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ADVERSE DRUG REACTION

Dr. Sahilah Ermawati

ADVERSE DRUG REACTION

as defined by WHO:

Any response to a drug which is


noxious and unintended and which
occurs at doses used in man for
prophylaxis, diagnosis or therapy.

ADR may result from:

Effects of the drug


Illness
(interaction with each other)

ADR: key points to remember


during therapy

Are undesirable
Are unintentional
Are suspected (not necessarily
proven)
May develop as a consequence of
therapy or other procedure

ADR

Not always the active ingredient


causing the problem but may also
be due to:

Solvent
Excipients
Formulation
Contaminants produced in the
manufacturing process.

Key Points in ADR


Reporting:

Identifying rare adverse effects


Monitoring newly introduced drug
where their safety profile is
relatively unknown
Hypothesis generating and raising
signals or flags
Supporting the regulatory policies in
promotion of drug safety (RA 3720)

Pharmaceutical causes

By altering the quality of drug


available for systemic absorption
By influencing release in such way
as to produce local

Systemic availability of drug may


be influenced by:

particle size
nature and quantity of excipients and
coating material
quality and quantity present in
particular preparation

Pharmacokinetic causes

The way the drug is handled by the


body during ADME may affect
humans in an adverse manner
Example:

diazepam in patients with liver failure


prolonged coma;
ototoxicity with aminoglycosides when
used in patients with renal failure

Pharmacodynamic causes

Increased sensitivity of target organs


in the body to drugs

PREDISPOSING FACTORS
IN ADR

Patient-related factors

presence of renal, hepatic and cardiac


disease
age
previous ADR or drug allergy
sex
genetic influence
misc. (diet, smoking, alcohol, environmental
exposures)

Drug-related factors

pharmaceutical properties
pharmacokinetic properties
pharmacodynamic properties

6 Classifications of ADR

Type
Type
Type
Type
Type
Type

A (Augmented)
B (Bizzare)
C (Continuous)
D (Delayed)
E (Ending Use)
F (Failure of Efficacy)

Type A or Augmented

refers to actions related to the


pharmacological activity of a drug

Extension effects predictable, dose


related responses arising from an
extension therapeutic effect.

Example:

Benzodiazepine
(anxiety
sedation and falls trauma

Furosemide
(diuresis)

electrolyte imbalance

neurosis)
water

and

Adverse effect - predictable, dosedependent reactions unrelated to the


goal of therapy

Examples:

Atropine dryness of mouth

Captopril cough

Codeine constipation

Nitroglycerin headache

Propranolol bronchial asthma

Type B reactions or Bizzare

refers to totally abnormal effects,


unrelated from the drugs known
pharmacological actions

Characteristics of Bizzare
Reactions
1. no formal dose-response curve and
very small doses of the drug may
elicit the reaction once allergy or
idiosyncrasy is established
2.

reactions
disappears
discontinuation of the drug

on

3. illness is often recognizable as an


immunological reaction
4.

undetectable during conventional


testing

5. little or no relation to the usual


pharmacological effects of the drug

6. delay between first exposure to


the drug and the occurrence of the
subsequent adverse reaction

Idiosyncrasy is an example of
bizzare reaction:

Genetically abnormal response


Dose-dependent

examples:
Genetic
Abnormality

Drugs

Idiosyncratic
Response

Abnormal
hemoglobin

Phenacitin
Sulfanilamides

Methemoglobinem
ia
Hemolytic anemia

Erythrocyte G6PDdeficiency

Aspirin
Sulfonamides
Vitamin C

Hemolytic anemia

Low plasma ChE


activity

Procaine

Local anesthetic
toxicity

Type C Reactions or Continuous

Long term effects are usually related


to the dose and duration of
treatment.

Example:

Ethambutol optical neuropathy

Type D reactions or delayed

Carcinogenesis

Hormonal
Gene toxicity
Suppression of immune response
Adverse Effects associated with
reproduction

teratogens

Type E Reactions or Ending of Use


(Withdrawal Syndrome)

Alcohol delirium tremens


Barbiturates restlessness, mental
confusion, convulsion
Clonidine rebound hypertension
Opioids narcotic withdrawal

Type F Reactions or Failure of


Efficacy

can be attributed to lack of efficacy of


drug products
Examples:

Failure to control infection (microbial


resistance)
Uncontrolled hypertension
Intractable pain

NOTE:

Counterfeit medicines are


responsible for some ADRs.