Drug Interactions — MCQs

Drug Interactions Indian Medical PG Practice Questions and MCQs

Question 151: A patient is being treated with warfarin for atrial fibrillation. Which of the following antibiotics has the highest potential to increase warfarin toxicity due to CYP enzyme inhibition?

A. Ciprofloxacin (Correct Answer)
B. Doxycycline
C. Ceftriaxone
D. Azithromycin

Explanation: ***Ciprofloxacin*** - Among the options listed, **ciprofloxacin** has the most documented potential to increase warfarin effect and bleeding risk. - However, the primary mechanism is **NOT through CYP enzyme inhibition** as stated in the question stem. - Ciprofloxacin's interaction with warfarin occurs through: (1) **disruption of intestinal flora** that produce vitamin K, and (2) possible weak inhibition of **CYP2C9** (the actual enzyme responsible for S-warfarin metabolism). - **Important note:** Ciprofloxacin primarily inhibits **CYP1A2**, which is NOT involved in warfarin metabolism. The question premise has limitations. *Azithromycin* - **Azithromycin** has minimal interaction with the **CYP450 enzyme system**. - Unlike erythromycin and clarithromycin (which inhibit CYP3A4), azithromycin does not significantly inhibit CYP enzymes. - It has a very low potential for clinically significant warfarin interactions. *Doxycycline* - **Doxycycline** has minimal effect on the **CYP450 enzyme system**. - It does not significantly affect **warfarin metabolism** and poses a low risk for drug interactions. - Any reported interactions are likely through disruption of vitamin K-producing gut bacteria rather than CYP inhibition. *Ceftriaxone* - **Ceftriaxone** is primarily eliminated via **renal and biliary excretion**. - It does not interact with the **CYP450 enzyme system**. - It has minimal potential to affect **warfarin metabolism** through CYP pathways. **Clinical Note:** Antibiotics that significantly increase warfarin toxicity through **CYP2C9 inhibition** (the relevant enzyme for warfarin) include **metronidazole**, **sulfamethoxazole-trimethoprim**, and **fluconazole** (antifungal). None of the options in this question are strong CYP2C9 inhibitors.

Question 152: Which of the following drugs acts as an enzyme inducer, potentially reducing the efficacy of other medications?

A. Ketoconazole
B. Rifampin (Correct Answer)
C. Cimetidine
D. Chloramphenicol

Explanation: ***Rifampin*** - **Rifampin** is a potent **CYP450 enzyme inducer**, particularly of **CYP3A4**, which metabolizes many medications. - This induction accelerates the metabolism of co-administered drugs, leading to **decreased plasma concentrations** and reduced therapeutic efficacy. *Ketoconazole* - **Ketoconazole** is a strong **inhibitor** of **CYP3A4**, meaning it slows down the metabolism of other drugs. - This can lead to **increased plasma concentrations** and potential toxicity of co-administered medications. *Cimetidine* - **Cimetidine** is a **CYP450 enzyme inhibitor**, predominantly affecting **CYP1A2, CYP2C9, CYP2D6,** and **CYP3A4**. - Its inhibitory action can prolong the half-life and increase the toxicity of other drugs, rather than reducing their efficacy through induction. *Chloramphenicol* - **Chloramphenicol** is a **CYP450 enzyme inhibitor**, particularly of **CYP2C19** and **CYP3A4**. - It decreases the metabolic clearance of other drugs, elevating their blood levels and increasing the risk of adverse effects.

Question 153: Which of the following antimicrobials should not be given to a chronic asthmatic patient managed on theophylline therapy?

A. Amoxicillin
B. Cefotaxime
C. Erythromycin (Correct Answer)
D. Cotrimoxazole

Explanation: ***Erythromycin*** - **Erythromycin**, a macrolide antibiotic, is a potent inhibitor of the **cytochrome P450 (CYP450) enzyme system**, specifically **CYP1A2**, which is the primary enzyme responsible for theophylline metabolism. - Co-administration of erythromycin can significantly **increase theophylline levels**, leading to toxicity such as **nausea, vomiting, seizures, or cardiac arrhythmias.** - This interaction is clinically significant and erythromycin should be avoided in patients on theophylline therapy. *Amoxicillin* - **Amoxicillin** is a penicillin-class antibiotic that has minimal interaction with theophylline metabolism. - It does not significantly inhibit the **CYP1A2 enzyme** and is generally considered safe to use with theophylline. *Cefotaxime* - **Cefotaxime**, a third-generation cephalosporin, does not significantly affect the metabolism of theophylline. - It does not inhibit **CYP1A2 enzymes** and is safe for use in patients on theophylline therapy. *Cotrimoxazole* - **Cotrimoxazole** (trimethoprim/sulfamethoxazole) may slightly increase theophylline levels by inhibiting some CYP450 isoenzymes, but its effect is generally less pronounced than that of erythromycin. - While caution and monitoring are advised, it is not as strongly contraindicated as erythromycin due to a lower risk of significant toxicity in most cases.

Question 154: Tadalafil should not be given with:

A. Vasodilators (Correct Answer)
B. Antibiotics
C. Vasoconstrictors
D. Valproate

Explanation: ***Vasodilators*** - Tadalafil is a **phosphodiesterase-5 (PDE5) inhibitor** that causes **vasodilation** by increasing cGMP levels, leading to smooth muscle relaxation. - Combining tadalafil with other **vasodilators**, particularly **nitrates**, can lead to a severe and potentially life-threatening drop in **blood pressure (hypotension)**. *Antibiotics* - While some antibiotics, particularly macrolides or azoles, can inhibit **CYP3A4** and increase tadalafil levels, this interaction is typically managed by dose adjustments rather than an absolute contraindication. - The primary concern with administering antibiotics and tadalafil concurrently is **pharmacokinetic interactions**, not a direct pharmacodynamic synergy leading to acute, severe adverse effects. *Vasoconstrictors* - Vasoconstrictors have an effect **opposite** to tadalafil, as they narrow blood vessels. - There is generally no contraindication for co-administration, and in fact, tadalafil's **vasodilatory effects** could potentially **counteract** some of the vasoconstriction, although concurrent use is not typically recommended for erectile dysfunction. *Valproate* - **Valproate** is an **anticonvulsant** and mood stabilizer, and there is no significant or clinically relevant drug interaction established with tadalafil. - It does not share common metabolic pathways or pharmacodynamic effects that would lead to dangerous interactions with tadalafil.

Question 155: Which of the following drug combinations does not exhibit synergistic action?

A. Levodopa and Carbidopa (enhanced Parkinson's treatment)
B. Enalapril and Hydrochlorothiazide (enhanced antihypertensive effect)
C. Hydrochlorothiazide and Triamterene (complementary action) (Correct Answer)
D. Glibenclamide and Metformin (enhanced glycemic control)

Explanation: ***Hydrochlorothiazide and Triamterene (complementary action)*** - This combination exhibits **additive/complementary action**, not true synergism. - **Hydrochlorothiazide** (a thiazide diuretic) works on the distal convoluted tubule to promote sodium and water excretion (with potassium loss), while **triamterene** (a potassium-sparing diuretic) works on the collecting duct to retain potassium. - Their combined diuretic effect is **additive** (1+1=2), not synergistic (1+1>2). - The combination is used to maintain electrolyte balance while achieving diuresis, but does not produce an enhanced therapeutic effect beyond the sum of their individual actions. *Enalapril and Hydrochlorothiazide (enhanced antihypertensive effect)* - **Enalapril** (an ACE inhibitor) and **hydrochlorothiazide** (a diuretic) exhibit **true synergism** in blood pressure reduction. - ACE inhibitors reduce **angiotensin II** and increase **bradykinin**, while diuretics reduce blood volume and activate the renin-angiotensin system (which ACE inhibitors then block). - Their combined effect produces **greater blood pressure reduction** than the sum of their individual effects (1+1>2). *Levodopa and Carbidopa (enhanced Parkinson's treatment)* - **Carbidopa** inhibits peripheral **dopa decarboxylase**, preventing the conversion of levodopa to dopamine outside the CNS. - This exhibits **pharmacokinetic synergism** by allowing more levodopa to cross the blood-brain barrier, where it is converted to **dopamine**. - The therapeutic effect is greatly enhanced (more CNS dopamine with lower levodopa doses and fewer peripheral side effects), demonstrating true synergism. *Glibenclamide and Metformin (enhanced glycemic control)* - **Glibenclamide** (a sulfonylurea) stimulates insulin release from pancreatic beta cells, while **metformin** (a biguanide) reduces hepatic glucose production and improves peripheral insulin sensitivity. - Their combined use provides **synergistic glycemic control** through complementary mechanisms, producing greater HbA1c reduction than either drug alone. - This represents **pharmacodynamic synergism** with enhanced therapeutic efficacy beyond additive effects.

Question 156: Which of the following medications can increase the nephrotoxicity of Amphotericin B?

A. Cyclosporin
B. Acyclovir
C. Vancomycin
D. All of the options (Correct Answer)

Explanation: ***All of the options*** - **Amphotericin B** is known for its nephrotoxic effects, which are exacerbated when co-administered with other nephrotoxic agents. - **Cyclosporin**, **Acyclovir**, and **Vancomycin** are all medications with known nephrotoxic potentials, and their co-administration with Amphotericin B significantly increases the risk of renal damage. *Cyclosporin* - **Cyclosporin** is an immunosuppressant that causes dose-dependent **renal vasoconstriction** and tubular damage, leading to nephrotoxicity. - Concurrent use with Amphotericin B elevates the risk of acute kidney injury due to **additive renal insults**. *Acyclovir* - **Acyclovir**, an antiviral drug, can cause **crystal nephropathy** and direct tubular toxicity, especially with rapid intravenous infusion or in dehydrated patients. - Co-administration with Amphotericin B compounds the likelihood of **renal dysfunction**. *Vancomycin* - **Vancomycin**, an antibiotic, can induce **acute tubular necrosis** and interstitial nephritis, particularly with high trough levels or prolonged therapy. - Its combination with Amphotericin B creates a **synergistic nephrotoxic effect**, increasing the risk of kidney damage.

Question 157: What is the effect of co-administration of rifampicin and ritonavir in patients suffering from AIDS?

A. Area Under Curve decreased by 10%
B. Area Under Curve decreased by 35% (Correct Answer)
C. Area Under Curve increased by 10%
D. Area Under Curve increased by 20%

Explanation: ***Area Under Curve decreased by 35%***- This is the **intended correct answer** for this question, though it should be noted that actual clinical data shows an even more severe interaction.- Rifampicin is a **potent inducer of CYP3A4**, the primary enzyme responsible for ritonavir metabolism.- Co-administration leads to significantly **increased ritonavir clearance** and substantial reduction in its Area Under the Curve (AUC).- **Clinical Note**: In practice, rifampicin reduces ritonavir AUC by approximately **75-85%**, making this combination generally contraindicated or requiring alternative antiretroviral regimens. The 35% figure in this question may reflect a specific study or exam context.*Area Under Curve decreased by 10%*- A 10% decrease would be considered a **clinically minor interaction**, whereas the rifampicin-ritonavir interaction is known to be **severe** due to strong enzyme induction.- This option does not reflect the significant impact of **CYP3A4 induction** by rifampicin on ritonavir's pharmacokinetics.- This magnitude of interaction would not typically require treatment modification.*Area Under Curve increased by 10%*- An increase in AUC would imply that rifampicin is **inhibiting** ritonavir metabolism, which is contrary to its known mechanism as an **enzyme inducer**.- This option is pharmacologically incorrect given rifampicin's role in **CYP450 enzyme induction**.- Rifampicin induces, not inhibits, drug-metabolizing enzymes.*Area Under Curve increased by 20%*- Similar to the 10% increase, a 20% increase in AUC would suggest **enzyme inhibition**, which is not the case with rifampicin.- Rifampicin's primary effect on ritonavir is to **accelerate its metabolism**, leading to reduced, not increased, systemic exposure.- The direction of this interaction is opposite to rifampicin's established pharmacological action.

Question 158: A patient on lithium therapy developed hypertension and was started on a thiazide diuretic. After a few days, he developed coarse tremors and other symptoms suggestive of lithium toxicity. What is the probable mechanism of interaction between thiazide diuretics and lithium?

A. Thiazide increases the tubular reabsorption of lithium (Correct Answer)
B. Thiazide inhibits the metabolism of lithium
C. Thiazides act as an add-on drug to lithium
D. None of the above

Explanation: ***Thiazide increases the tubular reabsorption of lithium*** - Thiazide diuretics cause a decrease in sodium reabsorption in the distal convoluted tubule, leading to increased sodium excretion in urine. - The kidneys, in an attempt to conserve sodium, increase reabsorption in the proximal tubule. Because **lithium** is reabsorbed similarly to sodium in the proximal tubule, this increased reabsorption also affects lithium, leading to a rise in its plasma concentration and toxicity. *Thiazide inhibits the metabolism of lithium* - Lithium is primarily excreted by the kidneys and is not significantly metabolized in the body. - Thiazide diuretics do not affect enzyme systems responsible for drug metabolism. *Thiazides act as an add on the drug to lithium* - This statement is vague and does not explain a mechanism of interaction leading to toxicity. - While both drugs might be prescribed concurrently for different conditions, "add on" does not describe a pharmacological interaction causing altered drug levels. *None of the above* - This option is incorrect because a clear and well-understood mechanism for the interaction between thiazide diuretics and lithium exists.

Question 159: Tadalafil should not be given with which of the following drugs?

A. Amlodipine
B. Hydralazine
C. Nitroglycerin (Correct Answer)
D. Losartan

Explanation: ***Nitroglycerin*** * Tadalafil is a **phosphodiesterase-5 (PDE5) inhibitor** used for erectile dysfunction and pulmonary hypertension. * **All nitrates** including nitroglycerin are **absolutely contraindicated** with PDE5 inhibitors due to synergistic vasodilation causing **severe, potentially fatal hypotension**. * The mechanism involves both drugs increasing cGMP levels through different pathways, leading to profound blood pressure drop. *Hydralazine* * Hydralazine is a **direct arterial vasodilator** acting through different mechanisms (increasing cGMP via nitric oxide). * While caution is advised, it is **not an absolute contraindication** with tadalafil. Blood pressure should be monitored but concurrent use is possible. *Amlodipine* * Amlodipine is a **calcium channel blocker** causing vasodilation by blocking calcium influx into vascular smooth muscle. * **Not contraindicated** with PDE5 inhibitors. May cause additive hypotensive effects requiring dose adjustment, but can be used together safely with monitoring. *Losartan* * Losartan is an **angiotensin II receptor blocker (ARB)** used for hypertension. * **No contraindication** with tadalafil. Both can be safely used together with routine blood pressure monitoring.

Question 160: Which of the following agents requires the MOST caution when combined with spironolactone due to increased risk of hyperkalemia:

A. ACE inhibitors (Correct Answer)
B. Beta-blockers
C. Amlodipine
D. Chlorothiazide

Explanation: ***ACE inhibitors*** - Spironolactone is a **potassium-sparing diuretic** that increases potassium levels by blocking aldosterone's effects in the collecting duct [1]. - **ACE inhibitors** also decrease aldosterone production [2], leading to reduced potassium excretion and a significant risk of **severe hyperkalemia** when combined with spironolactone [1, 2].*Beta-blockers* - While beta-blockers can cause a slight increase in plasma potassium by inhibiting cellular potassium uptake, this effect is generally modest and does not pose a major hyperkalemia risk when co-administered with spironolactone. - Their primary interaction concerns blood pressure and heart rate, not direct potassium handling.*Amlodipine* - Amlodipine is a **calcium channel blocker** that primarily causes vasodilation and does not significantly alter potassium balance. - Therefore, it does not substantially increase the risk of hyperkalemia when used concurrently with spironolactone.*Chlorothiazide* - Chlorothiazide is a **thiazide diuretic** that promotes potassium excretion, leading to a risk of hypokalemia. - When combined with spironolactone, a potassium-sparing diuretic, these agents can **partially offset each other's effects** on potassium balance, potentially reducing the risk of hyperkalemia compared to ACE inhibitors.

Practice by Chapter

Mechanisms of Drug Interactions

Practice Questions

Pharmacokinetic Interactions

Practice Questions

Pharmacodynamic Interactions

Practice Questions

Drug-Food Interactions

Practice Questions

Drug-Disease Interactions

Practice Questions

Clinically Significant Drug Interactions

Practice Questions

Computer Systems for Detecting Drug Interactions

Practice Questions

Management of Drug Interactions

Practice Questions

Drug Interactions in Special Populations

Practice Questions

Role of P-glycoprotein in Drug Interactions

Practice Questions

Want unlimited practice?

Get full access to all questions, explanations, and performance tracking.

Start For Free