THUC KHNG HISTAMIN

Phan Th Nh Qunh, MSc.B mn Ha Dc Ha L Dc Ha Hu CKhoa Dc, i hc Y Dc HuHISTAMIN THUC KHNG HISTAMINHistaminCht trung gian ng vai tr quan trng trong sc phn v v phn ng d ngng vai tr trong s iu ha tit dch v d dyc d tr nhiu nht trong t bo mast v cc ht bi tit ca t bo a kim

4(5-)(2-aminoethyl)imidazoleHa hc HistaminHistamin c tnh base Tn ti di cc dng hn hp cc dng h bin ion v dng khng mang in tch pH sinh l (pH = 7.4): 96.6% dng lin hp monocationpH cao: % dng dication cao hnDng kt tinh ca mui ca Histamin: ch yu l N-H

3Ha hc HistaminSARS tn ti trong thi gian ngn ca ca cc dng Histamin khng mang in tch thn du hn gip khuch tn qua mngNH3+ monocation: quan trng cho hot tnh ng vn ti cc receptor histaminDng h bin N-H: dng pharmacophore ti H1-receptor

4Ha hc HistaminMi lin quan lp th - hot tnh:Dng ng phn quay trans-gauche: quan trng i vi s gn kt trn receptor ca HistaminTrans: i lc vi c H1 v H2 receptorGauche: u th trn H3 receptor v khng gn kt vi H1 v H2 receptor

5Histaminc to thnh t histidin di tc dng ca histidin decarboxylase v pyridoxal phosphat

HistaminS gii phng histamin t t bo mast

7Receptor Histamin L receptor gn vi G-proteinCc loi receptor:H1: phn b no, ng tiu ha, tim mch, t bo lymphoH2: phn b t bo c tim, t bo thnh d dyH3: phn b TKTW, nim mc d dyH4: phn b lch, t bo T, tuyn c, bch cu i toanHistaminKhi histamin gn vi th th H1 gy ra mt s phn ng vi c th nh:Trn h tim mch: Lm gin mch v tng tnh thm mao mch nn gy ph n, vim, nga, pht ban; Lm tng nhp tim, tng lc co bp c tim v gy h huyt p.Trn ng h hp: Gy s mi, ngt mi, liu nh histamin cng c th gy co tht c trn kh ph qun, lm xut hin cc cn kh th ging hen ph qun.Trn h thn kinh: Kch thch u tn cng ca dy thn kinh cm gic gy nga v au.

9HistaminKhi histamin gn vi th th H2, c bit l t bo thnh d dy gy tng tit acid dch v, d dn n lot d dy, t trng.Thuc khng histamini khng cnh tranh vi th th histamin ti t bo chThuc khng histamin H1: Cnh tranh histamin ti th th H1, s dng trong iu tr d ngThuc khng histamin H2: Cnh tranh histamin ti th th H2, s dng trong iu tr lot d dy-t trng11Thuc khng histamin H112C ch tc dngLm mt hay c ch tc dng ca histaminC ch cnh tranh thun nghch ti receptor H1 ca histaminMt s thuc cng c th phong b s phng thch histamin (tuy nhin vi nng cao hn ng k so vi nng cn phong b receptor H1)

13Phn loiTh h I: Thuc c th i qua hng ro mu no, c tc dng trn receptor H1 c trung ng v ngoi vi, c tc dng an thn mnh, chng nn v c tc dng khng cholinergic ging atropin.

Th h II: Thuc rt t i qua hng ro mu no, c thi gian bn thi di, t tc dng trn H1 trung ng, ch c tc dng trn H1 ngoi vi, khng an thn v khng c tc dng chng nn, chng say tu xe, khng c tc dng khng cholinergic.14Th h 1 (loi c in)PromethazinClorpheniraminDexclorpheniraminAlimemazinDiphenhydraminTh h 2 (loi mi)AstemizolTerfenadinLoratadinCetirizinAcrivastinPhn loiPhn loiNhm thucTh h 1Th h 2Ch nhNga, ni m ay, s mi, vim khp do d ng, d ng thuc, Ho khanChng nn, say tu xe- Nga, ni m ay, s mi, vim khp do d ng, d ng thucTc dng phD ng, tng nhn pH HA th ngBun ngKh ming, to bnD ngH HA th ngBun ng (t)Kh ming, to bn (t)Chng ch nhMn cmNg c thuc m, thuc ngTE di 2 tui, ngi vn hnh my mcMn cmSuy ganTc dng dc l v tr liuiu tr triu chng ca vim mi d ng nh ht hi, s mi, nga, m ay v cn mn tnh, v mt s bnh c lin quan n HistaminThuc lm gim s lng, kch c, thi gian xut hin v nga trong m ay mn tnh khi dng thuc tc thiKhng c s khc nhau ng k v hiu qu tr liu ca thuc th h 1 v 2 trong iu tr cc chng ny

Tc dng dc l v tr liuThuyn gim cc triu chng ca hen v nhim khun h hp trn nh cm lnh, vim tai gia, v vim xoang (ch hen v nhim khun c vim d ng i km)Khng dng n c trong chong phn vC th dng km epinephrine gim cc triu chng qua trung gian receptor H1Dc ng hc Hp thu tt qua ng tiu ha Chuyn ha ch yu bi enzyme microsom gan Thi gian tc dng 4-6h Meclizin v cc thuc khng histamin th h mi c thi gian tc dng di ch dng 1 ln/ngyDc lc hc Khng histamin H1 c ch TKTW Chng bun nn, i ma Khng cholinergic

SARX = CH-O, N, CH, CH-Nn = 2-3R1,R2 = CH3Ar1, Ar2 c th lin kt vi nhauTh Br, Cl hay F vo v tr para ca nhn thm: hot lc tng

21Mt s thuc khng H1 thng dngPromethazinDn cht phenothiazin thuc nhm dimethylamino-ethyliu ch:

PromethazinTc dng:Khng histamin, chng nn, an thn, khng cholin Ch nh:Cc bnh d ngSay tu xe, bun nnD ng da tr nh, r dch nim mc, vim ph qun v co git trCht tin m, an thn trong sn khoaBnh d ng: nga, m ay, s mi, vim khp d ng, bin chng do mn cm penicillin, streptomycin,24PromethazinChng ch nh:Nhy cmNg c thuc ng hay thuc mang dng IMAOTr s sinh, PN c thai v cho con bTim di daTc dng ph:Bun ng, nng u, h HA t th, to bn, kh mingPromethazinLiu dng:NL: 25 mg x 3-4 lm/ngyTE: siro 1mg/ml, liu hay so vi NLTin m, cp cu: ng 50 mg/2ml, IM hay IV 0,15-0,3 mg/kgKem, thuc m: dng ngoi tr nga, gy t nhClopheniramin maleatThuc nhm propylaminDng ng phn quay phi Dexclopheniramin c tc dng mnh hn

Chuyn ha

27Clopheniramin maleat Tc dng: Khng histamin, t tc dng an thnChng tit acetylcholinCh nh:Vim mi d ngMy ay, vim da tip xcD ng thc nPh mch, ph QuinckeClopheniramin maleat Chng ch nh:Qu mnCn hen cpPh i tuyn tin litGlaucom gc hpTc c bng quang, mn v-t trngLot d dy Ngi cho con b, tr s sinh v thiu thngClopheniramin maleat Tc dng ph:Ng g, an thn, kh mingChng mt, bun nnTim: kch ng ch tim Tng tc thucVi IMAO: tng tc dng chng tit acetylcholinVi ethanol, thuc an thn gy ng: tng tc dng c ch TKTWVi phenytoin: c ch chuyn ha ng cClopheniramin maleatLiu dng:NL: 4-16 mg/24hTE: 0,3 mg/kg/24hTim phng nga phn ng d ng truyn mu, huyt thanh, sc phn v: 10-20 mg/ln, ti a 40 mg/24hDiphenhydramin Dn cht aminoethanol

Tc dng: an thn v khng cholinergic mnh

32Diphenhydramin Ch nh:D ng: thc n, daVim mi d ngChng mt, mt ng ParkinsonChng ch nh:PN c thaiNgi gi > 6-0 tuiVim lot tiu haDiphenhydraminTng tc thuc:Khng dng chung vi ru, benzodiazepin, IMAO v thuc chng trm cm 3 vngTc dng ph: Ng gtKh mingLon th gicLiu dng:NL: 25-30 mg x 3-4 ln/ngyTE: 12,5 mg x 3-4 ln/ngyTerfenadin Dn cht aminoethanol th h 2 Chuyn ha gan to cht chuyn ha c hot tnh

TerfenadinTc dng: Khng histamin khng gy ngCh nh: Vim mi, d ng ngoi da, m ayChng ch nh: Mn cm, suy gan nngTc dng ph: Nhc u, bun nn

TerfenadinTng tc thuc:Gy xon nh khi dng chung vi ketoconazol, KS macrolid rt khi th trng

37Fexofenadin Tc dng nhanh v t gy tng tc thuc do khng nh hng n h Cyt. P450 Khng histamin chn lc th th H1 ngoi binCh nh:Vim mi d ngMt nga , chy nc mtChng ch nh:TE < 12 tuiPN c thai v cho con bLiu dng: 60mg x 2 ln/ngyLoratadin v Desloratadin Desloratadin c tc dng mnh hnLoratadin: 10 mg/ngyDesloratadin: 5 mg/ngy

Loratadin v Desloratadin Tc dng:Khng histamin H1 mnh v ko diHot tnh chn lc trn H1 ngoi bin Ch nh:Vim mi d ngMy ay mn tnhD ng ngoi da Tc dng ph:Mt mi, nhc u, kh ming, ri laojn tiu ha,THANK YOU!