6. Metabolism

Question 1

Metabolism

Answer 1

Bio transformation: chemical alternation of drugs in the body

Question 2

Goal of Metabolism

Answer 2

Make drugs easier to excrete

Want to make lipophilic drugs hydrophilic for excretion

Question 3

Metabolism Phase I

Answer 3

Oxidation, reduction, hydrolysis

Cytochrome P-450 (CYP450) enzymes: CYP2D6, CYP3AY (decrease drug absorption) metabolize 90% of medication

Question 4

Prodrug

Answer 4

Requires bio transformation to its active metabolite

                 CYP450 enzyme Prodrug  —————————    Active (Inactive).                                         (Metabolite)

Codeine is a prodrug CYP2D6 must activate it to morphine to get pain relief

Question 5

CYP450 Inhibitors

Answer 5

Block metabolic activity of CYP enzymes - occurs quickly

                  CYP450 is inhibited Drug X.    —————————     Metabolite (Substrate, active).                            (Inactive )

Therefore increase in drug X and decrease in metabolites

Supratheraputic, increased toxicity

Question 6

CYP450 Inducers

Answer 6

Increase CYP activity by increasing enzyme synthesis (slow)

                  CYP450 is induced Drug X.    —————————     Metabolite (Substrate, active).                            (Inactive )

Decrease in Drug X and increase in metabolite - decreased therapeutic effect and levels of drug X become sub therapeutic

Question 7

Substrate

Answer 7

Drug that is metabolized ( may be inhibitor/inducer)

Question 8

What would be the clinical implications if drug X were a prodrug and it was exposed to an inhibitor? Inducer?

                  CYP450  Drug X.    —————————     Metabolite (Prodrug, inactive).                         (Active )

Answer 8

Inhibitor - the drug would not be converted to active form and therefore not work - subtheraputic

Inducer - the drug would be in active form to a toxic level, supratheraputic

Question 9

OTCs cause drug-drug interactions

Answer 9

ST. John’s Wort = potent CYP450 inhibitor

Question 10

Metabolism Phase 2

Answer 10

Conjugation ( addition of a polar molecule to a drug) to increase polarity, making drug more hydrophilic and easier to excrete

Reactions involve conjugation with an endogenous substance, which is usually a larger and /or polar molecule