9/12/15

PHN NG C HI CA THUC
(Adverse Drug Reaction)

ThS. Nguyn Nh H
TS. Bi Th Hng Qunh

Mc tiu
1. Trnh by c nh ngha v phn loi ADR
2. Trnh by c nguyn nhn v cc yu t nh hng
ca ADR
3. Trnh by c nh ngha, mc tiu v cc lnh vc u
tin ca cnh gic dc
4. Trnh by c cc phng thc theo di tnh an ton
ca thuc trn th trng

9/12/15

Ni dung
1

Khi nim ADR

Phn loi ADR

Nguyn nhn ca ADR

Yu t lm tng nguy c pht sinh ADR

i cng v Cnh gic dc

Pht hin, nh gi, d phng ADR

1. KHI NIM ADR

9/12/15

Ca lm sng
BN nam 78 tui, gn y phu thut t stent, nong
ng mch vnh.
Thuc ang s dng: sintrom (acenocumarol 4 mg
vin 1 ngy, 3 thng), enalapril 10 mg x 1 ln/ngy.
Nhp vin v chy mu chn rng khng cm c. INR
khi nhp vin = 10.
Vn ca BN l g???

Khi nim ADR

WHO
L phn ng:
- c hi
- khng c nh trc,
- xut hin liu thng dng cho ngi
phng, chn on, cha bnh hoc nhm thay
i mt chc nng sinh l
6

9/12/15

Khi nim ADR

Hip hi dc s M (ASHP) 1995
ADR l bt k p ng no khng mong i, khng d tnh
trc ca mt thuc m:
1.Cn ngng dng thuc
2.Cn thay i liu trnh iu tr
3.Cn i liu
4.Cn nhp vin iu tr
5.Cn iu tr h tr
6.Gy phc tp cho chn on
7.nh hng xu ti tin lng bnh
8.Hoc dn n tn thng tm thi hoc lu di, gy tn tt, t
vong

Mt s thut ng
Tc dng ph ca thuc (side effects)
Phn ng c hi ca thuc (adverse drug reactions)
Bin c c hi ca thuc (adverse drug events-ADEs)
Sai st trong dng thuc (medication errors)
Tai bin do thuc (drug misadventures)

9/12/15

Tc dng ph (side effects)

L tc dng (ca thuc):
khng nh trc
xy ra liu thng dng ngi
lin quan n c tnh dc l ca thuc.
TDP c th c li , c th tr thnh tc dng iu tr.
Sildenafil citrat (Viagra R)
Ban u th nghim iu tr tng huyt p v au tht
ngc ! TN pha I - hiu qu trn t nhng c th gy cng
dng ! C iu tr ri lon cng dng

Bin c c hi ca thuc
(Adverse drug events)
L bt k mt bin c no:
- Xy ra trong qu trnh s dng thuc khi iu tr
- Khng nht thit l do phc iu tr gy ra.
(nguyn nhn khng xc nh r do - bnh? thuc?...?)
VD:
BN ang dng thuc b sung st c , i cu ra phn en,
ngoi ra c tin s vim d dy ! ?

9/12/15

ADR vs. ADE

Diseases

Adverse Event

Diet

Genetics
Adverse Drug Reaction
(event attributed to drug)

Other
factors

Other Drugs
Events not attributed to drug

Environment

Compliance

11

Sai st trong iu tr
(medication errors)
L nhng bin c:
Phng nga c
C th dn n vic dng thuc khng thch hp hoc gy
hi cho BN
khi thuc ang c kim sot bi nhn vin y t, bnh nhn.
(National Coordinating Council for Medication Error Reporting and Prevention)

12

9/12/15

Sai st trong iu tr
(medication errors)
Vit tay kh c

Sai st trong iu tr
(medication errors)
ng gi hoc
ghi nhn tng
t
Sound alike,
look alike

14

9/12/15

Tai bin do thuc

15

Dch t ADR
T sut ph thuc vo phng php
nc, dn s v nh ngha v ADR
Nguyn nhn hng u, ng hng
th 4-6 gy t vong BN nhp vin
0,3% - 7% cc trng hp nhp vin

100.000

ngi M t

vong/nm
1,5

triu ngi nhp vin/

nm do ADR

6,7% b ADR nghim trng

* JAMA. 1998;279:1200-1205

30-60% ADR
c th c phng nga

16

9/12/15

Mt s thuc thng gy ADR

Khng sinh
Thuc tr ung th
Thuc chng ng mu
Thuc tim mch
Thuc h ng huyt
NSAID/thuc gim au
Thuc trn TKTW

17

H c quan thng b nh hng

H to mu
TKTW
Da/d ng
Chuyn ha
Tim mch
Tiu ha
Thn/Tit niu
H hp

18

9/12/15

2. PHN LOI ADR

Phn loi ADR

1. Theo tn sut xut hin
2. Theo mc nng
3. Theo thi gian khi pht
4. Theo biu hin lm sng
5. Theo mi quan h nhn qu (WHO)
6. Theo tc dng dc l

20

10

9/12/15

Phn loi ADR

Theo tn sut xy ra ADR

Him gp

t gp

Thng gp

ADR < 1/1000

1/1000 1/100

ADR > 1/100

(Dc th quc gia Vit Nam)

21

Phn loi ADR

Theo mc trm trng
Nh: Khng cn iu tr, gii c, thi gian nm vin khng
ko di
Trung bnh: C cn thay i iu tr, cn T c hiu, hoc
nm vin 1 ngy)
Nng: e da tnh mng, gy bnh lu di hoc cn chm
sc tch cc
T vong
22

11

9/12/15

Phn loi ADR

Phn ng c hi nghim trng ca thuc (FDA): L cc
phn ng c hi dn n mt trong nhng hu qu
t vong
e da tnh mng
phi nhp vin hoc ko di thi gian nm vin
li di chng nng n hoc vnh vin
gy d tt bm sinh thai nhi
cc hu qu tng t khc

23

Phn loi ADR

Theo thi gian khi pht
Cp tnh: (0 60 pht)

(4,3%)

Vd: PNC-G gy shock phn v

Bn cp: (1 24 gi)

(86,5%)

Vd: Sulfonamid gy nga, d ng

Chm :

(> 1 ngy)

(3,5%)

Vd: Corticoid gy hi chng Cushing

Aronson JK. Meyler's side effects of drugs. 15th.2005
24

12

9/12/15

Phn loi ADR

Theo mi quan h nhn qu - WHO (1998):
Chc chn
C kh nng
C th
Khng chc chn
Khng phn loi
Khng th phn loi
25

Phn loi ADR

Theo tc dng dc l (Rawlins & Thompson 1977)
TIU CHUN SO SNH

LOI A

LOI B

C th d on da vo
tc dng dc l

Khng

Ph thuc liu s dng

Khng

T l mc bnh

Cao

Thp

T l t vong

Thp

Cao

Hng gii quyt

(iu tr)

iu chnh liu

Ngng thuc

Pht hin

Giai on nc lm sng

Him

26
Talbot J. Stephens detection of new adverse drug reactions. 5th ed, 2004. p.92

13

9/12/15

Phn loi ADR

}

Theo tnh cht ca ADR m rng

A (augmented)

Gia tng

B (bizarre)

Bt thng

C (continuous)

Mn tnh

D (delayed)

Tc ng chm

E (ending of use)

Hi chng ngng thuc

F (failure of efficacy)

Khng hiu qu
27

Phn loi
- Theo tnh cht ca ADR m rng:
Loi

nh ngha

V d

A
(Augmented)

Gia tng

C th d on c
Ph thuc vo liu dng.
Thng gp
Him khi gy t vong.

H ng huyt do tim insulin

Chm nhp tim do chn beta
Xut huyt do warfarin

B (Bizarre)

L thng

Khng d on dc
Khng lin quan n liu
Khng thng gp
T l t vong cao..

Phn ng d ng vi penicillin
Hoi t t bo gan cp do halothan
Suy ty do chloramphenicol

C
(Continuous)

Mn tnh

L phn ng xy ra sau mt thi

gian iu tr lu di.

Hi chng Cushing do prednisolon

Ri lon chc nng i trng do thuc
x.

D
(Delayed)

Chm

L phn ng xut hin sau khi

ngng iu tr trong mt thi gian

Ung th do tc nhn alkyl ha trong

iu tr Hodgkin.
D dng xng mt tr em c m
dng isotrtinoin

E
(Ending of
use)

Hi chng
ngng
thuc

L phn ng xy ra sau khi ngng

dng thuc, c bit khi ngng t
ngt.

Suy tuyn thng thn sau khi dng

prednisolon.
Co git khi ngng dng phenobarbital
28
hay phenytoin.

14

9/12/15

29

30

15

9/12/15

Diethylstilbestrol (DES)
Estrogen tng hp
a vo th trng
1938
Ch nh: Phng sy
thai
USA: >3 triu ph n
s dng t nm
1940-1970

3. NGUYN NHN (C CH)

GY ADR

16

9/12/15

Nguyn nhn
1. V bo ch thuc
2. Thay i v dc ng hc
3. Thay i v dc lc hc

33

ADR Type A
Nguyn nhn v bo ch
1. Hm lng thuc
2. c tnh phng thch hot cht
Vd:
- Vin indomethacin (Osmosin) phng thch c kim sot b rt khi th
trng do t l cao gy xut huyt tiu ha
- vin nn KCl ! XHTH ! vin gii phng chm trnh to nng
cao ti ch
34

17

9/12/15

ADR Type A
Nguyn nhn v DH: Lm tng nng thuc trong
huyt tng v m ch
1.Hp thu: thc n, thuc,
nhu ng d dy-rut,
chuyn ha qua gan ln u
2.Phn b: thay i lu lng mu,
t l lin kt protein huyt tng,
tch ly thuc m
3.Chuyn ha: tc thy phn
hoc acetyl ha, hot tnh men gan
4.Thi tr: Gim lc cu thn

35

Induction :
- Overdose
- Alcohol
- Isoniazid
- Phenobarb.

PARACETAMOL
- Glucuronidation (50-60%)
- Sulfation (25-35%)

Cytochromes
P4501A2
P4502E1

GLUCURONIDE AND
SULFATE METABOLITES

TOXIC METABOLITE
(NAPQI)

Alcohol
fasting

Glutathione GSH
(2-4%)
MERCAPTURIC AND
CYSTEINE CONJUGATES

Source : Carl A. Burtis (1150)

Glutathione
deficiency

Hepatotoxicity

18

9/12/15

ADR Type A
Nguyn nhn v DLH: Lin quan receptor
1.

S nhy cm vi th th
Cafein gy mt ng

2.

S lng th th
Corticoid v th th bo tng

3.

C ch t iu ha sinh l
Atropin v nhp tim nhanh
-blocker v nhp tim chm
37

V d
Nguyn
nhn

V d

Tai bin

C ch

Dng bo
ch

Osmosin
(indomethacin SR)

Xut huyt

Nng phng thch

cht c hot tnh ti
rut cao

DH (*)

Digoxin

Bun nn, lon

nhp

Gim thi tr BN
suy thn

DLH

Indomethacin

Suy tht tri

mui nc

Tng tc
thuc (*)

Terfenadin v
erythromycin

Ko di khong
QT v xon nh

Ery c ch chuyn
ha terfenadin

(*) C th nh hng hp thu, phn b, chuyn ha, thi tr

38

19

9/12/15

ADR Type B
Nguyn nhn v bo ch
1. Sn phm chuyn ha hoc b phn hy
Vd: Sd Tetracyclin hi chng Fanconi
(tng bi tit a.a, glucose, aceton qua ng tit niu, tng nit amino trong huyt tng v tng nhy
cm nh sng)

2. T dc: cht mu, cht bo qun

Vd: DEG lm cht ha tan sulphanilamide
3. Sn phm ph trong qu trnh tng hp thuc
39

4. 3.

Tc dng ca t dc gy ADR

Cn ngt sulfanilamide
DEG lm cht ha tan
Gy c trn din rng ti M nm
1937, khin hn100 ngi t vong

Elixir Sulfanilamide
SE Massengil Co

" 1938, thng qua Federal Food Drug & Cosmetic Act, qui nh
yu cu th nghim c tnh ca thuc mi.

40

20

9/12/15

ADR Type B
Nguyn nhn v Dc lc hc:
1. Phn ng c ng (idiosyncratic) do di truyn
Thiu mu tan huyt ngi thiu G6PD ca hng cu: sulfonamid v
sulfon, nitrofurantoin, chloramphenicol, primaquin,

Tng nhit c th c tnh: Thuc gy m (halothan), gin c

(suxamethonium)

Vng da mt: thuc trnh thai ung

Thiu mu bt sn: cloramphenicol

2. Phn ng d ng do min dch

Cht l
Tp cht
Hapten
41

Thiu enzyme G6PD " thiu mu tn huyt do

primaquin, isoniazid

To gluthation

Men G6PD

42

21

9/12/15

4. YU T LM TNG NGUY C
PHT SINH ADR

u
Tui
Gii
Bnh km theo
Tin s d ng thuc
hoc phn ng vi thuc
45

22

9/12/15

Tui

Tr s sinh v ngi cao tui nguy c cao

Tr s sinh

Ngi cao tui

Cha y cc enzym lin quan

Lm dng thuc

n chuyn ha
Thi tr thuc cha y
VD: sulfamid (vng da - y bilirubin
ra khi protein)
cloramphenicol (xanh xm do

Suy gim chc nng c quan

(gan, thn)
Nhiu bnh km
Dng nhiu thuc, tng tc
thuc

thiu phn ng lin hp vi

a.glucoronic))

Tui

47

23

9/12/15

Gii
N c nguy c b ADR cao gp 1,5-1,7 ln nam gii
Vd
Thuc ko di khong QT
Lon to mu vi phenylbutazone v cloramphenicol

Bnh km theo
Suy gan thn
BN b AIDS: d b phn ng da nng vi cotrimoxazol
48

Nng theophylline / mu

g/ml

X gan
Bo

L
ch
n
g

ph

Tr
em
T.Gian

49

24

9/12/15

Chng tc, a hnh ku gen

Cc kiu hnh
ngi chuyn ha km
ngi chuyn ha nhanh
ngi chuyn ha siu nhanh

Yu t nguy c

c tnh ca thuc, T
dc
S dng nhiu thuc
Dng thuc liu cao,
ko di
51

25

9/12/15

Thuc
T dc (CaSO4 lactose)

Australia -1960s

ADR: rung gin nhn cu,nhn i, song th, khng kim sot li ni, mt cn bng , tr nh
52
ln ln, chm vn ng, tng tn sut ng kinh, tng ng huyt

ADR Frequency by Drug Use

60

Tn sut (%)

50
40
30
20
10
0

0-5

6-10

11-15

16-20

S lng thuc
May FE. Clin Pharmacol Ther 1977;22:322-8

53

26

9/12/15

Kt hp thuc
Tng tc thuc

Nguy c

Thi gian
c td

Warfarin (Coumadin) +
ciprofloxacin,
clarithromycin,
erythromycin,
metronidazole, bactrim

Tng td ca
warfarin

Thng
trong vng
1 tun

i KS

Warfarin +
acetaminophen

Tng xut
huyt, tng
INR

Bt k

Sd liu paracetamol
thp nht c th v theo
di INR

Warfarin + acetylsalicylic Tng xut

acid (aspirin)
huyt, tng
INR

Bt k

Ti a 100 mg aspirin/
ngy v theo di INR

Warfarin + NSAID

Bt k

Trnh sd chung. Trng

hp cn thit, sd cht
C COX-2 v theo di
54
INR khi cn

Tng xut
huyt, tng
INR

Khuyn co

! Nguyn tc phng trnh ADR

1. Trnh s dng nhiu thuc nu c th
2. Nm vng thng tin v loi thuc (tnh cht dc l, tng tc, c ch
chuyn ha, ADR)
3. Nm vng thng tin v i tng bnh nhn, ts d ng, cc bnh l, bt
thng kiu gen
4. Theo di nhng thuc c khong tr liu hp; theo di BN sm pht
hin cc phn ng c hi x tr kp thi

55

27

9/12/15

Ca lm sng 2
BN n 78 tui, tin s bnh mch vnh, gn y
phu thut t stent, nong ng mch vnh.
Thuc ang s dng: clopidogrel 75mg, aspirin 75 mg,
atorvastatin 80mg, nicorandil 30 mg v atenolol 50 mg.
Thi quen: Ht thuc, b cch y 1 nm
BN than phin b i phn en v c mu, nng hn trong
2 ngy qua.
BN khng c tin s b bnh ng tiu ha
Vn ca BN l g???
56

Ca Lm sng 3
BN n 28 tui ang nm ICU sau khi phu thut rut tha b v. Sau phu
thut, BN c cho ni ng thng truyn tnh mch, b bt rt v p ng
vi phn ng au. 3 ngy nay BN khng i ngoi c v ting m rut yu.
Thuc s dng:
Piperacillin 3 g IV

q6h

Metronidazole 500 mg IV

q8h

Heparin 5000 units SQ

q12h

Morphine 1 mg/mL

5 mg/h

Lorazepam 1-2 mg IV

q2h prn

Vn ca BN l g???

57

28

9/12/15

5. CNH GIC DC
(PHARMACOVIGILANCE)

Cnh gic dc
Khoa hc v nhng hot ng lin quan n vic pht
hin, nh gi, x l v ngn nga phn ng bt li
hoc bt k s c no lin quan n thuc.
M rng:
i tng: sp sinh hc, dc liu, sn phm mu, dng c
y t v vaccin

Phm vi:
ADR
Thuc km cht lng
Ng c thuc
Lm dng hoc dng sai thuc
59

29

9/12/15

Tm quan trng ca vic theo di ADR sau khi

thuc ra th trng

Thm ha Thalidomide 1962

Hn 5000 ca vn cn sng trn th gii

60

Thalidomide l mt th d in hnh v tc hi ca
ng phn i hnh quang hc:
THALIDOMIDE

Dng
Hu truyn (D)

Dng
T truyn (L)
Lng rt nh

An thn, gy ng

Qui thai
61

30

9/12/15

CC GIAI ON NGHIN CU PHT TRIN THUC

Years

Preclinical Testing
Laboratory and animal testing

Discovery
(2-10 Years)

4
8

Phase II 100-300 patient volunteers

- efficacy and side effects

Phase I 20-80 healthy volunteers

safety and dosage

10
12

Phase III 1,000-5,000 patient volunteers

- adverse reactions for long-term use

14

FDA Review/Approval
16

Additional post-marketing testing

62

Tm quan trng ca vic theo di ADR sau khi thuc

ra th trng

So snh h c quan ch
th v chut (42 hp cht)
Ging nhau
24%
Tng t
33%
Khc nhau
43%
63

31

9/12/15

S khc bit gia cc th nghim trc khi thuc ra

th trng v thc t iu tr
V d 1:
Trc khi ra

Sau khi ra

th trng (%)

th trng (%)

Ngi > 65 tui

18-25

50-65

Ph n

20-44

40-58

5-8

17-20

T type II

(Wieringa N.PW 2002)

V d 2: rofecoxib
Trc khi ra th trng: 5000 BN
Nm u tin:
hng triu BN trn khp th gii
64

Gii hn ca cc th nghim trc khi thuc ra th

trng
Hn ch v i tng tham gia nghin cu:
Tr em
Ngi cao tui
Cc bnh km theo
Kt hp vi thuc khc
v c mu!!!
! Khng th d on c hon ton ADR ca thuc trong
giai on trc khi a thuc ra th trng
65

32

9/12/15

Thi gian pht hin ADR quan trng sau khi thuc bt
u xut hin trn th trng
ADR

Thuc

Nm

Thuyn tc mch phi

Trnh thai ng ung

Nhi mu c tim

Trnh thai ng ung

Vng da

Halothane

Vim rut kt

Lincomycin

Vim rut kt

Clindamycin

Thiu mu bt sn

Phenylbutazone

Venning, GR. Br. Med. J. 286:365-368, 1983

H qu
Thuc b rt khi th trng
Thuc b ngng cp mi
Thay i nhn toa thng tin

Mediator (benfluorex)
1976 ! 2009

1999 ! 2004

1978 2011 !

Ngy 30.8.2010, Cc Qun l dc VN mi c cng vn s 260/Q-QLD gi cc s

y t, cc bnh vin v vic rt s ng k i vi bit dc Mediator (hot cht 67
benfluorex), s ng k: VN-4519-07

33

9/12/15

1997 ! 2/2000 !
thm ADR xon nh

ADR:bin chng nng trn

h hp, suy h hp, trn thn
kinh tr <2 tui
2006-2007 (M, Canada)
2010 (Php), 2012 (VN) CC cho tr < 2 tui

1997 ! 2011 (rt khi th trng)

ADR trn thn kinh (ng kinh, run,
suy nhc) + tim mch (ri lon dn
truyn tht)

DEXTROPROPOXYPHEN
Aspirin < Dextropropoxyphen < Codein < Morphin
* Dextropropoxyphen c th gy h ng huyt v c
i vi tim, gy lon nhp tim
* B chuyn ha gan to thnh norpropoxyphen gy
run c v co git

DI-ANTALVIC

Lentogesic
2010

Doxyfene

69

34

9/12/15

Diethylstilbestrol (DES)
Estrogen tng hp
a vo th trng
1938
Ch nh: Phng sy
thai
USA: >3 triu ph n
s dng t nm
1940-1970

35

9/12/15

6. PHT HIN, BO CO, NH

GI ADR

Phng php pht hin ADR

Phng php

u im

Nhc im

Vd

Bo co t
pht
(Spontaneous
reporting
system SRS)

- Pht hin nhanh

- Phn ng him gp hoc
trc y cha bit
-Chi ph thp
- Hnh thnh gi thuyt (tn
hiu)

- Bo co t hn thc t
-D b nh hng bi
yu t nhiu
-Khng xc nh c t
l mc
-Cht lng d liu

-Med watch
-Lareb

Gim st tch
cc (Intensive
monitoring)

-Xc nh c t
l mc bnh
- Phn ng him
gp hoc trc y cha
bit

- Hn ch v s
lng thuc bo
co

Theo di vic
k n
(Prescription
event
monitoring)

Phng php
dch t

Xc nh c mi quan h Nc phc tp v tn km
gia thuc-ADR
- Kim sot c
i tng nc

Nc lm sng
pha IV

-NC on h
-NC bnh
chng
Nc RCT

74

36

9/12/15

Theo di tnh an ton ca thuc v bng chng

Thuc

Trovofloxacin

Phn ng c hi

Bng chng

Quyt nh ca c
quan c thm quyn

c gan

SRS ADR

Rt khi th trng

Tolcapone (PD) c gan

SRS ADR

Ngng s dng

Bupropion

SRS ADR

Cnh bo
Rt khi th trng

ng kinh
Tng tc thuc

Cerivastatin

Tiu c vn

SRS ADR

c ch COX II

Nguy c tim mch

Th nghim LS Cnh bo

SSRI

T t tr em

Th nghim LS Cnh bo km hng

dn s dng

From Pharmacovigilance; Risk Management- a European Regulatory View. J.M Raine. 2007.

Bo co ADR

76

37

9/12/15

Thc trng cng tc bo co ADR

-2014 7787 bo co (80 bo co/1 triu dn - tiu chun ca WHO: 200 bo

co/1 triu dn)
-Cht lng bo co cn km: bo co thiu thng tin; thng tin ghi trn bo co
cha r rng, cha chnh xc, mu thun, m, kh c...

77

C s bo co ADR nm 2014
S
TT
1
2
3
4
5
6
7
8
9
10

Tn bnh vin
Bch Mai
Phm Ngc Thch
a khoa Nng
Ph sn Trung ng
Vit Nam-Thy in
Ung B
a khoa Qung Ninh
Hng Vng
T D
Da Liu
Nhn Dn Gia nh

Tnh/Thnh
ph
H Ni
TP HCM
Nng
H Ni
Qung Ninh
Qung Ninh
TP HCM
TP HCM
TP HCM
TP HCM

S lng
bo co
340
305
157
155
154

T l %

135
127
115
112
106

1.7%
1.6%
1.5%
1.4%
1.4%

4.4%
3.9%
2.0%
2.0%
2.0%

BV i hc Y Dc TP HCM 85 bo co

38

9/12/15

Phn loi thuc nghi ng theo h dc l

(2014)
Stt

Nhm thuc

Tng s

T l %

Khng sinh beta-lactam khc (Cephalospori th

h 1 4, Carbapenem...)

2497

32. 1

Thuc iu tr lao

1030

13.3

Khng sinh nhm Aminoglycosid

594

7.6

Khng sinh nhm beta-lactam, h penicillin

545

7.0

Khng sinh nhm quinolon

512

6.6

Chng vim, chng thp khp

501

6.4

Thuc khng virus

472

6.1

Thuc gim au v h st khc

240

3.1

240

3.1

225

2.9

Thuc iu tr st rt
10 Cc khng sinh nhm khc

Thuc lin quan n ADR (2014)

Stt

Hot cht

Tng s

T l%

Cefotaxim

829

10.7

Streptomycin

451

5.8

Ceftriaxon

396

5.1

Ceftazidim

378

4.9

Diclofenac

353

4.5

Ciprofloxacin
Rifampicin/isoniazid/
pyrazinamid

291

3.7

230

3.0

Amoxicillin/acid clavulanic

201

2.6

Cefuroxim

179

2.3

10

Ethambutol

176

2.3

39

9/12/15

H thng theo di ADR

(H thng cnh gic dc)
- Nhn bo co ADR

WHO

- Tng hp v bo ng
- Khuyn co ADR, a ra nhng cnh gic

B y t

khi dng thuc hoc cm lu hnh

- Thu nhn cc bo co

Trung tm DDI&
ADR quc gia

- Phn tch thm nh

- Tng hp, nh gi t l li/ hi
- Gi bo co ln B Y t
- Phn hi v cung cp thm thng tin

Ban gim c bnh vin

H thng ADR c s
y t

Theo di bo co ADR trnh ban gim

c

81

H thng CGD VN
B Y t
Cc Qun l dc

Cc Qun l Khm Cha Bnh

TT DI & ADR
QG

TT DI & ADR
Min Nam

Cng ty SX v
phn phi dc phm

Bnh vin
Thng tin
Bnh nhn

82

40

9/12/15

Ai nn bo co
i tng bo co VN (2014)
Bc s Y s
Dc s
iu dng N h sinh
Khc
Khng c thng tin

BV HYD: iu dng: 68 (80%)

Bc s-Y t: 5 (5.9%)
Dc s
2 (2.4%)

83

Nhng ADR (hoc AE) cn bo co

Thuc mi: tt c ADR (k c nh)
Thuc c nghin cu y /bit r: ADR nghim trng
hoc cha c ghi nhn
ADR xut hin vi tn s tng
ADR nghi ng do tng tc
ADR trong lnh vc c bit: lm dng thuc, PNCT-CCB
ADR do dng qu liu, do sai st trong iu tr
84

41

9/12/15

Mt s nguyn tc
Cng sm cng tt
Phi ngh n cc yu t khc c th gp phn lm cho
phn ng xy ra
B sung nhng d liu mi, k c nhng d liu nghi
ng bng cc bo co b sung
Bo co c vit r rng, d c, d hiu

85

42

9/12/15

Bi tp in form mu bo co ADR (ca LS1)

Thng tin bnh nhn:
VD: BN Nguyn Vn T., nam 78 tui, a ch - TP HCM;
cn nng 76 kg

Thng tin v ADR:

M t s c (Nhp vin ngy () v chy mu chn rng
khng cm c)
Ngy lm bo co
Kt qu xt nghim lin quan (INR khi nhp vin 10)

Thng tin v dc phm b nghi ng

Thuc dng km v thi gian t
Thng tin v ngi bo co

43

9/12/15

Phng php nh gi ADR

Thang phn loi v quan h nhn qu
- Thang WHO
- Thang Naranjo

89

Ca lm sng 4
Bo co ca: BN nam 43 tui, iu tr vim tuyn tin lit bng
ofloxacin t 26/7/2012, v olanzapin t u nm 2010
16/8/2012: Xut hin ban nga lan khp c th, ph (mt, cc chi
di). Nga ci thin km khi dng khng H1
17/8/2012: Ngng s dng ofloxacin v olanzapin. iu tr bng
corticoid bi ti ch
18/8/2012: Tn thng da phc hi
Phn loi ADR?

44

9/12/15

Thut ton Naranjo

NI DUNG

1. Trc y, c bo co kt lun no v phn ng ny khng ?

+1

2. S c c hi c xy ra sau khi thuc nghi ng c s dng khng ?

+2

-1

3. Phn ng c hi c c ci thin khi ngng thuc b nghi ng hay dng mt lai

thuc i khng ? (DECHALLENGE)

+1

4. Phn ng c hi c xy ra li khi cho bnh nhn dng tr li khng ?

(RECHALLENGE)

+2

-1

5. C nhng nguyn nhn no khc c th gy ra phn ng ny khng ?

-1

+2

6. Phn ng c xy ra li khi cho dng gi dc khng ?

-1

+1

7. C pht hin thy thuc trong mu (hay dch sinh hc khc) nng c
khng ?

+1

8. Phn ng c trm trng hn khi tng liu hay suy gim khi gim liu ?

+1

9. Trc y, bnh nhn c phn ng tng t vi mt lai thuc tng t nh vy

khng ?

+1

10. Phn ng c hi c c xc nhn bi mt chng c r rt khng ?

+1

91

Thang im nh gi Naranjo
nh gi ADR
Chc chn c ADR
(Definite ADR)

C kh nng xy ra ADR

Thang im
9
5-8

(Probable ADR)

C th xy ra ADR

1-4

(Possible ADR)

Nghi ng c ADR
(Doubtful ADR)

92

45

9/12/15

Thang quy kt phn ng c hi ca WHO

QH nhn qu

Tiu chun nh gi

Chc chn

Phn ng c mi lin h cht ch vi thi gian sd thuc nghi ng

Khng th gii thch bng tnh trng bnh l hoc thuc sd chung
Ngng sd thuc th triu chng ci thin
Phn ng l tc dng c hi c trng c bit ca thuc
Ti sd thuc cho phn ng c hi tng t

C kh nng

Phn ng c mi lin h hp l vi thi gian sd thuc

Nguyn nhn khng chc chn l do bnh l hoc thuc dng chung
Ngng s dng thuc th cc triu chng ci thin
Khng cn tht phi c thng tin v vic dng li thuc

C th

Phn ng c mi lin h hp l vi thi gian dng thuc

C th gii thch nguyn nhn bng bnh l hoc thuc dng chung
Thng tin v vic ngng s dng thuc c th thiu hoc khng r

Khng chc chn

Phn ng c mi lin h khng r rng vi thi gian dng thuc

C th gii thch nguyn nhn bng bnh l hoc thuc dng chung

C iu kin; cha phn

loi

Phn ng bt thng xy ra, nhng cn thm thng tin nh gi

Khng c mi quan h;
khng th phn loi

Bo co a ra 1 phn ng nghi ng l ADR nhng khng th nh gi v thng tin

khng y hoc khng thng nht; khng th thu thp thm thng tin b sung93hoc
xc thc li d liu

Nhng d liu b sung ang c nh gi

Ca LS 5
BN nam 86 tui hin ang nm vin v vim phi
Ngy hm nay BN b h ng huyt v phi truyn
Dextrose 50%
XN:
#ng huyt < 70 mg/dl
#Clcr: 35 ml/pht

Thuc s dng: Diabinese (chlorpropamide)

Vn ca BN l g???
94

46

9/12/15

Tm tt
Phn ng c hi ca thuc xy ra liu thng dng
trong iu kin bnh thng
ADR type A (lin quan n tnh cht dc l) thng
ph thuc liu v tnh cht DH ca thuc
Ci thin khi ngng/ gim liu

ADR type B (phn ng c ng) khng lin quan n

tnh cht dc l bit
Ci thin khi ngng thuc

Cnh gic dc: pht hin, bo co v xc nh ADR

thuc cn thit m bo sd thuc an ton
95

Mt thuc ch an ton khi tnh an ton c chng minh

trong thc t
(Walter and Evans, PDS 2003)
Khng c mt hp cht sinh hc no thc s an ton.
Ch c nhng ngi thy thuc bit s dng thuc mt
cch an ton
"There is no really "safe" biologically active drugs. There are only "safe"
physicians"

(Harold A. Kaminetzsky, 1963)

96

47

9/12/15

Ti liu tham kho

Sch:
Davies Textbook of Adverse Drug Reactions
Tisdale JA, Miller DA. Drug-Induced Diseases: Prevention,
Detection, and Management
Lee A. Adverse Drug Reactions. Pharmaceutical Press
C s d liu:
Meylers Side Effects of Drugs
Tin ngn:
Clin-Alert: available on-line
MedWatch website:
www.fda.gov/medwatch/
http://canhgiacduoc.org.vn/

97

Thank You!

48