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 A (Augmented) Type B (Bizzare) Type C (Continuous) Type D (Delayed) Type E (Ending Use) Type 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 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 drug’s 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

AbnormalityDrugs Idiosyncratic

ResponseAbnormal

hemoglobinPhenacitin

SulfanilamidesMethemoglobinem

iaHemolytic anemia

Erythrocyte G6PD-deficiency

AspirinSulfonamides

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 ADR’s.