Adverse Drug Reactions Flashcards
Define an adverse drug reaction
Any response to a drug which is noxious, unintended and occurs at doses used in man for prophylaxis, diagnosis or treatment
Describe an acute reaction
Occurs within 60 mins
E.g. broncoconstriction
Describe a sub-acute reaction
Occurs within 1-24hrs after exposure
E..g. rash, serum sickness
Describe a latent reaction
Occurs >2days later e.g. eczematous eruptions
How can you classify reaction severity?
• Mild - bothersome but requires no
change in therapy e.g. metallic taste with metronidazole
• Moderate - requires change in therapy,
additional treatment, or hospitalization e.g. amphotericin induced hypokalemia
• Severe- disabling or life-threatening e.g. kidney failure
How are ADRs classified?
Type A Augmented Type B Bizarre Type C Chronic Type D Delayed Type E End of treatment Type F Failure of treatment
Describe type A ADRs
Dose related response, with the side effects usually predictable but augmented. In some cases, the reactions are not necessarily related to the drugs pharmacological effect e.g.dry mouth and tricyclic antidepressants. Effects are usually reversible upon removal of the drug.
What are some reasons type A ADRs occur?
Too high a dose Pharmaceutical variation Pharmacokinetic variation Pharmacodynamic variation The last two commonly occur as a result of disease
What are some predisposing factors for ADRs?
Multiple Drug Therapy - Incidence of ADRs increase exponentially with the number of medicaments
Age - Elderly and neonates
Sex - ADRs more common in women
Intercurrent Disease - Renal and hepatic impairment
Race and Genetic Polymorphisms
Describe type B ADRs
"Bizarre effects", idiosyncratic and unprediactableBizarre Unpredictable Rare Cause serious illness or death Unidentified for months or years Unrelated to the dose
What is a exaggerated type A ADR associated with bat blockers?
Brachycardia
What is an exaggerated type A ADR associated with sulphonylureas and insulin?
Hypoglycaemia
What is a secondary type A ADR associated with sironalactone?
Gynaecomastia
What is a secondary type A ADR associated with beta blockers?
Bronchospasm
What factors affect absorption and cause pharmacokinetic variation?
Dose
Formulation
GI motility
First pass metabolism
What % of the general population are slow acetylators?
10%
Describe some diseases that can cause pharmacokinetic variation
Renal and hepatic impairment - If a drug is excreted by the kidneys toxic levels may build up
Cardiac Failure - Reduce drug absorption from the gut due to oedema. Poor renal perfusion and decreased GFR. Hepatic congestion
What is the main cause of type A ADRs?
Pharmacokinetic variation
What are some important factors in type B ADRs?
More common with macromolecules
- Proteins
- Vaccines
- Polypeptides
Patients with history of asthma, eczema etc.
HLA status
Presence of particular HLA increases risk of a type B reaction
Describe a type B ADR caused by pharmacokinetic variation
Erythrocyte glucose 6-phosphate dehydrogenase (G6PD) deficiency
Individuals with sex linked inherited deficiency of this enzyme are susceptible to red cell haemolysis when given drugs such as primaquine or sulphonamides
What drugs make patients with a certain genetic disorder susceptible to red cell haemolysis?
Erythrocyte glucose 6-phosphate dehydrogenase (G6PD) deficiency
Individuals with sex linked inherited deficiency of this enzyme are susceptible to red cell haemolysis when given drugs such as primaquine or sulphonamides
Describe a type C ADR
This type of ADR is related to the duration of treatment as well as the dose and does not occur with a single dose.
Semi-predictable
Iatrogenic Cushings disease from steroid use
Steroid induced osteoporosis
Opiate dependence
Tardive dyskinesia with neuroleptic drugs
NSAIDs causing analgesic nephropathy and duodenal ulcers
What is a type C ADR associated with long term steroid use?
Cushings syndrome
What is a type C ADR associated with steroid use?
Osteoporosis
