ADVERSE DRUG REACTION

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 pharmacological activity of a drug

the

Extension effects predictable, dose related responses arising from an extension therapeutic effect.

Example: Benzodiazepine (anxiety neurosis) sedation and falls trauma Furosemide (diuresis) water and electrolyte imbalance

Adverse effect - predictable, dose-dependent 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 on discontinuation of the drug

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
Abnormal hemoglobin Erythrocyte G6PDdeficiency Low plasma ChE activity

Drugs
Phenacitin Sulfanilamides Aspirin Sulfonamides Vitamin C Procaine

Idiosyncratic Response
Methemoglobinemia Hemolytic anemia Hemolytic anemia

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.