14032012

Adverse Drug Reaction

Dr.Datten Bangun MSc,SpFK & Dr.Zulkarnain Rangkuty,MS

Dept.Farmakologi & !erapeutik Fak.Kedokteran "S" M#DA$

All Drugs are Dangerous

No Drugs are Dangerous if used properly Some drugs have a low incidence of horrendous effects The most dangerous drugs have the greatest potential for benefit Some adverse effects can be predicted if you know the pharmacology (Type A) some are not (Type !)

Some drugs have a low therapeutic ratio Some drugs are dangerous in acute poisoning but not when used therapeutically Some adverse effects occur after a delay or after stopping

!AD

GOOD

How dangerous a drug is depends on the skill of the prescriber

The Risk to Benefit Ratio

'hen prescribing drugs a doctor must assess risk to benefit ratio in the individual patient by ()hoosing an appropriate class of drug then an appropriate individual agent
"#S$ !%N%&#T

(#s it effective * ('hat are the chances of adverse effect * (Are there features in this patient which affect choice eg other drugs+ organ failure+ aged (Tailoring the dose ()onsidering duration of treatment

Adverse Drug Reaction

( Response to a drug %!ic! is no&ious, unintended and occurs at doses used in man 'or prop!yla&is, diagnosis and t!erapy ()*+, ( Unwanted or harmful reaction experienced after the administration of a drug or combination of drugs under normal conditions of use and suspected to be related to drug

!pe of adverse reactions

( ( ( ( ( ( ( !pe A "Augmented# !pe $ "$i%arre# !pe & "&hronic# !pe D "Dela!ed# !pe ' "'nd of use# !pe ( " herapeutic failure# !pe ) ")enetic*genomic#

&+A,,-(-&A -./ .( ADR,

( ype A (Augmented , reactions , Reactions which can be predicted from the 0nown pharmacolog! of the drug , Dose dependent1 can be alleviated b! a dose reduction , '2g2 $leeding with anticoagulants1 brad!cardia with beta bloc0ers1 headache with nitrates1 postural h!potension with pra%osin

&+A,,-(-&A -./ .( ADR,

( ype B (Bi-arre, reactions

, &annot be predicted from the pharmacolog! of the drug , /ot dose dependent1 host dependent factors important in pre3disposition , '2g2 anap!yla&is %it! penicillin, anticonvulsant !ypersensitivity

&+A,,-(-&A -./ .( ADR,

( ype . (.!emical, reactions , $iological characteristics can be predicted from the chemical structure of the drug*metabolite , #.g. paracetamol !epatoto&icity ype D (Delayed, reactions , .ccur after man! !ears of treatment2 &an be due to accumulation , '2g2 ,econdar! tumours after treatment with chemotherap!1 teratogenic effects of phen!toin ta0en during pregnanc!1 analgesic nephropath!1 tardive d!s0inesia with antips!chotic agents1 , )enital &a after dietilstilbesterol in pregnant

&+A,,-(-&A -./ .( ADR,

( ype # ( #nd o' treatment, reactions , .ccur on withdrawal especiall! when drug is stopped abruptl! , '2g2 withdrawal sei%ures on stopping phen!toin1 adrenocortical insufficienc! on withdrawal of steroids

Type A
Associated with the pharmacology of the product Predictable Dose related Common Serious

Type B

/.

ype 0 !ypersensitivity
(Anap!ylactic type,

0mmediate !ypersensitivity reaction, resulting 'rom release o' p!armacologically active mediators.

1. ype 00 *ypersensitivity
.ytolytic or cytoto&ic reactions

(/, Mec!anism2
.omplement3dependent reactions rans'usion reactions #ryt!ro4lastosis 'etal Autoimmune !emolytic anemia .ertain drug reactions

5. ype *ypersensitivity (0mmune comple&3mediated,

(/, Reaction types Art!us reaction serum sickness .ollagen diseases

6. ype *ypersensitivity (.ell3Mediated ,

Delayed !ypersensitivity reaction (/, issue reaction2 reaction .onsist o' parenc!ymal destruction associated %it! perivascular lymp!ocytic and macrop!age reaction.

4. Type Hypersensitivity (Cell-Mediated )

Anti4ody3dependent cytoto&icit (AD..,. May 4e relevant to2 7ra't re8ection !e destruction o' targets too large to 4e p!agocytosed, suc! as parasites or tumor cells. cell3mediated

 Anti4ody3mediated cellular dys'unction

Myast!enia gravis2 muscle %eakness 7raves9 disease2 !ypert!yroidism

4reventing ADRs cont5d

( Age1 hepatic and renal disease ma! impair clearance of drugs so smaller doses ma! be needed2 )enetic factors ma! also predispose to certain ADRs ( 4rescribe as few drugs as possible and give clear instructions ( 6here possible use familiar drugs2 6ith new drugs be particularl! alert for ADRs and unexpected event2 ( -f serious ADRs are liable to occur warn the patient

4revention of Adverse Drug reactions

( /ever use an! drug unless there is good indication2 -f the patient is pregnant do not use the drug unless the need is imperative2 ( Allerg! and idios!ncras! are important causes of ADRs2 As0 if the patient had previous reactions2 ( As0 if the patient is alread! ta0ing other drugs including self medication

4reventing ADRs cont5d

( Age1 hepatic and renal disease ma! impair clearance of drugs so smaller doses ma! be needed2 )enetic factors ma! also predispose to certain ADRs ( 4rescribe as few drugs as possible and give clear instructions ( 6here possible use familiar drugs2 6ith new drugs be particularl! alert for ADRs and unexpected event2 ( -f serious ADRs are liable to occur warn the patient

terato eni!

eratogenicity is 4ased on:

( Su4stance 3333 t!alidomide ( Dose relatedness,lengt! o' e&posure ( ime course 33 /st semester ( Suscepti4ility

Type A -harmacologica .es lly predictable Dose dependent #ncidence 0orbidity 0ortality 0anagement .es High High /ow Dosage ad1ustment

Type ! No No /ow /ow High ST2-

( (

!pe A ADRs 7 intrinsic to the drug effects !pe $ ADRs 3 idios!ncratic

8echanisms of non dose3related " !pe $# ADR

( 4harmacod!namic causes 3target organs 7 genetic1 immunologic1 neoplastic or teratogenic

#ryt!rocyte glucose3;3p!osp!ate (7;<D, de'iciency

( Se&3linked in!erited de'iciency ( )eakened red cell mem4rane ( *emolysis 'rom prima=uine, sul'onamides, sul'ones and nitro'urantoin ( A'rican type3mild, Mediterranean type3 severe

Drugs t!at s!ould 4e avoided %it! 7;<D de'iciency

( ( ( ( ( Dapsone $irida-ole Met!ylene 4lue (met!ylt!ioninium .l, <rima=uine >uinolones (cipro'lo&acin, nalidi&ic acid, nor'lo&acin, o'lo&acin, ( Sul'onamides (.otrimo&a-ole,

8alignant h!perthermia
( Rapid rise in 4ody temperature (at least 1 . per !our, ( Associated %it! anest!etics and muscle rela&ants (succinylc!oline, ( Sti''ness o' skeletal muscle, !yperventilation, acidosis, !yperkalemia, increased activity o' sympat!etic $S outcome? #ith a s$dden release of "sso!iated intra!ell$lar ioni%ed Ca "ntidote& Dantrolene

<redisposing 'actors
( Multiple drug t!erapy ( Age /.#lderly3 !ypnotics, diuretics, $SA0DS, anti3!ypertensives, psyc!otropics, digo&in 1.Adults3 polyp!armacy 5..!ildren3 antiepileptics, cytoto&ic agents, anest!etic gases, anti4iotics (associated %it! !epatic 'ailure,, $a valproate

4redisposing factors
( Age 6. $eonates3 c!loramp!enicol, morp!ine, antiarr!yt!mics Reye9s syndrome 3 ? *epatoto&icity @ $a valproate

4redisposing factors
( 7ender 3 Females !ave /.A3/.B 'olds o' developing ADR t!an males 3 )omen are prone to develop 4lood dyscrasias %it! p!enyl4uta-one & c!loramp!enicol 3 *istaminoid reactions %it! neuromuscular 4locking drugs

<revention o' Adverse Drug reactions

( $ever use any drug unless t!ere is good indication. 0' t!e patient is pregnant do not use t!e drug unless t!e need is imperative. ( Allergy and idiosyncrasy are important causes o' ADRs. Ask i' t!e patient !ad previous reactions. ( Ask i' t!e patient is already taking ot!er drugs including sel' medication

<reventing ADRs cont9d

( Age, !epatic and renal disease may impair clearance o' drugs so smaller doses may 4e needed. 7enetic 'actors may also predispose to certain ADRs ( <rescri4e as 'e% drugs as possi4le and give clear instructions ( )!ere possi4le use 'amiliar drugs. )it! ne% drugs 4e particularly alert 'or ADRs and une&pected event. ( 0' serious ADRs are lia4le to occur %arn t!e patient

Dr$ ad'inistered

(t develops a ne# !ondition)sy'pto's

Dr$ s$spe!ted* +es Che!k literat$re

Do!$'ented *, (for the prod$!t or si'ilar !lass of prod$!ts) +es Hi hly s$ estive of "DR

-ot do!$'ented in literat$re

Dr$ !ontin$ed

Dr$ dis!ontin$ed

.orsenin of sy'pto's

/y'pto's i'prove (0ve de!hallen e)

"ny other possi1le !a$ses* ( Con!o'itant therapy ( 2nderlyin !onditions

Dr$ restarted

/y'pto's re!$r (0ve re!hallen e)