ADR-BDS Lec

8/9/2019 ADR-BDS Lec

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ADVERSE DRUG REACTIONS

Undesired effects of drugs occurring

under normal conditions of use

Remedy often proves worse than thedisease (William Pens)


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SIGNIFICANCE

A major cause of morbidity and

mortality

Account for 5% of acute medical

emergencies

10 to 20 % of hospitalized patients

suffer from an ADR


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CLASSIFICATION / TYPES

Type A (Augmented): Predictable

dose-related* pharmacodynamic effects e.g:

hypoglycemia with antidiabetics

hypokalemia with diuretics

* Poisons in small doses are the best medicines and usefulmedicines in too large doses are poisons (William Withering)


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Type ( Bizarre):

Unrelated to dose and pharmacodynamics

of the drug

enerally unpredictable!a"e genetic basis e.g:

#diosyncrasies

allergies


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Type C: $ssociated with long term use e.g:

analgesic nephropathy tardi"e dyskinesia

Type D:

%elayed reactions e.g: carcinogenesis

teratogenesis

Type E: &nd-of-use reactions e.g

adrenal insufficiency on steroid withdrawal

angina on stoppage of ' blockers


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CAUSES OF ADVERSE DRUG REACTIONS

nappropriate use of drugs

ured yesterday of my disease died last night of my physician (athew Prior)When you can cure by a regimen a"oid ha"ing recourse tomedicine and when you can effect a cure by means of a simplemedicine a"oid employing a compound one (+ha,es)

nade!uately monitored use

Drug"drug interactions #elf"medication nade!uately e$aluated and irrational drugs


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RECOGNITION OF ADRS

when an unexpected event takes place

for which there is no obvious cause occurs in a patient taking a drug possibility must always be considered

that it is drug-caused


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ESTALIS!"ENT OF

CAUSE#EFFECT RELATIONS!IP

DEFINITE: (P$%tu&' yp$ten%*$n)

+easonable time relationship with drug

administration

&"ent corresponds with known

pharmacological properties of the drug

&"ent ceases on stopping the drug

&"ent returns on restarting the drug


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POSSILE: (t&em$&%)

ime relationship reasonable

&"ent corresponds with known

pharmacological properties of the drug

ould ha"e resulted from patients

disease or other drugs


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CONDITIONAL: (em$yt*+ 'nem*') ime relationship reasonable

&"ent %/&0 1/ correspond with known pharmacological properties of the drug

&"ent 1/ reasonably e2plained by

patients disease DOUTFUL: (&'%)

&"ents not meeting the abo"e criteria


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FACTORS T!AT PREDISPOSE TO ADR

Related to the patient:

• Age of the patient

• Ability to metabolize & excrete the drug

• Underlying disease

• Genetic factors

• Pregnancy and lactation


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FACTORS T!AT PREDISPOSE TO ADR

rug-Related

Chemical nature

Nature of metabolites

Pharmacodynamic profile

Dose

Age of the drug

oute of administration

Concurrent therapy


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DRUG EVALUATION FOR ADR

Preclinical !valuation ("nimal studies)

• Acute toxicity studies

• Subacute toxicity studies

• Chronic toxicity studies

• Studies for mutagenesis/ carcinogenesis

• Studies for teratogenesis


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#linical evaluation

&hase"1 '(linical pharmacology studies)

*imited sample size '20"50)

+ealthy $olunteers 'or selected patients)

&harmaco,inetic studies

&harmacodynamic studies for efficacy - safety


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P'%e#, (C*n*+' *n-e%t*g't*$n)

(onducted on patients

*arger sample size '50".00)

&harmaco,inetic studies

&harmacodynamic studies for efficacy - safety


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P'%e#. (F$&m' te&'peut*+ t&*'%)

*arger scale trials in patients Randomized/controlled

fficacy - safety on a larger scale

(omparison ith other drugs


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P'%e# (P$%t#m'&0et*ng %u&-e*'n+e)

#ur$eillance for efficacy - safety (omparison ith other drugs


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STRATEGIES FOR PREVENTION OF ADR

A$ailability of safe and !uality drugs

Rational use of drugs

p"drug concept indi$idualization of therapy (ontinued medical education

$t is an absolute obligation on doctors to use only

those drugs about which they have troubled to informthemselves

Role of regulators

Documents

ADR-BDS Lec