Pharmacovigilance and Pharmacogenetics

Question 1

Define pharmacovigilance (2)

Answer 1

Identification, assessment and prevention of adverse drug reactions whilst optimising benefits.

Question 2

Describe the origins of pharmacovigilance. (1)

Answer 2

The thalidomide scandal.

Question 3

Define an adverse drug reaction. (2)

Answer 3

An unintended and harmful effect that occurs due to a drug given in the therapeutic range.

Question 4

Describe the two types of ADRs. (4)

Give at least one example of each type. (4)

Answer 4

Type A are dose related, common and well reported, reversible and manageable. Eg headaches with nitrates, hypoglycaemia with diabetes treatment, bleeding on warfarin.
Type B are not dose related, uncommon, unpredictable and irreversible. They indicate the drug needs to be stopped immediately. Eg anaphylaxis to penicillin.

Question 5

Describe the two things that can make the public less likely to take up the drug. Give an example of each type. (4)

Answer 5

Public scares - the pill and VTE (pregnancy has a much higher VTE).
Flawed study design being reported can also contribute to public opinion eg MMR and autism.

Question 6

Describe features of an ADR. (9)

Answer 6

Dose related - toxic, collateral, hypersusceptibility
Time related - independent, first dose, early or late administration, delayed, withdrawal.
Susceptibility - age, gender, ethnicity, genetic, disease.

Question 7

Give two specific examples of ADRs defined by the official features. (8)

Answer 7

Osteoporosis due to corticosteriods - collateral (within therapeutic range), late (months of treatment), age (older), sex (female)
Anaphylaxis due to penicillin - hyper-susceptibility (low threshold - subtheraputic range), first dose (within minutes).

Question 8

Describe 4 possible mechanisms of action for ADRs and give an example for each. (8)

Answer 8

Exaggerated response - bleeding on Warfarin
Desired effect at an alternative site - headaches on GTN
Secondary pharmacological effects - prolonged QT in some Beta blockers
Triggering an immune response - anaphylaxis.

Question 9

Describe the yellow card scheme. (3)

Answer 9

Method for reporting ADRs that’s most common. Specialises in reporting ADRs for recently introduced products and severe reactions in other therapeutics.

Question 10

Describe 4 advantages of the yellow card scheme. (4)

Answer 10

Reporting common and rare ADRs
Timely
Inexpensive
Accessible

Question 11

Describe 5 disadvantages of the yellow card scheme. (5)

Answer 11

Leads to under reporting 
Positive bias (only reporting severe) 
Duplication
Unhelpful publicity
Poor quality data

Question 12

Define pharmacogenetics. (2)

Answer 12

How an individuals’ genes may affect responses to a drug, or the drugs responses to the body.

Question 13

Define pharmacogenomics. (1)

Answer 13

Whole genome including epigenetics pharmacogenetics.

Question 14

Describe the pharmacogenetic considerations when prescribing carbamazepine. (3)

Answer 14

Has a split antigen profile meaning some payi should experience severe hypersensitivity cutaneous reactions (Stevens-Johnson’s Syndrome or epidermal necrolysis).

Question 15

Describe the pharmacogenetic considerations when prescribing ACEi. (3)

Answer 15

In Afro-Caribbean hypertensive patients, ACEi aren’t the first line because the general genetic profile of these patients is that they’re in a low Renin state.

Question 16

Describe how having an abnormal receptor type or impaired metabolism of a drug can affect the efficacy or toxicity of a drug. (3)

Answer 16

Impaired metabolism increases toxicity.
Abnormal receptors types reduce drug efficacy.
This means if you have both, you get lots of ADR toxic effects, but few desirable effects.