L5 pharmacovigilance

Question 1

Pharmacovigilance

Answer 1

Identification, assessment and prevention of adverse drug reactions while optimising benefits

Question 2

Who is responsible for pharmacovigilance

Answer 2

Prescribers
Patients
Carers 
Health care workers
- to report ADRs

Question 3

Mechanism to manage pharmacovigilance

Answer 3

Yellow card reporting

Question 4

What does thalidomide cause

Answer 4

Phocomelia- limited or no limb development

Question 5

How many cases are needed to make a change?

Answer 5

10

Question 6

What was changed due to the thalidomide cases?

Answer 6

• Adequate testing used
• Government regulations
• Reporting systems
• Most medicines cross the placenta

Question 7

What is thalidomide used for currently?

Answer 7

Malignant myeloma in over 65 yr olds

Question 8

Purposes of early phase trials

Answer 8

Identify serious ADRs

Question 9

Limitations of trials

Answer 9

Low frequency of reporting 
Low publishing data 
Confounding variables 
Small number of patients
Not representative 
Short duration
Specialist doctors are needed with short follow up
Concomitant therapeutics usually excluded

Question 10

Classes of ADR

Answer 10

Type A - Augmented

Type B - Bizarre

Question 11

Type A ADR

Answer 11

• Dose related
• Predictable - PK and PD
• common
• reversible
• Dose adjustment required

Question 12

Examples of type A ADR

Answer 12

Warfarin causing bleeding

Insulin causing hypoglycaemia

Question 13

Type B ADR

Answer 13

• not does related
• unpredictable
• uncommon
• serious or irreversible
• Stop treatment

Question 14

Type B ADR example

Answer 14

Penicillin anaphylaxis

Clozapine (used to treat schizophrenia) - agranulocytosis

Question 15

Mechanisms of ADR

Answer 15

• Exaggeration of response
• Desired pharmacological effect at alternative site/ additional site e.g. GTN spray causes headaches
• additional secondary pharmacological effect
• triggers immunological response - anaphylaxis

Question 16

Relative risk

Answer 16

Relative risk in a rare condition doesn’t affect no. of cases that much

Question 17

Advantages of reporting

Answer 17

Simple mechanism to report
Quick and inexpensive
Detects common and rare reactions
Accessible by all health care professionals and patients

Question 18

Negatives of reporting

Answer 18

under reporting 
Positive bias 
Duplication
Effect of publicity and media
Poor quality data

Question 19

Improving reporting

Answer 19

Implementing guidance
Medical reviews
Collecting data from under reported areas
Global approach - big data

Question 20

Pharmacogenetics

Answer 20

How individual genes may affect response to drugs or side effects

Question 21

Pharmacogenomics

Answer 21

Whole genome and epigenetic effect on drug interactions

Population and individual characteristics

Question 22

Individual variability

Answer 22

CYP P450 expression
Split antigen reaction
Enzyme deficiency - aldehyde dehydrogenase

Question 23

Abacavir example

Answer 23

Abacavir for HIV associated with hypersensitivity with patients that have the split antigen expressed
Therefore screening used - 75% reduction

Question 24

Carbamazepine example

Answer 24

Stevens-Johnson syndrome or severe toxic epidermal necrolysis reaction to another split antigen found in Asian people therefore avoid giving to Asian patient group

Question 25

Aldehyde dehydrogenase deficiency

Answer 25

Mutated ALDH2
Single point aa mutation
predominant in East Asian population

Question 26

Warfarin

Answer 26

Racemix mixture of S and R anomers (S 3-5 x more more potent)
Metabolised by different CYPs
Genetic polymorphism is the expression of particular CYP can change potency of warfarin therefore no standard dose and based of INR

Question 27

CYP 2D6

Answer 27

metabolises 25% of drugs but rate highly variable

6% of Caucasians have 2 null alleles therefore no CYP 2D6 activity

Question 28

Use of genetic polymorphism information

Answer 28

Personalised drug therapy
Rapid screening of gene variants
Knowledge can be used to target specific receptors or enzymes

e.g. cancer
vaccines for allergies
statin side effect prediction