Drug Metabolism Flashcards Preview

Pharmacology > Drug Metabolism > Flashcards

Flashcards in Drug Metabolism Deck (13):
1

Importance

1. Alters pharmacodynamics-makes drugs inactive or less active

2. Alters pharmacokinetics-increases drug clearance and shortens half-lives

3. Affects toxic properties

2

Phase 1 metabolism

Introduces or exposes a polar functional group on parent compound

3

Phase II Metabolism

Conjugation of endogenous compounds to phase I products to yield highly polar conjugates

4

First Pass Effect

Upon administration orally, drugs transported to the portal system to the liver where they are metabolized before reaching systemic circulation which can limit oral bioavailability or highly metabolized drugs

ONLY applies to drugs taken orally

5

Enzymes of Phase I metabolism

CYPs oxidize

Low specificity

Slow-could avoid first pass

Major actors are CYP3A4 and CYP2C9

6

Enzymes of Phase II Metabolism

Specific transferases couple highly polar endogenous compounds with drug metabolites

Major reactions are glucuronidation and glutathione conjugation

7

Glutathione conjugation

Phase II reaction needed to detoxify drugs and carcinogens

Can conjugate ROS to detoxify

8

Isoniazid metabolism

Phase 2 comes BEFORE phase 1

Resulting product is an electrophile. Take B6 while on isoniazid to prevent associated hepatotoxicity

9

Acetaminophen metabolism

Most common route is a phase II reaction

Second most common route is a phase II reaction

Third route is a phase I reaction, yielding first a product that can be excreted OR a product that could lead to HEPATIC CELL DEATH

10

Factors that can affect drug metabolism

Genetics
Age
Gender
Disease
Diet
Smoking
Environment
Drug-drug interactions
Drug-endogenous interactions

11

Genetic differences affecting isoniazid metabolism

NAT2 polymorphism in both alleles of NAT2 slows acetylation (phase II)

Either reduce dose or increase dose interval

12

Things that induce CYP drug metabolism

**St. John's Wart (at CYP3A)

Charcoal
Cruciferous veggies
Smoking
Chronic alcohol consumption

13

Things that inhibit CYP drug metabolism

*Grapefruit juice (CYP3A4)