Adverse drug reactions mw %+ Flashcards
ADR Definition
- Any response to a drug which is noxious, unintended and occurs at doses used in man for prophylaxis, diagnosis or treatment.
Classification of- Onset
- Acute- within 1 hour
- Sub-acute- 1 to 24 hours
- Latent- > 48 hours
Classification of severity
• Mild
» bothersome but requires no change in therapy
» Metallic taste with metronidazole
• Moderate
» requires change in therapy, additional treatment, hospitalization
» Amphotericin induced hypokalemia
• Severe
» disabling or life-threatening
» kidney failure
Classification of ADRs
- Type A Augmented
- Type B Bizarre
- Type C Chronic
- Type D Delayed
- Type E End of treatment
- Type F Failure of treatment
Type A and Type B
Augmented pharmacologic effects:
- Dose related
- Predictable
Type B Bizarre effects
- Idiosyncratic and unpredictable
Predisposing Factors
- Multiple Drug Therapy: incidence increase exponentially with the number of medicaments
- Inter-current Disease:renal and hepatic impairment
- Race and Genetic Polymorphisms
- Age -elderly and neonates
- Sex- more common in women
Type A Reactions
Due to excess pharmacological action:
- Bradycardia with beta-blockers
- Hypoglycaemia with sulphonylureas or insulin
- Easily reversible on reducing the dose or stopping the drug.
- Not usually life threatening.
- Most common of all ADRS accounting for 80% of all ADRs.
Types of type A ADRs
- Augmentation of the primary effect
- Secondary effect- due to the secondary pharmacology of a drug unrelated to the therapeutic effect.
However the ADR is still rationalisable from the known pharmacology of the drug.
Reasons for Type A ADRs
- Too high a dose
- Pharmaceutical variation
- Pharmacokinetic variation
- Pharmacodynamic variation
The last two commonly occur as a result of disease
Pharmacokinetic Variation
1.Absorption:
- Dose
- Formulation
- GI motility
- First pass metabolism
The majority of ADRs which arise through absorption problems result in therapeutic failure.
- Distribution
- Metabolism
- Elimination
Pharmacogenetic
A number of drugs are metabolised via acetylation which is under genetic control:
- 10% of the population are slow metabolisers
- Prone to drug toxicity
- Peripheral neuropathy with isoniazid
Disease
- Renal and hepatic impairment
* If a drug is excreted by the kidneys toxic drug levels may build up - Cardiac Failure
- Reduce drug absorption from the gut due to oedema
- Poor renal perfusion and decreased GFR
- Hepatic congestion
Pharmacodynamic Variation
- Most type A ADRs are pharmacokinetic in nature
- Some are due to altered Pharmacodynamic action:
- Natural variability in pharmacodynamic response
- Disease states can significantly alter response
Type B ADRs
Type B reactions are:
- Bizarre
- Unpredictable
- Rare
- Cause serious illness or death
- Unidentified for months or years
- Unrelated to the dose
Important factors in type B
- More common with macromolecules
- proteins
- vaccines
- polypeptides
- Patients with history of asthma, excema,
-
HLA (human leukoctye antigen) status
* Presence of particular HLA increases risk of a type B reaction
Teratogenesis
- Abnormal congenital malformations in the fetus following in utero exposure due to maternal medication use during 1st trimester of pregnancy.
