AN THN GY NG

I CNG:
- Trong mt vi trng hp, lo u bn chn mang ngha tt (to ng lc lm vic)
- Cht dn truyn TK: GABA (-AminoButyric Acid), Norephinephrin, Serotonin gy lo u, cng thng
- Thuc an thn, gii lo u l thuc gim kch thch TKTW, gim qu trnh hng phn v no.
- Gm: an thn nh (tr lo u cng thng), an thn mnh (tr lon thn ...) v thuc ng (gy ng nh gic ng sinh
l).
NHM THUC AN THN
BENZODIAZEPIN (BZD)
- Cht u tin tm thy: 1957 Clodiazepoxid (BD: Librium) bi Leo Sterrback
- Sau l Diazepam (BD: Valium)

Khung c bn: An thn: X: Clo / Brom

O
Gy ng:X: NO2 / Clo
R1 R2 R3 : thay i theo tng cht
R2
X 3H-Benzo[e][1,4]diazepin
R3

- C ch: BZD gn vo GABA-receptor m knh Cl- tng phn cc mng t bo

- Phn loi: 6 nhm
1. 1,4-Benzodiazepin: An thn, gy ng, chng co git v th gin c

An thn Gy ng (X: NO2) Th gin c

Nitrazepam Tetrazepam (BD: Myolastan)
(1-H, 2-H, 3-Phenyl)
Flunitrazepam
Diazepam (1-CH3, 2-H, 3-
(1-CH3, 2-H, 3-Phenyl) fluorophenyl)
Oxazepam Chng co git
(1-H, 2-OH, 3-Phenyl) Clonazepam (BD: Ritrovil)
Clorazepam
(1-H, 2-COOK, 3-Phenyl)
 2. Dn cht Triazolo-1,4-Benzodiazepin: Gy ng
Estazolam (Nutalon)
Khng c CH3 v Cl
Triazolam (Halcilon)
Alprazolam (Xanax)
Khng c Cl

3. Dn cht Imidazo-1,4-Benzodiazepin: Gy ng Loprazolam (Havlane)

4. Dn cht 1,5-Benzodiazepin: An thn, gii lo u Clobazam (Urbanyl)
5. Dn cht 2,3-Benzodiazepin: An thn, gii lo u Tofisopam (Seriel)
6. Dn cht 1,4-Thienodiazepin: An thn, gii lo u Clotiazepam (Veratran)

- Lin quan cu trc v tc dng:

Nhn benzen/d vng thm R1: di ca N-alkyl: khng

C7: thay bng nhm ht in nh hng tng tc thuc-
t tng hot tnh Recep,

Thay v tr khc: gim tc Nhm cng knh gim t/d

dng R2: phi c nhm nhn in t
D vng: t/d yu hn gn vi Receptor
A B O S: to tng tc chuyn
bit vi sub-BZD, gi
nguyn tc dng
R3: CH3/N imin (C=N): mt t/d
Vng phenyl: (5-phenyl) C ng vn, ko to i vn
Khng cn thit <clobazam>

Nhng to tnh thn du Ester nhm 3-hydroxy: t/d

Nu cng mt phng vi In vitro: khng c ni i vtri

vng A a/h nhiu t/d dl 4,5 / N4 khng a/h gn
Thuc-Recep
In vivo: C=N C-N: gim t/d

- Ho lp th:
Hu ht BZD khng cha C*
Vng B, 7 cnh to 1, 2 cu trc dng thuyn (a, b i xng qua gng, a mnh hn)
Dn cht th 3-hydroxy (lorazepam, oxazepam): hn hp racemic
- Ho l
Tnh kim: do c 2 N trong nhn <Clodiazepoxid kim kh mnh> P/ to mui vi HCl, lng
trong mi trng khan (HClO4, CH3COOH khan, ch th lc malachit)
P/ phn hu vng diazepam: HCl/100oC, diazepam orthoaminobenzophenon
Nu khng th N1 cht to thnh c nhm amin bc 1 nh tnh bng p/ diazo ho, to
phm mu azoic <Clodiazepoxid: carmin, Nitrazepam: , Oxazepam: tm>
CH N1 phn hu thnh N-methylaminobenzophenon khng to mu azoic
 Ch nh: Tc dng ph: u im:
An thn nh: D ng, Tc dng chn lc v an ton
Oxazepam, Lorazepam <ngn hn> Liu cao: chng mt, l ln, suy h t tc dng trn h hp
Clodiazepoxid, Diazepam, Lorazepam hp, h huyt p (dng tim) t tng tc thuc
c thm dng bt pha tim Mc quen thuc t hn thuc
Liu cao: c hin tng gy ng Chng ch nh: khc
Gy ng: tnh to khi thc dy Ngi b tm thn, trm cm
Nitrazepam, flunitrazepam <ko di> Ngi nhc c, suy h hp
Loprazolam, triazolam <ngn hn> PNCT, cho con b
Chng co git: clonazepam, diazepam, D ng vi BZD
ng kinh: diazepam Gim liu ngi gi, ngi suy
Gin c: tetrazepam nhc
THUC THNG DNG:
DIAZEPAM ALPRAZOLAM
Cng thc

Tnh cht Bt trng hoc vng nht, khng mi

D tan trong dmhc, kh tan trong nc
Tonc: 131-135oC
Tc dng iu tr mt ng, lo u, ng kinh, co tht c iu tr chng lo u, s hi v c
Hi hp, run, sng, co git do cai ru
Gim co tht c trong 1 s bnh TK
Tt cn co git, phi hp iu tr co git nng
Chng ch nh PNCT 3 thng u Tng t diazepam
Nhc c, glaucom gc hp
Tr < 6 tui
TT ngi li tu xe
Tc dng ph Ng g, mt mi, lo o n, thiu minh mn
Him: hng phn, co tht c, mt ng Liu cao: mt mi, RL tr nh, to bn, thm
n
Tng tc Ru Ketoconazol, itraconazol
Cimetidin: ko di thi gian t/d Ru
Ngng t ngt: hi chng cai thuc Ngng t ngt: hi chng cai thuc
Kim nghim nh tnh: trong H2SO4 : UV 365nm; trong H2SO4 10%/methanol: 3 nh: 242,258,366 nm
nh lng diazepam: PP acid-base trong mi trng khan acid acetic, cht chun l
HClO4
 NON-BENZODIAZEPIN <xem thm> da vo cu trc ho hc chia thnh 3 nhm:
- Carbamat: meprobamat
- Imidazopyridin: alpidem
- Phenothiazin : promethazin, promazin <xem bi khng Histamin H1>
DN CHT PYRIMIDINYLBUTYLPIPERAZIN <xem thm>
- Cng tc ng (gii lo u), khc c ch: gn vo th th 5-HT no
- Buspiron, Gepiron, ipsapiron
- Tc dng ch xy ra sau nhiu ngy dng thuc

NHM THUC GY NG
BENZODIAZEPIN:
- 1,4-Benzodiazepin: Nitrazepam, Flunitrazepam
- Dn cht Triazolo-1,4-Benzodiazepin: triazolam
- Dn cht Imidazo-1,4-Benzodiazepin: loprazolam
- Dn cht 1,5-Benzodiazepin: clobazam
- Dn cht 2,3-Benzodiazepin
- Dn cht 1,4-Thienodiazepi: clotiazepam
DN CHT IMIDAZOPYRIDIN V CYCLOPYRROLON
- Zolpidem (Stinox), Zolpiclon (Imovane)
PYRAZOLOPYRIMIDIN: Zaleplon (c ch ging zolpidem)
DN CHT UREID VNG M: bromisoval, carbromal, acetylcarbomal
DN CHT ALDEHYD:
Cloral hydrat: an thn cho tr em
t/d gy ng, chng co git (do thuc)
hiu qu sau 1h, ko di 4-8h,
dng lin tc sau 2 tun, hiu qu gim
DN CHT PIPERIDON:
Methyprylon, thalidomid (qui thai), glutethimid (duy nht cn c s dng)
T/d nh barbiturat trung bnh
Glutethimid: t/d tt nht trong cc non-barbiturat, hp thu khng u h tiu ho ca tng ngi
DN CHT QUALON HOC QUINAZOLON
Methaqualon (TERAFLON): gy ng (100-200mg), liu cao: o gic, lon thn
Mecloquanlon: t/d ging methaqualon, gy nghin
KHNG HISTAMIN V KHNG CHOLINERGIC: Nhm khng histamin H1
Cu trc ethanolamin: Diphenhydramin, doxylamin,
Cu trc phenothiazin: promazin, prometazin
Khng b qun l theo thuc k n
 NHM BARBITURAT (1860s)
- 1990s, b thay th bi BZD trong iu tr mt ng
- C ch: TKTW trn trc no tu sng c ch hot ng tk, c xng, c tim, c trn
- c tnh: TKTW, Cm ng men gan, Gy quen thuc & nghin
- Ch cn c s dng trong tc ng gy m v chng co git.

N1: H thay bng 1 gc alkyl (metyl) Dn cht barbiturate t/d

an thn, gy ng mnh
O th bng S dn cht thiobarbital
Acid barbituric: R1, R2: alkyl (thng, no, cha no, vng ...)
khng c t/d gy R3: metyl, H
ng X: O, S

- Lin quan cu trc v tc dng:

R1, R2: phi l chui hydrocarbon
Mch t 1-5 C / mch cha no: tng hot tnh
Mch = 5C: t/d gy ng gim (c th co git)
Gc phenyl: c R1 v R2 : mt t/d gy ng
ch 1 trong 2: tng t/d chng co git
R3: metyl (-CH3): gy ng mnh
Th trn Nito: th c 2 N bng metyl gy co git khng dng tr liu
Th O = S: t/d mnh, cc ngn gy m
- Ho l:
Phn ng chung:
Nhm di-imid d b thu phn Ch :
Nung trong kim: phn hu, gii phng Thiobarbiturat: mu lc
amoniac Hydantoin: xanh
Tnh acid: to mui vi kim mnh, tan D/c carbamat khng cho mu
trong nc P/ AgNO3/Na2CO3: trng bc barbituric
P/ KL mu: Cu2+, Ag+, Co+ mu Dd mui cobalt/amoniac, ethanol, methanol tuyt
P/ CuSO4 tm hoa c i: phc tm khng bn (P/ PARRI)
Phn ng phn bit: xc nh nhm th da vo phn ng c trng ca n
Phenobarbital: p/ phenyl: nitro ho (KNO3/H2SO4) dd mu vng cam
brom ho (nc brom) vng
Pentobarbital: xc nh S = p/ oxh (H2O2 hoc Br2) gc sulfat + BaCl2 khng tan trong acid hay
kim
Phn ng vi tinh th ca Deniges: mi barbituric va kt tinh (dng acid) s c hnh dng c bit
 - Phn loi:
T/ng ko di T/ng trung bnh T/ng ngn T/ cc ngn (tim IV)
t/d sau 1h, ko di 8-10h t/d sau 30p, ko di 6-8h t/d sau 10p, ko di 2-4h t/d ngay, ko di 30p-1h
Barbital Amobarbital Secobarbital Pentobarbital
Phenobarbital Heptabarbital Phenobatbital Thiobarbital
Mephobarbital Vinylbital (R2 khc vi t/ ko di) Thiamylal
Butobarbital Allobarbital Hexobarbital Methohexital
- Kim nghim
nh tnh: P/ mu, IR, UV
nh lng: PP o acid, mi trng khan, o bc, o brom
- Tc dng:
Gy ng, an thn
Chng co git trong ng kinh: metharbital, phenobarbital (liu gy ng), methobarbital (liu khng gy ng)
secobarbital, amobarbital (co git cp)
Gim au: butobarbital
Gy m: nhm t/ cc ngn; tin m: pentobarbital
- c tnh:
Cp: gp 5-10 ln liu ng: mt phn x, hn m, ngt th, h HA
Mn: quen thuc, nghin thuc
iu tr ng c: trc y: strychnin, ngy nay: cht i vn flumazenil
THUC THNG DNG:
ZOLDIPEM TARTRAT

Tnh cht Bt trng

Nng chy: 196oC
Tan t trong nc, ...
Tc dng Gn chn lc trn receptor GABA1
Chn lc gy ng, t t/d gin c, chng co git
Gim au mnh
Ch nh Tr mt ng, dng khng qu 10 ngy v dng ngt qung
Tc dng ph L m, ngy ngt, bun nn
Tng tc Ru
Gy hi chng cai nghin
Chng ch nh Cn trng ngi b bnh h hp: do gy c ch h hp