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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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DRUG EVALUATION FOR ADR
#linical evaluation
&hase"1 '(linical pharmacology studies)
*imited sample size '20"50)
+ealthy $olunteers 'or selected patients)
&harmaco,inetic studies
&harmacodynamic studies for efficacy - safety
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DRUG EVALUATION FOR ADR
P'%e#, (C*n*+' *n-e%t*g't*$n)
(onducted on patients
*arger sample size '50".00)
&harmaco,inetic studies
&harmacodynamic studies for efficacy - safety
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DRUG EVALUATION FOR ADR
P'%e#. (F$&m' te&'peut*+ t&*'%)
*arger scale trials in patients Randomized/controlled
fficacy - safety on a larger scale
(omparison ith other drugs
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DRUG EVALUATION FOR ADR
P'%e# (P$%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