SM42/43

Question 1

Glucuronidation

Answer 1

The MOST common Phase II reaction. Covalent attachment of glucuronic acid to drug metabolite

Question 2

Examples of exceptions to the general purpose of drug metabolism (drug inactivation)

Answer 2

1. Metabolization of codeine to morphine (metabolization to a more active drug)
2. Metabolism of acetaminophen by CYPs (creation of toxic product)

Question 3

CYP2D6

Answer 3

enzyme with the most clinically relevant polymorphisms

Polymorphisms affect metabolism of beta blockers (and other drugs targeting the CNS)

Question 4

CYP2C19 polymorphisms

Answer 4

polymorphisms of this enzyme affect metabolism of benzodiazepines (“___azepams” and proton pump inhibitors (“___prazoles”)

Question 5

CYP2C9 polymorphisms

Answer 5

polymorphisms affect metabolism of warfarin and non-steroidal anti-inflammatory agents (NSAIDS)

Question 6

Monoamine oxidase (MAO) metabolizes epinephrine from the adrenal medulla, as well as tyramine, an exogenous amine from food. This ability to metabolize xenobiotics and endogenous agents is called _________

Answer 6

cometabolism

Question 7

Midazolam is a type of _________ used as premedication prior to surgery for its ______ effects

Answer 7

benzodiazepine, sedative

Question 8

How do benzodiazepines work?

Answer 8

Benzodiazepines increase inhibitory transmission via GABAa receptors. GABAa receptors incorporate a chloride channel and open more frequently in the presence of a benzodiazepine

Structurally, all benzodiazepines have a unique diazepine ring (7 membered ring with 2 nitrogens)

Question 9

Common suffixes for benzodiazepines

Answer 9

azolam, azepam

Question 10

________ uses CYPs to be metabolized into two other active metabolites, explaining its long lasting effect

Answer 10

diazepam

Question 11

Inactivation of all ________ occurs by glucuronide formation

Answer 11

benzodiazepines

Question 12

All possible CYP dependent phase 1 rxns

Answer 12

All are a type of oxidation

hydroxylation type 1 (aliphatic)
hydroxylation type 2 (aromatic)
S-oxidation
N-oxidation
N-dealkylation
O-dealkylation

Question 13

All possible cyp independent phase 1 rxns

Answer 13

Oxidations, hydrolysis, and reduction:

1) Cyp independent oxidations (e.g ethanol metabolized to acetate via dehydrogenases)
2) Ester hydrolysis via esterase enzyme
3) Epoxide detoxification via epoxide hydrolases
4) Reduction - super rare

Question 14

Types of phase II reactions

Answer 14

SAGGMeths:
-sulfate conjugation via sulfotransferases

• acetylation via n-acetyltransferases
• glucuronidation via UDP-glucuronyl transferases
• glutathione addition via glutathione s-transferase (GST)
• methyl group addition via methyltransferases