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CC THUC CHNG VIM NON STEROID

(Non Steroid Anti Inflamation Drugs- NSAIDs)

1. Tc dng
1.1 Tc dng chng vim
C tc dng trn hu ht cc loi vim khng k n nguyn nhn
C ch chng vim:
- c ch sinh tng hp Protaglandin(PG) do c ch c hi phc
cyclooxygenase(COX) lm gim PGE2 v PGF1 l nhng cht trung gian ho hc
ca phn ng vim
Khi tn thng mng t bo gii phng phospholipid mng. Di tc dng ca
phospholipase A2 cht ny chuyn thnh acid arachidonic. Sau met mt di tc
dng ca lipooxygenase(LOX), acid arachidonic to thnh c leucotrien c tac sng co
kh qun, mt khc di tc dng cu cyclooxygenase, acid chidonic to ra PGE2(gy
vim au), prostacyclin(PGI2) v thromboxan A2(TXA2) tc ng n s lng ng
tiu cu.

C ch tc dng ca NSAIDs
Enzym cyclooxygenase(COX)
C 2 loi COX l COX-1 v COX-2.
COX-1 hay PGG/H2 synthetase-1 c tc dng duy tr cc hot ng sinh l
bnh thng ca t bo l mt enzym cu to. Enzym ny c mt hu ht cc m:
thn, d dy, ni mc mch mu, tiu cu.. Tham gia trong qu trnh sn xut cc PG
c tc dng iu ho cc chc phn sinh l , n nh ni mi, bo v t bo do cn
gi l enzym gi nh
COX-2 hay PGG/H synthetase-2 c chc phn thc y qu trnh vim. Thy
hu ht cc m vi nng rt thp, cc t bo tham gia vo phn ng vim(bch
cu n nhn, i thc bo, bao hot dch khp, t bo sn). Trong cc m vim, nng
d COX-2 cao ti 80 ln do cc kch thch vim gy cm ng v hot ho mnh COX2 V th COX-2 cn gi l enzym cm ng

Nh vy thuc c ch COX-1 c nhiu tc dng ph khng mong mun thuc


c ch COX-2 mnh s c tc dng chng vim mnh m t gy tc dng ph.

Vai tr sinh l ca COX-1 v COX-2


- Lm vng bn mng lysosom: vim trong qu trnh thc bo cc i thc
bo lm gii phng c enzym ca lysosom(hydrase, aldolase, phosphatase acid,
collagenase..)lm tng thm qu trnh vim. Nh kh nng lm bn vng mng
lysosom cc NSAID c th ngn cn gii phng c enzym phn gii c ch qu trnh
vim

- Mt s c ch khc: i khng vi cc cht trung gian ho hc ca vim do


tranh chp vi c cht ca enzym, c ch di chuyn bch cu, c ch phn ng KNKT
1. Tc dng gim au:
Tc dng tt vi cc chng au do vim khng c tc dng vi au ni tng
2. Ngoi ra c ch h st v chng ngng kt tiu cu(tham kho)
Tc dng h st:

Tc dng chng ngng kt tiu cu:

C ch chng ngng kt tiu cu ca cc NSAIDs

CC PROSTAGLANDIN(PG)
1. Sinh tng hp:
PG c tng hp ngay ti mng t bo. Mng t bo cha nhiu phospholipid,
di tc dng ca phospholipase A2 ca mng s gii phng ra c acid bo t do
khng bo ho, cha 20 nguyn t C l acid arachidonc hay cn gi l acid eicosa5,6,11,14-tetraenoic, acid prostanoic. Acid arachidonic khi c gii phng ra s tr
thnh c cht cho nhiu enzym to ra c cht chuyn ho khc nhau: cc
prostaglandin, cc leucotrinen di teen gi chung l c eicosanoid

Ghi ch:

PLA2: phospholipase A2; 5-LOX: 5 lipooxygenase; 12- LOX: 12


lipooxygenase; COX: cyclooxygenase; PGG2: prostaglandin G2; PGH2: prostaglandin
H2; TxA2: Thromboxan A2; TxB2: Thromboxan B2; PGD2: prostaglandin D2; PGE2:
prostaglandin E2; PGF2: Prostaglandin F2; PGI2: prostaglacyclin; 6c PGF1: 6 ceto
prostaglandin F1; HPETE: acid hydroperoxyeicosatetratenoic; HTTE: acid
hydroperoxyeicosatetraenoic; LTA4, B4, C4, D4, E4: LeucotrienA4, B4, C4, D4, E4
2. Phn loi v vai tr sinh l ca cc prostaglandin
Acid arachidonic cht tin thn ca cc PG c 20 nguyn t C gm mt vng 5
cnh v 2 chui nhnh

Theo cu trc cu vng 5 cnh, chia c PG thnh cc nhm t tn theo ch ci:


PGA, PGB
Trong mi nhm cc PG li c phn bit bng cc s vit sau ch ci. S
ch s ng ni i ca chui bn nh PGA1, PGE2
Loi 1 c mt ng ni i gia C13- C14
Loi 2 c 2 ng ni i gia C13-C14 v C5-C6
Loi 3 c 3 ng ni i gia C13-C14, C5- C6, C17 -C18

Tt c cc PG u c OH C15, di mt phng ca phn t(biu th bng nt


----, nu trn mt phng l nt m )
Khi 2 chui nhnh trn cng mt phng nu chui c mng COOH di
mt phng th c gi qui c l PG(nh PGF2) ngc li gi l

Cc loi PG

Corticoid c ch phospholipase A2 nn c ch s to thnh acid arachidonic, do


c ch tng hp c PG v leucotrien. Cn cc NSAID do c ch cyclooxygenase
nn ch c ch tng thp PG, acid arachidonic vn c to thnh nn c th s tng
tng hp leucotrien gy tc dng ph ca thuc NSAID(nh cn hen gi)

S sinh tng hp PG

V tr tc ng cu peroxydase trong sinh tng hp PG


3. Tc dng ca PG

Trn tim mch:


- PGE c tc dng gin mch nht l mao ng mch, cc c vng trc mao
mch v c vng sau mao tnh mch. Cc tnh mch ln khng chu nh hng ca
PGE
- PGD2 gy gin c mch v co mch. nng thp phn ln cc mch u
gin(mch tng, mch vnh v mch thn) ch c mch phi li co
- PGF2 gy co mch c ng mch v tnh mch phi
- Thromboxan A2 gy co mch mnh
- Leucotrien(LT): LTC4 v LTD4 gy h HA do lm gim th tch tun hon v
gim co bp c tim(v lm gim lu lng mch vnh).Tc dng quan trng ca LT l
lm thot huyt tng ti mao mch hn histamin ti 100 ln
Trn mu:
- PGI2 c ch ngng kt tiu cu, n c tng hp ti ni mc mch mu c
vai tr kim sot s ngng kt tiu cu chng gy nghn mhc
- TXA2 l sn phm chuyn ho chnh ca acid arachidonic ti tiu cu c tc
dng lm ngng kt tiu cu ngc vi tc dng ca PGI2 v rt nhy cm vi tc
dng c ch ca aspirin
- LTB4 l tc nhn ho hng ng mnh vi bch cu a nhn, bch cu a
acid v bch cu n nhn
- PG c ch chc phn v s tng sinh ca lympho km hm p ng min dch.
PGE2 c ch s bit ho ca lympho B, s tng sinh ca lympho T v s gii phng
cc lymphokin
Trn c trn:
Trn c trn kh-ph qun:

- Cc PGF v PGD2 gy co v c PGE gy gin


- Prostaglandin peroxid(PGG v PGH) v TXA2 gy co kh qun
- PGI2 gy gin v i khng vi cc tc nhn gy co kh ph qun
- LTC4 v LTD4 gy co ph qun mnh hn histamin 100 ln
Trn t cung:
- Cc PGF v TXA2 gy co t cung khng cha v cha
- Cc PGE lnm gin t cung khng cha
Trn nhu ng ng tiu ho:
- Cc PGE v PGF gy co tht c dc ca d dy rut trong khi c vng thng
li gin di tc dng ca PGE v co tht vi PGF
- PGG, PGH, PTXA2, PGI2 gy co bp rut nhng yu hn PGE, PGF
- Cc LT gy co bp mnh rut
Trn s bi tit ca d dy rut:
PGE c ch bi tit acid ca d dy di tc dng ca kch thch ca thc n,
histamin hoc gastrin. Mt khc kch thch sn xut dch nhy v gy gin mch l
nhng tc dng bo v nim mc d dy
Trn thn:
- PGE2 v PGI2 lm tng dng mu ti thn gy li niu tng thi Na+ v K+.
Cc PGE cn c ch ti hp thu nc cu ADH. Cng vi PGI2 v PGD2, PGE gy
tit renin do tc dng kch thch trc tip ln t bo ht cnh cu thn
- TXA2 lm gim dng mu ti thn gim sc lc cu thn
4. S dng PG trong iu tr:

- Gy sy thai lc
- Bo v nim mc d dy: Misoprostol(Cytotec): tng t PGE1
- iu tr lit dng: PGE1
- Duy tr ng thng ng mch: PGE1
- iu tr THA phi nguyn pht: PGI2
Cc nhm thuc NSAIDs
* Loi c ch COX khng chn lc:
- Nhm Salicyllic: Acid acetylsalicylic(Aspirin)
- Nhm Indol:
+ Indomethacin
+ Sundilac
- Nhm Pirazolon: Phenylbutazon
- Nhm acid enolic: Oxicam
- Nhm acid propionic: Ibuprofen, naprofen, ketoprofen
- Nhm dn xut acid phenylacetic: Diclofenac
- Nhm dn xut acid heteroarylacetic: Tolmetin, ketorolac
* Loi c ch chn loc COX-2:- Nhm furanon c nhm th diaryl: Rofecoxib
- Nhm pyrazol c nhm th diaryl: Celecoxib
- Nhm acid indol acetic: Etodolac
- Nhdm sulfonanilid: Nimesulid

1. Nhm acid salicylic: Aspirin


Hin nay c nhiu thuc mi tt hn nn Aspirrin thng ch dng chng
ng vn tiu cu
2. Nhm Indol: Indomethacin- Chng vim mnh hn hydrocortison 4 ln
- Tc dng gim au lin quan mt thit vi tc dng chng vim. T l chng
vim/liu gim au bng 1
- c tnh: lot tiu ho(d dng bng ng tim v c chu k gan- rut) v
nhc u vng trn(do cng thc tng t nh serotonin). Cn gp gam bch cu,
gim tiu cu, phn ng qu mn
3. Nhm pyrazolon: Phenylbutazon- Tc dng chng vim tt c bit i
vi vim dnh khp, thi gian bn thi di >3 ngy
- c tnh: lot d dy d dng bng ng tim, gi natri gy ph, THA, phn
ng d ng, gim bch cu, suy tu
4. Nhm acid enolic: dn xut oxicam: piroxicam v tenoxicam
- Tc dng chng vim mnh v ngoi tc dng c ch COX cn c ch
proteoglycanse v collagenase ca m sn. Tc dng gim dau xut hin nhanh na
gi sau khi ung
- Thi gian bn thi di: 2-3 ngy
- t tan trong lipid nn d thm vo m bao khp b vim t thm vo cc m
khc v vo thn kinh gim c nhiu tai bin
- Thng ch nh trong cc vim mn tnh v thi gian bn thi di
- Bit dng:
+ Piroxicam(Felden): 10-40mg/ngy

+ Tenoxicam(Tilcotil): 20mg/ngy
+ Meloxicam(Mobic): vin nn: 7,5mg v 15mg, liu ti a 15mg/ngy
5. Nhm dn xut acid propionic:
- Liu thp c tc dng gim au, liu cao hn c tc dng chng vim
- Nhm ny t c tc dng ph hn nht l trn ng tiu ho do s dng
nhiu trong cc trng hp vim khp mn tnh
- Cc bit dc:
+ Ibuprofen: vin 200-300-400mg, liu 1200-1600mg/mgy
+ Naproxen: vin 250mg, liu 250 2 ln/ngy
+ Fenoproxen vin nang 300-600mg, liu 6004 ln/ngy
+ Ketoprofen: vin nang 50mg, liu 502-4 ln/ngy
6. Nhm dn xut ca acid phenylaceticiclofenac- Tc dng c ch COX
mnh hn indomethacin v nhiu thuc khc. Cn lm gim nng acid arachidonic
t do trong bch cu do ngn cn gii phng hc thu hi acid bo
- Hp thu nhanh v hon ton qua ng tiu ha nhng ch c 50% vo c
tun hon v chuyn ho trong qu trnh hp thu
- Thi gian bn thi l 1-2 gi nhng tch lu bao khp nn tc dng vn gi
c lu
- Ch inh trong vim khp mn tnh, cn dgn gim au trong vim c, au
sau m v au do kinh nguyt
- Tc dng ph t
- Liu: vin 50-100mg, liu 100-150mg/ngy

7. Nhm dn xut acid heteroarylacetic: Tolmetin


- Tc dng chng vim, gim au, h st tng t aspirin nhng d dung np
hn
- Thi gian bn thi 5h
- Liu ti a 2g/ngy
Loi c ch chn lc COX-2:
c im:
- c ch chn lc COX- 2 nn tc dng chng vim mnh v c ch COX-1 yu
nn cc tc dng ph v tiu ho, mu, thn, cn hen.. gim nhiu
- Thi gian bn thi di 20h nn ch cn ung mi ngy 1 ln
- Hp thu d qua ng tiu ho d thm vo cc m v dch bao khp nn c
nng cao trong m vim ch nh tt cho vim xng khp v vim khp dng thp
1. Nhm furanon c nhm th diaryl: Refecoxib(Vioxx)
Hin nay cm dng v tng nguy c t t bnh nhn tim mch
2. Nhm pyrazolon c nhm th diaryl: celecoxib(Celebrex)
- c ch COX-2 mnh hn COX-1 t 100-400 ln
- Gn mnh protein huyt tng
- Thi gian bn thi 11h
- Liu 1002 ln/ngy

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