Variability due to genetic differences

Question 1

How might genetic differences impact on drug dosage?

Answer 1

Different people may have polymorphisms in their genes that mean they produce varying amounts of enzymes or they might produce different enzymes all together. This may mean different drugs or different doses are required for different people.

Question 2

What is pharmacogenomics and pharmacogenetics?

Answer 2

Pharmacogenomics = investigation of variations of DNA and RNA as related to drug response.

Pharmacogenetics = a subset of pharmacogenomics which investigates the influence of these variations on drug response.

Question 3

What percentage of variability is predictable and what is unpredicatable?

Answer 3

50% = predictable (eg genetic differences identified, different renal function identified)

50% = unpredictable - there is always going to be some uncertainty about the dose you should give someone

Question 4

What can individual variation mean for drug taking?

Answer 4

It may mean they are more or less effective at metabolizing a drug. It may mean they have an adverse reaction to the drug. It may mean they have unfavorable drug interactions.

Question 5

What are some variations among alcohol and acetaldehyde dehyrdogenases?

Answer 5

Alcohol dehydrogenase breaks down alcohol into an acetaldehyde (toxic/a carcinogen) and then acetaldehyde dehydrogenous breaks down the this compound into the harmless acetic acid (vinegar).

There are several genetic variations of these drugs such as ADH22 (increased ADH activity so heaps of acetaldehyde produced) and ALDH22 (decreased ALD so heaps of acetaldehyde). If these two enzymes are paired together then you have very little ethanol as it is broken down so fast but lots of acetaldehyde so you dont get drunk but get adverse reactions like flushing.

Around 50% or more of asians have this variation.