Pharmacogenetics/genomics

Question 1

What is favanism

Answer 1

G-6-Pase deficiency - X linked

Question 2

Define pharmacogenetics

Answer 2

Pregenomic era - studies of the role of genetics in drug responses - based on mainly on polymorphisms

Question 3

Define Pharmacogenomics -

Answer 3

Compares phenotypes in genotypic groups, science that allows us to predict a response based on individual genetic makeup

Question 4

what is polygenic complexity

Answer 4

drug responses that result from multiple genetic determinants

Question 5

What is isonaizid - how is it eliminated

Answer 5

anti tb drug still used - half life of 30 mins to up to 7.5 hours
Eliminated by N-acetyltransferase (phase 2 - conjugates with acetic acid)

Question 6

What are the phase 1 and phase 2 enzymes

Answer 6

Phase 1 - cytochromes

Phase 2 - conjugating enzymes

Question 7

describe 2 forms of N-acetyltransferase enzyme

Answer 7

Fast acetylators: carry gene for efficient enzyme
Slow acetylator: carry one for less efficient enzyme, eliminate the drug more slowly - gives them a higher concentration in the blood = higher toxicity = irreversible liver damage and death.

Question 8

Geographic distribution of slow acetylators

Answer 8

Egypt, Morocco, Saudi - more than 70% are slow acetylators. South Africa and eurpeans 40-70% frequency of slow acetylators.

Question 9

Describe CYP2D6

Answer 9

Low levels of enzyme in liver but metabolises a large amount of drugs. The enzyme is also called debrisoquine hydroxylase (debrisoquine is an antihypertensive).

Question 10

Describe CYP2D6 polymorphisms [4]

Answer 10

1. SNP
2. Single base deletion / addition
3. entire gene deletion - some don’t even have the enzyme
   4 - gene replication - up to 13 copies - very high metabolic activity

Question 11

CYP2D6 phenotypes

Answer 11

1. Poor metabolisers - 7-10% very slowly - so toxic concentrations - lower doses to be given,
2. Intermediate 10-15%- diminished capacity
3. Extensive metabolisers -73-82%= typical rate
4. Utrarapid 1-2% of the population) - drugs may not reach therapeutic concentration - you need to increase the dose

Question 12

Prevalence of CYP2D6 metabolisers

Answer 12

Ethopians = ultrarapid
Orientals = very poor metabolisers.

Question 13

Which enzyme is responsible for metabolising Codeine

Answer 13

CYP2D6 converts to morphine. 7% of caucasians are missing one gene