12/21/2016

NI DUNG TRNH BY
1. i cng

THUC H ST, GIM AU,

2. Tc dng v c ch tc dng

CHNG VIM KHNG STEROID

3. Cc dn xut
4. Cc tc dng KMM ca thuc CVKS

TS.Trn Thanh Tng

B mn Dc l
i hc Y H Ni

5. Nguyn tc dng thuc CVKS

1

Mc tiu hc tp

Mc tiu hc tp (tip)
3. Trnh by c c im tc dng v ch nh ca cc

1. Phn tch c c ch tc dng v 4 tc dng chnh

thuc: dn xut oxicam, dn xut acid propionic,

ca thuc chng vim khng steroid (CVKS).

paracetamol v thuc c ch chn lc COX-2.

2. Trnh by c c im tc dng v ch nh ca cc

4. Trnh by c cc tc dng khng mong mun, cch

thuc: aspirin, indomethacin, diclofenac.

phng v nu ng nhng nguyn tc khi s dng

thuc CVKS.
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Ti liu hc tp

I. i cng

1. Dc l hc, NXB Gio dc

-

2. Dc l hc lm sng, NXB Y Hc

Tn khc:
+ Chng vim khng steroid (CVKS) - phn bit vi

3. Ti liu tham kho:

nhm steroid c nhn sterol

- Dc th Quc gia VN 2002

+ NSAIDs = Non Steroidal Anti Inflammatory Drugs

- Cng vn 687/QLD-K ca Cc Qun l Dc, BYT

- L nhm thuc hay c dng nht hin nay

- Goodman & Gilman, The pharmacological basis of

therapeutics, 12th Edition

C cu trc ho hc khc nhau

- Rang & Dales Pharmacology, 7th Edition

- British National Formulary 2014

II. TC DNG V C CH

I. i cng

H st, gim au, chng vim, chng ngng kt tiu cu

- C cng tc dng: h st, gim au, chng vim, chng kt

2.1. Tc dng h st

tp tiu cu vi cc mc khc nhau. Tr nhm para

- Tc dng: h st do mi nguyn nhn, l thuc cha triu chng

aminophenol (paracetamol) ch c tc dng h st, gim au

- C ch:

- T l liu chng vim/gim au ca cc thuc khc nhau

+ Cht gy st ngoi lai vo c th s gy tng PGE1, E2 vng di

i gy st

+ Aspirin v hu ht thuc CVKS 2

+ CVPS c ch COX tng hp PG E1, E2 vng di i

+ Indomethacin, piroxicam: 1

Trn TKTW: rung c, h hp

Trn TKTV: gin mch, chuyn ho, tit m hi

- Hay b lm dng nn d gy tai bin

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H st
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2.2. Tc dng gim au

2.1. Tc dng h st

Thuc
h st

- Tc dng
+ Tt vi cc au nh v au khu tr

(-)

+ Khc vi tc dng ca morphin: khng gim au ni

St

tng, khng gy ng, khng gy khoi cm, khng gy

nghin
- C ch:
Lm gim tng hp PG F2
F2 gim tnh cm th (t
(tng
tnh tr) ca ngn cc si thn kinh cm gic vi:

C ch tc dng h st
9

2.3. Tc dng chng vim

GC

- Tc dng: vi mi nguyn nhn gy vim

(+)

Phospholipid mng
(t bo b tn thng)

(-)

Lipocortin

Phospholipase A2

Acid arachidonic
LOX

10

2.3. Tc dng chng vim

- H st, gim au, chng vim (CVKS)

- Glucocorticoid (GC)

COX: Cyclooxygenase
LOX: Lypoxygenase

bradykinin,, histamin, serotonin

bradykinin

(-)

- C ch:
+ c ch COX tng hp PG E2, F1
F1
(l cc cht trung gian ho hc ca phn ng vim)

CVKS

+V
V
ng bn mng lysosom
lysosom ng
ngn gii phng cc enzym
phn gii.

COX

+ i khng cht trung gian ho hc ca phn ng vim,

Leucotrien

c ch s di chuyn ca BC, c ch s kt hp KN + KT.

Prostaglandin
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2.4. Tc dng chng ng

ng
ng kt tiu cu

2.4. Tc dng chng ng

ng
ng kt tiu cu
- C ch:
ch:
+ Liu thp:
thp: tc dng ln tiu cu lm tng hp

Tiu cu

thromboxan A2

PGG2/H2

+ Liu cao:
cao: tc dng ln thnh mch lm tng hp
prostacyclin,, nh
prostacyclin
nhng tc dng trn tiu cu vn mnh hn.
hn.
Ngoi ra:
ra: lm gim tng hp prothrombin

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2.4. Tc dng chng ng

ng
ng kt tiu cu

14

CVKS DNG CHNG NG MU

CVKS c ch thromboxan synthetase gim tng hp TXA2

ca tiu cu c ch ngng kt tiu cu.
Tiu cu khng t tng hp protein khng ti to c enzym
Aspirin c ch khng hi phc sut i sng tiu cu (8-11 ngy).
- Aspirin c tc dng chng ngng kt tiu cu in hnh,
liu thng dng 40-100mg/ngy.
- CC khi nghi c st xut huyt.

Phng nguy c tc mch do ngng kt tiu cu bnh nhn tim mch

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III. Cc dn xut

III. Cc dn xut
C CH TC NG CA CC THUC CVKS
TXA2

Phospholipid mng t bo

Tiu cu

Chn lc COX2
Acid Arachidonic

c ch COX no
s c li ?

PG

COX2

COX1

Prostaglandin I2
Thn

Prostaglandin
Cyclooxygenase (COX)

Prostaglandin E 2
D dy

Vim
NSAIDs

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III. Cc dn xut

3.1. Dn xut acid salicylic

NSAIDs
1

DX acid salicylic

Aspirin

DX indol

Indomethacin, sulindac

DX acid enolic (oxicam)

Piroxicam, meloxicam,
tenoxicam

DX acid propionic

Ibuprofen, naproxen,
ketoprofen, oxaprozin

DX acid phenyl acetic

Diclofenac

c ch chn lc COX-2

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Cc ch phm:

Acid salicylic

Acid acetylsalicylic (aspirin)

Methyl salicylat

c ch chn lc COX-2
Celecoxib, etoricoxib, parecoxib

Thuc gim au, h st

7

DX para aminophenol

Paracetamol
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* Aspirin (acid acetyl salicylic)

* Aspirin (acid acetyl salicylic)

- Tc dng

- Ch nh

+ Liu thp: h st, gim au

+ Gim cc cn au nh v va

+ Liu cao: chng vim

+ H st

+ Chng ng vn tiu cu ngay t liu 40-100mg/ngy

+ Chng vim cp v mn (nh vim khp dng thp,

+ Trn s thi tr uric:

vim khp dng thp thiu nin, vim xng khp...)

. Thp: thi uric (nng bnh gt)

+ D phng nguy c tc mch do ngng kt tiu cu

. Cao: thi uric

ngi c bnh l tim mch

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- Tc dng khng mong mun

- Tc dng khng mong mun

+ Trn ng tiu ho:

+ Hi chng Salicyle: bun nn, tai, ic, l ln

PGE2 c tc dng: to cht nhy,

+ c ng

kch thch phn bo

+ Ng c: khi dng liu > 10g

bo v ng tiu ho

+ Liu cht: 20g vi ngi ln

CVKS c ch to PGE2 lm cho acid v pepsin tn cng

- Ch phm

gy lot d dy - t trng

Aspirin PH8, Aspirin, Aspgic (lysin acetyl salicylat)

Cch phng: ung thuc sau n, vin nn c bao, ung cng thuc
bo v d dy misoprostol, c ch bm proton (PPIs).

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3.3. Dn xut Enolic (Oxicam)

3.2. Dn xut Indol

* Indometacin

* Piroxicam (Felden), Tenoxicam (Tilcotil)

- Tc dng chng vim mnh so vi aspirin

- Tc dng chng vim mnh

- Khng dng cha st n thun

- Thi gian tc dng di

- T l gp c tnh cao t 20 - 50%

- t gn vo m, d thm vo t chc bao khp b vim, t

thm vo thn kinh t tai bin

- Sinh kh dng 100%

- Ch nh: vim mn tnh, au sau phu thut

- Thm c vo dch khp

* Meloxicam (Mobic)

- Ch nh: vim khp, au dy thn kinh

Trn lm sng c ch COX2 gp 10 ln COX1

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3.5. Dn xut Propionic:

3.4. Dn xut Phenyl acetic

* Diclofenac (Voltaren)

* Ibuprofen, naproxen

c im tc dng

c im tc dng

- c ch COX mnh hn indomethacin

- t/2 ngn nhng tch ly dch bao khp nn tc dng di

indomethacin
=> dng nhiu trong vim khp mn tnh.

- Ngoi ng ung, c ch phm bi ngoi da.

Ch nh: + Vim khp mn tnh

Ch nh

+ Gim au nh v va

- Vim khp mn, thoi ha khp, vim a khp

- Gim au cp v mn

t TDKMM, nht l trn ng tiu ha so vi aspirin,

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+ H st

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3.6. c ch chn lc COX2

3.6. c ch chn lc COX2

- c im tc dng

TXA2

Phospholipid mng t bo

Acid Arachidonic

Tc dng chng vim mnh, t TDKMM

Tiu cu

Chn lc COX2
PG

COX2

COX1

Prostaglandin I2
Thn

t/2 di nn ch ung 1 ln/ngy

Khng dng d phng nhi mu c tim do kt tp tiu

cu ch ph thuc COX1 (vn dng aspirin)

Prostaglandin
Cyclooxygenase (COX)

Prostaglandin E 2
D dy

cc m b vim

Vim
NSAIDs

- Tai bin:

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3.6. c ch chn lc COX2

D thm vo m, dch bao khp => nng cao trong

Ch nh tt cho au do vim xng khp

3.6. c ch chn lc COX2

Cc thuc nhm coxib hin ang dng

Huyt khi tc mch, gy t qy:

* Celecoxib (Celebrex)

Do gim PGI2 t bo ni mc mch nhiu

- c ch chn lc trn COX2 gp 100-400 ln

Gy co mch thn, gy tng tit renin lm THA:

t/2 = 11h, liu 100mg x 2 ln/ngy,

thp khp 200mg x 2 ln/ngy

Do lm gim PGE2, PGI2 (cht gin mch thn)

Mt s thuc b rt khi th trng: valdecoxib

- Ch nh: au do vim xng khp

(2005), rofecoxib (Vioxx, 2004), ...

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3.6. c ch chn lc COX2

THUC C CH CHN LC COX-2

* Etoricoxib
- Hp thu khng hon ton (83%)
-

t/2 = 20-26h, liu 60-90mg hoc 120mg x 1 ln/ngy.

Hay c ch nh cho cc trng hp vim khp

M: hin cp php duy nht celecoxib

Anh, Vit Nam: celecoxib, etoricoxib v parecoxib

* Parecoxib *
-

Tin cht ca valdecoxib

Dng t ln gim au sau phu thut, dng tim

*
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Rang &Dales Pharmacology, 7th Edition. BNF 2014

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3.7. Dn xut para aminophenol

* Paracetamol (acetaminophen)

* Paracetamol (acetaminophen)
- c im tc dng:

Ch nh tt cho nhng ngi khng dng c aspirin

Gim au - h st:

(lot tiu ha, ri lon ng mu).

Cng & thi gian tc dng tng t aspirin.

- c tnh:

Chng vim:

Khng tc dng khng thuc nhm thuc CVKS.

c ch COX ca paracetamol, khng c ch s hot ha bch cu

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C nguy c gy phn ng ph nghim trng trn da

(Cng vn 687/QLD-K ca Cc Qun l Dc, BYT)

L do: trong vim c nng cao cc peroxyd, lm mt tc dng

trung tnh nh cc CVKS khc

Lm sng: paracetamol c dng h st, gim au.

Liu thng thng: khng gy tn thng ng tiu

ha, mt thng bng base-acid, ri lon ng mu.

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* Paracetamol (acetaminophen)

Paracetamol (acetaminophen)
Cc dng ch phm

Dng liu cao (> 10g), sau 24 gi, xut hin hoi t t
bo gan c th tin trin ti cht sau 5 - 6 ngy. Do
paracetamol b oxy ha gan to ra

N-acetyl parabenzoquinonimin (c vi t bo gan)

iu tr sm bng N-acetyl-cystein (tin thn ca
glutathion), bnh nhn c th qua khi. Sau 36 gi, gan
b tn thng, kt qu s km.
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IV. CC TC DNG KMM CA CVKS

STT

TD KMM

C ch

IV. CC TC DNG KMM CA CVKS

Bin php phng

STT TD KMM

- Ung thuc sau n no

(tr dng vin bao tan trong
- c ch COX
PGE2 rut v nn bao film)
- Khng dng cho ngi c
Lot d dy- bi tit cht
nhy,
c
ch
tin
s lot d dy-t trng
t trng
phn bo nim - Trnh dng liu cao, ko di
Biu hin: au mc ng
- Dng km thuc bo v nim
thng v, xut tiu ho
mc d dy t trng, thuc
huyt tiu ha
- Kch ng ti gim tit acid
cao
ch
- Thay thuc: paracetamol vi
mc ch h st, gim au
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Ko di
thi gian
chy mu
Biu hin:
chy mu
kh cm,
chn rng,
tit, di
da,...

C ch

Bin php phng

- Khng dng cho ngi ang

b xut huyt hoc c nguy c
- c ch tng hp b xut huyt
- Kim tra cng thc mu,
thromboxan A2
(chng ng mu) nng prothrombin thng
- Liu cao: tng xuyn
hp prothrombin - Khng dng cng thuc
khng vitamin K
- Thay thuc: paracetamol vi
mc ch h st, gim au
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IV. CC TC DNG KMM CA CVKS

STT

TD KMM
Cn hen gi
Biu hin: cn kh
th sau khi dng
thuc

C ch

Bin php phng

- Tng tng hp - Khng dng cho

leucotrien
ngi c tin s HPQ
- Thay thuc:
glucocorticoid

Nng bnh gt
- Tranh chp
vi acid uric
Biu hin: au ngn
ng thn
chn ci, cc khp
tit uric
sau khi dng aspirin
liu thp

IV. CC TC DNG KMM CA CVKS

- Khng dng aspirin

liu thp cho ngi b
gt

STT

TD KMM

C ch

Bin php phng

Tn thng gan
Biu hin: vim
gan, vng da sau
khi dng
paracetamol,
diclofenac

- Thn trng vi ngi suy

- Cht chuyn gim chc nng gan
ho gy c - Kim tra chc nng gan 2
t bo gan
tun/ ln
- Thay thuc khc, gii c
sm

Tn thng thn
Biu hin: i
albumin, vim thn
cp, v niu

- Thn trng vi ngi suy

- c ch tng gim chc nng thn
hp PGI2 - Kim tra chc nng thn
co mch thn 2 tun/ ln
- Thay thuc khc

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IV. CC TC DNG KMM CA CVKS

STT

TD KMM

C ch

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IV. CC TC DNG KMM CA CVKS

Bin php phng

STT

TD KMM
Ri lon thn kinh
Biu hin: chng
mt, nhc u khi
dng indomethacin

C ch

Cng thc
- Theo di pht hin sm
cu to ca
- Thay thuc khc
indomethacin
gn ging
serotonin

Tim mch, huyt p Lm gim

Thn trng cho nhng
tng
hp
ngi c nguy c, theo
Biu hin: tng huyt
PGE2,
PGI2
di cc TD KMM
p, NMCT, t qu
(tr aspirin liu thp)

Ri lon th gic
Biu hin: nhn m,
gim th lc, thay i
nhn cm mu sc
sau khi dng
ibuprofen

c khi mang thai - Gim tit

PG co
Biu hin: chm
tht c trn t
10 chuyn d, d tt
cung
thai nhi
- C ch
khc cha r

Cha r

Ngng thuc v
khm chuyn khoa
mt

43

Bin php phng

- Trnh dng thuc CVKS

trong thi k mang thai
- Theo di pht hin sm
d tt
- Theo di st giai on
chuyn d
44

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V. Nguyn tc s dng CVKS

V. Nguyn tc s dng CVKS

1. Chn thuc tu vo c th

6. Dng liu tn cng 5 -7 ngy sau dng liu duy tr

2. Ung trong hoc sau n

7. Phi hp thuc:

3. CC vi ngi c tin s lot d dy - t trng, trng

hp cn thit phi dng thm thuc bo v ng tiu ho
4. Thn trng: suy gan, suy thn, d ng, cao huyt p

- Khng dng phi hp 2 thuc cng nhm

- Khng dng cng thuc chng ng mu
- Lu tng tc vi mt s thuc khc

5. iu tr ko di: kim tra cng thc mu, chc nng thn

2 tun/ln
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N THUC
Chn on: au lng cp
1. Mobic 7,5mg

x 10 vin

(Meloxicam)
Mi ln ung 1 vin, ngy 2 ln sau n no
2. Mydocalm 50mg

x 20 vin

(Tolperison)
Mi ln ung 2 vin, ngy 2 ln
3. Voltaren 1% 20g

x 1 tube

(Diclofenac)
Xoa vng au ngy 4 ln

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