CPT7 - Pharmacovigilance & Pharmacogenetics

Question 1

4 features of pharmacovigilance

Definition
Mechanism of ADRs x4
Serious ADRs x5
Reporting ADRs

Answer 1

1.) Definition - identification, assessment, and subsequent prevention of adverse drug reactions (ADR) whilst optimising benefits

2. ) Mechanism of ADRs - 4
   - exaggerated response
   - effect at alternative site: GTN causing a headache
   - secondary pharmacological effect: QT length
   - triggering an immunological response: anaphylaxis
3. ) Serious ADRs - categories:
   - fatal, life-threatening, prolonged hospitalisation, long term disability, congenital abnormalities
4. ) Reporting ADRs - use of yellow card system to MHRA
   - can be used by anyone, not just healthcare professionals
   - may suffer from under-reporting

Question 2

4 differences between type A (augmented) and type B (bizarre) adverse drug reactions

Dose
Predictability
Frequency
Reversibility

Examples
Other Sub-Classifications

Answer 2

1. ) Dose - type A is dose related whilst B is not
   - type A needs dose adjustment to stop the ADR
   - type B needs the treatment completely stopped
2. ) Predictability - type B is unpredictabile whilst type A has predictable pharmacokinetics and dynamics
3. ) Frequency - type A is common whilst B is rare
4. ) Reversibility - A is reversible whilst B is irreversible
5. ) Examples
   - type A: bleeding w/ warfarin, hypoglycemia w/ diabetes medication
   - type B: anaphylaxis w/ penicillin, agranulocytosis w/ clozapine
6. ) Other Sub-Classifications - CDE
   - C: chronic | D: delayed | E: end of use

Question 3

4 features of pharmacogenetics

Definition
Genetic Polymorphism
CYP2D6
Use of Pharmacogenetics x4

Answer 3

1.) Definition - how individual genes may affect responses to a drug

2. ) Genetic Polymorphisms - changes in pharmacokinetics and pharmacodynamics
   - often occurs w/ metabolic enzymes (esp. CYPs)
   - e.g. Aldehyde-DH deficiency in east asian population
3. ) CYP 2D6 - involved in metabolism of 25% of drugs
   - variability in rate of drug metabolism is > x100
   - 6% of Caucasians carry 2 null alleles at CYP2D6 gene
4. ) Use of Pharmacogenetics
   - cancer: targeting particular somatic changes
   - statins: predicting ADRs (esp muscle damage)
   - allergy vaccines: prevent ADRs
   - personalising drug therapy

Question 4

3 examples of pharmacogentics in use

Antihypertensive Treatment
Abacavir
Carbamazepine

Answer 4

1. ) Antihypertensive Treatment
   - CCB the primary choice in Afro-Caribbeans due to having lower renin levles
   - also angioedma more prevalent in Afro-Caribbean
2. ) Abacavir - used in treatment for HIV
   - causes hypersensitivity in 8% of patients
   - caused by split antigen reaction so screening lead to a reduction in 75% in reactivity
3. ) Carbamazepine - used in treatment of epilepsy
   - causes a cutaneous reaction (Steven-Johnson Syndrome) in reaction to a split antigen
   - found mainly in Asian patients