Session 4: Pharmacovigilance & Pharmacogenetics

Question 1

What is pharmacovigilance?

Answer 1

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

Question 2

Who’s responsible for pharmacovigilance?

Answer 2

Prescribers

Patients

Carers

Pharma

Regulatory agencies (MHRA)

Question 3

What are the two subtypes of adverse drug reactions?

Answer 3

Type A - Augmented

Type B - Bizzare

Question 4

Explain the properties of Type A ADRs.

Answer 4

They are dose related and predictable following a pattern according to pharmacokinetics and pharmacodynamics.

These ADRs are common and are also reversible, usually with dose adjustment.

Question 5

Explain the properties of Type B ADRs.

Answer 5

They are not dose related and are unpredictable.

These ADRs are uncommon and serious. They can also be irreversible and treatment needs to be stopped.

Question 6

Give examples of Type A ADRs.

Answer 6

Bleeding due to warfarin use.

Hypoglycaemia in diabetes medication.

Question 7

Give examples of Type B ADRs.

Answer 7

Anaphylaxis in penicillin use.

Agranulocytosis in clozapine use.

Question 8

What are adverse drug reactions?

Answer 8

Unintended and noxious effects attributable to therapeutic given within normal therapeutic range.

Question 9

ADRs of diethylstilboestrol.

Answer 9

Used to prevent premature labour but can cause vaginal cancer in those exposed in utero.

This affects the foetus, not the mother.

Question 10

ADRs of treating children with CF with large doses of pancreatic enzymes.

Answer 10

Fibrosing colonopathy.

Question 11

Give the 4 broad mechanisms of action of ADRs.

Answer 11

Exaggerated response to intended action of the drug

Desired pharmacological effect at alternative/additional site (Like GTN giving a headache)

Additional/secondary pharmacological effect (QT length)

Triggering an immunological response like anaphylaxis.

Question 12

Limitations of pre marketing clinical studies and ADRs.

Answer 12

Small number of patients

Limited by age and possible gender

Selceted following precise diagnoses.

The clinical trial may be short so long term effects may not be visible.

Pregnant, elderly and children might not be accurately represented.

Question 13

What is pharmacogenetics?

Answer 13

How individual gene may affect response to drug or drug response on body.

Question 14

What is pharmacogenomics?

Answer 14

More broadly the whole genome and affects on drugs also considering epigenetics.

Question 15

Explain the side effects of Abacavir treatment in HIV relating to pharmacogenetics.

Answer 15

Hypersensitivity in 8% of patients treated for HIV.

Called a split antigen reaction.

Question 16

Explain the side effects of patients taking carbamazepine associated with pharmacogenetics.

Answer 16

Cutaneous reaction (Stevens-Johnson syndrome or more severe toxic epidermal necrolysis).

Reaction to split antigen in Asian patients.

Question 17

Give the most common example of pharmacogenetics.

Answer 17

Primary step 1 antihypertensive treatment where ACEi and ARBs are not the primary choice in African Caribbean populations as it can cause angioedema and renin is typically lower in African Caribbean population.

Question 18

Give examples of genetic polymorphism relating to pharamacogenetics.

Answer 18

PK and PD can be affected. An example is aldehyde dehydrogenase deficiency by a mutated ALDH2 in East ASian and Northern Europeans.

Metabolic enzymes in general are common to be involved in genetic polymorphism, particularly CYPS.

Warfarin and INR as well.

Question 19

Give examples of action of CYP 2D6.

Answer 19

Metabolism of 25% of drugs.

Including certain antidepressants, antipsychotics, betablockers and opioid analgesics.

Question 20

How does CYP2D6 vary in the population relating to pharmacogenetics?

Answer 20

6& of the caucasian poplation carry two null alleles at the CYP2D6 gene meaning it doesn’t work properly.

This leads to decreased first pass metabolism and drugs such as metoprolol and bradycardia accumulation as a result of reduced metabolism.

The metabolism can also re-route like paracetamol and toxic NAPQI intermediate.

Question 21

Why are CYP450 polymorphisms important in tailoring therapeutics?

Answer 21

Because it means that individuals will have different variations of drug metabolism leading to drugs having various degrees of effect.

This means that there can be a toxic build up of the drug in one person and not in another.