c, 1981P Kige-o@
$a c, 1981P hou 1991P M,paron $a c, 1986P Yen&rick $a c, 1994P !itt-edohn $a
c, 1994P !o@e 1985P Vca*e $a )orri, 1977P VcM-ro6 $a c, 1996P Prien $a c,
1972P Zi_kin $a c, 19944( ac thuoc chong -oa'n tha%n8 "a;c *iet -a
ha-operi&o-8 co the< "0'c &ung "e< "ie%u tr9 tNnh tra'ng kQch "ong cho "en khi
"a't "0'c hieu Rua5 t thuoc "ie%u tr9 hng ca5.( ac thuoc chong -oa'n
tha%n kho+ng "ie<n hNnh nh c-o/apine hoa;c cac thuoc chong -oa'n tha%n
kho+ng "ie<n hNnh co tac "ong -e+n he &opa.ine8 ,erotonine $a cac thu'
the< khac8 cu#ng co hieu Rua5 tre+n hng ca5. kho+ng -oa'n tha%n8 hoa;c co
-oa'n tha%n 3Kano$ $a c, 1994P a-a*re,e $a c, 19918 1996P Br6e $a c, 1996P
D-apheke 1991P VcM-ro6 $a c, 1991P Pri$itera $a c, 1993P 2.a-- $a c, 1996P
2uppe, $a c, 19928 1994P earate $a c, 19954( Tu6 nhie+n8 $0i ri,peri&one -a'i ghi
nhan tQnh chat -a. ta1ng trieu chng hng ca5.P c-o/apine -a'i co tac
&u'ng -a. gia5. hng ca5. $a chu k6 nhanh( 7u $a68 kho+ng pha5i tat ca5
*enh nha+n hng ca5. "e%u -oa'n tha%n $a tNnh tra'ng -oa'n tha%n ket h0'p $0i
hng ca5. cu#ng co the< ho%i phu'c khi "ie%u tr9 "a%6 "u5 $0i thuoc "ie%u tr9
hng ca5. 3ohen $a !ipin,ki 1986P Bennig $a c, 1995P \oo&@in $a ca.i,on
1991P Prien $a c, 19724(
ab V6#8 -a.otrigine $a ga*apentin "a# "0'c &ung trong -a+. ,ang "oi
$0i cac tr0ng h0'p roi -oa'n -0#ng c'c khang tr9 3a-a*re,e $a c, 1996P
[a-&en $a Ye,,-inger 19954( Thuoc chong "ong kinh .0i -a /oni,a.i&e
cu#ng co tac &u'ng "ie%u tr9 hng ca5. trong .ot th5 nghie. .05 3Dan*a
$a c, 19944( ac tac &u'ng phu' th0ng ga;p nhat cu5a ga*apentin $a
-a.otrigine -a choang $ang8 "au "a%u8 chng nhNn "o+i8 that "ie%u $an
"ong8 *uo%n no+n $a no+n8 gia5. th9 -'c8 *uo%n ngu58 .et .o5i8 phat *an
"o58 ta1ng ca+n 3Ke6&oun $a c, 1995P Vat,ou $a c, 1996P V(c( Vc!ean 1995P
Ve,,enhei.er 1995P \(!( Vorri, 19954( \a*apentin co -ie+n Ruan "en tNnh tra'ng
ga+6 han8 ta1ng "ong $a c0n th9nh no 05 .ot ,o tre5 e. .a ha%u het
trong nho. tre5 na6 co roi -oa'n ta1ng "ong gia5. chu 6 3!ee $a c, 1996P
Ta--ian $a c, 19964(
Thuoc c che ke+nh ca-ci nh $erapa.i- "a# co nghie+n cu th5
nghie. co .u "o+i tre+n cac *enh nha+n hng ca5. $a hng ca5. nhe'
37o,e $a c, 1986P 7u*o$,k6 $a c, 1986P \ar/a C Tre$ino $a c, 1992P \iannini
$a c, 19848 19858 1987P Yo,ch- $a Do/e.6 1989P Pa//ag-ia $a c, 19934( S0i
$erapa.i- ,o ,anh co hieu Rua5 t0ng "0ng -ithiu. trong 4 C 5 tua%n nghie+n
cu( Serapa.i- $a ni.onipine cu#ng "0'c ghi nhan co tac &u'ng "ie%u hoa
khQ ,aOc tre+n .ot ,o K) hng ca5. $a co chu k6 nhanh 3Karton $a \it-in
1987P \iannini $a c, 1987P \oo&nick 1985P Vanna 1991P Pa//ag-ia $a c, 1993P
[ehr $a c, 19884P nghie+n cu th5 nghie. .u $0i ni.o&ipine tre+n 11
*enh nha+n chu k6 nhanh 3\ar/a C Tre$ino $a c, 1992P Yo,ch- $a Do/e.6
19894( Tu6 nhie+n8 co nghie+n cu -a'i nhan tha6 $erapa.i- -a'i ke. hieu
Rua5 h0n -ithiu. trong "ie%u tr9 hng ca5. 3[a-ton $a c, 19964(
ac thuoc chong -oa'n tha%n nh c-orpro.a/ine8 ha-operi&o-8 pi.o/i&e8
thio=anthene $a thiori&a/ine &ung "0n "oc hoa;c phoi h0'p $0i -ithiu. cu#ng
co hieu Rua5 trong c0n cap hoa;c "ie%u tr9 &u6 trN 3Uh-_or, $a c, 1981P Kige-o@
$a c, 1981P hou 1991P M,paron $a c, 1986P Yen&rick $a c, 1994P !itt-edohn $a
c, 1994P !o@e 1985P Vca*e $a )orri, 1977P VcM-ro6 $a c, 1996P Prien $a c,
1972P Zi_kin $a c, 19944( ac thuoc chong -oa'n tha%n8 "a;c *iet -a
ha-operi&o-8 co the< "0'c &ung "e< "ie%u tr9 tNnh tra'ng kQch "ong cho "en khi
"a't "0'c hieu Rua5 t thuoc "ie%u tr9 hng ca5.( ac thuoc chong -oa'n
tha%n kho+ng "ie<n hNnh nh c-o/apine hoa;c cac thuoc chong -oa'n tha%n
kho+ng "ie<n hNnh co tac "ong -e+n he &opa.ine8 ,erotonine $a cac thu'
the< khac8 cu#ng co hieu Rua5 tre+n hng ca5. kho+ng -oa'n tha%n8 hoa;c co
-oa'n tha%n 3Kano$ $a c, 1994P a-a*re,e $a c, 19918 1996P Br6e $a c, 1996P
D-apheke 1991P VcM-ro6 $a c, 1991P Pri$itera $a c, 1993P 2.a-- $a c, 1996P
2uppe, $a c, 19928 1994P earate $a c, 19954( Tu6 nhie+n8 $0i ri,peri&one -a'i ghi
nhan tQnh chat -a. ta1ng trieu chng hng ca5.P c-o/apine -a'i co tac
&u'ng -a. gia5. hng ca5. $a chu k6 nhanh( 7u $a68 kho+ng pha5i tat ca5
*enh nha+n hng ca5. "e%u -oa'n tha%n $a tNnh tra'ng -oa'n tha%n ket h0'p $0i
hng ca5. cu#ng co the< ho%i phu'c khi "ie%u tr9 "a%6 "u5 $0i thuoc "ie%u tr9
hng ca5. 3ohen $a !ipin,ki 1986P Bennig $a c, 1995P \oo&@in $a ca.i,on
1991P Prien $a c, 19724(
Phoi h0'p thuoc chong -oa'n tha%n $0i *en/o&ia/epine nh -ora/epa.8
c-ona/epa.8 co the< -a. gia5. thie<u -ie%u thuoc chong -oa'n tha%n nhaL.
tranh ngu6 c0 tac &u'ng phu' $a t0ng tac $0i thuoc "ie%u tr9 hng ca5.
32ach, 1990P 2a-/.an $a c, 1986P Ku,ch $a c, 198948 cu#ng nh giup kie<.
,oat nhanh tNnh tra'ng kQch "ong h0n &ung thuoc chong -oa'n tha%n "0n "oc
3houinar& $a c, 1983P \ar/a C Tre$ino $a c, 1989P 2a-/.an $a c, 19864(
Ken/o&ia/epine co the< "ie%u tr9 t *an "a%u .a kho+ng ca%n phoi h0'p $0i
thuoc chong -oa'n tha%n8 trong "ie%u tr9 hng ca5. 3Kra&@edn $a c, 1990P
o-@e-- $a !ope/ 1987P !eno= $a c, 1986P Vo&e-- $a c, 1985P 2anto, $a Vorton
19874( Phoi h0'p8 hoa;c kho+ng phoi h0'p gi#a *en/o&ia/epine $0i thuoc
chong -oa'n tha%n8 cu#ng co the< "0'c chI "9nh "e< ca5i thien tNnh tra'ng kQch
"ong $a giac ngu5(
6.2. Lithiu,:
!ithiu. 3M,ka-ith8 !itho*i&8 !ithonate4 "0'c B7U chap thuan cho "ie%u tr9
hng ca5. t 19708 ,au h0n 20 na1. t khi cohn B(c(a&e 3K2 ta+. tha%n Ac4
co nh#ng *ao cao "a%u tie+n( Thuoc "0'c &ung "e< "ie%u tr9 ngaOn ha'n8
&ai ha'n $a "ie%u tr9 phong nga roi -oa'n -0#ng c'c `( ho "en hien na68
-a thuoc &u6 nhat "0'c chng .inh -a co ca5 hai tac &u'ng "ie%u tr9 cap
$a &u6 trN( Thuoc con &ung "e< "ie%u chInh trong roi -oa'n tra%. ca5.
na;ng( !ithiu. "0'c nghie+n cu nhie%u nhat( o hieu Rua5 "ie%u tr9 c0n
cap $a "ie%u tr9 phong nga hng ca5.8 tra%. ca5. trong roi -oa'n -0#ng
c'c 32chou 199748 co hieu Rua5 tre+n c0n hng ca5. ro# ret8 c0n kho+ng "e%u8
kho+ng co chu k6 nhanh $a trong nh#ng tr0ng h0'p kho+ng ca%n thuoc
chong -oa'n tha%n 3Ko@&en 1995P \e-en*erg $a Yopkin, 1993P Y(2( Yopkin, $a
\e-en*erg 1994P 2chou 19974(
LGHGIGHa duc hc:
Yoa ho'cT -a ngu6e+n to ki. -oa'i kie%. nho. `U 3cung nho. )atri8
Da-i8 Zu*i8 e,i8 Branciu.4( Trong t' nhie+n8 co 2 -oa'i -ithiu.8
6
!i 37(42E4 $a
7
!i
392(58E4( Dhoa5ng 1(597g -ithiu. car*onate cha khoa5ng 300.g -ithiu.(
Tac o(ng -c l&: -ithiu. "0'c hap thu nhanh $a hoan toan trong
"0ng tie+u hoa8 "a't no%ng "o "Inh hu6et t0ng ,au 1 C 1(5 gi0 uong
&a'ng thuoc tie+u chua<n $a "a't no%ng "o "Inh ,au 4 C 4(5 gi0 uong &a'ng
thuoc phong thQch cha. phong thQch co kie<. ,oat( !ithiu. kho+ng gaOn
ket $0i protein hu6et t0ng8 cu#ng nh kho+ng chu6e<n hoa8 "0'c "ao tha5i
Rua than( Th0i gian *an hu56 trong hu6et t0ng -uc *an "a%u -a 1(3 nga68
$a ,au khi &ung h0n 1 na1.8 th0i gian na6 -a 2(4 nga6( Yang rao .au
na#o chI cho phep $an chu6e<n cha. cha'p -ithiu. "i Rua8 "o -a -6 &o chI
ca%n &ung 1 -ie%u &u6 nhat -ithiu. trong nga6 $N kho+ng ga+6 ngo "oc $a
neu ngo "oc -a+u &ai thN kho ho%i phu'c( Th0i gian *ai tiet f -ithiu. -a 18
C 24 gi0 05 ng0i tr05ng thanh tre5 $a ngaOn h0n 05 tre5 e.8 &ai h0n 05
ng0i gia( ?o thanh tha5i cu5a than $0i -ithiu. gia5. "i neu ,u6 gia5.
chc na1ng than( Tra'ng thai ca+n *aLng -ithiu. "a't "0'c ,au 5 C 7 nga6
&ung "e%u "a;n( Keo phN -a. ta1ng thanh tha5i -ithiu.( Kai tiet -ithiu. phc
ta'p h0n trong thai k68 ta1ng *ai tiet8 nhng gia5. -a'i khi cho *u( !ithiu. con
*ai tiet Rua ,#a .e'8 $a *ai tiet "ang ke< Rua pha+n $a .o% ho+i( !ithiu.
con tap trung ta'i tu6en giap $a than cao h0n ,o $0i trong hu6et thanh(
ach gia5i thQch ta'i ,ao -ithiu. co the< co hieu Rua5 "ie%u hoa khQ
,aOc $aFn con kho kha1n( )hie%u gia5 thu6et "0'c "a;t ra8 *ao go%.T tha6
"o<i $an chu6e<n ion Rua .ang8 a5nh h05ng "en chat &aFn tru6e%n tha%n
kinh $a cac pepti&e, tha%n kinh8 cac "0ng &aFn tQnh hieu tha%n kinh $a he
thong chat &aFn tru6e%n th hai(
/ che tac -ung cuMa lithiu,: ion -ithiu. 1
+
"0'c cho -a tac "ong
-e+n he thong tru6e%n tin th 2 noi *ao( Theo cope $a [i--ia., 3199448 Vandi
$a c, 3199548 -ithiu. c che .ot $ai *0c cu5a chu6e<n hoa cu5a cac
chat pho,phat8 cu#ng nh hoa't "ong cu5a \ C protein( !ithiu. con c che ,'
kQch thQch cu5a .ot ,o chat &aFn tru6e%n tha%n kinh -e+n .en a&en6-ate
c6c-a,e .a kho+ng -a. triet thoai hoa't "ong c0 *a5n cu5a .en a&en6-ate
c6c-a,e 3Ke-.aker $a c, 1983P M*,tein $a c, 1980P eohar $a c, 19824( Tac
"ong na6 ga+6 a5nh h05ng -e+n hoa't "ong tha%n kinh(
LGHGHGChi d[nh tr[ Iiu:
=oi loan lNng cc I: -ithiu. kie<. ,oat giai "oa'n cap $a nga1n
nga tai phat 05 80E *enh nha+n roi -oa'n -0#ng c'c ` $a .ot ,o Qt
*enh nha+n co c0n ho<n h0'p(8 roi -oa'n -0#ng c'c chu k6 nhanh8 hoa;c tha6
"o<i khQ ,aOc trong *enh -6 na#o( !ithiu. kh05i phat hieu Rua5 t0ng "oi
cha.8 co tac "ong chong hng ca5. ,au khi &ung 1 C 3 tua%n( 7o "o8
th0ng pha5i ,5 &u'ng ke. *en/o&ia/epine8 thuoc chong -oa'n tha%n 7ZU
hoa;c 27U8 hoa;c $a-proate trong nh#ng tua%n "a%u( Kenh nha+n co c0n ho<n
h0'p8 hoa;c hng ca5. -oa'n khQ ,aOc8 chu k6 nhanh8 hoa;c -a'. &u'ng chat ke.
theo8 hoa;c co *enh -6 th'c the< "ap ng ke. $0i -ithiu. ,o $0i c0n hng
ca5. "ie<n hNnh(
Tra$, caM, lNng cc: -ithiu. co hieu Rua5 "ie%u tr9 tra%. ca5.
trong roi -oa'n -0#ng c'c `8 cu#ng nh co the< phoi h0'p tr9 -ieu trong roi
-oa'n tra%. ca5. na;ng( ung $0i tr9 -ieu *aLng -ithiu.8 tr9 -ieu the+. *aLng
$a-proate ha6 car*a.a/epine th0ng "0'c &ung na'p tot $a ha'n che =uat
hien c0n hng ca5.(
Dhi giai "oa'n tra%. ca5. =uat hien 05 K) "ang &ung -ithiu. "ie%u tr9
&u6 trN8 ne+n =e. =et "en cha<n "oan pha+n *iet ,u6 giap &o -ithiu.8 -a'.
&u'ng chat $a ke. "ap ng $0i -ithiu.( Dhi "o8 co the< ta1ng -ie%u -ithiu.
3"en 1 C 1(2.MRW!48 ket h0'p tr9 -ieu *aLng hor.on tu6en giap nga6 ca5 khi
chc na1ng tu6en giap *Nnh th0ng8 "ie%u tr9 *aLng $a-proate hoa;c
car*a.a/epine8 ,5 &u'ng phu h0'p thuoc chong tra%. ca5. hoa;c &ung
choang "ien 3MT4( Dhi giai "oa'n tra%. ca5. "a# ho%i phu'c8 nh#ng tr9 -ieu
the+. $ao ne+n ngng -a'i8 chI "0n tr9 -ieu *aLng -ithiu.8 neu &ung na'p tot
tre+n -a+. ,ang(
:ie$u trB -u& trO: "ie%u tr9 &u6 trN *aLng -ithiu. -a. gia5. t65 -e tai
-a'i8 .c "o na;ng $a th0i gian to%n ta'i cu5a c0n hng ca5.8 tra%. ca5.
trong roi -oa'n -0#ng c'c `( !ithiu. co hieu Rua5 phong nga c0n hng ca5.
tot h0n c0n tra%. ca5.8 ne+n "ie%u tr9 *o< ,ung *aLng thuoc chong tra%.
ca5. co the< -a ca%n thiet8 co the< &ung -ie+n tu'c hoa;c ngaOt Rua5ng( Ya%u
nh pha5i -uo+n "ie%u tr9 &u6 trN *aLng -ithiu. ,au c0n th hai cu5a roi -oa'n
-0#ng c'c `8 hoa;c chI -a c0n "a%u tie+n 05 tre5 $9 thanh nie+n hoa;c *enh
nha+n co tie%n ,5 gia "Nnh *9 roi -oa'n -0#ng c'c `8 co ngu6 c0 t' ,at cao8
co kh05i phat "ot ngot hoa;c co c0n "a%u tie+n -a c0n hng ca5.( ac
nghie+n cu -a+. ,ang cho tha6 -ithiu. -a. gia5. "en 6 C 7 -a%n t65 -e t5
$ong &o hanh $i t' ,at 05 K) -0#ng c'c `( !ithiu. cu#ng co hieu Rua5 "ie%u
tr9 roi -oa'n khQ ,aOc chu kN na;ng(
Dh05i "a%u cu5a "ie%u tr9 &u6 trN ,au giai "oa'n hng ca5. "a%u tie+n "0'c
=e. -a cach "ie%u tr9 tot nhat( o nhie%u ngu6e+n nha+n gia5i thQch "ie%u
na6( Th nhatT *9 .ot c0n hng hng ca5. ,e# co ngu6 c0 *9 c0n tiep theo(
Th haiT nh#ng *enh nha+n "ap ng $0i "ie%u tr9 *aLng -ithiu.8 neu ngng
thuoc thN co ngu6 c0 tai phat cao gap 28 -a%n ng0i *Nnh th0ng( Th *aT
neu *enh nha+n "a# "ap ng $0i "ie%u tr9 -ithiu. .a ngng thuoc thN 05
c0n hng ca5. ,au ,e# ke. "ap ng( ?ie%u tr9 &u6 trN -ithiu. tiep ,au "ie%u
tr9 c0n cap thN -a. ta1ng hieu Rua58 $a -a. gia5. t65 -e t5 $ong( Vot giai
"oa'n hng ca5. ha6 tra%. ca5. co the< =uat hien khi "ang "ie%u tr9 &u6 trN
*aLng -ithiu. $0i th0i gian t0ng "oi ngaOn nhng kho+ng pha5i $N $a6 -a
that *a'i tr9 -ieu( Tu6 nhie+n8 "ie%u tr9 "0n "oc *aLng -ithiu. co the< gia5.
&a%n hieu Rua5 ,au $ai na1. ,5 &u'ng( )eu =uat hien tNnh tra'ng na68 ne+n
*o< ,ung the+. car*a.a/epine hoa;c $a-proate thN ,e# "a't hieu Rua5(
!ie%u "ie%u tr9 &u6 trN -ithiu. th0ng pha5i hieu chInh tu6 theo no%ng
"o hu6et t0ng8 th0ng thap h0n trong "ie%u tr9 giai "oa'n cap( )eu ngng
-ithiu.8 ne+n gia5. -ie%u t t $N neu kho+ng ,e# co ngu6 c0 =uat hien c0n
tra%. ca5.Whng ca5. tai &ieFn(
Ph0ng phap th5 nghie. -ithiu. -aT -ie%u *aOt "a%u -a 300.g -ithiu.
*icar*onat8 ta1ng -ie%u 300.g .oFi 3 C 4 nga6 $a ne+n "anh gia no%ng "o
hu6et t0ng 2 -a%nWtua%n neu kho+ng ,u6 gia5. chc na1ng than( Dhi "a#
=ac -ap "0'c no%ng "o "ie%u tr98 ca%n "0'c theo &o#i no%ng "o -ithiu. .oFi
thang trong 3 thang "a%u8 $a ,au "o -a .oFi 3 thang(
=oi loan tra$, caM, naPng: -ithiu. co hieu Rua5 "ie%u tr9 -a+u &ai
cho roi -oa'n tra%. ca5. na;ng nhng kho+ng hieu Rua5 *aLng cac thuoc
chong tra%. ca5.( Sai tro th0ng ga;p nhat cu5a -ithiu. trong roi -oa'n
tra%. ca5. na;ng -a ta &0'c cho $iec ,5 &u'ng thuoc chong tra%. ca5. 05
nh#ng *enh nha+n khang tr9 $0i "0n tr9 -ieu thuoc chong tra%. ca5.( o
khoa5ng 50 C 60E *enh nha+n kho+ng "ap ng $0i thuoc chong tra%. ca5.
tr05 ne+n "ap ng khi &ung ke. $0i 300.g -ithiu.Wnga6( o nh#ng
tr0ng h0'p "ap ng thuoc co the< =uat hien nga6 trong nga6 ,5 &u'ng8
nhng th0ng pha5i ,au $ai tua%n .0i co the< tha6 hieu Rua5( !ithiu.
&ung "0n "oc cu#ng co hieu Rua5 $0i tra%. ca5. trong roi -oa'n -0#ng c'c
`( -ithiu. cu#ng co hieu Rua5 $0i roi -oa'n tra%. ca5. na;ng neu co tQnh
chat chu k6 ro# ret(
=oi loan caM, Quc phan lie(t +a@ ta, tha$n phan lie(t: *enh
nha+n co trieu chng khQ ,aOc no<i *at kie<u -0#ng c'c ha6 kie<u tra%.
ca5. trong roi -oa'n ca5. =uc pha+n -iet cu#ng "ap ng $0i "ie%u tr9 *aLng
-ithiu.8 nhng neu trieu chng no<i *at -a -oa'n tha%n thN ke. "ap ng
h0n( T khi co thuoc 27U8 7ZU cho $iec "ie%u tr9 roi -oa'n ca5. =uc pha+n
-iet thN -ithiu. "0'c &ung $0i $ai tro ta &0'c nhie%u h0n( ?ie%u na6 ro# ret
h0n $0i *enh nha+n co trieu chng khang tr9 $0i 27U hoa;c 7ZU( ?a;c tQnh
na6 kho+ng chI $0i *enh nha+n co trieu chng ca5. =uc no<i *at8 .a
con hieu Rua5 $0i tr0ng h0'p co trieu chng -oa'n tha%n no<i *at( Kenh
nha+n ta+. tha%n pha+n -iet neu kho+ng the< &ung thuoc chong -oa'n tha%n8
cu#ng co -0'i khi &ung -ithiu. "0n tr9(
/hA Bnh %hac: .ot ,o nghie+n cu cho tha6 -ithiu. con "ie%u tr9
"0'c cac *enh -6 ta+. tha%n khac8 cac *enh -6 kho+ng pha5i ta+. tha%n8
nhng hieu Rua5 cha "0'c =ac "9nh ro# rang( !ithiu. co tac &u'ng chong
ga+6 han &o khQ ,aOc8 ta+. tha%n pha+n -iet8 tu nha+n *a'o -'c8 tre5 *9 roi
-oa'n ng =58 hanh $i t' hu56 hoa'i cu5a cha. phat trie<n ta+. tha%n(
LGHGJGChng chi d[nh:
hong chI "9nh cu5a -ithiu. kha nhie%u8 nhT chc na1ng than kho+ng
o<n "9nh8 &ao "ong8 hoa't "ong *at th0ng nut =oang8 *enh tu6en giap8
nhat -a ,u6 giap( !ithiu. ga+6 ngu6 c0 cao *9 &9 &a'ng M*,tein ti. 05 tre5 e.
3)ora $a c, 19744 $0i ngu6 c0 tu6et "oi -a 0(1 C 0(7E 3M&.un& $a gak-e6
1990P caco*,on $a c, 1992P Da--en $a Ten&*erg 1983P ea-/,tein $a c, 199043,o
$0i 0(01E trong &a+n ,o chung4( )gu6 c0 &9 tat *a<. ,inh khi &ung -ithiu. -a
4E C 12E ,o $0i 2E J 4E 05 nho. chng 3ohen $a c, 19944(
LGHGKGThn trng v tc dng ph:
Tac &u'ng phu' ga+6 roi -oa'n chc na1ng than cu5a -ithiu. "oi ho5i khi
,5 &u'ng pha5i "anh gia KA) $a creatinine .oFi 3 C 6 thang hoa;c th0ng
=u6e+n h0n( Tu6 nhie+n tac &u'ng phu' tre+n than na6 co the< "a5o ngh9ch khi
ngng -ithiu.P kho+ng tha6 tNnh tra'ng ,u6 than .at phu'c ho%i &o &ung -ithiu.
keo &ai 3Yet.ar $a c, 19914( !ithiu. con co the< ga+6 "a nieu &o c che
$a,opre,,in8 ga;p 05 khoa5ng 60E *enh nha+n 3!okkegaar& $a c, 198548 $a
co the< ga+6 *ien chng na;ng nhT .at n0c8 ngo "oc -ithiu.8 .at ca+n
*aLng "ien gia5i( TNnh tra'ng "a nieu co the< "a5o ngh9ch khi ngng -ithiu.
nhng co the< $aFn con to%n ta'i nhie%u thang 3Za.,e6 $a o= 1982P 2i.on
$a c, 19774(
2u6 giap nhe' "a5o ngh9ch co the< ga;p 05 20E *enh nha+n &ung
-ithiu. 3!in&,te&t $a c, 1977P V6er, $a c, 19854( Zoi -oa'n hoa't "ong tu6en
can giap cu#ng ga;p pha5i nhng hie.8 $0i *ie<u hien ,u6 can giap nhe'(
Tac &u'ng phu' $e% tha%n kinh cu#ng ga;p pha5i khi &ung -ithiu. 3Se,tergaar&
$a c, 19804 nhT run 3co the< "ie%u tr9 *aLng cac *eta C *-oRuant8 S7
proprano-o- chia 2 -a%nWnga6 $0i -ie%u thap h0n 80.gWnga648 gia5. trQ nh0
chu5 Ruan 3ga;p 05 28E *enh nha+n &ung -ithiu.4 3\oo&@in $a ca.i,on 19904(
!ithiu. cu#ng tac "ong "en ti. $0i *ie<u hien tha6 "o<i ,ong T 3,ong T
&e't hoa;c "a#o4 ga;p 05 20 C 30E *enh nha+n8 tac "ong "en nut =oang8
ga+6 *-oc nh: that( ac tac &u'ng phu' khac nhT .u'n8 *an "o58 $a<6 nen8
ru'ng toc8 .o5ng &a8 *uo%n no+n8 tie+u cha568 ta1ng *a'ch ca%u(
)eu Rua -ie%u -ithiu. 3&o gi0i ha'n "ie%u tr9 he'p $a rat ga%n $0i -ie%u
ngo "oc48 tNnh tra'ng ngo "oc -ithiu. co the< =a#6 ra8 ga+6 tac "ong na;ng
ne% -e+n tha%n kinh(
Dau hie(u +a@ trie(u chng ngo( o(c lithiu,
Ngo oc t nhe en trung bnh (nong o 1.5 2.0 mEq/!
Ye tie+u hoa )o+n8 "au *u'ng8 kho+ .ieng(
Ye tha%n kinh That "ie%u8 choang $ang8 noi -Qu rQu8 rung giat nha#n
ca%u8 ngu5 -9. hoa;c kQch "ong8 6eu c0(
Ngo oc t trung bnh en n"#ng (nong o t 2.0 2.5 mEq/!
Ye tie+u hoa han a1n8 *uo%n no+n $a no+n &ai &ahng(
Ye tha%n kinh )hNn .08 giat c0 05 chi8 ta1ng pha5n =a' ga+n c08 .ua
$0n8 "ong kinh8 ngat8 ,a5ng8 tha6 "o<i MM\8 ,5ng
,08 ho+n .e+8 ,u6 tua%n hoan(
Ngo oc n"#ng (nong o tre$n 2.5 mEq/!
?ong kinh toan the< hoa8 tie<u Qt $a ,u6 than8 t5
$ong(
Hn 80 bnh nhn dng lithium c tc dng ph. Do , gim thiu nguy c tc
dng ph, cn theo di st sao nng lithium trong mu v c can thip thch hp khi c tc
dng ph. BN cn c bo trc v tc dng ph v gi vai tr quan trong trong vic pht
hin tc dng ph nhm hn ch ti a mc nng khi xut hin. Nn khuyn BN thay i
lng nc v mui s dng trong ngy, v c th nh hng n mc thi tr lithium, v
c th lm tng hay gim nng lithium. Dng mui Natri qu nhiu s lm gim nng
lithium. Ngc li, dng qu t mui Natri li c th gy ng c lithium. Gim lng djch c th
c th gy ng c lithium.
Tc dng ph da dy rut: gm bun nn, gim ngon ming, nn v tiu chy; c th
gim tc dng ny bng cch chia liu, ung lithium vi thc n. Khi bj tiu chy, c th s
dng nhng cht cm tiu chy nh loperamide, bismuth subsalicilate, diphenoxylate c
atropine.
Tng cn: tng cn do tc ng ca lithium n chuyn ha carbohydrate. Cng c th
do lithium gy suy gip, ph do lithium, hay ung qu nhiu nc do tnh trng kht khi ung
lithium.
Tc dng ph thn kinh: run t th do lithium c bin 8 12Hz, nht l khi a
thng tay ra trc, a thng ngn tay, khi thao tc kho lo. Run c th gim khi chia liu
trong ngy, khi dng dng phng thch chm, gim tiu th caffein, iu chinh li nhng thuc
dng km, khi kim sot c lo u. Thuc i vn th th nh propranolol (30
120mg/ngy chia liu ln); primidone (50 250mg/ngy) thng c th gim run. Nu bnh
nhn h kali huyt, b sung kali th c th gim run. Khi ang dng lithium m bj run nhiu, c
th bj ng c lithium v cn jnh lng, tm sot ng c.
Tc dng ph nhn thc: lithium c lin quan tnh trng kh chju, cm gic mt tu
ch, phn ng chm, gim tr nh. Nu c triu chng ny th phi thn trong v l nguyn
nhn gy khng tun th iu trj. Chn on phn bit tnh trng ny vi ri lon trm cm, suy
gip, tng calci mu, do thuc khc . Cng c mt s bnh nhn c tnh trng mt mi v suy
gim nhn thc nhe theo thi gian.
Cc tc dng ph thn kinh khc: khng thng gp, bao gm: hi chng parkinson
nhe, tht iu, lon vn ngn, mc d 2 triu chng sau c th gp trong ng c lithium.
Lithium him khi no gy ra bnh l thn kinh ngoi bin, tng p luc ni so lnh tnh, tnh trng
ging nhc c nng, tng nguy c co git.
Tc dng ph thn: tc dng ph thng gp nht thn l a niu v th pht l
chng kht nhiu. Gp 25 35 bnh nhn v gy i tiu trn 3L/ngy. a niu nguyn pht
l do tnh i khng ca lithium vi ADH. Nu a niu r rt, cn nh gi chc nng thn v
nc tiu 24 gi, xc jnh thanh thi creatinine. iu trj tnh trng ny l b sung djch, dng
lithium liu thp nht c th, dng lithium liu duy nht trong ngy. C th ci thin bng iu trj
thiazide, li tiu gi kali (amiloride, spironolactone, triamterene .). Nu bt u dng li
tiu, nn gim liu lithium mt na.
Tc dng ph thn nng nht, nhng him, thng chi c khi dng lithium hn 10
nm, l tnh trng x ha m thn k. Biu hin: gim dn t l loc cu thn, tng creatinine
huyt thanh, him khi suy thn. Lithium thng c lin quan vi hi chng cu thn, biu hin
nhim acid ng ln xa.
Tc dng ph tuyn gip: lithium thng gy gim thong qua v lnh tnh hormon
tuyn gip. C tnh trng u gip (5), li mt hi phc, cng gip, suy gip (7 10). Suy
gip thng gp ph n (14) nhiu hn nam gii (4.5). Ph n thng c nguy c suy
gip trong 2 nm u iu trj. Bnh nhn ang dng lithium iu trj ri lon lng cuc tng
nguy c suy gip gp 2 ln nu ho c chu ky nhanh. Khong 50 bnh nhn iu trj lu di
bng lithium c bt thng trong xt nghim tuyn gip, khong 30 c tng TSH. Nu c biu
hin suy gip, cn phi b sung levothyroxine. Do , khi iu trj bng lithium, cn theo di tnh
trng tng TSH mi 6 12 thng.
Tc dng ph tim mach: ging vi tnh trng h kali huyt trn CG, do tnh trng thay
th kali ni bo bng ion lithium. Thay i CG thng gp nht l: sng T det hoc o. Bin
i ny thng lnh tnh v bin mt khi ngng lithium.
Lithium gy c ch hot ng to nhjp ca nt xoang, thng gy lon nhjp xoang,
block tim, c giai on ngt. Do , chng chi jnh lithium khi c hi chng suy nt xoang. Mt
s him trng hp c lon nhjp tht v suy tim sung huyt do lithium. Ng c tim do lithium
thng gp bnh nhn n qu nht (t mui), dng li tiu, thuc c ch men chuyn, mt
cn bng in gii, suy thn.
Tc dng ph v da: thng c lin quan vi liu. Bao gm: c dng trng c, nang
b, ban dt sn, lot trc xng chy, lm nng tnh trng vy nn. Nu vy nn nng hn,
hoc ban dng trng c nng th phi ngng lithium. Tnh trng rng tc do lithium cng gp.
nu iu trj mn trng c bng tetracycline, nn theo di nng lithium v tetracycline lm
tng gi lithium.
LGHGFGLiu Iung v hung dn Im sng: tt c bnh nhn mun iu trj bng
lithium cn phi sng loc lm sng v cn lm sng. Cn lm sng: creatinine
huyt thanh ( creatinine nc tiu 24 gi nu nghi ng chc nng thn), in
gii, chc nng tuyn gip (T3, T4, TSH), cng thc mu, CG, test thai ph
n ang tui sinh.
Nng lithium huyt thanh c hiu qu iu trj c cho l khong 0.8 1.2mq/L.
Liu khi u ngi trng thnh l 300mg x 3 ln/ngy. ngi gi hay ngi c suy chc
nng thn, chi nn dng liu khi u 300mg x 1 2 ln/ngy. Sau khi n jnh liu lng,
liu t 900 1200mg/ngy s t nng huyt thanh l 0.6 1.0mq/L; vi liu 1200
1800mg/ngy t nng 0.8 1.2mq/L. Liu duy tr c th chia lm 2 3 ln/ngy vi dng
thuc phn gii bnh thng, v dng liu duy nht vi dng thuc phn gii chm. Chia liu
nhiu ln gip gim tc dng ph d dy, trnh lm nng lithium t inh tng cao t ngt.
Theo di cn lm sng: cn theo di st nng lithium huyt thanh. Sau khi n jnh,
nn tm sot mi 2 6 thng, ngoi tr trng hp c triu chng ng c lithium, khi khng
p ng trj liu. Nn c CG chun trc iu trj v nn kim tra CG hng nm.
Nng lithium c hiu qu cho cn hng cm l 1 1.5mq/L. Trong iu trj duy tr,
nng l 0.4 - 0.8mq/L. Nu khng p ng trj liu sau 2 tun vi nng lithium trong gii
hn v c th c triu chng ng c khi tng liu lithium, nn gim dn liu lithium trong 1 2
tun v i sang thuc iu ha kh sc khc.
6.3. VaIproate:
Valproate, hay acid valproic c dng iu trj cn hng cm, cn hn hp trong ri
lon lng cuc . Nhng chi jnh khc ca valproate l bnh l ng kinh, phng nga
migraine.
Valproate l acid carboxylic nhnh n. Thuc chuyn thnh acid khi vo n d dy.
C nhiu dng trnh by: acid valproic, divalproex (hn hp 1:1 ca acid valproic v valproat, v
dng valproat sodium tim. Cn c dng phng thch chm. Nhng tt c u c hiu qu
tng ng nhau, v di tc ng ca mi trng acid ca d dy, tt c u chuyn thnh
ion valproate.
Valproate hp thu nhanh v hon ton trong 1 2 gi qua ng ung. t nng
inh trong huyt tng sau 4 5 gi sau khi ung. Thi gian bn hy trong huyt tng l 10
16 gi. Valproate gn kt cao vi protein. Khi protein gn kt vi valproate bo ha, valproate
tu do s c hiu qu iu trj nu nng tu do ny t 50 100 g/mL. Dng phng thch
chm t nng inh thp hn v nng ti thiu cao hn, nn c th dng 1 ln/ngy.
Valproate c chuyn ha bc u gan trong qu trnh glucoronidase v bj oxi ha ty
th.
C s sinh ha cho hiu qu iu trj ca valproate vn cha c bit nhiu. C ch
c cho l c lin quan l nng cao hot ng ca GABA ( -aminobutyric acid), iu chuyn i
nhy hiu in th knh Na, v tc ng ln cc peptides vng h i.
LGJGIGChi d[nh tr[ Iiu:
Ri Ioan Iung cc type I:
"iai #o$n hng c%&' khong 2/3 bnh nhn c cn hng cm p ng vi valproate.
Hu ht bnh nhn hng cm p ng sau 1 4 ngy khi nng valproate huyt tng trn
50g/mL. p ng iu trj chng hng cm thng lin quan rt cao vi nng trong khong
50 - 150 g/mL. Khi dng valproate tng dn liu, nng huyt tng c th t c sau
khong 1 tun iu trj, nhng hin nay, vi chin lc iu trj ng ung t nng huyt
tng c tnh trj liu trong vng 1 ngy th c th kim sot hng cm trong vng 5 ngy.Tc
ng chng hng cm trong thi gian ngn ca valproate c th tng ln nu dng kt hp vi
lithium, carbamazepine, hoc thuc DRA. Do valproate c tc ng ph thun li vi nhn
thc, da liu, tuyn gip v thn, nn thng c a thch s dng cho iu trj hng cm cp
tr em v ngi gi.
"iai #o$n h(n h)p' vin phng thch chm divaproex c chng thuc l iu trj c
giai on hng cm, giai on hn hp trong ri lon lng cuc, c hoc khng c lon thn.
Bnh nhn ny cng c cng lc tnh trng kch ng, gin d, trm ut v cu kinh.
"iai #o$n tr& c%& *+ng c,c' valproate c c tnh iu trj ngn hn giai on trm
cm trong ri lon lng cuc , nhng hiu qu ny thng km hn so vi hiu qu chng
hng cm. Trong s cc triu chng trm cm, valproate c hiu qu tt vi triu chng kch
ng hn so vi triu chng lon cm. Trong thuc hnh lm sng, valproate thng dng nh
trj liu h tr vi thuc chng trm cm ngn nga kh nng pht trin thnh hng cm,
hoc chu ky nhanh.
-i.u tr/ phng nga' valproate c tc ng trong iu trj phng nga trong ri lon
lng cuc , lm cho cn hng cm nhe hn, t trm trong hn, v din ra ngn/nhanh hn. Khi
so snh truc tip vi lithium, valproate c hiu qu km hn mt cht, v dung np tt hn
lithium. Thuc c bit c hiu qu vi bnh nhn ri lon lng cuc chu ky nhanh, chu ky cuc
nhanh, v tnh trng lon kh sc, hng cm hn hp, hng cm ca bnh l thuc th, cng
nh bnh nhn lm dng cht, bnh nhn c cn hong lon, bnh nhn khng p ng hon
ton vi lithium.
Tm thn phn Iit v ri Ioan cm xc phn Iit: valproate thc y p ng vi trj
liu chng lon thn trong tm thn phn lit, ri lon cm xc phn lit. Valproate dng n
c c hiu qu km vi triu chng lon thn v thng dng kt hp vi nhng thuc khc
i vi nhm triu chng ny.
Cc ri Ioan tm thn khc: valproate c hiu qu vi nhiu ri lon tm thn khc,
bao gm: cai ru, ngn nga ti pht nghin ru, ri lon hong lon, ri lon sau sang
chn (PTSD posttraumatic stress disorder), ri lon iu khin xung ng, ri lon nhn cch
ranh gii, hnh vi kch ng, sa st tm thn. Khi dng vi nhng trng hp, hiu qu thng
km v thng p ng trj liu c lin quan n bnh l ri lon lng cuc kt hp.
LGJGHGThn trng v tc dng ph:
Mc d valproate c dung np tt v an ton khi s dng, nhng cng c nhng thn
trong khi s dng. Hai tc dng ph nng n nht l do nh hng n ty v gan. Nguy c c
th c l ng c gan c th gy t vong nhng bnh nhn tr, nht l nu dng chung vi
phenobarbital, nu c bnh l thn kinh, c bit l bnh l chuyn ha s sinh. T l ng c
gan khi chi dng n c valproate l 0.85/100.000, nhng khng c bnh nhn no trn 10
tui bj t vong do tc dng ph ny. Tuy nhin, nu c triu chng l m, mt mi, chn n,
bun nn, nn, ph, au bng khi ang iu trj bng valproate, phi xem xt kh nng bj ng
c gan. Chi c tng chi s trong xt nghim chc nng gan khng phi l lin quan n tnh
trng ng c gan. Mt s him trng hp bj vim ty, thng xut hin trong 6 thng u
iu trj v nu xut hin thng gy t vong. Do , cn nh gi chc nng tuyn ty, nng
men amylase huyt thanh. Nhng tc dng ph nng khc do iu trj bao gm: bnh l no
do tng amoniac mu, gim tiu cu. Gim tiu cu v ri lon chc nng tiu cu thng xut
hin nht khi dng liu cao valproate, gy tng thi gian chy mu.
Thng khng nn dng valproate thai ph v c lin quan n tnh trng khuyt ng
thn kinh (VD: chng ch i t sng), t l khong 1 4 khi dng tam c nguyt th 1.
C th gim nguy c chng ng sng ch i bng b sung acid folic mi ngy (1 4mg/ngy).
Tr b me m ngi me c dng valproate th c kh nng c valproate trong huyt thanh vi
nng khong 1 10 nng valproate huyt thanh ca me, nhng khng gy nguy c
no cho tr. Do , khng chng chi jnh dng valproate ph n cho con b.
Khng nn chi jnh valproate nhng bnh nhn mc bnh l gan.
Valproate thng gy kh khn tr vj thnh nin v ph n tr. C th c tnh trng
bung trng a nang ph n khi dng valproate. Ngay khi khng p ng tiu chun bnh l
ny th nhng ph n vn c bt thng kinh nguyt, rng tc, chng rm lng. C nhng
tc dng ph v chuyn ha nh: khng insulin, tng insulin huyt.
Nhng tc dng ph nng ca vaIproate
Ng c gan Him, tc dng ph c trng ca valproate.
Nguy c 1/118000(ngi trng thnh).
Nguy c cao: a trj liu, nh hn 2 tui, chm pht trin tm thn, t l
1/800
Vim ty Him, tc dng ph c trng ca valproate.
Tn sut: 2/2416 (0.0008)(th nghim lm sng). Khng thy trn lm
sng.
Ti pht nu dng tr li. C th c bt thng amylase.
Tng amoniac huyt Him. Thng gp khi kt hp vi carbamazepine.
C lin quan vi tnh trng run. p ng vi dng L-carnitine.
Ri lon ure mu chu
ky
Phi ngng dng valproate v protein.
Chng chi jnh dng valproate trong ri lon ure huyt chu ky.
Gy qui thai Nt ng sng: 1 4
T vn v dng acid folic phi hp vitamine B
An thn ngi gi Dng liu thp hn bnh thng.
Theo di thng xuyn dinh dng v tiu th nc
Gim tiu cu Gim liu nu c triu chng (c vt bm, chy mu nu rng).
Thng xut hin nu nng valproate trn 110g/mL n v 135 g/mL
nam
Bng tc dng ph ca vaIproate
1 Thng gp: kch thch d dy rut, bun nn, an thn, run, tng cn, rng tc.
2 Khng thng gp: nn, tiu chy, tht iu, lon vn ngn, tng men gan.
3 Him: ng c gan, gim tiu cu hi phc, ri lon chc nng tiu cu, ri lon ng mu,
ph, vim ty xut huyt, gim bch cu ht, bnh l no v hn m, yu c h hp v
suy h hp.
Tng cn l tc dng ph thng gp ca valproate, nht l khi dng lu di, nhng c
th ci thin nu c ch n gim calori nghim ngt. Rng tc gp 5 10, mt s him
c th rng sch tc. Nu rng tc, mt s nh lm sng khuyn nn b sung vitamine cha
km v selenium. C khong 5 10 bnh nhn tng men gan ng k, c th tng gp 3 ln
bnh thng, v thng tr v bnh thng nu ngng thuc. Vi valproate liu cao (trn
1000mg/ngy), c th gy h natri huyt t nhe n trung bnh, thng do tng tit hormon
ADH, s hi phc nu gim liu. u liu valproate c th gy hn m v t vong.
LGJGJGTuong tc thuc:
Valproate thng c dng km vi nhng thuc hng thn khc. Mt tng tc
thuc chc chn l vi lithium nu c hai thuc u dng vi liu iu trj, thng l gy run do
tc ng i vn th th . Kt hp valproate v DRA c th lm tng tnh bun ng, v cng
c th gp tc dng ph ny khi dng chung vi cc cht c ch thn kinh trung ng (nh
ru .), v lm tng nng ca tc dng ph ngoi thp (nhng p ng vi thuc chng
parkinson). Valproate c th kt hp mt cch an ton vi carbamazepine, hoc thuc SDA.
C l tng tc thuc gy phin toi nht l vi thuc lin quan vi lamotrigine. T khi
chng minh c kh nng iu trj ca lamotrigine trong ri lon lng cuc, iu trj kt hp
ca 2 loi thuc ny thng gp hn trc. Khi valproate c nng cao gp 2 ln lamotrigine
th s c nguy c xut hin hng ban nng n.
Nng huyt thanh ca carbamazepine, diazepam, amitriptyline, nortriptyline,
phenobarbital c th tng khi dng cng vi valproate v ngc li vi phenytoin, desipramine.
Nng valproate c th gim khi dng km vi carbamazepine v tng khi dng km vi
guanfacine, amitriptyline, fluoxetine. Valproate c th bj carbamazepine, diazepam, aspirin cnh
tranh trong gn kt vi proteine huyt tng. Nhng bnh nhn dng chng ng (aspirin,
arfarin) nn c theo di khi dng km vi valproate, nh gi nguy c khng mong
mun l tng kh nng khng ng.
Bng tuong tc thuc ca vaIproate
Lithium Tng run
Chng lon thn Tng bun ng, tc dng ph ngoi thp, sng, sng s.
Clozapine Tng bun ng, hi chng l ln
Carbamazepine Lon thn cp, tht iu, bun nn, ng ljm; c th lm gim nng
valproate huyt tng
Chng trm cm Amitriptyline v fluoxetine c th lm tng nng huyt thanh ca valproate.
Diazepam Valproate lm tng nng huyt thanh ca diazepam
Clonazepam Cn vng thc (him, chi xut hin bnh nhn c ng kinh)
Phenytoin Valproate lm gim nng huyt thanh ca phenytoin
Phenobarbital Valproate lm tng nng ca phenobarbital, tng bun ng
Thuc gy c ch h TKT Tng bun ng
Khng ng Lm tng kh nng khng ng
LGJGKGLiu Iung v hung dn Im sng: khi bt u dng valproate, nn nh gi
chc nng gan c bn, m cng thc mu, test thai k, test ng mu, nng
amylase huyt thanh. Trong qu trnh iu trj, nn nh gi jnh k cng thc
mu, men gan mi thng trong giai on trj liu u tin v mi 6 24 thng sau
. Men gan tng (c th n gp 3 ln bnh thng) cng thng gp v khng
cn thay i liu.
Vi cn hng cm, liu khi u khong 20 30mg/kg/ngy (ng ung) nhanh
chng kim sot triu chng. Liu ny thng c dung np tt nhng cng c th gy an
thn, run ngi gi. Hnh vi kch ng c th n jnh nhanh chng bng liu valproate tim
tnh mch. Nu khng c cn hng cm, tt nht nn bt u liu thp v tng dn nhm gim
thiu tc dng ph nh: bun nn, nn, bun ng. Liu u tin nn khong 250mg lc n. C
th tng liu n 250mg x 3 ln/ngy sau mi 3 6 ngy. Nn theo di nng huyt thanh
sau khi bt u liu u tin. Nng huyt thanh iu trj ng kinh l 50 - 150g/mL,
nhng c th tng n 200 g/mL cng vn c dung np tt. Vi ri lon tm thn, cng c
th dng tng ng, thng l khong 50 - 125 g/mL. Hu ht bnh nhn t c nng
trj liu vi liu 1200 1500mg/ngy (chia lm 2 ln). Khi bnh nhn p ng tt, chi cn
dng liu duy nht trong ngy trc khi ng.
6.4. Carbamazepine v oxcarbamazepine:
Ban u, c dng iu trj ng kinh cc b v ng kinh ton th ha, au thn kinh
sinh ba. Ngoi M, cc nc khc dng nh mt thuc chon lua hng u iu trj cp
tnh v duy tr trong ri lon lng cuc . Mi n nm 2004, FDA chp nhn carbamazepine
dng phng thch chm c hiu qu iu trj ri lon lng cuc.
C carbamazepine v oxcarbamazepine c cu trc tng tu nhau v ging vi thuc
chng trm cm ba vng. Oxcarbamazepine khc carbamazepine vj tr nhm carbohydrate
(CH) c thay bng nhm carboxy (CO). iu ny lm thay i chuyn ha thuc tr nn an
ton hn, dung np tt hn. Hiu qu trj liu thng qua vic phong ta th knh natri, tc ng
ln th th ty th v th th adenoxine A1. Ring oxcarbamazepine tc ng ban u ln ngay
knh Na. Tuy nhin, trong bi ny chi cp n carbamazepine.
Carbamazepine c hp thu chm v kh on. Thc n lm tng hp thu. Nng
inh huyt tng c th t c sau 2 8 gi v liu sn sng trj liu t c sau 2 4
ngy. C kh nng gn kt protein n khong 70 80. Thi gian bn hy thay i t 18 54
gi, trung bnh l 26 gi. Nu chi jnh iu trj ko di, thi gian bn hy trung bnh li l 12 gi,
do carbamazepine cm ng men gan CP450, nht l tnh tu cm ng ca qu trnh chuyn
ha carbamazepine. Tnh cm ng men gan t ti a sau 3 5 tun iu trj.
c chuyn ha gan v cht chuyn ha 10, 11-epoxide c tc ng chng ng
kinh. Tc ng iu ha kh sc ca thuc vn cha c hiu r. Dng lu di carbamazepine
c lin quan n tnh trng tng phn t epoxide. Tc ng chng ng kinh ca
carbamazepine c cho l do lm trung gian bng cch gn kt vi knh Na ph thuc in
th trong tnh trng bt hot v ko di trng thi khng hot ng ny. Th n l lm gim
hot ng knh Ca ph thuc in th v v vy lm gim dn truyn qua qua synap. Tc ng
tip na l lm gim vn chuyn qua knh th th N-methyl-D-aspartate (NMDA), ng vn
cnh tranh vi th th adenosine A1 v tc ng n cht dn truyn thn kinh catecholamine
h thn kinh trung ng. Trong khi , bt c c ch no lin quan n tc ng iu ha kh
sc vn cha c r.
LGKGIGChi d[nh tr[ Iiu:
Ri Ioan Iung cc giai doan hung cm: tc ng chng hng cm cp ca
carbamazepine xut hin trong vi ngy u iu trj. Khong 50 70 p ng vi thuc trong
vng 2 3 tun u iu trj. Cc nghin cu nghj thuc c hiu qu vi nhng bnh nhn
khng p ng vi lithium, nh hng cm lon kh sc, chu ky nhanh, tin s gia nh bt li
v ri lon kh sc. Tc ng ny c th tng khi kt hp vi lithium, valproate, hormon gip,
cc thuc DRA, SDA. Mt s bnh nhn chi p ng vi carbamazepine nhng khng p ng
vi lithium, valproate hoc thuc khc.
Ri Ioan Iung cc diu tr[ phng nga: thuc hiu luc iu trj phng nga ti
pht, nht l bnh nhn ri lon lng cuc , ri lon cm xc phn lit, hng cm lon kh
sc.
Trm cm cp: nhm bnh nhn trm cm khng trj p ng tt vi carbamazepine.
Nhng bnh nhn trm cm cp nng hoc t mn tnh dng nh p ng tt vi
carbamazepine. Mc d vy, carbamazepine vn l thuc thay th (ch khng phi l thuc
chon lua hng u) vi bnh nhn trm cm, ging nh CT.
Cc chi d[nh khc: thuc gip kim sot triu chng trong cai ru. Mc d khng c
tnh gy nghin nh benzodiazepine (BZD), nhng khng c cc c tnh u th nh BZD
trong cai ru v c nguy c c tc dng ph nn carbamazepine chi c dng hn ch vi
bnh l ny.
Carbamazepine cn c nghj dng iu trj trng thi bng n ti din ca PTSD.
C nhng nghin cu khng chng nghj rng carbamazepine c hiu qu kim sot hnh vi
xung ng, gy hn d khng c triu chng lon thn, k c tr em v ngi gi.
Carbamazepine cn c hiu qu iu trj hnh vi kch ng, gy hn khng cp tnh trong tm
thn phn lit, ri lon cm xc phn lit. Nhng bnh nhn c triu chng dng tnh ni bt
c th cng p ng, nu c cn bng n gy hn, xung ng.
LGKGHGThn trng v tc dng ph: thuc c dung np tng i tt. Tc dng ph
nhe v d dy rut (bun nn, nn, au d dy, to bn, tiu chy, chn n),
TKT (tht iu, chong vng) thng gp nht. Mc nng ca cc tc dng
ph ny s gim nu gim liu dn v dng liu t nng huyt tng ti
thiu. Ngc vi lithium, valproate v nhng thuc khc c tc dng kim sot
ri lon lng cuc, carbamazepine khng gy tng cn.
Hu ht cc tc dng ph ca carbamazepine c lin quan vi nng huyt tng cao
hn 90g/mL. Tc dng ph him gp nht, nhng nng n nht l ri lon v mu, vim gan,
v phn ng da trm trong.
Cc tc dng ph ca carbamazepine
Tc dng *i0n 1uan vi *i.u Tc dng ph #2c 3ng
Nhn i, nhn m. Gim bch cu ht
Chng mt Hi chng Steven ohnson
Ri lon d dy rut Thiu mu bt sn
Gim kh nng thuc hnh. Suy gan
Tc dng ph huyt hoc Sn nga
Vim ty
Loan tao mu: tc ng huyt hoc ca thuc khng lin quan vi liu. Lon to mu
nng (thiu mu bt sn) gp khong 1/125.000 ngi iu trj bng carbamazepine. Khng c
mi lin quan gia chng gim bch cu (khong 1 2) v thiu mu bt sn e doa tnh
mng. Nu c cc triu chng sau th phi bo ng tnh trng lon sn nng: st, au hong,
ni mn, m xut huyt, vt bm, tnh trng d chy mu. Theo di tc dng ph huyt hoc
nn theo jnh ky: 3, 6, 9 v 12 thng. Nu khng c biu hin tnh trng c ch ty xng, nn
tng khong cch nhng ln theo di.
Vim gan: trong nhng tun u iu trj, carbamazepine c th gy vim gan vi tng
men gan, nht l men transaminase, vim ti mt vi tng bilirubin v phosphatase alkaline.
Tng nhe men transaminase c th gp, nhng nu tng hn gp 3 ln so vi bnh thng th
phi ngng thuc ngay. Vim gan c th ti xut hin nu dng li v c th gy t vong.
Tc dng ph da: khong 10 15 c tnh trng hng ban sn lnh tnh trong 3 tun
u, ngng thuc th ht tnh trng ny. Mt s bnh nhn c hi chng da c th gy nguy
him tnh mng, bao gm: vim da trc vy, hng ban a dng, hi chng Steven ohnson,
hoi t biu m do ng c (epidermal necrolysis). Kh nng phi cp cu do nhng vn v
da nng lm cc nh lm sng thng ngng carbamazepine chi khi mi c ni bt ky loi sn
no. Nguy c ni sn ca valproate v carbamazepine tng ng nhau trong 2 thng u,
nhng v sau, carbamazepine c nguy c cao hn. Ni sn dng nh chi l sn lnh tnh,
cho thy thuc c hiu qu, v c th dng tip tc. C th phng nga bng prednisolone
40mg/ngy.
Tc dng thn: carbamazepine thng gy i tho nht khng do lithium. Hot tnh
ny do tc ng truc tip hay gin tip ln th th vassopressin. C th dn n h Na huyt v
ng c nc, nht l ngi gi khi dng liu cao.
Tc dng ph khc: carbamazepine gy gim dn truyn tim (mc d t hn so vi
TCA), do , c th lm nng bnh tim c sn. Nn dng carbamazepine mt cch thn trong
bnh nhn bj glaucome, ph i tin lit tuyn, tiu ng v lm dng ru. Carbamazepine
thng hot ha chc nng th th vasopressin, gy ra hi chng tit ADH khng thch hp,
c trng bng h Na huyt, v him hn l ng c nc. iu ny i nghjch vi tc dng
thn ca lithium. Tuy nhin, thm carbamazepine dng km vi lithium khng lm o nghjch
tc ng ca lithium. Tnh trng l ln, yu t nhiu, au u khi dng carbamazepine l triu
chng bo ng cn phi xt nghim in gii.
Carbamazepine him khi gy ra tnh trng tng nhy cm p ng min djch, vi biu
hin: st, ni mn, tng bch cu i toan, v c th vim c tim nguy kjch.
Tnh trng bt thng u mt nh, gim sn sinh mng v chng t sng ch i c
th do thai ph dng carbamazepine trong thai ky. Do , khng nn dng carbamazepine
trong thai ky ngoi tr tht su cn thit. Carbamazepine cn c tit qua sa me.
LGKGJGTuong tc thuc: carbamazepine lm gim nng ca kh nhiu thuc khc
do cm ng men CP 3A4 ca gan. Carbamazepine lm gim nng trong
mu ca thuc nga thai ng ung. Thuc cng khng nn kt hp vi MAO,
nn phi ngng MAO 2 tun trc khi bt u dng carbamazepine.
Nc p nho c ch chuyn ha ca carbamazepine gan. Khi valproate,
carbamazepine dng chung, nn gim liu carbamazepine v valproate s bj carbamazepine
thay th trong kt ni vi protein, v do , cn tng liu valproate.
Bng tuong tc thuc ca carbamazepine
Carbamazepine Im nh hung dn nng d
huyt tuong thuc khc
Thuc khc nh hung dn nng d huyt
tuong ca carbamazepine
4ar!a&a56pin6 *& gi%& n7ng #8 cc thuc'
Acetaminophen
Alprazolam
Amitriptyline
Bupropion
Clomipramine
Clonazepam
Clozapine
Cylosporine
Desipramine
Dicumarol
Doxycycline
Doxepin
Doxycycline
thosuximide
Felbamate
Fentanyl
Fluphenazine
Haloperidol
Hormon trnh thai
mipramine
Phenytoin
Theophylline
Valproate
arfarin
Thuc *& t9ng n7ng #8 car!a&a56pin6'
Allopurinol
Cimetidine
Clorithromycine
Danazol
Diltiazem
rythromycine
Fluoxetine.
Fluvoxamine
Gemfibrozil
traconazol
Ketoconazol
soniazid
Lamotrigine
Loratadine
Macrolidesnefazodone
Nicotinamide
Propoxyphen
Valproate
Verapamil
4ar!a&a56pin6 *& t9ng n7ng #8'
Clomipramine
Phenytoin
Primidone
Thuc *& gi%& n7ng #8 car!a&a56pin6'
Carbamazepine (tu cm ng)
Cisplatin
Felbamate
Phenobarbital
Rifampin
Theophyllin
Valproate
LGKGKGLiu Iung: liu mc tiu ca carbamazepine cho tc ng chng hng cm l
1200mg/ngy. Dng carbamazepine phng thch nhanh cn dng n 3 4
ln/ngy, iu ny d gy bin chng. Do dng phng thch chm c a
dng hn, v chi cn dng 1 2 ln/ngy.
Nng huyt thanh c hiu qu chng hng cm vn cha xc jnh c, nhng
chng ng kinh, cn nng huyt tng l 4 - 12g/mL.

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HA DC TR LIU

ThS. BS. Trn Trung Ngha

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