drug metabolism

Question 1

advantage of drug being lipophilic

Answer 1

can access tissues

Question 2

advantage of drug being water soluble

Answer 2

stays in blood and can be excreted

Question 3

what is drug metabolism

Answer 3

lipid soluble drugs are designs, and are converted in the body to water soluble

Question 4

phases of drug metabolism

Answer 4

phase 1 produces a reactive group to drug to increase polarity, so that phase 2 can occur, where water soluble conjugate added to reactive group

Question 5

explain phase 1- and what carries it out in liver

Answer 5

drug either undergoes oxidation, where new fuctional group is created to form electrophile, or hydrolysis/reduction, where new functional group is unmasked to form nucleophile- oxidation most common (hydroxylation comes first) : done by cytochrome P450 in SER of hepatocytes- 57 enzymes needed these reactive functional groups allow water soluble conjugate to be added

Question 6

phase 1 in aspirin

Answer 6

acetyl group is replaced by H to form salicylic acid

Question 7

different products of phase 1 metabolism

Answer 7

active parent drug becomes inert metabolite most commonly, active parent drug becomes active metabolite, prolonging effect inactive parent drug becomes active metabolite (prodrug)

Question 8

routes of phase 2 metabolism (aspirin)

Answer 8

side chains are added, most commonly glucuronidation- low affinity/high capacity, meaning more likely to occur at high drug dosages- aspirin: UDP-glucoronic acid added

Question 9

phase 2 metabolism (paracetamol) with problem

Answer 9

sulfation is high affinity low capacity- most paracetamol in low doses is sulfated, but once dosage is increased, it undergoes glucuronidation some paracetamol converted into an electrophile called NAPQI via glutathione conjugation in phase 1- then converted into glutathione conjugate via phase 2, but if phase 2 doesn’t occur as glutathione is not present, it can lead to paracetamol overdose as electrophiles are very reactive

Question 10

explain other less common phase 2 metabolism pathways

Answer 10

acetylation involves drug having R group of aromatic amine, and reacting ith acetyl coA methylation involves methyl group amino acid conjugation is either reacting with carboxylic acid group of AA, or its amino group

Question 11

importance of drug metabolism

Answer 11

decreases half life, hence exposure duration is lower, so less likely to accumulate therefore, potency/duration can be changed, so pharmacology of drug determined by metabolism