4.1 Pharmacovigilance and pharmacogenetics

Question 1

what is pharmacovigilence?

Answer 1

Monitor safety of all medicines throughout usage, pro-active risk
management

Question 2

who collects data on pharmacovigilence?

Answer 2

European Medicines agency MRHA

Question 3

why is thalidomide no longer prescribed as a sedative?

Answer 3

as although one enantiomer does have sedative effects, another causes phocomelia and limb malformation

Question 4

what is phocomelia?

Answer 4

congenital absence of the proximal portion of a limb or limbs, the hands or feet being attached to the trunk by a small, irregularly shaped bone. adj., adj phocome´lic.

Question 5

what is done to ensure pharmacovigilence?

Answer 5

adequate testing, government regulation,
reporting systems, implications of unfounded claims, most medicines
cross the placenta, avoidance of unnecessary use during pregnancy

Question 6

what is a serious ADR?

Answer 6

Fatal
Life-threatening
Prolonged hospitalisation
Long term disability
Congenital abnormalities
- along with medical judgement

Question 7

what is the difference between an adverse drug event and an adverse drug reaction?

Answer 7

an adverse drug event is an injury that occurs during treatment, and is
not necessarily caused by the drug itself. Where as an adverse drug reaction is in response to a drug that is noxious and unintended.

Question 8

there are 5 major classes of ADRs, what are they?

Answer 8

A = augmented (dose dependent, frequent and predictable 
B = bizarre (not dose related/ dose independent and unpredictable)
C = chronic (rare response due to long term exposure)
D = delayed (time dependent, very rare)
E = end of treatment ( withdrawal effects)

Question 9

what are the 4 broad mechanisms of action of adverse drug reactions?

Answer 9

Exaggerated response
Desired pharmacological effect at alternative/additional site (GTN – headache)
Additional/secondary pharmacological effect (QT length)
Triggering an immunological response (anaphylaxis)

Question 10

what are the limitations in evaluating the safety and the efficacy of a new drug in pre-marketing clinical studies?

Answer 10

• Small number of patients
• Limited by age and possibly gender
• Selected following precise diagnoses
• Short, well defined duration
• Specialist doctors and continuous follow-up
• Concomitant therapeutics usually excluded

Question 11

what system is currently in place to report ADRs?

Answer 11

Yellow card scheme
recently introduced products – all suspected ADRs inc. minor ones, all reactions to vaccines

Established products – serious or unusual suspected reactions (life threatening, disabling or prolonging hospitalisation)

Question 12

what is pharmacogenomics?

Answer 12

The study of genetically determined variations in responses to drugs in humans or in laboratory organisms.

Question 13

what factors contribute to intervariability in drug response?

Answer 13

• Age
• Race/ethnicity
• Weight
• Gender
• Concomitant Diseases
• Concomitant Drugs
• Compliance
• Social factors
• Biomarkers
• GENETICS

Question 14

what is meant by personalised medicine?

Answer 14

uses new approaches to better manage patients health and target therapies to achieve the best outcome in the management of a patients disease or predisposition to disease

Question 15

what are the 4 P’s of personalised medicine?

Answer 15

prediction and prevention
precise
personalised
participatory

Question 16

what are HLA alleles?

Answer 16

HLA alleles, also known as human leucocyte antigens are located on the short arm of chromosome 6, the most polymorphic region of the human genome.

Question 17

why is there genomic testing before prescribing abacavir?

Answer 17

as patients with specific HLA antigens are predisposed to developing serious hypersensitivity reactions with multiorgan involvement when taking abacavir

Question 18

why is there genomic testing before prescribing carbamazepine?

Answer 18

as patients with specific HLA antigens (increased frequency in south east asians) are predisposed to developing toxic epidermal necrolysis and steven-johnson syndrome

Question 19

why do codeine painkillers not work for many people?

Answer 19

As codeine (along with antidepressants, antipsychotics and beta blockers) are broken down by CYP 2D6 enzyme. Many caucasians lack this enzyme and therefore cannot metabolise these drugs.