- Gay te tiem ngam: la tiern thuoc gay te VaG dudi da d~ thuoc tham VaG than kinh Phuong phap nay thuong dung khi nh6 rang, trich mun nhot,
2. DAN XUAT CVA ACID BARBITURIC 1 Lien quan gifiacau true va tile dung
NH-CO
/1 6 "'-
OC2 5CH2
"'-3 4 /
NH-CO
Hlnh 3.3. Cong thltc cua acid barbituric
Acid barbituric Ia acid manh, d~ phan ly, kho khuech tan qua mang sinh hoc nen kh6ng co tac dung. Khi thay hydro a C5bang cac g6c R, va R2, ta duoc dftnxuat cua acid barbituric (barbiturat). Barbiturat co tinh acid yeu, it phan ly, tan trong lipid va tham qua mang sinh hoc, vao than kinh trung uong, vi vay co tac dung an than gay ngu. Khi thay d6i cau true, d9 ion hoa va d9 tan trong lipid cua thu6c se thay d6i, t6c d9 xam nhap va ai luc cua thuoc vdi than kinh trung uong cling thay d6i theo. Ket qua la gay ra su khac nhau ve cuong d9 tac dung, thoi gian tac dung va tham chi ca tac dung. M9t s6thay d6i ve cau true co lien quan den tac dung g6m:
- Neu chi thay mot H a C5 thay bang g6c R thi tac dung gay ngil yeu, neu thay ca 2 H a C5bllng 2 g6c Rl va R2thi tac dl,lnggay ngu tang. Tuy nhien, neu m~chCtrong g6c R dai hdn 5C, tac dl..mggay ngu l~i giam.
- Neu gocRl vaRzla m~chthfug thi tac dl,lllgben hdn m~ nhanh, m~chvang. - Neu Rl va R2la cac g5c no thi tac dl,lngyeu hdn g6c chua no.
- Neu 1 trong 2 g6c Rl ho~c R2 la g6c phenyl thi thu6c co them tac dl,lng ch6ng co gi~t (phenobarbital) nhung neu ca Rl va R2 deu Ia g6c phenyl thi tac dl,lnggay ngu bi mat.
- Ngoai ra, thay d6i m9t so'vi tri khac cua barbiturat cling anh huang Wi tac dl,lngcua thu6c nhu: thay 0 a C2bllng S, ho~c thay H a Nl va N3bllng CH3 se t~o ra dftn xuat co tac dl,lng gay me nhanh, m~nh va ngiin (thiopental, hexobarbital).
2.2. Phan lo~i
Dlja vao thdi gian tac dl,lng,chia cac barbiturat thanh 4 nhom (bang 3.4.)
Bang 3.4. Phan lo~i thuoc an than gay ngu dan xuat clla acid barbituric
Nh6m thuoc TMi gian tac dl:lng Thuoc di~n hinh
Tac dl,lng df:li 8-12gio Phenobarbital, barbital, butabarbital, aprobarbital.
Tac dl,lng trung blnh 4 - 8 giO Amobarbital, pentobarbital, heptabarbital, cyclobarbital ...
Tac dl,lng ngan 1- 3 giO Hexobarbital, secobarbital
Tac dl,lng rat ngan 30 - 60 pMt Thiopental, thiobarbital, thialbarbital...
2.3. Phenobarbital
Dude. dong. hoe.
Phenobarbital hap thu t6t qua duong tieu hoa, khi can co th~ tiem tinh mach. Khong nen tiem dudi da va tiem b:1pvi gay dau va d~ hoai ti't noi tiem. Sau khi uong thuoc khoang 60 phut, xuat hien tac dung va duy tri duoc 8- 12 gio. Phenobarbital lien ket vdi protein khoang 50%, phan b6 rong VaGcac mo, d:)c biet la nao, qua duoc nhau thai va sua me, Chuyen hoa d gan bang phan ung hydroxyl hoa tao chat chuyen hoa khong co hoat tinh. Thai trir chu yeu qua nude ti~u, t6c d9 thai tru phu thuoc VaGpH nude ti~u (pH nude ti~u giam lam cham thai tru thuoc, tac dung keo dai va nguoc lai),
Ttic dung va co ehe'
- Tren than kinh trung uong: phenobarbital co tac dung uc che th~n kinh trung udng. Tuy thu9C VaGlieu lUQng,thu6c co tac dVng an th~n, gay ngu, ch6ng d9ng kinh, ch6ng co gi~t.
+ An th~n (lieu thap): thu6c lam giam 10 l:1ng, b6n ch6n, tl:;10cam giac thoai mai, d~ chiu, d~ dang di VaGgiac ngii..
+ Gay ngu (lieu trung binh): barbiturat tl:;10ra dUQcgiac ngii. tudng tlj giac ngu sinh ly, nhung co nhieu giac md.
+ Ch6ng d9ng kinh (lieu trung binh ho:)c lieu cao): thu6c co tac dVng ch6ng d9ng kinh cdn IOn va d9ng kinh cvc b9 (cvc b9 v~n d9ng ho:)c cam giac) do uc che slj ph6ng di~n qua muc d nao, d6ng thdi lam tang ngudng dap ung cua cac nd ron th~n kinh trung udng voi kich thich. Cd che: phenobarbital va cac barbiturat co tac dVng uc che th~n kinh trung udng b~ng cach tl:;1othu~n lQicho acid gama-amino - butyric (GABA)g:1n VaGreceptor GABA (xem chi tiet dph~n d~n xuat benzodiazepin).
Ngoai ra, phenobarbital con tang cUdng chat d~n truyen uc che glycin val ho:)c uc che chat dftn truyen kich thich la acid glutamic. dn6ng d9 cao uc che ca kenh Na+.
- Tac dVng tren cac cd quan:
+dlieu dieu tri, thu6c lam giam nh~ hOl:;1td9ng cua cae cd quan trong cd th~. d lieu cao, gay uc che tim, hl:;1huyet ap, uc che ho hap, d~ gay r6i 10l:;1nho hap (do lam giam dap ung cua trung tam ho hap voi n6ng d9 CO2), Ngoai ra, con lam giam hOl:;1td9ng cd trdn, giam chuy~n hoa, giam than nhi~t, giam suc 19Cc~u th~n, giam bai ni~u, trudng hQp n:)ng gay vo ni~u.
+ Phenobarbital lam tang cUdngtac dVng cua cac thu6c uc che th~n kinh trung udng khac nhu: clorpromazin, thu6c gay me, rUQuva d6i khang
voi tac dVng kich thich th~n kinh tru~g udng cua strychnin,
Chi dinh.
- Co giat, d(mg kinh con Ion, phong co giat do s6t caodtre nho
- Tien me.
- Cac trang thai than kinh bi kich thich 10 au, ding thang. - Cac trang thai mat ngu nang (it dung).
- Tang bilirubin huyet, vang da d tre so sinh.
- Ngoai ra, phenobarbital con duoc phoi hop vdi cac thuoc khac d~ dieu tri con dau that nguc, dau mra dau, nhoi mau nao va mot so' r6i loan d h~ than kinh trung uong.
Ttic dung khong mong muon va d{jc tinh
- Tac dung khong mong muon:
Thuong lien quan tdi tac dung uc che' than kinh trung uong nhu budn ngu, ngu ga, nhuc dau, ch6ng mat, hi l~n, mat digu hoa d9ng tac, rung gi~t nhan cau, C6 th~ glllptac dung nghich thuong: mat ngu, kich thich, c6 con ac mong, so hai.
Cac tac dung khong mong mu6n khac g6m: r6i lo~n chuy~n h6a porphyrin, di ung (ml1nngua, viem da, viem mi~ng...) giam h6ng c~u, thieu mau do thieu acid folic.
- D9Ctinh cap:
Thudng glllpkhi dung ligu cao gap 5- 10 l~n ligu binh thudng. Bi~u hi~n ng9 d9Cla ngu sau, mat phan x~, h~ than nhi~t, gian d6ng ti'f, tr\lY tim m~ch, tr\lY ho hap, hon me c6 th~ ti'fvong.
Xi'ftri: thai nhanh thu6c ra kh6i co th~ (gay non, u6ng than ho~t, truygn dung dich kigm nhu NaHC03 1,4%, thu6c lqi ti~u, ...). Trq ho hap, tu~n hoan.
- D9Ctinh m~n (quen thu5c):
Thudng glllpkhi dung thu5c keo dai. Khi da quen thu6c, neu ngling d9t ng9t se glllph9i chung cai thu5c: co gi~t, me sang, mat ngu, dau co khop ...
Xi'ftri ng9 d9Cm~n b~ng cach giam ligu thu6c til til truoc khi ngilng h:1n.
Chong chi dinh
Suy ho hap. Suy gan nlllng.
R6i lo~n chuy~n h6a porphyrin.
TU(Jngtcic thuoc
Phenobarbital la chat gay cam ung m~nh cac enzym chuy~n h6a thu6c d cytocrom P450, vi v~y lam giam holllcmf(t tilc d\lng cua nhigu thu6c ph6i hqp.
Cac thu6c sau day khi dung d6ng thdi voi phenobarbital holllc cac barbiturat khac se bi giam tac d\lng: thu6c ch6ng dong mau d~n xuat coumarin, sulfa mid ch6ng ti~u dUdng, thu6c ch6ng tr~m cam ba vong, khang sinh rifampicin, griseofulvin, cac corticoid, vien u6ng tranh thai ...
Ban than phenobarbital con gay tu cam ling, vi vay khi dung lau dai tac dung cua chinh no cung bi giam.
Nguoc lai, m9t so thuoc lai lam tang tac dung cua phenobarbital, nhu:
phenylbutazon, thuoc an than kinh va cac thuoc uc che than kinh khac.
cu«phdm valieu dung
Che pham: Gardenal,vien nen 15, 50 va 100mg.Luminal, dang tiem, ong 1mL chua 200mg.
Lieu dung:
Anthan: 30-120mgt 24h.
Gay ngu: 100- 320mg truce khi di ngu.
Chong co giat: 100- 300mgt 24h, chia 2- 3 lan,
2.4. Cac barbiturat khae
Cac barbiturat d€u co tac dung, chi' dinh, chong chi' dinh, tac dung khong mong muon, tuong tac thuoc tuong tu nhau. Cac thuoc chu yeu khac nhau d
thci gian xuat hien tac dung, thoi gian duy tri tac dung va cuong d9 tac dung. Cac chi' dinh va li€u dung cua cac barbiturat di~n hinh duoc trinh bay trong bang 3.5.
Bang 3.5. chi d!nh valieu dung ella m9t56barbiturat
Tim thuoc
chi djnh Lieu dung 24 gid
(Bi~t dut;1c)
Amobarbital - An than, gay ngu, tien me Uong: 100- 200mg
(Amytal) - £)(:mgkinh Tiem: 100- SOOmg,lieu toi da 1000mg
Aprobarbital
An than, gay ngu Uong: 40mg- 160mg
(Alurate)
Butabarbital - An than, gay ngu
Uong: SO-100mg
(Butisol) - Tien me
Emtobarbital - An than, gay ngu
Uong: 20- 100mg/lan x 1- 3 Ian
(Embutal) - Tien me
Phenobarbital - An than, gay ngu
(Gardenal, - Chong co gi~t Uong, tiem: 30-320mgl 24h
Luminal) - Tien me
Secobarbital - Gay ngu
Uong 100mg- 300mg
(Seconal) - Tien me Thiamytal
Gay me tinh m~ch Khai me 2-SIl9Ikg, duy tri me 2S- SOmg
(Surital)
Thiopental Gay me tinh m~ch Khai me 2-6mgl kg, sau d6 duy tri me £)ieu tr! con d¢ng kinh Toi da 19/1angay me.Tiem 7S -2S0mg/lan