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

11/15/2013

1

PGS. TS. Nguyn Ngc Khi

BM. Dc lm sng, Khoa Dc

H Y Dc TP.H Ch Minh

1

S DNG THUC TRN I TNG C BIT

C th ha vic s dng thuc

2

Bnh Ngi bnh

Tnh trng sinh l

Tnh trng bnh l

DC NG HC

DC LC HC

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C th ha vic s dng thuc

3

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

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

4

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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

5

S dng thuc cho ph n c thai

6

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7

1957 1962

Thalidomid


8

Phn chia t bo

2 TB 4 TB 8 TB

Ti phi

6 ngy

< 17 ngy: gy sy thai,

nu thai vn pht trin khng b nh hng

Saladin: Anatomy & Physiology: The Unity of Form

and Function, Fifth Edition, The McGrawHill Companies, 2010

11/15/2013

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9

Tnh mch m

ng mch m

Saladin: Anatomy & Physiology: The Unity of Form and Function, Fifth Edition, The McGrawHill Companies, 2010


10

DD

qua dng bo

Dinh dng qua nhau thai

Pha

dng bo Pha

Nhau thai

TUN

Saladin: Anatomy & Physiology: The Unity of Form and Function, Fifth Edition, The McGrawHill Companies, 2010

11/15/2013

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11

Thuc (MW < 1000)

Thuc (MW >1000)

Khuch tn th ng

Khuch tn th ng

Lp dng bo

Mao mch bo thai

Mu t m

Protein

vn chuyn

Vn chuyn thuc qua nhau t m sang thai nhi

James M Ritter, A Textbook of Clinical Pharmacology and Therapeutics, Hodder Arnold, 2008


12

1757 ngy: Thi k phi/to thnh c quan

Thalidomid Androgen ACEI

Cc thuc c t bo Progestogen Carbamazepin

Ru Danozol Carbimazol

Warfarin Diethylstilbestrol Phenytoin

Retinoid ng v phng x

Thuc chng ng kinh Vi loi vaccin sng

Ribavarin Lithium

Cc thuc c kh nng gy qui thai

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13

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


14

Tc dng ca thuc trn bo thai v tr s sinh

Thuc Tc dng c th c Ghi ch

ACEI Thiu oxy mu (thai nhi v

tr s sinh), h huyt p, ri

lon chc nng thn, thiu

i, chm tng trng trong

t cung

Theo di thai nhi nu

iu tr lu di trong

ba thng th hai

hoc th ba

-blocker nh

atenolol

Chm nhp tim tr s sinh,

h huyt p v tng ng

huyt

Triu chng thng

nh v ci thin trong

vng 48 gi. Khng

c tc dng lu di

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15


Corticosteroid

(liu cao)

c ch tuyn thng thn

thai nhi

Ph thuc liu v

khong cch iu tr

NSAID ng ng ng mch sm

(nh hng tun hon thai

nhi) v suy thn ca thai nhi

(gim lng nc tiu)

Trnh s dng sau

tun 28. Nu phi s

dng, theo di

thng xuyn tun

hon thai nhi

Opioid Triu chng cai thuc tr

s sinh

Suy h hp

Nguy c nu s

dng lu di

Nguy c nu s

dng gn khi sinh



16


Phenothiazin Triu chng cai thuc tr

s sinh v triu chng ngoi

thp thong qua

Quan st t nht 48

gi. Cc triu chng

c th ko di trong

vi tun

Thuc chng

trm cm ba

vng (TCA)

v SSRI

Triu chng cai thuc tr

s sinh

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


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17

ADME THUC

i ma Lm trng d dy Nhu ng rut

Cm ng CYP 450

Ch.ha

Hp thu

Th tch phn b Albumin huyt tng

N. thuc ( )

Thi tr Lu lng mu qua thn

James M Ritter,

A Textbook of Clinical Pharmacology

and Therapeutics, Hodder Arnold, 2008


18

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

ADME / A S hp thu

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19

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..)

ADME D / S phn b


20

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

ADME M / S chuyn ha

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21

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

ADME E / S thi tr


22

Phn loi theo FDA

A

B

C

D

X

Phn loi Australia

A

B1

B2

B3

C

D

X

Phn loi Thy in

A

B1

B2

B3

C

D

Phn loi thuc trn thai k

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23

Phn loi nh ngha

A dng rng ri cho PNCT c chng minh khng gy hi, d tt

B 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 C th gy tc dng c hi cho thai nhi do tc dng dc l Khng gy d tt

D B nghi ng hoc cho rng lm tng t l d tt hay hy hoi khng hi phc thai nhi

X Nguy c cao gy d tt, hy hoi vnh vin thai nhi

Phn loi thuc trn thai k Theo FDA


24

Phn loi nh ngha

A

Th lm sng trn 1 lng ln PNCT v khng c

bt k mt nguy c no trn bo thai.

B1 Th trn lm sng vi s lng PNCT gii hn v

th trn sc vt khng thy nguy c no.

B2

Th trn lm sng vi s lng PNCT gii hn

khng thy bt k mt nguy c no nhng th

nghim trn sc vt khng c y hay

khng c thc hin.

Phn loi thuc trn thai k Theo Australia

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25

Phn loi nh ngha

B3

Th trn lm sng vi s lng PNCT gii hn

m khng thy bt k mt nguy c no nhng

th nghim trn sc vt cho thy gia tng nguy

c trn bo thai.

C C hi trn bo thai hay tr s sinh m khng

gy ra d tt. Tc dng c th c o ngc.

D Thuc gy hoc tng nguy c ph hy bo

thai. Thuc cng c th c tc dng dc l ph.

X Khng s dng cho PNCT hay nghi ng c thai.

Phn loi thuc trn thai k Theo Australia


26

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

Nguyn tc dng thuc

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27

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

Nguyn tc dng thuc


28

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

Khng sinh

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29

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

Gim au


30

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

Thuc chng nn

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31

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

Thuc tr lot d dy


32

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

Thuc tim mch

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Sd thuc cho ngi ang cho con b

33


34

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

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35

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


36

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

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37

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.


38

Cc thuc lm tng tit sa

Thuc khng th th dopamin:

Domperidon (MOTILIUM)

Metoclopramid (PRIMPERAN)

Thuc tr ri lon tm thn: haloperidol, clopromazin,

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39

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.


40

Lu

C th dn n ng c tr s sinh nu thuc vo sa vi lng

c tc dng.

Thuc c t bo

Ergotamin

Octreotid

Thuc nhun trng kch thch

Sulphonylurea

Li tiu thiazid

Vitamin A/dn xut retinoid (vd etretinat)

Amiodaron

Aspirin

Benzodiazepin

Cloramphenicol

Ciclosporin

Ciprofloxacin

Cocain

Thuc nga thai

Nhng thuc khng s dng khi ang cho con b

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S dng thuc cho tr s sinh/tr em

41


42

Phn loi tui tr em

Phn loi tr em Tui

S sinh thiu thng (premature) Sinh khi < 38 tun thai

S sinh thng (newborn, neonate)

Di 1 thng tui

Tr 1 nm tui (infant, baby) T thng 1 12 thng tui

Tr nh (young child) > 1 n 6 tui

Tr ln (older child) > 6 n 12 tui

Thanh thiu nin (adolescent) > 12 n 18 tui

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43

ADME / A S hp thu ng ung (tr < 1 tui)

Yu t c im H qu

Acid dch v pH d dy cao

-Gim hp thu thuc c tnh

acid yu: aspirin, phenytoin,

phenobarbital

-Thi gian thuc lu d dy

lu

-Gim thi gian lu ca

thuc ti rut

Gim SKD theophylin

PTKD (SKD tr 1 tui: 50%,

tr ln , ngi ln 80%)

Tc lm rng d dy

Chm hn ngi ln

Nhu ng rut Mnh hn tr ln


44

ADME / A S hp thu ng ung (tr < 1 tui)

Yu t c im H qu

H enzym, acid mt

Cha hon chnh: amylase v

lipase thp

-Enzym amylase: khng phn

tch ester: cloramphenicol

palmitat

-Gim hp thu thuc, vitamin

tan /lipid

Nim mc tiu ha

Cha hon chnh

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45

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)


46

ADME / A S hp thu ng tim

Yu t c im H qu

C bp Nh

Kh bit chnh xc SKD

Ti mu Cha y

ng qua da

Yu t c im H qu

Da Mng Kh nng thm thuc mnh,

khng sd lidocain, corticoid... Nc ti da Cao (tr thiu

thng)

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47

ADME / A S hp thu

Tr s sinh:

Qua ng tiu ha: chm

Tim: tim tnh mch

Da mng v hp thu qua da c tnh ton thn nu s dng ch

phm ti ch (corticosteroid mnh)

ng tim / qua da


48

ADME / A S hp thu

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

ng trc trng

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49

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


50

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

.

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51

T l nc v dch ngoi bo

La tui Tng lng nc

(%)

Dch ngoi bo (%)

S sinh thiu thng 85 50

S sinh thng 75 45

3 thng 75 30

1 nm 60 25

Ngi ln 60 20

ADME D / S phn b


52

ADME M / S chuyn ha

Oxy ha,

Kh ha, Thy phn

Phn ng lin hp

PHN CC

CHUYN HA CHT

(D tan trong nc, thi tr ra khi c th)

GIM

GIM

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53

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


54

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)

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55

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

Tr sinh sm

48 gi 18 gi

5-22 ngy tui 6 gi

Tr sinh bnh thng

1-4 tun tui 3 gi

Ngi ln 2 gi

Giai on pht trin T1/2 ca gentamicin /huyt tng


56

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

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57

ADME E / S thi tr Phng trnh Schwartz

CrCl (mL/min/1,73 m2) = k (chiu cao - cm)/SCr

Tui k

Nh cn 1 tui 0,33

Sinh thng 1 tui 0,45

1-12 tui 0,55

14-21 tui (n) 0,55

14-21 tui (nam) 0,70

Schwartz et al. 1987.

/wEPDwU


58

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

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59

Tnh liu tr em

Tnh liu Tnh t liu ngi ln

p dng

Theo cn nng Ph bin nht

Theo tui Trng hp cn nng b thay i hay khng c o

Theo din tch b mt c th

Cn chnh xc: thuc tr ung th, thuc c khong tr liu hp


60

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.

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61

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


62

Nguyn tc dng thuc


Tr < 2 tui

Khng dng

Thuc tiu chy: diphenoxylat, loperamid

Thuc chng nn: metoclopramid (Primperan)

Thuc co mch: phenylpropanolamin, ephedrin,

pseudoephedrin

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63

Nguyn tc dng thuc


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.


64

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

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65

Nguyn tc dng thuc


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.


66


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.

Nguyn tc dng thuc

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67

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


68

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

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69

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

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