Drug Metabolism

Question 1

What is detrimental to oral activity

Answer 1

Metabolic enzymes

• if its metabolised rapidly, lifetime is short. This doesn’t apply to prodrugs which are made active using metabolic reactions

Question 2

Describe phase 1 metabolism

Answer 2

Reactions which add a polar functional group to a drug

Question 3

Describe phase 2 metabolism

Answer 3

Reactions which add polar molecule to functional group already present on a drug or its metabolites

Question 4

What group is least susceptible to P450 enzymes

Answer 4

Quaternary carbon atoms

Group such as methyl groups and allylic and benzylic carbons are susceptible to oxidation by CP450 enzymes

Question 5

alkenes and aromatic groups can be metabolised to diols. How does this occur?

Answer 5

uses enzymes CYP450 and epoxide hydrolase.
CYP450 will catlayse formation of a epoxide from aromatic ring or alkene.
the epoxide hydrolase catlayses hydrolysis o expoide to make a diol

Question 6

what enzyme is not used in phase 1 metabolic reaction

• flavin-containing monooxygenases
• monoamine oxidases
• glucuronyltransferase
• esterases

Answer 6

glucuronyltransferase

This enzyme works by catalysing transfer or attaching sugar moiety onto polar functional group.
this occurs in phase 2

Question 7

how does monoamine oxidase work and which phase does it work in

Answer 7

catalyses formation of aldehydes rom primary amines in phase 1

Question 8

how does esterases work and in which phase

Answer 8

catalyses hydrolysis of esters in phase 1 metabolic reactions

Question 9

which doesnt occur in phase 1

• reduction of ketones
• conjugation to alchols
• oxidation of alkyl groups
• ester hydrolysis

Answer 9

conjugation to alcohols

Question 10

what role does methyl group play

Answer 10

susceptible metabolic group

Question 11

how can you increase polarity and water solubility of a drug

Answer 11

replace aromatic ring with nitrogen containing heterocyclic ring

Question 12

how can you ncrease hydrophobic character of drug

Answer 12

remove polar functional group

add extra alkyl group

replace alkyl group with larger alkyl group

Question 13

how does adding an methyl group cause the drug lifetime to decrease

Answer 13

it is metabolised by oxidative enyme CYP450 to alcohol or carboxylic acid. The resulting polar metabolites are rapidly excreted.

Question 14

phosphate prodrugs are …… polar in nature than the parent drug

Answer 14

more

they are more water soluble and less likely to cross cell membranes and are more susceptble to metabolism