CETP Drug Interactions 1 — Questions and Answers
Question 1: Which enzyme system is primarily responsible for metabolizing the majority of drugs, making it the most common site of pharmacokinetic drug-drug interactions?
- Cytochrome P450 (CYP) system (Correct answer)
- Monoamine oxidase (MAO)
- Glucuronosyltransferase (UGT)
- Acetylcholinesterase
Correct answer: Cytochrome P450 (CYP) system
The cytochrome P450 enzyme system in the liver metabolizes approximately 70-80% of all drugs, making it the most frequent source of clinically significant drug-drug interactions.
Question 2: A patient stabilized on warfarin begins taking fluconazole for a fungal infection. What is the most likely pharmacokinetic outcome?
- Decreased warfarin levels due to enzyme induction
- Increased warfarin levels due to CYP2C9 inhibition (Correct answer)
- No change in warfarin levels
- Decreased warfarin absorption from the GI tract
Correct answer: Increased warfarin levels due to CYP2C9 inhibition
Fluconazole is a potent CYP2C9 inhibitor; since warfarin is primarily metabolized by CYP2C9, co-administration leads to elevated warfarin plasma levels and increased bleeding risk.
Question 3: Grapefruit juice inhibits which intestinal enzyme, thereby increasing the bioavailability of certain calcium channel blockers and statins?
- CYP2D6
- CYP1A2
- CYP3A4 (Correct answer)
- CYP2C19
Correct answer: CYP3A4
Grapefruit juice irreversibly inhibits intestinal CYP3A4, reducing first-pass metabolism of drugs such as felodipine, simvastatin, and lovastatin, leading to elevated plasma concentrations.
Question 4: Which drug-drug interaction mechanism is occurring when two highly protein-bound drugs compete for albumin binding sites, potentially increasing the free fraction of one drug?
- Pharmacodynamic synergism
- Protein-binding displacement (Correct answer)
- Enzyme induction
- Renal tubular competition
Correct answer: Protein-binding displacement
Protein-binding displacement occurs when a drug with higher albumin affinity displaces a previously bound drug, transiently increasing its free (active) concentration.
Question 5: The concurrent use of an SSRI and a monoamine oxidase inhibitor (MAOI) can cause which potentially fatal adverse reaction?
- Neuroleptic malignant syndrome
- Stevens-Johnson syndrome
- Serotonin syndrome (Correct answer)
- Anticholinergic toxicity
Correct answer: Serotonin syndrome
Combining SSRIs with MAOIs causes excessive serotonergic stimulation, leading to serotonin syndrome characterized by hyperthermia, neuromuscular abnormalities, and autonomic instability.
Question 6: Which type of drug interaction occurs when two drugs with opposing pharmacological effects are combined, such as a beta-agonist and a beta-blocker?
- Pharmacokinetic antagonism
- Pharmacodynamic antagonism (Correct answer)
- Chemical incompatibility
- Chelation interaction
Correct answer: Pharmacodynamic antagonism
Pharmacodynamic antagonism results when two drugs exert opposing effects at the same or related receptors, reducing the efficacy of one or both agents.
Question 7: Rifampin (rifampicin) is a potent inducer of CYP3A4. Which of the following clinical consequences would most likely result from co-administering rifampin with oral contraceptives?
- Increased contraceptive effect due to higher estrogen levels
- Reduced contraceptive efficacy due to accelerated hormone metabolism (Correct answer)
- Additive hepatotoxicity without affecting contraceptive levels
- Increased rifampin toxicity due to competitive inhibition
Correct answer: Reduced contraceptive efficacy due to accelerated hormone metabolism
Rifampin induces CYP3A4, dramatically accelerating the metabolism of ethinyl estradiol and progestin in oral contraceptives, leading to subtherapeutic hormone levels and contraceptive failure.
CETP Drug Interactions 1
Which enzyme system is primarily responsible for metabolizing the majority of drugs, making it the most common site of pharmacokinetic drug-drug interactions?