Pharmacovigilance And Pharmacogenetics

Question 1

What is phocomelia?

Answer 1

A rare congenital deformity in which the hands and feet are attached close to the trunk. Associated with Thalidomide, a teratogen

Question 2

Describe a Type A (augmented) ADR

Answer 2

Dose related
Predictable
Common
Reversible
Sorted with dose adjustment 
E.g. hypoglycaemia and insulin

Question 3

Describe a Type B (Bizarre) ADR

Answer 3

Not dose related
Unpredictable
Uncommon
Serious
Irreversible
Need to stop treatment
E.g. Anaphylaxis and penicillin and Agranulocytosis with Clozapine

Question 4

Diethylstilboestrol is given to prevent premature labour, but what is the ADR?

Answer 4

It causes vaginal cancer in those exposed in utero

Question 5

Children with cystic fibrosis are treated with large doses of pancreatic enzymes, but what ADR is associated?

Answer 5

Fibrosing colonopathy

Question 6

What are the 4 mechanisms of action for an ADR?

Answer 6

Exaggerated response
Desired pharmacological effect at alternative/additional site
Additional/secondary pharmacological effect
Immunological response (anaphylaxis)

Question 7

What are the limitations of premarketing clinical studies and ADRs?

Answer 7

Small number of patients
Limited by age and possibly gender
Selected following precise diagnoses
Short, well defined duration
Continuous follow up and concomitant therapeutics usually excluded

Question 8

Person-person variability contributes to how many ADR’s

Answer 8

7%

Question 9

Person-person variability contributes to how many fatal drug reactions?

Answer 9

3/1000

Question 10

What % of patients treated with Abacavir suffer a hypersensitivity reaction?

Answer 10

8%

Question 11

Screening for the split antigen in Abacavir treated HIV patients reduces reactivity by what %?

Answer 11

75%

Question 12

What cutaneous reactions can occur as a result of taking Carbamazepine?

Answer 12

Stevens-Johnson Syndrome
Or more severe toxic epidermal necrolysis
Predominantly in Asian patients

Question 13

S is how many times more potent than R in warfarin - INR racemix

Answer 13

3-5 times

Question 14

CYP 26D is responsible for the metabolism of what % of drugs?

Answer 14

25%

Question 15

What % of Caucasians carry 2 null alleles at CYP 2D6 gene locus?

Answer 15

6%

Question 16

Where is the gene locus for CYP 2D6?

Answer 16

19

Question 17

What is the result of having 2 null alleles at the CYP2D6 locus?

Answer 17

Decreased first pass metabolism

Question 18

If a patient has 2 null alleles at CYP26D and takes Metoprolol, what is the consequence?

Answer 18

Bradycardia and accumulation as a result of reduced metabolism