Pharmacogenetics affecting PK and PD

Question 1

drug entry and metabolism in liver

Answer 1

from GI, enters the hepatic portal system to the liver before it enters systemic circulation.
within the liver, drugs can be broken down or eliminated

Question 2

what is heavy first pass mechanism

Answer 2

increased elimination in the liver which leads to decreased drug in circulation.

Question 3

two phases of drug metabolism in liver

Answer 3

phase 1: reactive centres introduced to drug molecules
phase 2: conjugation of polar/charged groups at reactive centres

Question 4

effects of metabolism by liver

Answer 4

1. increase hydrophilicity and molecular size
2. decrease passive diffusion across membrane
3. decrease binding affinity for target molecules
4. promote excretion

Question 5

cytochrome P450 as a reactive centre mechanism

Answer 5

powerful oxidising agent

Question 6

types of genetic changes affecting conjugation

Answer 6

substitutions in SNPs
indels (tandem repeats/normal gene)

Question 7

types of conjugation reaction players

Answer 7

1. glutathione
2. glycine
3. sulfation
4. methylation
5. hydrolysis

Question 8

variations in acetylation reaction effects

Answer 8

decreases metabolism of drugs if slow acetylation for clearance, leading to accumulation of drugs within the liver

Question 9

thiopurine-S-methyltransferase (TPMT) variation in gene lead to

Answer 9

decreased enzyme activity-> toxicity from drugs

Question 10

ATP-binding cassette (ABC) mechanism of action

Answer 10

translocate metabolite out of cell