BI 2

THUC KHNG HISTAMIN

V THUC C CH GII PHNG HISTAMIN
MC TIU HC TP
Sau khi hc xong bi ny, sinh vin c kh nng:
1. Trnh by c cu trc chung, phn loi theo cu trc ha hc v theo tc dng
ca thuc khng histamin v thuc c ch gii phng histamin.
2. Gii thch c mi lin quan cu trc tc dng ca nhm thuc khng histamin
th th H1; ng dng ca mi lin quan ny trong bo ch v s dng nhm thuc.
3. Gii thch c mi lin quan cu trc - tnh cht l ho ca nhm thuc khng
histamin th th H1; ng dng ca mi lin quan ny trong bo ch, kim
nghim v s dng nhm thuc.
4. Gii thch c mi lin quan cu trc tnh cht l ho ca mi dc cht; ng
dng ca mi lin quan ny trong bo ch, kim nghim v s dng thuc.
H2
H2
C
C
NH2
1. i cng HC2 HC NH2
histidin1.1. Histamin - ngun gc, hot tnh
H
N
N
H
N
N
COOH
-decarboxylase
Histamin l cht
ni sinh, c vai tr sinh l nht nh, trong c th c tng hp t histidin:
Histamin tn ti trong c th dng t do c hot tnh v dng lin hp khng c hot
tnh. Dng lin hp c d tr trong dng bo.
Do nhng tc ng khc nhau i vi c th, l nhng yu t khng nguyn, histamin
t do cng cc cht trung gian c tc dng c gii phng nhiu t dng lin hp,
theo c ch khng nguyn khng th, s gy ra ri lon bnh l. Histamin gn vi v
tc dng th th H1, c nhiu thnh mao mch, c trn rut, t cung, kh ph
qun v mt s th th c bit mi, mt, da. Cc ri lon chnh do histamin gy
ra trong trng hp ny gm:
- Gy gin ng mch nh, tng tnh thm qua thnh mch gy ph n, sung huyt.
- Tng co bp c trn kh ph qun, ng tiu ha, ng niu, sinh dc.
- Tng tit dch ca cc tuyn ngoi tit.
- Tc dng ln thn kinh ngoi bin v thn kinh trung ng.
Chnh tc dng qua mt s th th c bit gy ra cc triu chng d ng c trng.
1.2.Thuc khng histamin
Gm cc cht khng histamin th th H 1, cc th th c bit v cc cht c ch
gii phng histamin t dng bo. Thuc khng histamin th th H 2 c trnh by
trong bi Thuc nh hng n chc nng d dy - rut.
1.2.1. Cu trc ha hc
Vic nghin cu thuc khng histamin bt u t nm 1937. Cho ti nay, hng nghn
cht c th nghim v hu ht cc cht ang dng mang cu trc chung (tr
thuc c ch gii phng histamin):
1

R1

Ar1
X
Ar2

H2
C

H2
C

N
R2

Ar1: l gc thm hoc gc thm gn methyl.

Ar2: l phenyl hoc gc d vng nh 2-pyridyl.
n v X c th l: C (no hoc khng no), cu trc >C-O-, hoc >N- (bc III). Khi
aminoethyl l mch nhnh th thng c N(CH3)2; N c th thuc vng no. Ar1 v Ar2
c th phi hp thnh h 3 vng cha 2 nhn thm. dn cht phenothiazin c ngoi
l l: mch 2-aminoethyl c mang nhm th -CH 3 v tr 2 (xem promethazin) hoc
ko di thnh 2-methyl-3aminopropyl (xem trimeprazin).
1.2.2. Phn loi
Da vo cu trc, trong n v X ng vai tr quan trng, c th chia thuc khng
histamin thnh 6 nhm dn cht chung (tr thuc c ch gii phng histamin):
- Dn cht alkylamin: X l C
- Dn cht ethanolamin: X l >C-O- Dn cht ethylendiamin: X l N v 2-aminoethyl- thuc mch thng.
- Dn cht piperazin: X l C-N v mch 2-aminoethyl l cu phn ca vng piperazin.
- Dn cht piperidin: X l C=C v mch 2-aminoethyl l cu phn ca vng piperidin.
- Dn cht phenothiazin: X l N ca nhn phenothiazin v c ngoi l.
Tuy nhin, vn cn c mt s t cht c dng, c tc dng tt, khng th xp vo
mt trong 6 nhm dn cht trn.
Da vo c ch tc dng, c th chia thuc khng histamin thnh 2 nhm:
- Cc thuc khng histamin th th H 1 (cc thuc khng histamin thc th): nng
tc dng cc cht ny chim ch ca histamin th th H 1. Histamin b v hiu
ha. Vy nhm cc cht ny tc dng giai on mun ca qu trnh phn ng d
ng.
- Nhm cc cht c ch gii phng histamin: in hnh cho nhm ny l cromolyn v
nedocromil, c ch gii phng histamin t do v cc cht trung gian km theo t
dng bo. Cc cht ny tc dng ngay giai on u, hay giai on sm ca phn
ng d ng.
C hai c ch tc dng u tun theo quy lut khi lng, ngha l khi nng thuc
gim xung thp hn nng tc dng th histamin li thng th th th H 1, hoc li
c gii phng nhiu t dng bo.
Da vo tc dng trn thn kinh trung ng, thuc khng histamin thc th c chia
thnh 3 th h:
- Thuc khng histamin th h I: gm cc cht c tc dng ln h thn kinh trung
ng, c ch hoc kch thch. Thng gp cc cht c ch thn kinh trung ng, th
hin bi tc dng an thn, gy ng.

- Thuc khng histamin th h II gm cc cht khng c tc dng ln thn kinh trung

ng, do khng thm c qua hng ro mu no, nn khng c tc dng an thn v
khng gy bun ng.
- Thuc khng histamin th h III gm cc ng phn quang hc hoc cht chuyn ha
c hot tnh ca th h II, c hot tnh mnh hn hoc tc dng khng mong mun trn
tun hon, h hp yu hn cht gc.
Bng: Phn loi thuc khng histamin thc th
Dn cht

Th h I

Th h II

Th h III

Ethylendiamin

Tripelennamin, antazolin,
pyrilamin

Ethanolamin

Diphenhydramin,
dimenhydrinat,
doxylamin,
carbinoxamin, clemastin

Phenothiazin

Promethazin, trimeprazin,
methdilazin

Alkylamin

Acrivastin

(propylamin)

Clorpheniramin,
dexclorpheniramin,
brompheniramin,
triprolidin

Piperazin
(cyclizin)

Cyclizin, meclozin,
buclizin, hydroxyzin,

Cetirizin

Levocetirizin

Piperidin

Cyproheptadin, azatadin

Astemizol,
terfenadin,
loratadin

Fexofenadin,
desloratadin

Astemizol, terfenadin: hin khng c dng do c tnh cao vi h tun hon v h

h hp.
1.2.3. Lin quan cu trc tc dng
C th so snh hnh thc cu to ca histamin v thuc khng histamin c nhng yu
t ging v khc nhau.

Khi cc cht khng c carbon bt i th trong hu ht cc trng hp, nu nguyn

t ny ni trc tip vi C s 1 ca mch 2-aminoethyl th ng phn (D) c hot tnh,
ng phn (L) hu nh khng c tc dng, dng dc dng l ng phn (D) hoc hn
hp racemic (v d trng hp clorpheniramin maleat). Nu C bt i cch C s 1
ca mch 2-aminoethyl, tc l cch xa N, th ng phn (L) li c tc dng mnh hn
(D) (v d : carbinoxamin, cetirizin). Nu C bt i v tr 2, tc l ni trc tip vi N,
th ng phn (D) v (L) tc dng tng ng nhau, dng dc dng thng l hn
hp racemic (v d: promethazin, meclizin).
Dn cht gn halogen thng lm tng hot tnh, v v tr ti u l para ca nhn
phenyl (v d: clorpheniramin, carbinoxamin, cetirizin, meclizin, loratadin).
Nu gn thm mt s nhm chc thn nc, c th lm gim hoc mt tc dng khng
mong mun trn thn kinh trung ng, do khng c tc dng an thn, gy ng (v
d: cetirizin, loratadin, fexofenadin).
Xem cc v d ti Lin quan cu trc - tc dng thuc khng histamin H1. Ppta

(chn file video)

1.2.4. Tc dng, ch nh
Tc dng: khng histamin (co mch, gim tit dch ca cc tuyn ngoi tit, gim co
c trn,..), mt s c tc dng khng cholinergic v an thn, ko theo gy ng cc
mc khc nhau.
Ch nh: cc triu chng d ng nh v va, mt s ch nh khc nh phng v chng
nn do say tu xe, nn ph n c thai, kch thch n ngon, an thn nh,
2. Dc cht i din
2.1. Cc thuc khng histamin th th H1
2.1.1. Dn cht alkylamin
CLORPHENIRAMIN MALEAT
Bit dc: Trimeton
Cng thc:

C16H19ClN2,C4H4O4 = 390,9
Tn khoa hc: (3RS)-3-(4-clorophenyl)-N,N-dimethyl-3-(pyridin-2-yl)propan-1-amin
hydrogen (Z)-butendioat.

Tnh cht:
Bt kt tinh trng hoc gn nh trng, khng mi. D tan trong nc, tan trong
ethanol 96%.
L - ho tnh v ng dng:
Clorpheniramin maleat mang tnh cht ca nhn pyridin, nhn benzen, nit bc 3,
clo hu c, acid maleic kt hp v ca c phn t.
+ Tnh base kh mnh (do N trong nhn pyridin v N bc 3, pKa 9,2):
Dng base khng tan trong nc, tan c trong acid. ng dng: ch to dng
dc dng maleat tan trong nc, thun li bo ch dng thuc c sinh kh
dng cao.
To ta vi cc thuc th chung ca alcaloid. ng dng: nh tnh bng phn ng
to ta picrat v o nhit nng chy ca ta (196-2000C).
ng dng: nh lng bng phng php o acid mi trng khan, dng acid acetic
khan, ch th tm tinh th v HClO4 0,1M.
+ Nhn thm (nhn pyridin v nhn benzen):
Hp th t ngoi. ng dng: nh tnh, nh lng bng phng php quang ph
t ngoi, pht hin vt cht trong cc phng php sc k.
Ph hp th UV: o vng 230 350 nm, c max = 265 nm vi A (1%, 1 cm) =
200 -230 (C 0,003%; HCl 0,1M)
+ Clo hu c:
B v c ha thnh clorid. ng dng: nh tnh clorid bng phn ng vi bc
nitrat.
+ Carbon bt i v tr 3:
Lm quay mt phng dao ng ca nh sng phn cc. ng dng: nh tnh, nh
lng, th tinh khit bng phng php o gc quay cc.
+ Acid maleic kt hp:
Cho phn ng mu vi nc brm, resorcin/ H2SO4 c. ng dng: nh tnh.
Xc nh acid maleic: Kim ha DD ch phm bng NaOH long, chit b
clorpheniramin bng ether (3 ln), thu lp nc; ly mt phn dch nc, thm DD
resorcinol/ H2SO4 c; un cch thy nng trong 15 pht; khng xut hin mu. Phn
cn li ca lp nc thm nc brom, un cch thy 15 pht n si ri ngui.
Thm DD resorcinol/ H2SO4 c, un cch thy tip 15 pht, xut hin mu xanh lam.
+ C phn t:
o ph hng ngoi, so snh vi ph IR chun; o nhit nng chy (1320
136 C.); lm sc k lp mng.
Tc dng - ch nh:
L thuc khng histamin th h 1, c dng trong cc trng hp:
D ng ng h hp trn (cp hoc mn): vim mi d ng, s mi ma; vim
mng kt d ng, nga hoc vim d ng mt.
D ng da (my ay, chng da ni qung, pht ban); ph Quincke; d ng thuc,
thc n; phn ng d ng vi cc sn phm mu v huyt thanh ( nhng bnh nhn
nhy cm).
5

 Phi hp trong iu tr sc phn v.

Dng phi hp vi thuc ho, thuc gim au h nhit, thuc chng hen tng tc
dng ca cc thuc ny.
Liu dng: ngi ln 4 mg/ln x 4 - 6 ln/ 24 gi; ti a 40 mg/ 24 gi.
Dng bo ch:
Vin nn 2 mg; 4 mg; thuc tim 10 mg/ ml; 100 mg/ ml; thuc nc hoc siro 2 mg/ 5
ml; cc dng vin tc dng chm 6 mg, 8 mg; 12 mg.
DEXCLORPHENIRAMIN MALEAT
Bit dc: Polaramin.
L ng phn hu tuyn, c iu ch t clorpheniramin nh sau: Cho
clorpheniramin maleat (racemic) tc dng vi acid (+) phenylsuccinic c
clorpheniramin phenylsuccinat (I). Gii phng (+) clorpheniramin base t (I) bng
cch cho (I) tc dng vi NaOH. Cui cng cho phn ng vi acid maleic theo t l
ng phn t, c (+) clorpheniramin maleat, vi tn gi dexclorpheniramin maleat.
Tnh cht:
Bt kt tinh trng, khng mi. nng chy 110 115 0C. Tan d trong nc (1/1,1),
alcol, cloroform; rt t tan trong ether. Dung dch nc c phn ng acid vi giy qu.
Tc dng - ch nh:
C tc dng mnh gp 2 ln clorpheniramin maleat vi cng liu lng (do ng phn
t tuyn khng c tc dng). Ch nh v tc dng khng mong mun tng t
clorpheniramin maleat, liu dng bng mt na.
2.1.2. Dn cht ethanolamin
DIPHENHYDRAMIN HYDROCLORID
Bit dc: Benadryl.
Cng thc:

C17H21NO,HCl = 291,8
Tn khoa hc: 2-(diphenylmethoxy)-N,N-dimethylethanamin hydroclorid.
Tnh cht l ha - phng php kim nghim:
Bt kt tinh trng, khng mi. D b sm mu khi tip xc vi nh sng. Nhit chy
168 1720C. Rt d tan trong nc, alcol v cloroform; tan trong aceton, khng tan
trong ether. Dung dch nc trung tnh vi giy qu.
Ch tnh cht do cha nhn thm, do base amin, acid hydrocloric kt hp. ng dng
cc tnh cht ny vo kim nghim:
nh tnh:

o ph IR, so snh vi ph IR chun.


Ph hp th UV: o vng 230 350 nm, c max = 253, 258 v 264 nm vi A
(1%, 1 cm) = 12, 15, 12 (C 0,05%; ethanol 96%)

o chy ca cht th: 168-1720C.

Dung dch nc cho phn ng ca ion Cl-.

Phn ng mu: Thm 2 ml H2SO4 c vo 0,05 ml dung dch th 5%, xut hin
mu vng m; thm 0,5 ml HNO 3 c, chuyn sang mu , thm 5 ml cloroform v
lc, lp cloroform c mu tm m.
Th tp cht lin quan: bng TLC.
nh lng: trong mi trng khan, dng acid acetic khan c mt acetat thy ngn, ch
th tm tinh th v HClO4 0,1M.
Tc dng - ch nh:
L mt thuc khng histamin c tc dng khng cholinergic (gim tit, chng ho,
chng nn), du thn kinh (an thn, gy ng), c dng trong cc trng hp:

D ng ng h hp trn (cp hoc mn): vim mi d ng, s mi ma;

vim mng kt d ng.

D ng da (my ay, chng da ni qung, pht ban); ph Quincke; d ng thuc,

thc n; phn ng d ng vi cc sn phm mu v huyt thanh ( nhng bnh nhn
nhy cm).

Phi hp trong iu tr sc phn v.

Phng v chng say sng, say tu xe, nn.

Do c vi thnh gic nn cn thn trng khi ang dng thuc c hi cho thnh
gic (v d cc khng sinh aminosid).
Liu dng: ngi ln 25 - 50 mg/ln x 3 - 4 ln/ 24 gi; ti a 400 mg/ 24 gi.
Dng bo ch:
Vin nn 25 mg; 50 mg; thuc tim 10 mg/ ml; 50 mg/ ml; thuc nc hoc siro 12,5
mg/ 5 ml; thuc m, kem 2%.
Ghi ch:
lm thuc chng nn, ngi ta dng dng mui vi 8-clorotheophyllin, thnh phn
ny ng gp ng k vo tc dng chng nn ca diphenhydramin (xem
dimenhydrinat).
Thay cc gc phenyl trong cng thc trn bng 2-pyridyl v p-clorophenyl th c
carbinoxamin maleat (bit dc Clistin, l mt thuc khng histamin c hiu lc
mnh).

2.1.3. Dn cht phenothiazin

PROMETHAZIN HYDROCLORID
Bit dc: Phenergan; Diprazin.
Cng thc:

C17H20N2S,HCl = 320,9
Tn khoa hc: (2RS)-N,N-dimethyl-1-(10H-phenothiazin-10-yl)propan-2-amin
hydroclorid.
Tnh cht l ha - phng php kim nghim:
L tnh:
Bt kt tinh mu trng hoc trng ng, khng mi, v ng v t li. Rt nhy vi tc
dng ca nh sng, b m hoc lu s i mu dn sang xanh l. Nng chy 215
2250C. Rt d tan trong nc, tan trong alcol, cloroform, khng tan trong ether, aceton,
ethylacetat. Dung dch nc c pH 4 5.
Ha tnh:
Ha tnh c bn ca promethazin l d b oxy ha do nhn phenothiazin. Phn ng d
xy ra cc v tr 3, 6, 9: v tr 3, 6 c th gn OH hoc =O; nguyn t S c th b
oxy ha thnh dng: >S=O hoc >SO2 ty mc oxy ha. Cc tc nhn H2SO4,
HNO3, Br2, FeCl3 u c th oxy ha c promethazin. Cc sn phm thng c
mu hng n . AgNO3 cng oxy ha c promethazin nn khi th ion Cl - bng
AgNO3 phi kt ta promethazin base bng NaOH, lc loi b, sau mi pht hin
ion Cl- trong dch lc.
Tnh base do amin bc 3 mch nhnh: cho kt ta vi cc thuc th chung ca
alcaloid, v d kt ta vng vi acid picric; cho php nh lng bng php o acid
base.
nh tnh:

o ph IR, so snh vi ph IR chun.

Dung dch nc cho phn ng ca ion Cl-.

Phn ng mu vi acid nitric: thm t t HNO 3 c vo dung dch ch phm,

xut hin ta tan nhanh, dung dch c mu chuyn sang cam ri vng. un si,
xut hin ta cam v dung dch mu .

Dng TLC
Th tp cht lin quan: tp lin quan ch yu l phenothiazin, c pht hin bng
TLC.
nh lng:


Trong mi trng khan, dng acid acetic khan c mt acetat thy ngn, ch th
tm tinh th hoc o th, HClO4 0,1M.

nh lng phn HCl kt hp bng dung dch NaOH chun trong mi trng
nc, c mt alcol v cloroform, cloroform s tch ring dng base.

nh lng bng phng php o hp th nh sng t ngoi 249 nm.

Tc dng - ch nh:
Khc vi dn cht pheniramin, nguyn t C bt i promethazin (hoc trimeprazin)
gn N ca mch 2-aminoethyl hn, tc dng ca cc ng phn (D) v (L) tng
ng nhau.
Tc dng khng histamin mnh, k c tc dng an thn, gy ng, khng cholinergic.
Trong cc thuc khng histamin, promethazin ni bt c dng trong tin, hu phu
thut, phng chng nn khi gy m, phu thut, phi hp (vi meperidin hoc thuc
gim au khc) gim au sau phu thut.
Ch nh: vim mi d ng, cc triu chng d ng da, phn ng d ng vi mu, huyt
thanh, an thn, gy ng, phng v chng nn, phi hp thuc gim au, thuc gim
ho,
Dng bo ch:
Vin ung hoc thuc n 12,5; 25; 50 mg. Dung dch tim 25; 50 mg/ 5 ml; siro 6,25;
25 mg / 5 ml.
Bo qun: ng trong l thy tinh mu, nt kn, trnh nh sng.
TRIMEPRAZIN TARTRAT
Tn khc: Alimemazin tartrat.
Bit dc: Theralne.
Cng thc:

(C18H22N2S)2,C4H6O6 = 747,0
Tn khoa hc: (RS)-dimethyl (2-methyl-3-phenothiazin-10-ylpropyl)amin (2R,3R)tartrat.
Tnh cht l ha - phng php kim nghim:
Bt kt tinh mu trng n trng ng, khng mi. B bin mu dn ngoi nh sng.
Nng chy 160 1640C. D tan trong nc, tan trong cloroform, t tan trong alcol,
rt t tan trong ether.
Ch tnh cht do nhn phenothiazin v amin bc III.
nh tnh:

o ph IR, so snh vi ph ca cht chun.


Ph hp th UV: o vng 230 350 nm, c max = 255 v 310 nm (C 0,008%;
amoniac 5M - methanol).

Phn ng mu: vi hn hp ng th tch H2SO4 v formol cho mu ta.

Phn acid tartric: dung dch cht th trong nc, kim ha bng DD NaOH
long, tch ring dng base bng ether, ly lp nc em acid ha ri thm thuc th
natri amoni methavanadat, xut hin mu cam.
Th tp cht lin quan: tp lin quan ch yu l phenothiazin, c pht hin bng
TLC.
nh lng:
Trong mi trng khan, dng acid acetic khan c mt acetat thy ngn, ch th tm tinh
th hoc o th, HClO4 0,1M.
Tc dng - ch nh: Tng t promethazin.
Dng bo ch: Vin 2,5 mg; vin tc dng chm 5 mg; siro 2,5 mg/ml.
Ghi ch:
Nu gn vo v tr 10 ca nhn phenothiazin quinuclidin-3-yl-methyl (I) ta c
mequitazin (bit dc Primalan), mt khng histamin c tc dng an thn yu hn
promethazin.
2.1.4. Dn cht ethylendiamin
TRIPELENNAMIN HYDROCLORID
Bit dc: Pyribenzamin.
Cng thc:
CH3

CH2
N

H2
C

H2
C

HCl

N
CH3

C16H21N3,HCl = 291,8
Tn khoa hc: 2-[benzyl[2-(dimethylamino)ethyl]amino]pyridin mono hydroclorid.
Cng dng dng mui citrat.
Tnh cht l ha - phng php kim nghim:
Bt kt tinh trng, d b sm mu khi tip xc vi nh sng. Nhit chy 188
1920C. D tan trong nc, dung dch trung tnh vi giy qu; tan trong ethanol,
cloroform, tan t trong aceton; khng tan trong ether, benzen, ethylacetat.
Ch tnh cht do nhn thm v mui hydroclorid ca amin bc III.
nh tnh: ph IR, ph UV, phn ng ca Cl-.
Th tp cht lin quan: bng TLC.
nh lng:
Trong mi trng khan, dng acid acetic khan c mt acetat thy ngn, ch th tm tinh
th hoc o th, HClO4 0,1M.
Tc dng - ch nh:
Khng histamin th h I, c ch nh cho:

10


Cc th vim mi d ng.

D ng n thun: my ay, ph mch, chng da v ni.

Gim v phng phn ng i vi mu, huyt thanh bnh nhn c tin s phn
ng qu mn.
Dng bo ch:
Vin 25 mg, 50 mg; vin tc dng chm 25; 50 v 100 mg.
2.1.5. Dn cht piperidin
CYPROHEPTADIN HYDROCLORID
Bit dc: Periactin.
Cng thc:

C21H21N,HCl,1H2O = 350,9
Tn
khoa
hc:
4-(5H-dibenzo[a,d]cyclohepten-5-yliden)-1-methylpiperidin
hydrochlorid
Tnh cht l ha - phng php kim nghim:
L tnh:
Bt kt tinh trng hoc trng ng, khng mi, v hi ng. Tng i bn vi nh
sng, khng kh v hi m nhit phng. Chy khong 162 0C, dng khan
2500C. t tan trong nc, tan c trong ethanol, khng tan trong ether.
Ha tnh:
Ch tnh cht do cc gc thm v ni i lin hp vo nhn, tnh cht ca mui HCl
ca base amin.
nh tnh: o ph IR, UV, TLC.
Th tinh khit: th acid, tp lin quan (bng TLC).
nh lng:
Ha ch phm vo hn hp alcol acid hydrocloric 0,01M (50:50). Chun bng
NaOH 0,1M, dng in th k, ghi th tch gia hai im c bin i th t ngt.
Tc dng - ch nh:
L mt khng histamin c tc dng khng serotonin, khng aldosteron v an thn, gy
ng. Dng cho cc trng hp:

D ng nh v va.

Phng v chng chng au na u.

Kch thch n ngon ngi gy yu, chn n, thn kinh d b kch thch.
Dng bo ch: vin nn 4 mg; siro 2 mg/ 5 ml.
Ghi ch:

11

Trong cng thc ca cyproheptadin, nu thay C 6 bng N ( phenyl thnh pyridyl),

gn Cl vo C2 ca phenyl cn li, b ni i 10 -11, thay CH 3 bng COOC2H5 ta
c loratadin (loratidin, bit dc Clarytin) l mt khng histamin tricyclic khng
c tc dng an thn, khng khng cholinergic, tc dng ko di. Thng ung 10 mg/
ln/ 24 gi tr vim mi d ng.
2.1.6. Dn cht piperazin
c im chung:
C th coi l cc dn cht ethylendiamin mch vng. Tc dng khng histamin cng
in hnh, t gy bun ng. Tc dng chng nn v chng chng mt ch yu do chng
khng muscarinic trung ng v lm mt kch thch tin nh. Dn cht chuyn ha
norclocyclizin c th gy qui thai.
MECLOZIN HYDROCLORID
Tn khc: meclizin.
Bit dc: Antivert, Bonine.
Cng thc:

C25H27ClN2,2HCl = 463,9
Tn khoa hc: 1-(p-cloro--phenylbenzyl) -4-(m-methylbenzyl) piperazin
dihydroclorid.
Nguyn t C bt i gn N ca amin (III), tng t nh cc dn cht phenothiazin,
cc ng phn (D) v (L) c tc dng tng ng nhau, dng dc dng l racemic.
Nguyn t Cl v tr para ca nhn phenyl lm tng tc dng.
Gc methylphenyl nh hng n tnh cht dc ng hc v s chuyn ha thuc
trong c th, meclizin c tc dng ko di. Nu c Cl v methylphenyl u c thay
bng H th c cyclizin (bit dc Marezin), cht ny c ch nh tng t nhng tc
dng ngn hn hn meclizin, khng dng cho ph n c thai (ph n c thai vn dng
c meclizin vi liu thp v trong thi gian ngn).
Ch nh: phng v chng nn, chng mt do say tu xe, gim chng mt v cc hi
chng ng pht do ri lon tin nh. Meclizin c t tc dng khng mong mun.
HYDROXYZIN HYDROCLORID
Bit dc: Atarax.
Cng thc:

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C21H27ClN2O2,2HCl = 447,8
Tn
khoa
hc:
(RS)-2-[2-[4-[(4-chlorophenyl)phenylmethyl]piperazin-1yl]ethoxy]ethanol dihydrochloride.
Dng dc dng l racemic.
Tc dng - ch nh:
L mt thuc khng histamin c tc dng an thn ng k, khng khng cholinergic.
c dng lm gim lo lng, cng thng k c trong ngoi khoa (trc v sau khi
gy m); chng say tu xe, bun nn, nn, chng mt; chng d ng ( bnh my ay
mn tnh hoc cc d ng trn da khc).
Ghi ch:
Dn cht chuyn ha ca hydroxyzin (oxy ha chc OH alcol ca hydroxyzin thnh
-COOH) c tn l cetirizin (dng dc dng l racemic, mui hydroclorid, bit dc
Zyrtec), c tc dng an thn, gy ng, khng cholinergic u rt yu, khng khng
serotonin. Cht ny c tc dng khng histamin ko di, c dng cho cc th vim
mi d ng, my ay t pht mn tnh vi liu 5 10 mg/ ln / 24 gi di dng vin
nn hoc siro. Hin nay cetirizin c dng ph bin.
2.2. Cc cht c ch gii phng histamin
Cc cht ny ngn chn sm s gii phng histamin. V cu trc, cc cht in hnh
(cromolyn, nedocromil) khng mang cu trc chung ca cc cht khng histamin thc
th nh nu phn i cng.
CROMOLYN NATRI
Tn khc: cromoglycat natri (acid cromoglycic).
Bit dc: Gastrocrom, Nasalcrom, Opticrom.
Cng thc:
C23H14Na2O11 = 512,3
Tn khoa hc: 1,3-bis(2-carboxychromon-5-yloxy)2-hydroxypropan dinatri.
Tnh cht l ha - phng php kim nghim:
Bt kt tinh mu trng, khng mi, v hi ng, ho nc. Chy khong 261 0C,
khng b bin dng. Tan trong nc; khng tan trong alcol, cloroform. B x phng
ha bi NaOH.
nh tnh: ph IR, UV, so snh vi ph chun.
Th gii hn acid kim, oxalat, tp lin quan (TLC).
nh lng: o hp th UV, max = 326 nm, m phosphat pH 7,4, so snh vi cht
chun.
Tc dng - ch nh:
O

Na+

O-

Na+

O-

HO

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Cromolyn l cht n nh dng bo, ngn cn s v t bo ny khi c khng nguyn,

tc l ngn cn s gii phng histamin v cc cht phn v. Cromolyn khng khng
tc dng ca histamin, khng c tc dng lm co mch hoc chng vim. Cromolyn d
hp thu qua ng tiu ha, t phi (7-8%), t mt (0,03%); c bi tit nguyn vn
qua ng mt v nc tiu.
Ch nh:

Hen, cho c hen nng, phng v ngn cn cn co tht ph qun cp tnh,

co tht ph qun do vn ng;

Vim mi d ng; vim d ng nim mc mt (vim kt mc, gic mc, gic

kt mc),..

iu tr chng v dng bo (mastocytosis) n nh dng bo.

Dng bo ch: vin ung 300 mg; bt phun mi, dung dch nh mt, nh mi 2% 4%.
Bo qun: trnh m, nh sng.

CU HI T LNG GI

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