Adverse Drug Reactions and Pharmacogenetics

Question 1

Why are the elderly susceptible to ADRs?

Answer 1

1. Lower oral absorption
2. Increased total body fat, decreased total body water changes Vdist.
3. Decreased protein binding in blood
4. Decreased metabolism from old livers

Question 2

Why are children susceptible to ADRs?

Answer 2

1. Immature phyisology

2. Physiology ranges depending on age

Question 3

Why are pregnant women susceptible to ADRs?

Answer 3

Maternal changes in TBF and TBW

Decrease in plasma protein.

Question 4

Type A vs Type B ADRs?

Answer 4

Type A - predictable from drug pharmacology. Effect at site of action, dose depednet, easily recognised.

Type B - unpredictable hypersensitivity reactions.
Subdivided into allergic reaction (B/T cell response) or non-allergic reaction (drug directly binds to immune cells to activate immune system).

Question 5

What is favism, and why is it a problem?

Answer 5

Favism is deficiency in glucose-6-phosphate dehydrogenase (G6PD).

G6PD generates NAPDH for pentose phosphate pathway.
RBCs carry O2, and thus are at risk of free radical damage, relying on G6PD/NADPH protection.
Deficiency = free radicals damage RBCs, causing haemolysis.

Question 6

Describe the metabolism of alcohol and the differences between Caucasian and East Asian genetics.

Answer 6

Alcohol is metabolised by alcohol dehydrogenase (ADH) to form a toxic metabolite, acetaldehyde.

Acetaldehyde is converted to acetate by aldehyde dehydrogenase 2 (ALDH2).

East Asians have genetic variation that results in decreased ALDH2 activity. Acetaldehyde accumulates, causing flushing.