1 Flashcards
(20 cards)
What does ADME stand for in pharmacokinetics?
ADME stands for Absorption, Distribution, Metabolism, and Excretion.
Why is studying drug metabolism and elimination important?
It determines a drug’s pharmacological or toxicological activity, impacts dosing and frequency, and prevents toxic accumulation in the body.
What is the “first-pass effect”?
The first-pass effect refers to the metabolism of an orally administered drug by gut and liver enzymes before it reaches systemic circulation, reducing its bioavailability.
Name three routes by which drugs can be excreted unchanged.
Urine (renal), bile (biliary), and exhaled air (e.g., volatile anesthetics).
How does lipophilicity of a drug influence its metabolism?
Lipophilic (non-polar) drugs tend to accumulate in membranes or fat, so they require metabolic conversion to more polar forms for renal excretion.
What are the two major phases of drug metabolism?
Phase 1 (functionalization/activation) and Phase 2 (conjugation/anabolism).
In Phase 1 metabolism, what are the three main reaction types?
Oxidation (mostly via CYP450), reduction, and hydrolysis.
What is added or exposed on a drug molecule during Phase 1 metabolism?
A functional group, such as a hydroxyl (–OH), amino (–NH₂), or thiol (–SH) group, to create a “handle” for Phase 2 conjugation.
Why can some Phase 1 metabolites be more toxic or carcinogenic than the parent drug?
Because the introduction of reactive groups may create electrophilic intermediates that can bind cellular macromolecules, leading to toxicity.
What is the primary purpose of Phase 2 metabolism?
To conjugate (attach) polar moieties (e.g., glucuronic acid, sulfate, amino acids, glutathione, acetyl groups) to make metabolites more water-soluble for excretion.
Which organ is the principal site for both Phase 1 and Phase 2 metabolism?
The liver.
Name two other tissues (besides the liver) where drug metabolism can occur.
Intestines (gut wall) and kidneys; also lungs, skin, and nasal mucosa to a lesser extent.
What family of enzymes catalyzes most Phase 1 oxidations?
Cytochrome P450 (CYP450) monooxygenase enzymes.
In the CYP450 monooxygenase reaction, which two enzymes collaborate?
Cytochrome P450 enzyme and NADPH–cytochrome P450 reductase.
What cofactor is oxidized to NADP⁺ during a CYP450-mediated reaction?
NADPH is oxidized to NADP⁺.
Give one example of a drug oxidized by CYP450.
Nifedipine is oxidized by CYP3A4.
How does grapefruit juice affect CYP450 activity?
Grapefruit juice inhibits certain CYP450 enzymes (notably CYP3A4), reducing metabolism of drugs and potentially increasing their plasma concentrations.
What dietary component induces CYP450 enzymes?
Brussels sprouts (and cruciferous vegetables) can induce certain CYP450s.
What defines a “prodrug”?
A compound administered in an inactive (or less active) form that requires metabolic conversion (often Phase 1) to become pharmacologically active.
Provide one example of a prodrug and its active metabolite.
Aspirin (acetylsalicylic acid) is hydrolyzed to salicylic acid; aspirin is anti-platelet, salicylic acid is anti-inflammatory.
