Pharmacology: Drug Metabolism

Question 1

drug metabolism

Answer 1

enzymatic conversion of drug to another chemical entity

Question 2

what parts of the body contribute to drug metabolism and which is the most important

Answer 2

liver - most important, skin, gut mucosa, kidneys, lungs

Question 3

where are hepatic drug metabolising enzymes embedded

Answer 3

smooth ER of hepatocytes

Question 4

what happens during phase I of drug metabolism

Answer 4

oxidation, reduction, hydrolysis

Question 5

what is involved in and what happens during oxidation

Answer 5

cytochrome p450 enzymes/microsomal haemoproteins incorporate and O2 molecule into the drug creating a hydroxyl group

Question 6

what bonds are susceptible to hydrolysis reactions

Answer 6

ester and amide

Question 7

what happens in people who:

• lack p450 cytochrome activity
• have high p450 cytochrome activity

Answer 7

• high plasma levels = adverse effects

- low plasma levels = decrased effects

Question 8

what are cytochrome p450 proteins

Answer 8

heam proteins involved in liver drug metabolism (CYP1, 2, 3)

Question 9

what does p450 drug oxidation require

Answer 9

p450 enzyme, 02, NADPH, a flavoprotein

Question 10

what happens during phase II

Answer 10

drug combines with a polar molecule forming a water-soluble metabolite
this usually terminates all biological activity and product is readily excreted via kidneys

Question 11

what mechanisms does phase II happen by

Answer 11

• mainly conjugation

- also methylation, sulphination, acetylation

Question 12

what is the rate limiting factor of drug metabolism

Answer 12

enzymation processes due to limited enzyme numbers

Question 13

what type of drugs go straight to phase II

Answer 13

those with pharmacologically active metabolites when administered