Chuong 15 Va 16-Bai Giang-2010-Handouts Hoa Duoc

1
THU
THU
C
C
NH H
NH H
NG CH
NG CH
C NNG
C NNG
D
D
D
D
Y
Y
RU
RU
T
T
PGS.TS. Nguyn Hi Nam
CHNG 15
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2
C
C
c
c
lo
lo
i
i
thu
thu
c
c

nh
nh
h
h
ng
ng
ch
ch
c
c
nng
nng
d
d
d
d
y
y

ru
ru
t
t
Thuc iu tr lot d dy, t
trng
Thuc nhun trng v ty
Thuc iu tr a chy
Thuc gip tiu ha (t c)
Thuc gy nn v chng nn
(chng 10, HDI)
3
I. THU
I. THU
C I
C I
U TR
U TR
VIM LO
VIM LO
T
T
D
D
D
D
Y T
Y T
TR
TR
NG
NG
4
M
M
C TIU H
C TIU H
C T
C T
P
P
Trnh by c cc nguyn nhn chnh v
cc tc nhn gy lot d dy, t trng; t
k tn cc nhm thuc v vai tr mi
nhm dng trong iu tr lot d dy, t
trng.
V c CTCT chung, T/C l, ha chung ca
cc thuc c ch H2 v c ch bm proton.
Trnh by c T/C l, ha v ng dng cc
tnh cht trong nh tnh, nh lng cc
thuc: Cimetidin v ng loi; Omeprazol
v ng loi.
5
i
i
cng
cng
Nguyn nhn gy lot:
+ H. pylori
+ Dng thuc chng vim steroid/phi
steroid
+ Stress
+ Ung th d dy, tuyn ty
Tc nhn gy lot: HCl v pepsin
Thuc iu tr:
+ Khng sinh (nu nhim H. pylori).
+ Cc antacid (trung ha acid dch v)
+ Thuc chng tit acid
+ Thuc bo v nim mc d dy (bao vt
lot)
6
C
C
c
c
kh
kh
ng
ng
sinh
sinh
kh
kh
ng
ng
H. pylori
H. pylori
Tetracyclin, Amoxicillin, Clarithromycin,
Metronidazol, Tinidazol, Furazolidon.
Phi hp hai thuc:
* Amoxicillin (1000mg) + Clarithromycin
(500mg)
* Amoxicillin (1000mg) + Metronidazol
(500mg)
* Clarithromycin (250mg) + Tinidazol
(500mg)
(dng cng 1 thuc chng tit acid v c
th dng cng 1 thuc bao vt lot)
7
C
C
c
c
antacid
antacid
L nhng cht c kh nng trung ha HCl
d dy.
Cc thuc hay dng l cc nhm hydroxyd,
Magnesi hydroxyd hoc hn hp cha c 2
cht ny.
Hin nay, do c nhiu thuc chng tit acid
tt nn cc antacid ch dng gim au tm
thi khi qu au do lot.
Mt s thuc:
- Nhm hydroxyd gel
- Magnesi hydroxyd
- Maalox (Nhm hydroxyd gel + Magnesi
hydroxyd)
8
Thu
Thu
c
c
ch
ch
ng
ng
ti
ti
t
t
acid
acid
Hai nhm:
Thuc c ch tit acid
Thuc c ch bm proton
9
Thu Thu c c ch ch ng ng ti ti t t acid: acid: Thu Thu c c kh kh ng ng H2 H2
Thuc khng th th H2: Histamin
tc ng ln th th H2 thnh d
dy tit ra HCl. Nhng cht c ch
cnh tranh vi histamin trn th th
ny c gi l thuc khng th th
H2 v c dng lm thuc chng tit
acid. Cc thuc: cimetidin, ranitidin,
famotidin,
10
Thu
Thu
c
c
kh
kh
ng
ng
th
th
th
th
H2
H2
V cu to ha hc, tt c u c 1 d vng
5 cnh, mt mch nhnh -CH
2
SCH
2
CH
2
-R.
Tn gi ...tidin. C 4 thuc nhm ny hin
dng trong iu tr l: Cimetidin, Ranitidin,
Famotidin v Nizatidin.
Ch nh iu tr:
* Phng v iu tr lot d dy, t trng.
* Phng v iu tr chng nng, n kh
tiu do tng acid d dy.
* iu tr hi chng Zollinger-Ellison; bnh
tng tit acid.
* iu tr bnh hi lu thc qun d dy.
11
CIMETIDIN
CIMETIDIN
(
(
HCl
HCl
)
)
Tn KH: 2-cyano-1-methyl-3-[2-[[(5-methylimidazol-4-
yl)methyl]thio]ethyl]guanidin.
L, ha tnh:
+ Bt kt tinh trng hoc gn nh trng, dng base t
tan trong nc, tan trong acid v c long. pKa = 6,8.
+ Nhn thm: Hp th bc x t ngoi (nh tnh = pp
qut ph UV, o hp th ring, SKLM; nh lng =
pp o quang, HPLC).
+ Tnh base: Tan trong acid v c, ng dng pha ch
phm tim; nh tnh = p/ vi TT chung ca alcaloid
(acid silicovolframic); nh lng = pp o acid/mt
khan.
(+ P/ ca ion Cl
-
)
N
HN
CH
2
S CH
2
CH
2
H
N C
N
H
N CH
3
CN
CH
3
1
2
3
12
CIMETIDIN ( CIMETIDIN (HCl HCl) )
nh tnh
+ IR, UV, SKLM, o mp
+ P/ vi TT alcaloid
+ P/ ca ion clorid (nu l mui HCl)
+ T/d vi acid citric/anhydrid acetic tm (BP2007)
nh lng: o quang, HPLC, o acid/mt khan
CD: nh phn chung.
N
HN
CH
2
S CH
2
CH
2
H
N C
N
H
N CH
3
CN
CH
3
1
2
3
13
C C c c thu thu c c kh kh ng ng th th th th H2 H2 kh kh c c c c ng ng
nh nh m m
S
H
N
H
N
HN
N O
S
H
N
H
N
HN
N N
S
H
N
H
N
O HC
NC
Metiamid
Cimetidin
Ranitidin
NO
2
N
S
H
N
H
N
S
N HC
Nizatidin
NO
2
N
S
H
N
H
N
S
N CH
Tiotidin N
NC
H
2
N
H
2
N
S
H
N
H
N
S
N N
Famotidin
N
H
2
N
H
2
N
SO
2
NH
2
O
H
N
O
O
Roxatidin
N
O
CH
3
14
C C c c thu thu c c kh kh ng ng th th th th H2 H2 kh kh c c c c ng ng nh nh m m
T/C l, ha, nh tnh, nh lng:
tng t cimetidin.
Cng dng: tng t cimetidin
So snh mt s thuc:
Thuc Hot
lc
Liu Tc dng ph
Cimetidin 1 300mg x
3-4
ln/ngy
c ch P450 lm gim
chuyn ha mt s thuc;
khng androgen
Ranitidin 10 150mg x 2
ln/ngy
t tc dng ph hn so vi
cimetidin
Famotidin 30 20mg x 2
ln/ngy
t tc dng ph hn so vi
cimetidin
15
Thu
Thu
c
c
ch
ch
ng
ng
ti
ti
t
t
acid:
acid:
Thu
Thu
c
c

c
c
ch
ch
bm
bm
proton
proton
Thuc c ch bm proton: Bc cui
cng a acid vo lng d dy c thc
hin bi enzym H+/K+ ATPase (bm
proton). Thuc c tc dng c ch enzym
ny c tc dng chng tit acid. Hin c 5
cht dng trong iu tr l Omeprazol;
Lansoprazol; Pantoprazol; Rabeprazol v
Esomeprazol (ng phn ca Omeprazol).
Cc cht ny c ch bt thun nghich
enzym nn c tc dng ko di (mc d
thi gian bn thi ch khong 1,5-3 gi); tc
dng mnh nht l lc i. V vy, ngy ch
ung 1 ln, trc ba n sng.
16
Thu Thu c c c c ch ch bm bm
proton proton
CTCT chung: u l dn cht ca 2-
sulfinylmethyl pyridin ca
benzimidazol- u c tn ...prazol.
H
1
2
3
4
5
1
2
3
O
N
N S
N
4
5
R
5
R'
3
R'
4
R'
5
TC chung:
+ Bt kt tinh trng hoc hu nh trng, kh tan/H
2
O.
+ Nhn thm: Hp th UV (nh tnh, nh lng).
+ Rt d b phn hy trong mi trng acid.
+ Tnh acid: H v tr 1, ch phm dd mui natri.
+ Tnh base: Nhn pyridin, nh tnh, nh lng.
CD:
+ iu tr lot d dy, t trng. Ngoi tc dng chng tit acid, cc
hp cht ny cn c tc dng dit H.pylori.
+ Dng trong tt c cc trng hp cn gim tit acid.
17
OMEPRAZOL
OMEPRAZOL
Tn KH: 5-methoxy-2-[[(4-methoxy-3,
5-dimethylpyridin-2-yl)methyl]sulfinyl]-1H-
benzimidazol.
TC:
+ Bt kt trng, gn nh trng. Rt kh tan/nc, aceton, isopropanol,
tan/dicloromethan, methanol, ethanol. n nh/ dung dch ph
thuc pH. Khng bn/mtrng acid, bn/mtrng kim.
+ Hp th mnh bc x t ngoi (nh tnh, nh lng).
+ C tnh acid: pKa
1
= 8,7. Tan trong cc dd kim to mui. Cc mui
ny cho ta hoc phc mu vi mt s ion kim loi. L = pp o
kim, dm ethanol, ch th o th.
+ C tnh base: pKa
2
= 3,97. Tan trong cc dd acid v c. Cho p/
vi cc TT alcaloid (nh tnh). nh lng = pp o acid/mt khan.
+ Khng vng bn trong mi trng acid (dng bo ch l vin bao
tan trong rut) hoc bt ng kh dng mui natri, pha tim khi
dng.
H
N
N
N
S
CH
3
O
OCH
3
CH
3
CH
3
O
1
2
3
4
5
1
2
3
4
5
6
6
7
18
OMEPRAZOL
OMEPRAZOL
Tn KH: 5-methoxy-2-[[(4-methoxy-3,
5-dimethylpyridin-2-yl)methyl]sulfinyl]-1H-
benzimidazol.
TC l, ha ng dng trong bo ch, kim nghim:
Bo ch:
+ Bn trong mt kim, to mui natri pha dung dch mui natri
tim.
+ Khng bn trong mt acid bo ch vin bao tan/rut.
nh tnh:
+ IR, UV, HPLC, o nhit nng chy, lm SKLM
+ C tnh acid: pKa1 = 8,7. Tan trong cc dd kim to mui. Cc
mui ny cho ta hoc phc mu vi mt s ion kim loi.
+ C tnh base: pKa
2
= 3,97. Tan trong cc dd acid v c. Cho p/ vi
cc TT alcaloid.
nh lng: o quang hoc o acid/mt khan
H
N
N
N
S
CH
3
O
OCH
3
CH
3
CH
3
O
1
2
3
4
5
1
2
3
4
5
6
6
7
19
CTCT
CTCT
m
m
t
t
s
s
thu
thu
c
c

c
c
ch
ch
bm
bm
proton
proton
Omeprazol
(Losec/Prilosec/Lomac)
Lansoprazol
(Prevacid, Lupizol)
Esomeprazol
(Nexium)
Pantoprazol
(Protium/Protonix)
Rabeprazol
(AcipHex)
20
C
C
c
c
thu
thu
c
c
bao
bao
v
v
t
t
lo
lo
t
t
Hin cn hai thuc hay dng: sucralfat
v bismuth subsalicylat
O
O
CH
2
OR
RO
OR
OR
O
CH
2
OR
OR
RO
CH
2
OR
R= SO
3
[Al
2
(OH)
5
]
.

16
H
2
O
O C OBiO
OH
C
7
H
5
BiO
4
P.t.l.: 362
,
11
sucralfat
bismuth subsalicylat
21
Bismuth
Bismuth
subsalicylat
subsalicylat
O C OBiO
OH
C
7
H
5
BiO
4
P.t.l.: 362
,
11
L tnh: Tinh th nh, hnh lng tr, khng
tan/nc, ethanol, tan/acid v c (phn hy).
Ha tnh: d b thy phn to acid salicylic v bismuth hydroxyd.
- Thy phn = dd kim, lc. Acid ha dch lc thu c acid salicylic
(cho phn ng vi FeCl
3
to mu tm).
- Ta thu c sau khi thy phn v lc (bismuth hydroxyd): ha tan
trong dd HCl. Thm NH
3
to ta trng khng tan/ dd kim, tan/ dd
acid.
- nh lng: v c ha, nh lng = pp o Complexon (CT vng
xylenol, mu tm vng).
Bi(OH)
3

3
HCl BiCl
3
Bi(OH)
2
Cl
2
NH
4
+

2
Cl + + + =
2
NH
3
C ONa O
ONa
+ FeCl
3
H
+
O
Fe
O
O
22
Bismuth
Bismuth
subsalicylat
subsalicylat
O C OBiO
OH
C
7
H
5
BiO
4
P.t.l.: 362
,
11
Tc dng v cng dng:
Tc dng:
- Lm gim nhu ng rut, tng hp thu cht lng v cht
in gii rut: iu tr a chy.
- C tc dng khng khun, k c H.pylori; lm gim c
t E.coli.
- Kch thch to cht nhy, natri bicarbonat, to phc hp
lycoprotein bao ly ch lot.
Ch nh:
- iu tr lot d dy, t trng.
- iu tr v phng a chy.
23
Thu
Thu
c
c
nhu
nhu
n
n
,
,
t
t
y
y
Thuc nhun trng v ty: l nhng cht
gip cho s i tin c d dng. Ty theo c
ch tc dng m chia lm nhiu loi nh thuc
nhun trng do kch thch (Bisacodyl); mui
nhun trng (cc mui magnesi); nhun trng
do tng thm thu (Lactulose); do to nhiu
phn (dn cht polysaccarid v cellulose); do
lm trn (du khong); nhun trng do lm
mm phn (mui docusat).
Ch nh: dng iu tr to bn v tho phn.
24
Bisacodyl
Bisacodyl
Tn KH: 4,4'-(2-pyridylmethylen)
diphenyl diacetat
N
CH
O C CH
3
O C CH
3
O
O
1
2
3
4
4
'
1
1
'
L tnh:
+ Bt kt tinh trng hoc hu nh- trng. Kh tan trong n- c, hi
tan/ethanol, ether, d tan/ cloroform; tan/ cc dung dch acid v
c long.
+ Hp th UV tt nh tnh, nh l- ng.
+ Ph IR, so snh vi chun.
Ha tnh: tnh base vd b thy phn
+ Thy phn aldehyd, acid acetic, phenol:
- Dch thy phn + FeCl3 tm
- Dch thy phn + AgNO3 Ag
- Dch thy phn un vi acid sulfuric mi ethyl acetat
25
Bisacodyl Bisacodyl
+ Tnh base
- Ha vo nc khng tan, thm dd HCl tan, thm acid
silicovolframic ta trng (p vi TT alcaloid).
- L = pp o acid/ mt khan (tnh base yu).
Cng dng:
- Kch thch cc ngn dy thn kinh cm gic trn nim mc rut
nn lm tng nhu ng rut.
- Dng iu tr to bn, lm sch rut trc khi phu thut, soi
hoc chiu chp trc trng.
- Do gy kch ng d dy nn dng bo ch l vin bao tan rut
vin t trc trng; dung dch tho tht.
N
O C CH
3
O C CH
3
CH
O
O
NaOH
t
o
N
C H
O
OH
CH
3
COOH
2
2
Phn ng thy phn:
26
Thu
Thu
c
c
i
i
u
u
tr
tr
a
a
ch
ch
y
y
a chy l bnh do nhim khun, nhim c,
km hp thu, km tiu ha, do khi u, do
ri lon chc nng rut, do d ng...V
vy, iu tr a chy, ngoi vic iu tr
nguyn nhn gy bnh th phi iu tr c
triu chng v b sung nc v cc cht
in gii mt.
Trong trng hp a chy nng, i vi tr
em v ngi gi, cn truyn dung dch cc
cht in gii. lm ngng a chy,
ung Loperamid; Diphenoxylat, Bismuth
subsalicylat cng c tc dng tt.
27
ORS (ORAL REHYDRATION SALTS)
y l hn hp mui v ng dng b li lng nc v
cht in gii mt.
Thnh phn ORS lun c NaCl; KCl; Glucose; NaHCO3 (hoc
natri citrat) vi s lng khc nhau ty mi cng thc. Khi
dng, ha tan trong mt lng nc ghi trn nhn, ung mi
ln mt t.
nh tnh cc thnh phn:
+
AgCl ;
+ [Ag(NH
3
)
2
]Cl H
2
O
NH
4
OH
AgCl AgNO
3
Cl
+ Na
3
[Co(NO
2
)
6
] K
2
Na[Co(NO
2
)
6
K
+
NaMg[(UO
2
)
3
(CH
3
COO)
9
].
9
H
2
O Na Mg[(UO
2
)
3
(CH
3
COO)
8
]
+
O
CH
2
OH
HO
OH
OH
2
CuO
COOH
OH
CH
2
OH
HO
OH
Cu
2
O
Ion citrat Ca Calci citrat
2
+
+
OH OH
28
nh lng:
- Ion natri, kali: PP o ph pht x nguyn
t.
- Ion clorid: PP o bc
- Ion citrat: PP o acid/ mt khan
- Ion bicarbonat: PP o acid/ mt nc.
- Glucose: PP o iod
Cng dng:
- B nc v in gii
29
Diphenoxylat
Diphenoxylat
HCl
HCl
Tn KH: Ethyl-1-(3-cyano-
3,3-diphenyl-propyl)-4-
phenylpiperidin-4-carboxylat
hydroclorid
C CH
2
CH
2
N
CN
COOC
2
H
5
HCl
.
1
2 3
4
2
3
1
L tnh:
Bt kt tinh trng hoc hu nh- trng, khng mi hoc hu nh-
khng mi; kh tan trong n- c visopropanol; hi tan trong
ethanol, aceton; d tan trong cloroform vdicloromethan; thc t
khng tan trong ether vhexan.
Hp th UV mnh nh tnh, nh l- ng.
Ph IR, so snh vi chun
30
Diphenoxylat
Diphenoxylat
HCl
HCl
C CH
2
CH
2
N
CN
COOC
2
H
5
HCl
.
1
2 3
4
2
3
1
Ha tnh:
L ha tnh ca nhm ester, nit bc 3 (tnh base) v phn HCl kt
hp:
un ch phm vi dd NaOH30% v iod to iodoform (CHI
3
) mi
c bit.
Tc dng vi TT alcaloid cho ta hoc mu c trng.
Tc dng vi dd AgNO3 to ta trng.
nh lng = pp o acid/ mt khan hoc pp o quang.
Cng dng
Lm gim s vn ng ca rut; iu tr a chy cp v mn tnh.
31
Loperamid
Loperamid
HCl
HCl
Tn KH: 4-[4-(4-clorophenyl)-4-
hydroxypiperidin]-N,N-dimethyl-
2,2-diphenylbutyramid hydroclorid
L tnh:
Bt kt tinh rt nh hoc v nh hnh, mu trng hoc trng hi
vng. t tan trong n- c, tan/ethanol, d tan/methanol..
Hp th UV mnh nh tnh, nh l- ng.
Ph IR, so snh vi chun
N C CH
2
CH
2
CON(CH
3
)
2
OH
Cl
HCl
.
C
29
H
33
ClN
2
O
2
HCl P.t.l.:
.
513
,
5
32
Loperamid
Loperamid
HCl
HCl
Ha tnh:
L ha tnh ca nhm chc amid, tnh base ca nhn piperidin, vho
tnh ca acid hydrocloric kt hp :
un ch phm vi dd kim gii phng dimethylamin lm xanh
giy qu v c mi c bit.
Tc dng vi TT alcaloid cho ta hoc mu c trng.
Tc dng vi dd AgNO3 to ta trng.
nh lng = pp o acid/ mt khan hoc pp o quang. Cng c th
nh lng = pp o kim/dung mi ethanol, dd chun NaOH 0,1N,
CT o th.
Cng dng
Lm gim s vn ng ca rut; iu tr a chy cp v mn tnh.
N C CH
2
CH
2
CON(CH
3
)
2
OH
Cl
HCl
.
C
29
H
33
ClN
2
O
2
HCl P.t.l.:
.
513
,
5
33
HORMON V
HORMON V
C
C
C CH
C CH
T
T
TNG T
TNG T
Chng 16
H
O
HO
OH
O
O
O
Nguyn Hi Nam, B mn Ha Dc
Tel. 9330531/ Email: nhnam@etal.uri.edu
34
Ph
Ph
n
n
I.
I.
Hormon
Hormon
Steroid
Steroid
Hormon sinh dc nam
Hormon sinh dc n
Hormon v thng thn
- Glucocorticoid
- Mineralocorticoid
35
Mc
Mc
Ti
Ti
u
u
c
c
a
a
Ph
Ph
n
n
I
I
* V - c cc khung cu to c bn, trnh by
- c c ch tc dng, phn nhm, lin quan
cu trc-tc dng (nu c), tnh cht l, ha
chung v ng dng trong nh tnh, nh l- ng
ca cc nhm hormon steroid.
* Vi mt s thuc chnh trong tng nhm: vit
- c tn khoa hc*, phn tch - c cng thc
cu to - a ra cc tnh cht l, ha hc v
ng dng trong nh tnh, nh l- ng. Nu
- c tc dng, ch nh ca cc thuc ny.
*hoc t danh php v - c CTCT
36
C
C
u
u
tr
tr
c
c
chung
chung
hormon
hormon
steroid
steroid
Hormon sinh dc, hormon v thng
thn.
Cu trc: 3 khung c bn
Estran (18 C)
(estrogen)
H
H H
Androstan (19 C)
(androgen)
Pregnan (21 C), 17-ethyl
(progestin, corticoid)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
17
18
19
17
18
19
20
21
A B
C D
37
Danh
Danh
ph
ph
p
p
c
c
a
a
hormon
hormon
steroid
steroid
Estra- Androst- Pregn-
Estra-1,3,5(10)-
trien-3,17-diol
Pregn-4-en-3,20-
dion
Androst-4-en-17-
hydroxy-3-on
H
CH
3
H H
OH
H
HO
17-Estradiol
H
CH
3
H H
CH
3
O
Testosteron
OH
H
CH
3
H H
CH
3
O
H
O
Progesteron
H
Estran (18 C)
H
Androstan (19 C)
Pregnan (21 C),
H
H
H H
H
H
H H
H
38
C
C
c
c
Nh
Nh
m
m
Hormon
Hormon
Steroid
Steroid
Steroid
Hormon sinh dc nam
Hormon sinh dc n
Hormon v thng thn
- Glucocorticoid
- Mineralocorticoid
Hormon sinh dc nam
39
Hormon Hormon sinh sinh d d c c nam nam
Ngu
Ngu
n
n
g
g
c
c
,
,
t
t
c
c
d
d
ng
ng
Ngun gc:
- T bo k tinh hon (ch yu)
- V thng thn, bung trng, nhau thai
Tc dng
- Tc dng hormon (tc dng androgen): pht
trin gii tnh, c quan sinh dc, c im gii
tnh.
- Tc dng i lp estrogen.
- Tc dng tng dng (tng ng ha protid, gi
nit, mui calci, phospho tng c bp v xng
40
Hormon Hormon sinh sinh d d c c nam nam
Ch
Ch
nh
nh
chung
chung
Nam gii:
- Thiu nng sinh dc, chm pht
trin c quan sinh dc
- Nhc c, long xng, gy yu
N gii:
- Ri lon kinh nguyt, hi chng
sau mn kinh
- U x t cung, ung th v, ung
th t cung
41
M
M
T
T
S
S
HORMON
HORMON
SINH
SINH
DUC
DUC
NAM
NAM
CH
3
OH
O
CH
3
H
F H
CH
3
HO
H
Fluoxymesteron
CH
3
OH
O
CH
3
CH
3
OH
O
CH
3
H
H H
CH
3
Testosteron
Methyltestosteron
42
T
T
nh
nh
ch
ch
t
t
l
l
h
h
c
c
chung
chung
Bt kt tinh trng, kh tan/nc,
tan/nhiu dung mi hu c.
C nhiu C bt i l 1 pp nh
tnh, nh lng hoc th tinh khit.
C ni i lin hp in t hp
th UV TLC, o UV, HPLC nh
Hp th nh sng hng ngoi
ph IR c trng.
43
a s c nhm ceton vi ni i lin
hp:
+ cho p/ Zimmerman tm
+ p/ vi phenylhydrazin (2,4-
dinitrophenylhydrazin) ta vng
hydrazon
P/ oxi ha bng H
2
SO
4
hoc hn hp
H
2
SO
4
/formol cho mu hunh quang
c trng.
Nu l ester ca acid no mch thng:
thy phn ri p/ vi FeCl
3
T
T
nh
nh
ch
ch
t
t
ha
ha
h
h
c
c
chung
chung
44
Lin
Lin
quan
quan
c
c
u
u
tr
tr
c
c
t
t
c
c
d
d
ng
ng
c
c
a
a
c
c
c
c
testosteron
testosteron
CH
3
OH
O
CH
3
Cn cho
tc dng
androgen
B 19-CH
3
:
td tng
dng
11-OH:
tc dng
-C=O: gim tc
dng; Ester ha:
tc dng ko di
17-alkyl: bn vi
enzym gan
9-F/Cl: tc dng,
gim chuyn ha
Kh ha: tng tc
dng 4 ln
11
9
17
19
45
iu ch
Cc androgen
Testosteron propionat
CH
3
O
O
CH
3
H
O
CH
3
H H
CH
3
O
O
CH
3
H
H H
AD (
androstendion)
CH
3
O
O
CH
3
H
O
CH
3
H H
Testosteron propionat
Diosgenin
Acid hydrodeoxycholic
Cholesterol
Sterol (stigmasterol, sitosterol)
DHEA
Mycobacterium fortuitum
CH
3
OH
O
CH
3
H
H H
CH
3
CH
2
COCl
pyridin
Testosteron
S 1
46
Tnh cht l/ha hc-T/L
- Phn ng vi H
3
PO
4
/EtOH (2/1), un 5, lnh, +
HOOC-CHO (acid glyoxylic) tm, hunh quang
.
- Phn ng Zimmerman (mu tm)
- To hydrazon vi phenylhydrazin hoc 2,4-
dinitrophenylhydrazin.
- Phn propionat: dch thy phn tc dng vi
hydroxylamin to natri propionohydroxamat; thm
FeCl
3
c mu gch:
- Ph IR; Gc quay cc ring = 83-90
o
- UV (+): TLC (th tp), T, lng
Cc androgen
Testosteron propionat (tip)
CH
3
O
O
CH
3
H
O
CH
3
H H
H
3
C
O
H
N
ONa
H
+
FeCl
3
H
3
C
O
H
N
O
-
3
Fe
47
Cng dng
ung khng c tc dng do b ph hy
gan. Thng dng tim bp, tc dng ko
di (24 h)
- iu tr thay th thiu nng sinh dc nam,
ri lon chc nng sinh dc, lit dng
- Cho n: iu tr ung th v, d con, bung
trng, ri lon kinh nguyt
- Tc dng tng dng (tng ng ha
protid)
Cc androgen
Testosteron propionat (tip)
48
CH
3
OH
O
CH
3
H
H H
CH
3
Cc androgen
Methyltestosteron
iu ch
CH
3
O
HO
CH
3
H
H H
Androstenolon
CH
3
OH
O
CH
3
H
H H
Methyltestosteron
CH
3
MgI
CH
3
OH
HO
CH
3
H
H H
CH
3
CrO
3
CH
3
S 2
Tng bn
vi enzym oxi
ha kh gan
49
Cc androgen
Methyltestosteron (tip)
CH
3
OH
O
CH
3
CH
3
Tnh cht l, ha-T/L
- Phn ng Zimmerman
- Phn ng to hydrazon
- Phn ng oxi ha
- Ph IR c trng
- Gc quay cc ring
- UV(+): TLC, HPLC (nh tnh, th tinh khit,
nh lng)
Cng dng: bn gan so vi testosteron (c
th ung)
- Tng t testosteron propionat cho nam gii.
- Phi hp estrogen iu tr ri lon kinh
nguyt, a kinh, cc triu chng tin mn
kinh, long xng sau mn kinh.
50
Hormon sinh dc
nam
Hormon sinh dc
n
Hormon v thng
thn
- Glucocorticoid
- Mineralocorticoid
Phn
Phn
lo
lo
i
i
steroid
steroid
hormon
hormon
Steroid
Hormon sinh dc
n
51
Hormon sinh dc n: Phn loi
1. Cc estrogen t nhin v dn
cht
2. Cc progestin
H
CH
3
H H
O
HO
Estron
H
CH
3
H H
O
H
O
Progesteron
52
C
C
c
c
Estrogen:
Estrogen:
Ngu
Ngu
n
n
g
g
c
c
T
T
c
c
d
d
ng
ng
Ngun gc: nhau thai, bung trng tit
ra
Tc dng:
+ Nng sinh l: lm pht trin gii tnh,
c quan sinh dc n, c tnh gii.
+ Liu cao: c ch lm trng khng pht
trin, khng lm t c chng th thai.
+ Tng calci mu, ng ha protein.
+ i khng testosteron (h/m sinh dc nam)
53
C
C
c
c
Estrogen:
Estrogen:
Ch
Ch
nh
nh
+ Thay th hormon trong suy
bung trng, ct bung trng, ri
lon tin v sau mn kinh (c long
xng).
+ Trnh thai (liu cao hn)
+ Bnh nam ha ph n
+ Ung th tuyn tin lit
54
I.
I.
C
C
c
c
estrogen
estrogen
t
t
nhin
nhin
v
v
d
d
n
n
ch
ch
t
t
1) Cc estrogen t nhin: Estron,
Estradiol, estriol v ester: Estropipat,
estradiol monobenzoat
2) Cc estrogen bn tng hp:
ethinylestradiol
3) Cc phi steroid tng hp c tc dng
estrogen (diethylbestrol) hoc khng
estrogen (clomiphen citrat v
raloxifen hydroclorid).
55
Lin
Lin
quan
quan
c
c
u
u
tr
tr
c
c
t
t
c
c
d
d
ng
ng
c
c
a
a
c
c
c
c
estrogen
estrogen
H
CH
3
H H
O
HO
Quan trng
cho hot tnh
estrogen
Cn cho
hot tnh
estrogen
Ester/ether ha:
tc dng ko di
Estradiol: Gn thm
ethinyl bn gan
Kh ha tng tc dng 8
ln (-estradiol)
Thm 16-OH
gim hot tnh 20
ln
56
M
M
T
T
S
S
A
A
I
I
DI
DI
N
N
H
CH
3
H
H H
OH
H
O
O
HO
OH
CH
3
H
H H
C CH
Estradiol
monobenzoat
Ethinylestradiol
57
T
T
nh
nh
ch
ch
t
t
l
l
h
h
c
c
chung
chung
Bt kt tinh trng, kh tan/nc
(tr estropipat), tan/nhiu dung mi
hu c.
C ni i lin hp in t hp
th UV TLC, o UV, HPLC nh
Hp th nh sng hng ngoi ph
IR c trng.
58
C nhm OH phenol: cho p/ vi
FeCl
3
xanh.
P/ oxi ha bng H
2
SO
4
hoc hn hp
TT c trng cho mu hunh quang
c trng.
Nu c phn acid mch thng
(aliphatic acid): thy phn ri p/ vi
FeCl
3
Nu c nhm ethinyl cho phn ng
to ta trng vi AgNO
3
T
T
nh
nh
ch
ch
t
t
ha
ha
h
h
c
c
59
Estradiol
Estradiol
monobenzoat
monobenzoat
iu ch:
Estradiol Estradiol monobenzoat
H
CH
3
H
H H
OH
H
O
O
Benzoyl clorid
1mg/5ml TT xanh nh vng;
Xanh/UV
365
; thmH
2
SO
4
long
hng + hunh quang vng
Tnh cht/nh tnh
- Thy phn to estradiol
(vi FeCl
3
to phc tm)
- Vi thuc th sulfomolybdic cho hunh quang c
trng.
- Ph IR c trng; gc quay cc ring
- UV (+): nh tnh, th tp cht khc, nh lng
(o UV, HPLC)
Cng dng
- Ging estropipat, tc dng ko di
17-Hydroxyestra-
1,3,5(10)-trien-3-yl
benzoat
60
Ethinylestradiol
Ethinylestradiol
iu ch
HO
O
CH
3
H
H H
Estron
CH KC
HO
OH
CH
3
H
H H
Ethinylestradiol
C CH
HO
OH
CH
3
H
H H
C CH
1mg/1ml H
2
SO
4
c cam;
Xanh/UV
365
; pha long tm+ ta tm
Tng bn
vi enzym oxi
ha kh gan
S 6
Tnh cht/nh tnh
- To mui bc kt ta trng
- Vi FeCl
3
to phc tm
- Phn ng mu vi acid sulfuric cho hunh quang c
trng.
- Ph IR c trng
- Gc quay cc ring: = -(27-30)
o
- UV (+): nh tnh, th tp cht khc, nh lng
nh lng: to mui bc vi AgNO
3
gii phng
HNO
3
. lng HNO
3
bng NaOH, xc nh im tng
ng bng in th k
19-Nor-17-pregna-1,3,5(10)-
trien-20-yne-3,17-diol
61
Ethinylestradiol
Ethinylestradiol
(
(
ti
ti
p
p
)
)
HO
OH
CH
3
H
H H
C CH
AgNO
3
HO
OH
CH
3
H
H H
C CAg
HNO
3
Cng dng: do 17-ethinyl nn t chu nh hng ca
enzym gan hn bn hn khi ung.
- Ging estropipat: + Thiu nng bung trng
+ Ri lon sau mn kinh
+ Ung th tin lit tuyn, ung th v
- Chng rng non liu thp, phi hp vi cc
progestin trong cc thuc trnh thai phi hp
Phn ng
62
Hormon sinh dc n
Cc Progesteron: Ngun gcTc dng
Ngun gc: do vt th vng (hong
th) tit ra.
Tc dng:
- Nng sinh l: lm dy nim mc,
tng sinh v n to t cung; tng tit nim
dch; gim co bp t cung, gim p ng
vi oxytocin;
- Liu cao: c ch phng non chng
th thai. i khng testosteron, tng thi
Na
+
.
63
Hormon sinh dc n
Cc Progesteron: Cng dng
+ Dng trong thiu nng vt th vng.
+ Phng sy thai nhiu ln, da sy
thai.
+ Chng th thai.
+ Bng huyt, bng kinh, ri lon
kinh nguyt
+ Mt s ung th ni mc t cung,
ung th v.
64
T
T
nh
nh
ch
ch
t
t
l
l
h
h
c
c
chung
chung
C ni i lin hp in t hp th
UV TLC, o UV, HPLC nh tnh,
nh lng hoc th tinh khit.
IR c trng.
65
T
T
nh
nh
ch
ch
t
t
h
h
a
a
h
h
c
c
c
c
hung
hung
Phn ng Zimmerman
To hydrazon:
+ Vi phenylhydrazin to hydrazon mu vng
+ Vi 2,4-dinitrophenylhydrazin to hydrazon
mu
R
1
R
2
C=O + NH
2
NH-Ph R
1
R
2
C=N-NH-Ph
P/ oxi ha bng H
2
SO
4
hoc hn hp TT c
trng cho mu hunh quang c trng.
Nu c phn acid mch thng (aliphatic acid):
thy phn ri p/ vi FeCl
3
Nu c nhm ethinyl cho phn ng to ta
trng vi AgNO
3.
66
T/C l, ha T, L
- Phn ng Zimmerman (ceton): tm
- To hydrazon:
mu
R
1
R
2
C=O + NH
2
NH-Ph R
1
R
2
C=N-NH-Ph
- Phn ng oxi ha
- Ph IR c trng
- Gc quay cc ring: = 134-137
o
- Hp th UV:
+ TLC: nh tnh, th tp lin quan
+ HPLC: UV detector (PP ch yu hin nay)
Progesteron
Progesteron
H
CH
3
H H
CH
3
O
H
O
t
o
67
Cng dng:
L hormon chnh trong c th. Dng
iu tr thay th khi:
- Thiu nng vt th vng, ri lon
kinh nguyt, v sinh
- Phng sy thai
- Trnh thai
- Ung th ni mc t cung (liu cao)
Progesteron
Progesteron
(
(
ti
ti
p
p
)
)
H
CH
3
H H
CH
3
O
H
O
68
dn cht 19-nortestosteron
Norethindron acetat
H
CH
3
H H
O
O
H
O
CH
3
H
TC l, ha T, L
Phn ng vi AgNO
3
to ta trng
Phn ng ca phn acetat
Phn ng Zimmerman
To hydrazon:
mu
R
1
R
2
C=O + NH
2
NHPh R
1
R
2
C=NNHPh
Ph IR c trng
Gc quay cc ring
Hp th UV: + TLC, HPLC: nh tnh, th tp
lin quan, nh lng
69
Norethindron
Norethindron
acetat
acetat
(
(
ti
ti
p
p
)
)
nh lng
To mui bc vi AgNO
3
gii phng HNO
3
.
lng HNO
3
bng NaOH, xc nh im
tng ng bng in th k.
o UV, HPLC
Cng dng: l progestin c tc dng
estrogen v androgen yu
Trnh thai.
iu tr thay th sau mn kinh, a kinh,
lc ni mc t cung.
Hi chng tin mn kinh.
Ung th v (liu cao).
70
Levonorgestrel H
H H
OH
O
H
H
H
3
C
TC l, ha T, L
- Phn ng vi AgNO
3
to ta trng
- Phn ng Zimmerman
- To hydrazon:
+ Vi 2,4-dinitrophenylhydrazin to hydrazon mu
R
1
R
2
C=O + NH
2
NH-Ph R
1
R
2
C=N-NH-Ph
- Ph IR c trng
- Gc quay cc ring: = -30 -37
o
- Hp th UV: + TLC, HPLC: nh tnh, th tp lin
quan, nh lng
71
nh lng
To mui bc vi AgNO
3
gii phng HNO
3
.
lng HNO
3
bng NaOH, xc nh im
tng ng bng in th k.
o UV, HPLC
Cng dng
- Trnh thai
- Trnh thai khn cp
- iu tr thay th sau mn kinh
Levonorgestrel (tip) H
H H
OH
O
H
H
H
3
C
72
Phn loi
Steroid
Hormon sinh dc n
Hormon sinh dc nam
Hormon v thng thn
- Glucocorticoid
- Mineralocorticoid
Hormon v thng thn
- Glucocorticoid
- Mineralocorticoid
73
Glucocorticoid
Glucocorticoid
:
:
T
T
c
c
D
D
ng
ng
Trn chuyn ha:
+ Glucid: tng to glycogen gan, tng to glucose
t protein v acid amin.
+ Protid: c ch tng hp protid, tng d ha protid.
+ Lipid: thay i s phn b lipid.
Trn chuyn ha:
Tc dng chng vim, d ng, c ch min
dch:
+ Chng vim: c ch phospholipase A2, gim tng
hp leucotrien v prostaglandin.
+ Chng d ng: c ch phospholipase C, gim gii
phng histamin v cc cht trung gian gy d ng.
+ c ch min dch
Trn chuyn ha:
Tc dng chng vim, d ng, c ch min
dch:
+ Chng vim: c ch phospholipase A2, gim tng
hp leucotrien v prostaglandin.
+ Chng d ng: c ch phospholipase C, gim gii
phng histamin v cc cht trung gian gy d ng.
+ c ch min dch: lm teo cc c quan lympho
gim t bo lympho, c ch chc nng thc bo, c
ch sx khng th, etc.
74
c
c
i
i
m
m
c
c
u
u
t
t
o
o
CH
3
O
CH
3
OH
O
OH
11
9
16
-OH
=O
-CH
3
F, Cl
-OH,
-CH
3
=
Pregn-4-en-17,21-dihydroxy-3,20-dion
75
LIN QUAN C
LIN QUAN C
U TR
U TR
C
C
-
-
T
T
C D
C D
NG
NG
CH
3
O
CH
3
OH
O
11
9
16
X
OH
Cc nhm chc cn
cho c hot tnh
aldosteron v cortisol:
- 4, 3,20-dion
Cc nhm chc
cn cho hot
tnh cortisol:
11-ceton/-OH;
17,21-OH
1:
chng
vim (x4)
F, Cl: c chng
vim v
aldosteron
-OH, -CH
3
: hi
gim td chng
vim nhng gim
nhiu td aldosteron
Ester
ha/acetonid
ha 16,17-OH:
td ti ch
-CH
3
, F:
td
chng
vim
76
T
T
nh
nh
ch
ch
t
t
l
l
h
h
c
c
chung
chung
C ni i lin hp in t hp th
UV TLC, o UV, HPLC nh tnh,
nh lng hoc th tinh khit.
IR c trng.
77
T
T
nh
nh
ch
ch
t
t
h
h
a
a
h
h
c
c
c
c
hung
hung
(1)
(1)
- Phn ng Zimmerman
- To hydrazon:
mu
R
1
R
2
C=O + NH
2
NH-Ph R
1
R
2
C=N-NH-Ph
- Mt s phn ng c trng khc:
78
T
T
nh
nh
ch
ch
t
t
h
h
a
a
h
h
c
c
c
c
hung
hung
(2)
(2)
- Phn ng oxi ha:
OH
O
OH
[O]
(H
2
SO
4
)
OH
O
OH
OH
-H
2
O
OH
O
O
H
OH
O
N NHPh
OH
HO
N
NPh
HO
N
NPh
-H
2
O
H
+
Fale yellow
(Porter-Silber
reaction)
NH
2
-NHPh
79
T
T
nh
nh
ch
ch
t
t
h
h
a
a
h
h
c
c
c
c
hung
hung
(3)
(3)
Cc phn ng do
tnh kh ca
nhm -CHO:
OH
O
OH
[O]
(H
2
SO
4
)
OH
O
O
H
N
N
N
N
Ph
Ph
Ph
Cl
TPT
N
N
HN
N
Ph
Ph
Ph
Formazon
(red)
(colorless)
AgNO
3
(Ag
+
/NH
3
)
Ag
0
Hg
0
Hg
++
(K
2
HgI
4
)
80
ng
ng
d
d
ng
ng
- nh lng:
+ o mu: sau phn ng vi
phenyltetrazolium clorid hoc xanh
tetrazolium.
+ HPLC, o hp th t ngoi.
- Th tp cht khc: TLC, HPLC
81
Glucocorticoid Glucocorticoid t t nhin nhin
Hydrocortison
Hydrocortison
acetat
acetat
CH
3
O
CH
3
OH
HO
O
O
O
CH
3
nh tnh/nh lng
- [O] = H
2
SO
4
: nu m dn, pha long = nc mt
mu
- Thy phn = H
3
PO
4
, xc nh acid acetic = FeCl
3
hoc
phn ng vi hydroxylamin sau to phc vi FeCl
3
- Cc tnh cht chung khc (xem phn chung).
Cng dng:
- Thiu nng, suy hoc ct (chun b ct) thng thn.
- Shock, d ng mnh, hen nng v c tnh.
- Chng vim cc loi.
82
Glucocorticoid Glucocorticoid b b n n t t ng ng h h p p
Prednisolon
Prednisolon
CH
3
O
CH
3
OH
HO
O
OH
- Phn ng mu vi acid sulfuric c: sau 5 cho
mu m, hunh quang nu/UV365; pha
long = nc mu nht dn v hunh quang
vng/UV365 v c ta bng xm.
- Cc tnh cht l ha tng t hydrocortison.
- C tc dng ti ch (khc prednison). Ch nh
chung ca glucocorticoid. Dng ung, tim hoc
dng ngoi.
- Hay dng cc dng ester khc nhau.
83
Glucocorticoid Glucocorticoid b b n n t t ng ng h h p p
Dexamethason
Dexamethason
CH
3
O
CH
3
OH
HO
O
OH
F
CH
3
iu ch: bn tng hp t diosgenin (xem ti liu)
- So vi prednisolon: thm 9-F v 16-CH
3
.
- So vi hydrocortison th thm 1-en (
1
), 9-F v 16-
CH
3
.
- Cc tnh cht l ha chung.
- Cng dng: chng vim, sc, ph no, u no, hen, vim
mi d ng.
- Dng dng: ung tim, phun m, kem, m
84
Ph
Ph
n
n
II:
II:
C
C
c
c
hormon
hormon
kh
kh
c
c
Hormon tuyn yn
Hormon tuyn gip v cc thuc
khng gip trng
Hormon tuyn tu v cc thuc iu
tr tiu ng
85
Mc
Mc
ti
ti
u
u
Trnh by - c bn cht cu to, pp iu
ch v tc dng, ch nh ca insulin.
Tn 4 nhm thuc iu tr tiu - ng. T/C
l ho chung ca nhm sulfonylurea.
Nu - c cc c trng cu to, t
trnh by - c tnh cht l, ha v ng
dng trong pha ch, kim nghim, bo
qun ca cc thuc: natri levothyroxin,
glibenclamid, metformin, propylthiouracil.
86
Hormon
Hormon
tuy
tuy
n
n
gi
gi
p
p
v
v
thu
thu
c
c
kh
kh
ng
ng
gi
gi
p
p
tr
tr
ng
ng
Hai hormon chnh: thyroxin (T4,
levothyroxin), triiodothyronin (T3,
liothyronin).
Cc tnh cht l, ha hc ging nhau.
Liothyronin hot lc mnh hn, tc
dng nhanh hn, hp thu tt hn
qua ng ung.
87
Natri
Natri
levothyroxin
levothyroxin
HO
I
I
O CH
2
CH
NH
2
COONa
I
I
Ngun gc: tng hp (chit xut t tuyn gip, 1915).
T/C l-ho chnh:
- Tan/dd kim long; IR; UV (+) (l = pp o A
hoc HPLC); Gc quay cc ring (-5-6
o
, dm:
ethanol-NaOH 1N (2:1)
- V c ha cho p/ ca ion Na
- un vi H
2
SO
4
cho hi mu tm
- Cho p/ vi TT Ninhydrin
- Gc phenol: + FeCl3
CD: tr thiu nng gip, phng iu tr bu gip.
Natri (2S)-2-amino-3-[4-(4-hydroxy-3,5-
diiodophenoxy)-3,5-diiodophenyl]propanoat
88
Propylthiouracil
Propylthiouracil
2,3-dihydro-6-propyl-2-
thioxopyrimidin-4(1H)-on
NH
H
N H
3
C
O
S
Ngun gc: tng hp
T/C l-ho chnh:
- Tnh acid: kh tan/nc, tan/dd kim long
- V c ha = nc brom, x ion sulfat to thnh
- Dng mui kim cho ta, phc mu vi ion kloi
nng
- IR; UV (+) (l = pp o UV hoc HPLC, t =
SKLM)
L: pp o kim (NaOH 0,1N, CT o th)
CD: tr u nng gip.
89
Hormon
Hormon
tuy
tuy
n
n
t
t
y
y
&
&
thu
thu
c
c
t
t
ng
ng
h
h
p
p
i
i
u
u
tr
tr
ti
ti
u
u

ng
ng
Tuyn ty c nhng m t bo c bit gi l
o ty. Gia o l cc t bo tit ra insulin c
tc dng h ng huyt; xung quanh l cc t
bo tit ra glucagon c tc dng lm tng
ng huyt.
Insulin
L mt polypeptid gm 51 acid amin. iu ch
bng phn lp t tuyn ty ln, b. iu ch
insulin ngi bng cch bn tng hp t insulin
ln hoc b v bng cng nh ti t hp ADN.
Dng iu tr i tho ng typ 1. i vi o
tho ng typ 2, insulin ch dng khi cc bin
php khng c hiu qu.
Dng bo ch: Thuc tim.
90
THU
THU
C T
C T
NG H
NG H
P I
P I
U TR
U TR
I TH
I TH
O
O
NG
NG
Thuc tng hp iu tr bnh i tho
ng c tc dng iu tr i tho ng
typ 2. Theo cu to, c 4 nhm:
1. Cc sulfonylure nh: tolbutamid;
clopropamid; tolazamid; acetohexamid;
glibenclamid; glipizid; gliclazid.
2. Cc biguanid nh metformin.
3. Cc thiazolidindion nh pioglitazon;
rosiglitazon.
4. Cc cht c ch -glucosidase nh
acarbose.
91
C
C
c
c
sulfonylurea
sulfonylurea
Tnh cht l-ha chung:
Hp th UV
Tnh acid mui Na, sau kt ta vi
AgNO
3
, to phc mu vi ion kloi
Thy phn = acid CO
2
Thy phn = kim NH
3
V c ha = cht oxi ha: SO
4
-2
H
N C
O
H
N
R
S
O
O
Ar
92
GLIBEN
GLIBEN
-
-
CLAMID
CLAMID
Tnh cht:
Cng dng:
1-[4-[2-(5-cloro-2-methoxybenzamido)-
ethyl]benzensulfonyl]-3-cyclohexylurea
Kch thch t bo tit insulin, dng iu tr i
tho ng typ 2.
Dng bo ch: Vin nn 1,25 n 5mg.
Cl
OCH
3
C
O
NH CH
2
CH
2
SO
2
NH C
O
NH
- Khng tan trong nc v cc dm hu c, tan
trong cc dung dch kim long.
- C ha tnh chung ca nhm sulfonylure iu tr
i tho ng. pKa khong 5,3.
- nh lng = pp o kim, dm ethanol, cht chun
NaOH, ch th phenolphtalein.
93
1,1-dimethylbiguanid HCl.
METFORMIN
METFORMIN
Tnh cht l-ha v kim nghim:
Nhm biguanid:
+ Tc dng dd kim to NH3
+ Tc dng vi -naphtol trong mi trng kim v
natri hypobromid to mu hng.
+ Tnh base: t = TT alkaloid, l = pp o acid/mt khan
Nhm HCl kt hp:
+ nh tnh Cl-
+ L HCl kt hp = dd NaOH
C th dng IR hoc TLC nh tnh (hin mu =
thuc th l hn hp natri nitroprussiad v kali
fericyanid)
NH
N
H
N
NH
NH
2
H
3
C
CH
3
.HCl
94
Cng dng:
- Khng kch thch t bo tit insulin m tng
nhy ca insulin th th, tng s dng glucose
ngoi vi, gim tp glucose, tng d tr glycogen,
gim hp thu glucose gim ng niu.
Dng iu tr i tho ng typ 2, hay kt hp vi
sulfonylurea hoc insulin.
Lu : Metformin c c ch cnh tranh vi phc yu
t ni vitamin B12 trn th th ca n c th gy
thiu mu nu dng lu ngy.
NH
N
H
N
NH
NH
2
H
3
C
CH
3
.HCl
METFORMIN
METFORMIN
(
(
ti
ti
p
p
)
)

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