Drug Interactions Flashcards

Which enzyme system is primarily responsible for metabolizing the majority of drugs, making it the most common site of pharmacokinetic drug-drug interactions?

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.

A patient stabilized on warfarin begins taking fluconazole for a fungal infection. What is the most likely pharmacokinetic outcome?

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.

Grapefruit juice inhibits which intestinal enzyme, thereby increasing the bioavailability of certain calcium channel blockers and statins?

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.

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?

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.

The concurrent use of an SSRI and a monoamine oxidase inhibitor (MAOI) can cause which potentially fatal adverse reaction?

Answer: Serotonin syndrome

Combining SSRIs with MAOIs causes excessive serotonergic stimulation, leading to serotonin syndrome characterized by hyperthermia, neuromuscular abnormalities, and autonomic instability.

Which type of drug interaction occurs when two drugs with opposing pharmacological effects are combined, such as a beta-agonist and a beta-blocker?

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.

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?

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.

Oral fluoroquinolone antibiotics should be taken at least 2 hours before or 6 hours after antacids containing aluminum or magnesium because of which interaction mechanism?

Answer: Chelation forming insoluble complexes that reduce fluoroquinolone absorption

Polyvalent cations (Al3+, Mg2+, Ca2+, Fe2+) chelate fluoroquinolones in the GI tract, forming insoluble complexes that are poorly absorbed, significantly reducing antibiotic bioavailability.

A patient stabilized on lithium therapy is prescribed ibuprofen for arthritis pain. What pharmacokinetic change should the pharmacist anticipate?

Answer: Increased lithium levels due to reduced renal clearance

NSAIDs inhibit renal prostaglandin synthesis, reducing renal blood flow and decreasing lithium clearance, which raises lithium plasma levels and increases toxicity risk.

Co-administration of simvastatin with which medication carries the highest risk of inducing rhabdomyolysis?

Answer: Gemfibrozil

Gemfibrozil inhibits OATP1B1 and CYP2C8, significantly reducing simvastatin clearance and increasing muscle exposure, leading to a markedly elevated risk of myopathy and rhabdomyolysis.

Digoxin toxicity risk increases significantly when which electrolyte imbalance is caused by a concomitant medication?

Answer: Hypokalemia

Hypokalemia increases the binding of digoxin to Na+/K+-ATPase and enhances its toxic effects; loop and thiazide diuretics can precipitate this interaction by causing potassium wasting.

St. John's Wort (Hypericum perforatum) reduces plasma levels of many medications including cyclosporine and HIV protease inhibitors through which primary mechanism?

Answer: Induction of CYP3A4 and P-glycoprotein

St. John's Wort is a potent inducer of CYP3A4 and P-glycoprotein, accelerating the metabolism and efflux of many drugs, leading to subtherapeutic concentrations.

Tetracycline antibiotics should be taken on an empty stomach and avoided within 2 hours of dairy products because dairy causes which interaction?

Answer: Chelation of tetracycline by calcium ions, reducing absorption

Calcium ions in dairy products chelate tetracyclines to form poorly soluble, non-absorbable complexes in the GI tract, significantly reducing bioavailability.

A patient on warfarin is started on amiodarone for atrial fibrillation. The pharmacist should counsel prescribers to expect which change and take which action?

Answer: Increased INR; reduce warfarin dose and increase monitoring

Amiodarone inhibits CYP2C9 (and CYP3A4), substantially reducing warfarin clearance and elevating INR; the warfarin dose typically needs to be reduced by 30-50% with close INR monitoring.

Which antihypertensive drug class can blunt the hypoglycemia warning signs (tachycardia, tremor) in diabetic patients taking insulin or sulfonylureas, masking a dangerous drug interaction?

Answer: Non-selective beta-blockers

Non-selective beta-blockers mask sympathetically-mediated hypoglycemia symptoms such as tachycardia and tremor, while also prolonging hypoglycemia by inhibiting gluconeogenesis.

Concurrent use of ACE inhibitors with potassium-sparing diuretics (e.g., spironolactone) poses which primary electrolyte risk?

Answer: Hyperkalemia

Both ACE inhibitors (by reducing aldosterone) and potassium-sparing diuretics reduce renal potassium excretion; combined use carries a significant risk of life-threatening hyperkalemia.

A patient taking methotrexate for rheumatoid arthritis requires antibiotic therapy. Which antibiotic combination carries the highest risk of serious methotrexate toxicity?

Answer: Trimethoprim-sulfamethoxazole (TMP-SMX)

TMP-SMX inhibits renal tubular secretion of methotrexate (raising its levels) and also inhibits dihydrofolate reductase synergistically with methotrexate, dramatically increasing bone marrow suppression toxicity.

Which monitoring parameter is most critical when a patient on vancomycin is also prescribed an aminoglycoside antibiotic?

Answer: Serum creatinine and renal function

Both vancomycin and aminoglycosides are nephrotoxic; their combination carries a synergistic risk of acute kidney injury, requiring close monitoring of serum creatinine and drug levels.

Dopamine antagonists (e.g., metoclopramide, haloperidol) reduce the therapeutic efficacy of which medication used in Parkinson's disease?

Answer: Levodopa/carbidopa

Dopamine antagonists block dopamine receptors in the striatum, directly opposing the mechanism of levodopa, thereby reducing its antiparkinsonian effects.

Which drug interaction mechanism is primarily responsible for the reduced efficacy of ciprofloxacin when co-administered with sucralfate?

Answer: Chelation of ciprofloxacin by aluminum ions in sucralfate, reducing absorption

Sucralfate contains aluminum hydroxide, whose Al3+ ions chelate ciprofloxacin in the GI tract, forming poorly absorbed complexes and reducing fluoroquinolone bioavailability by up to 90%.