Su Dung Thuoc Tren Doi Tuong Dac Biet - PGS - Ts. Nguyen Ngoc Khoi

11/15/2013
S DNG THUC TRN I TNG C BIT

PGS. TS. Nguyn Ngc Khi
BM. Dc lm sng, Khoa Dc H Y Dc TP.H Ch Minh
C th ha vic s dng thuc
Bnh
Ngi bnh Tnh trng sinh l Tnh trng bnh l
DC NG HC DC LC HC
11/15/2013
C th ha vic s dng thuc

Cc i tng c bit
Tr em Ngi cao tui Ph n c thai
Ph n cho con b
Ngi suy gan Ngi suy thn
3
Mc tiu
1. Trnh by c s thay i v hp thu - phn b - chuyn ha thi tr ngi mang thai, tr em 2. Trnh by c nguyn tc s dng thuc nhng i tng ny 3. Trnh by c cch s dng mt s thuc chnh nhng i tng ny
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Ni dung
1.
S dng thuc cho ph n c thai /cho con b
2.
S dng thuc cho tr s sinh v tr em
S dng thuc cho ph n c thai
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Thalidomid
1957 1962

Phn chia t bo
2 TB
4 TB
8 TB
Ti phi 6 ngy
Saladin: Anatomy & Physiology: The Unity of Form and Function, Fifth Edition, The McGrawHill Companies, 2010
< 17 ngy: gy sy thai, nu thai vn pht trin khng b nh hng
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Tnh mch m ng mch m
Dinh dng qua nhau thai DD qua dng bo
TUN Pha dng bo Pha Nhau thai
10
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Vn chuyn thuc qua nhau t m sang thai nhi
Thuc (MW < 1000)
Mu t m
Khuch tn th ng Protein vn chuyn Khuch tn th ng
Thuc (MW >1000)
Lp dng bo Mao mch bo thai
James M Ritter, A Textbook of Clinical Pharmacology and Therapeutics, Hodder Arnold, 2008
11

1757 ngy: Thi k phi/to thnh c quan Cc thuc c kh nng gy qui thai Thalidomid Cc thuc c t bo Ru Warfarin Retinoid Thuc chng ng kinh Ribavarin Androgen Progestogen Danozol Diethylstilbestrol ng v phng x Vi loi vaccin sng Lithium
12
ACEI Carbamazepin Carbimazol Phenytoin
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Thi k thai
Cc c quan tip tc pht trin v hon thin Thai t nhy cm hn thi k phi Cc cht c lm gim tnh hon thin v cu trc v chc nng ca cc c quan: TKTW, mt, rng, tai, b phn sinh dc ngoi
13

Tc dng ca thuc trn bo thai v tr s sinh
Thuc ACEI Tc dng c th c Thiu oxy mu (thai nhi v lon chc nng thn, thiu i, chm tng trng trong t cung Ghi ch Theo di thai nhi nu ba thng th hai hoc th ba
tr s sinh), h huyt p, ri iu tr lu di trong
-blocker nh Chm nhp tim tr s sinh, Triu chng thng

atenolol h huyt p v tng ng huyt nh v ci thin trong vng 48 gi. Khng c tc dng lu di
14
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Thuc Corticosteroid (liu cao) NSAID Tc dng c th c c ch tuyn thng thn thai nhi ng ng ng mch sm (nh hng tun hon thai nhi) v suy thn ca thai nhi (gim lng nc tiu) Triu chng cai thuc tr s sinh Suy h hp Ghi ch Ph thuc liu v khong cch iu tr Trnh s dng sau tun 28. Nu phi s dng, theo di thng xuyn tun hon thai nhi Nguy c nu s dng lu di Nguy c nu s dng gn khi sinh
15
Opioid

Thuc Tc dng c th c Phenothiazin Triu chng cai thuc tr s sinh v triu chng ngoi thp thong qua Thuc chng trm cm ba vng (TCA) v SSRI Triu chng cai thuc tr s sinh Ghi ch Quan st t nht 48 gi. Cc triu chng c th ko di trong vi tun Nguy c nu s dng lu di v / hoc gn lc sinh. Quan st t nht 48 gi
Roger Walker, Clinical Pharmacy and Therapeutics, 5e, Churchill Livingstone, 2012
16
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ADME
i ma Lm trng d dy Nhu ng rut THUC
Hp thu
Th tch phn b Albumin huyt tng N. thuc ( ) Ch.ha Thi tr
James M Ritter, A Textbook of Clinical Pharmacology and Therapeutics, Hodder Arnold, 2008
17
Cm ng CYP 450
Lu lng mu qua thn

ADME / A S hp thu
Nhu ng rut, d dy gim 30-40% ba thng th 2 v 3 nh hng s hp thu ca thuc ung Thng kh ph nang, lu thng mu phi tng 30%, nim mc d xung huyt, lu lng mu da tng thn trong khi s
dng thuc ng h hp, bi ngoi da hay t m o

Gin mch ti ch, lng mu vo c vn v s ti mu vo m ngoi bin tng s hp thu khi tim bp tng Cui thai k, lung mu chm hn chi di tim vo mng, i s hp thu khng u, tim tay v vai hp thu tt hn
18
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ADME D / S phn b
Th tch mu ca m tng khong 20% gia thai k, khong 50% cui thai k v bnh thng li sau khi sinh nh hng s phn b (thuc tan nhiu trong nc) Nng albumin gim khng cn hiu chnh liu v nguyn
nhn ny
Lng m tng 3-4 kg tng th tch phn b cc thuc tan nhiu trong lipid (thuc ng , gy m..)
19

ADME M / S chuyn ha
Tng hot ng ca enzym cytochrom P450 CYP3A4, CYP2D6, CYP 2A6 v CYP 2C9 enzym uridin 5'-diphosphat glucuronosyltransferase (UGT)
(UGT1a1, UGT1A4 v UGT2B7)
Gim hot ng ca CYP1A2 and CYP2C19 Kh d on
20
10
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ADME E / S thi tr
Trong vng vi tun u ca thai k, tc lc cu thn (GFR) tng khong 50% v tip tc tng. Do , nhng loi thuc ny c bi tit ch yu khng thay i qua thn nh lithium, digoxin v penicilin
tng s thanh thi

nng n nh (steady state concentration) thp hn. Lu : Ampicilin Cefuroxim Ceftazidim Cefazolin Pipericilin Atenolol Sotalol Digoxin Lithium Dalteparin sodium Enoxaparin sodium
21

Phn loi thuc trn thai k
Phn loi theo FDA A B Phn loi Australia A B1 B2 Phn loi Thy in
A
B1 B2 B3
C
D X
B3 C
C D
D
X
22
11
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Phn loi A B nh ngha dng rng ri cho PNCT c chng minh khng gy hi, d tt c chng minh khng gy d dng trn sc vt. dng cho mt s lng c hn PNCT khng thy lm tng t l gy hi, d tt C th gy tc dng c hi cho thai nhi do tc dng dc l Khng gy d tt B nghi ng hoc cho rng lm tng t l d tt hay hy hoi khng hi phc thai nhi Nguy c cao gy d tt, hy hoi vnh vin thai nhi
23
Theo FDA
D X

Phn loi nh ngha Th lm sng trn 1 lng ln PNCT v khng c A bt k mt nguy c no trn bo thai. Th trn lm sng vi s lng PNCT gii hn v B1 th trn sc vt khng thy nguy c no. Th trn lm sng vi s lng PNCT gii hn khng thy bt k mt nguy c no nhng th B2 nghim trn sc vt khng c y hay khng c thc hin.
24
Theo Australia
12
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Phn loi nh ngha Th trn lm sng vi s lng PNCT gii hn m khng thy bt k mt nguy c no nhng B3 th nghim trn sc vt cho thy gia tng nguy c trn bo thai. C hi trn bo thai hay tr s sinh m khng C gy ra d tt. Tc dng c th c o ngc. Thuc gy hoc tng nguy c ph hy bo D X thai. Thuc cng c th c tc dng dc l ph. Khng s dng cho PNCT hay nghi ng c thai.
25
Theo Australia

Nguyn tc dng thuc
Kh nng nh hng xu cho pht trin thai nhi. Hu nh khng th xc nh cc nh hng nh
Thay i sinh l ca b m.
Kh khn trong nghin cu Nn gi nh tt c cc loi thuc c hi cho n khi c kim chng
26
13
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Nguyn tc dng thuc
Gim thiu dng thuc
S dng liu lng nh nht c hiu qu

Thai nhi l nhy cm nht trong ba thng u c hng dn v vic s dng thuc trong thai k Nguy c ca ht thuc l, ru, thuc khng k n
27

Khng sinh
Cc khng sinh an ton nht trong thai k l cc penicillin v cephalosporin Trimethoprim gy qui thai (l thuyt - i khng acid folic)
Aminoglycosid: gy c tnh trn tai.

Fluoroquinolon (Vd: ciprofloxacin): nn trnh Metronidazol (qui thai ng vt) cn nhc trong nhim trng huyt Khng virus: khng nn s dng
28
14
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Gim au
Paracetamol: gim au nh (aspirin) Ibuprofen: khng vim NSAID (khi cn)
Opioid qua nhau thai. Pethidin: gim au khi sinh c ch trung tm h hp
M nghin opioid
hi chng cai thuc cho tr

chlorpromazin
29

Thuc chng nn
Bun nn v i ma (ph bin trong giai on u) Khng dng thuc: chia nh ba n, nng cao u Promethazin hoc cyclizin: khng histamin,
Prochlorperazin: thay th thuc trn khi khng hiu qu

Metoclopramid: an ton v hiu qu (khi sinh, cui thai k), khng khuyn co s dng thng xuyn trong giai on u ca thai k
30
15
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Thuc tr lot d dy
Thuc khng acid: gim triu chng Cimetidin v ranitidin: khng nh hng thai nhi Sucralfat: khuyn co (khng hp thu) Omeprazol (+ c ch bm proton) khng d liu
Misoprostol: chng ch nh v gy sy thai
31

Thuc tim mch
Methyldopa hoc labetalol: Cao huyt p trong thai k Hydralazin: truyn nhm gim huyt p trong tin sn git Nifedipin phng thch c KS: c s dng i vi cao huyt p trong thai k Thuc li tiu: khng nn bt u iu tr c ch men chuyn angiotensin v i khng th th angiotensin II: khng s dng
32
16
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Sd thuc cho ngi ang cho con b
33

Vai tr ca sa m
Vi tr:
Dinh dng (carbohydrat, protein, lipid, acid amin, vitamin, khong cht), sc min dch, pht trin tr no, cc cht khc Vi ngi m: Tr li vc dng c, gim nguy c ung th v, c t cung
34
17
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Yu t nh hng n lng thuc qua sa m
Thuc dng ngi m: loi thuc, tnh cht ca thuc, liu dng, ng dng
Yu t lin quan n bi tit sa: lng sa sn xut (b nh

hng bi thc n, thuc) Lng sa thc t tr b
35

Yu t nh hng n lng thuc qua sa m
Thuc d vo sa Tan trong lipid
Phn t lng nh
Lin kt km protein huyt tng Base yu (pH sa< pH huyt tng)
Roger Walker, Clinical Pharmacy and Therapeutics, 5e, Churchill Livingstone, 2012
36
18
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Cc thuc lm gim tit sa
Estrogen: trong thuc nga thai Androgen Levodopa, bromocriptin Li tiu thazid IMAO Clomiphen: thuc tr v sinh Vitamin B6 liu cao Ergotamin, dihydroergotamin.
37

Cc thuc lm tng tit sa
Thuc khng th th dopamin: Domperidon (MOTILIUM) Metoclopramid (PRIMPERAN) Thuc tr ri lon tm thn: haloperidol, clopromazin,
38
19
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Nguyn tc s dng
Hn ch s dng thuc. Chn thuc an ton cho tr b m, t l qua sa thp, thi tr
nhanh.
Trnh dng thuc liu cao, ko di. Cn nhc li ch/ nguy c. Nn cho tr b trc khi dng thuc.
39

Lu
C th dn n ng c tr s sinh nu thuc vo sa vi lng c tc dng. Nhng thuc khng s dng khi ang cho con b Amiodaron Aspirin Thuc c t bo Ergotamin
Benzodiazepin
Cloramphenicol Ciclosporin Ciprofloxacin Cocain Thuc nga thai
Octreotid
Thuc nhun trng kch thch Sulphonylurea Li tiu thiazid Vitamin A/dn xut retinoid (vd etretinat)
40
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S dng thuc cho tr s sinh/tr em
41

Phn loi tui tr em
Phn loi tr em
S sinh thiu thng (premature) S sinh thng (newborn, neonate) Tr 1 nm tui (infant, baby) Tr nh (young child) Tr ln (older child) Thanh thiu nin (adolescent)
Tui
Sinh khi < 38 tun thai Di 1 thng tui T thng 1 12 thng tui > 1 n 6 tui > 6 n 12 tui > 12 n 18 tui
42
21
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ADME / A S hp thu
Yu t Acid dch v Tc lm rng d dy c im pH d dy cao
ng ung (tr < 1 tui)

H qu
Nhu ng rut
-Gim hp thu thuc c tnh acid yu: aspirin, phenytoin, phenobarbital Chm hn ngi ln -Thi gian thuc lu d dy lu -Gim thi gian lu ca Mnh hn tr thuc ti rut Gim SKD theophylin ln PTKD (SKD tr 1 tui: 50%, tr ln , ngi ln 80%)
43

ADME / A S hp thu
Yu t c im
Cha hon chnh: amylase v lipase thp
ng ung (tr < 1 tui)

H qu
H enzym, acid mt
-Enzym amylase: khng phn tch ester: cloramphenicol
palmitat Nim mc tiu ha Cha hon chnh -Gim hp thu thuc, vitamin tan /lipid
44
22
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ADME / A S hp thu
Tr em: ung (lng) Km chnh xc v liu lng Hp thu nhanh hn Lu cc thuc c tc dng ph nng cao v khng hiu qu nu nng y thp (carbamazepin v theophylin).
ng ung (tr < 1 tui)
45

ADME / A S hp thu
Yu t C bp c im Nh Kh bit chnh xc SKD
ng tim
H qu
Ti mu
Cha y
ng qua da
Yu t Da Nc ti da c im Mng Cao (tr thiu thng) H qu Kh nng thm thuc mnh, khng sd lidocain, corticoid...
46
23
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ADME / A S hp thu
Tr s sinh:
Qua ng tiu ha: chm Tim: tim tnh mch
ng tim / qua da
Da mng v hp thu qua da c tnh ton thn nu s dng ch phm ti ch (corticosteroid mnh)
47

ADME / A S hp thu ng trc trng
Khi khng dng c ng ung: ang m, i ma,

nhu ng rut chm / tng nhanh hay t ng ht mi-d dy. Trnh c chuyn ha pha 1 qua gan Tr s sinh: cha d liu, gy chn thng C ch trong nhiu trng hp H st: paracetamol An thn: cloralhydrat Chng co git: diazepam To bn: glycerin
48
24
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ADME / A S hp thu
Nim mc rt mng, nhiu mch mu Thuc gy co mch, hp thu nhanh mnh c th gy ng c Cc thuc naphazolin, ephedrin, pseudoephedrin: khng dng tr < 2 tui
Nim mc mi
49

ADME D / S phn b
Lng m: tng i thp + Lng nc: cao Gim phn b cc thuc tan trong cht bo (v d: diazepam) Albumin huyt tng thp + Tnh cht gn kt thay i Gn kt thuc - protein huyt tng gim tr s sinh Tng tnh thm qua hng ro mu no tng nguy c tc dng ph trn thn kinh trung ng .
50
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ADME D / S phn b T l nc v dch ngoi bo
Dch ngoi bo (%) 50 45 30 25 20
51
La tui S sinh thiu thng S sinh thng 3 thng 1 nm Ngi ln
Tng lng nc (%) 85 75 75 60 60

ADME M / S chuyn ha
Oxy ha, Kh ha, Thy phn
GIM
PHN CC Phn ng lin hp
GIM
CHUYN HA CHT (D tan trong nc, thi tr ra khi c th)

52
26
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ADME M / S chuyn ha
Enzym mono-oxygenase: 2-40% so vi ngi ln Glucoronosyltransferase lin hp morphin, cloramphenicol, bilirubin: hon thin khi tr 3 tui Tuy nhin: c dao ng, khng phi l quy lut
53

ADME M / S chuyn ha
Mi sinh: enzym gan cha pht trin (tr non thng) Cloramphenicol "hi chng xm Sau 4 tun: Pht trin nhanh T l gan / trng lng c th > 50% so vi ngi ln Tng chuyn ha Thuc iu tr ngi m kch thch enzym tr s sinh (v d: barbiturat)
Phenobarbiton chuyn ha nhanh

(do cm ng enzym gan ln hn)
54
27
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ADME E / S thi tr
Thn (lc, bi tit v ti hp thu): gim tr s sinh Tc lc cu thn (GFR) tng nhanh trong bn tun u tin thay i trong thi tr thuc
Giai on pht trin

Tr sinh sm 48 gi
T1/2 ca gentamicin /huyt tng

18 gi
5-22 ngy tui

Tr sinh bnh thng 1-4 tun tui Ngi ln
6 gi
3 gi 2 gi
55

ADME E / S thi tr
Tui GFR - lc cu thn (mL/pht) B s sinh thng B 2 thng tui B 6 thng tui B 3 tui Ngi ln 30 - 40 70 - 80 100 - 110 100 - 150 120 - 150
56
28
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/wEPDwU

Phng trnh Schwartz
ADME E / S thi tr
CrCl (mL/min/1,73 m2) = k (chiu cao - cm)/SCr Tui Nh cn 1 tui Sinh thng 1 tui 1-12 tui 14-21 tui (n) 14-21 tui (nam) k 0,33 0,45 0,55 0,55 0,70
57
Schwartz et al. 1987.

Tnh liu tr em
Tr < 1 tui: (Fried) Liu = tui (thng) x liu ngi ln/ 150 Tr > 1 tui: (Young) Liu = tui (nm) x liu ngi ln/ (tui + 12) Tr > 2 tui: (Clark) Liu = cn nng (kg) x liu ngi ln/ 70 Tr bo ph tnh theo cn nng l tng (CNLT) CNLT = [chiu cao (cm)2 x 1,65]/ 1000 Thuc c khong tr liu hp, tnh theo din tch da Liu = Din tch da (m2) x liu ngi ln/ 1,8
58
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Tnh liu tr em
Tnh liu Tnh t liu ngi ln
p dng
Theo cn nng Theo tui Theo din tch b mt c th
Ph bin nht Trng hp cn nng b thay i hay khng c o Cn chnh xc: thuc tr ung th, thuc c khong tr liu hp
59

Nguyn tc dng thuc
Tr em khng phi l ngi ln thu nh

1. S cn thit ca iu tr Nhim virus, khng cn dng khng sinh Nhiu bnh tr em t khi khng cn iu tr Khng dng ba bi cloramphenicol, sulfamid.
60
30
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Nguyn tc dng thuc
2. La chn thuc thch hp
Tr s sinh Chloramphenicol c cao tr s sinh, ch dng trong nhng trng hp ring bit (vim np thanh qun, mng no do H. influenzae) Sulfamid gy vng da nhn no tr s sinh Camphor, menthol: lit h hp Thuc co mch naphazolin, ephedrin: tng huyt p, v m hi, tm ti
61

Nguyn tc dng thuc
2. La chn thuc thch hp
Tr < 2 tui Khng dng Thuc tiu chy: diphenoxylat, loperamid Thuc chng nn: metoclopramid (Primperan) Thuc co mch: phenylpropanolamin, ephedrin,
pseudoephedrin
62
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Nguyn tc dng thuc
2. La chn thuc thch hp Tr < 6 tui Khng dng Tetracylin ph hy men rng (< 7 tui) Aspirin h st gy hi chng Reye (nn dng paracetamol) Codein, dn cht thuc phin (cn anticholeric, paregoric). Khng dng ba bi cloramphenicol, sulfamid.
63

Nguyn tc dng thuc
3. La chn ng dng thuc thch hp Tr s sinh Tim tnh mch. Liu chnh xc lng, ch n s cn bng dch Tr em di nm tui: c th kh nut Ung ch phm hng / v d chu Ch phm lng
64
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Nguyn tc dng thuc
3. La chn ng dng thuc thch hp Bi da CORTICOID C th tng ng dng ton thn c ch trc h i - tuyn yn - thng thn: Chm ln HC Cushing Cc loi tinh du, menthol, long no, methyl salicylatgy suy (lit) h hp.
65

Nguyn tc dng thuc
3. La chn ng dng thuc thch hp Bnh xt (salbutamol): thng ch sd tr em trn 10 tui Nh hn: spacer Tim bp ch c s dng khi cn thit (au hn) S dng t trc trng: khi tim tnh mch kh khn. tr b i ma.
66
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Lu
Nhng khc bit v p ng thuc tr em (thng tr < 1 tui) H thn kinh trung ng
H tim mch
H thng iu ha thn nhit D ng da
67

Lu
Tc dng khng mong mun bt thng tr em Chm ln: corticoid. Xm rng vnh vin: tetracyclin. Tng p lc s no: corticoid, acid nalidixic, qu liu vitamin A, vitamin D, nitrofurantoin Vng da: novobiocin, sulfamid, vitamin K3. Dy th sm: androgen. Bin dng sn khp: fluoroquinolon
68
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Tc dng ph
Tc dng bt li ca cc loi thuc tr em c tng t nh ngi ln.
Ngoi ra: Corticosteroid mn (bao gm c liu cao corticosteroid dng ht) c ch tng trng. Aspirin: trnh sd tr em di 16 tui hi chng Reye Tetracyclin xng v rng Fluoroquinolon tn hi sn
69
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Su Dung Thuoc Tren Doi Tuong Dac Biet - PGS - Ts. Nguyen Ngoc Khoi

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Su Dung Thuoc Tren Doi Tuong Dac Biet - PGS - Ts. Nguyen Ngoc Khoi

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11/15/2013

S DNG THUC TRN I TNG C BIT

C th ha vic s dng thuc

Ngi bnh Tnh trng sinh l Tnh trng bnh l

C th ha vic s dng thuc

S dng thuc cho ph n c thai /cho con b

S dng thuc cho tr s sinh v tr em

S dng thuc cho ph n c thai

S dng thuc cho ph n c thai

S dng thuc cho ph n c thai

< 17 ngy: gy sy thai, nu thai vn pht trin khng b nh hng

S dng thuc cho ph n c thai

S dng thuc cho ph n c thai

Dinh dng qua nhau thai DD qua dng bo

TUN Pha dng bo Pha Nhau thai

S dng thuc cho ph n c thai

Thuc (MW >1000)

Lp dng bo Mao mch bo thai

S dng thuc cho ph n c thai

ACEI Carbamazepin Carbimazol Phenytoin

S dng thuc cho ph n c thai

S dng thuc cho ph n c thai

tr s sinh), h huyt p, ri iu tr lu di trong

-blocker nh Chm nhp tim tr s sinh, Triu chng thng

S dng thuc cho ph n c thai

S dng thuc cho ph n c thai

S dng thuc cho ph n c thai

Lu lng mu qua thn

S dng thuc cho ph n c thai

dng thuc ng h hp, bi ngoi da hay t m o

S dng thuc cho ph n c thai

S dng thuc cho ph n c thai

(UGT1a1, UGT1A4 v UGT2B7)

Gim hot ng ca CYP1A2 and CYP2C19 Kh d on

S dng thuc cho ph n c thai

tng s thanh thi

S dng thuc cho ph n c thai

S dng thuc cho ph n c thai

S dng thuc cho ph n c thai

S dng thuc cho ph n c thai

S dng thuc cho ph n c thai

S dng thuc cho ph n c thai

Gim thiu dng thuc

S dng liu lng nh nht c hiu qu

S dng thuc cho ph n c thai

Aminoglycosid: gy c tnh trn tai.

S dng thuc cho ph n c thai

Opioid qua nhau thai. Pethidin: gim au khi sinh c ch trung tm h hp

hi chng cai thuc cho tr

S dng thuc cho ph n c thai

Prochlorperazin: thay th thuc trn khi khng hiu qu

S dng thuc cho ph n c thai

Misoprostol: chng ch nh v gy sy thai

S dng thuc cho ph n c thai

Sd thuc cho ngi ang cho con b

Sd thuc cho ngi ang cho con b

Sd thuc cho ngi ang cho con b

Yu t lin quan n bi tit sa: lng sa sn xut (b nh

Sd thuc cho ngi ang cho con b

Sd thuc cho ngi ang cho con b

Sd thuc cho ngi ang cho con b

Sd thuc cho ngi ang cho con b

Sd thuc cho ngi ang cho con b