Drug Interactions — MCQs

Drug Interactions Indian Medical PG Practice Questions and MCQs

Question 11: Theophylline levels are increased by all of the following, except?

A. Erythromycin
B. Smoking (Correct Answer)
C. Cimetidine
D. Congestive Heart Failure (CHF)

Explanation: ### Explanation Theophylline is a methylxanthine with a narrow therapeutic index (10–20 µg/mL), primarily metabolized by the hepatic cytochrome P450 enzyme system, specifically **CYP1A2**. **Why Smoking is the Correct Answer:** Cigarette smoking (specifically polycyclic aromatic hydrocarbons) acts as a potent **enzyme inducer** of CYP1A2. This increases the metabolism of theophylline, leading to **decreased** serum levels. Therefore, smokers often require higher doses of theophylline to achieve therapeutic effects. **Why the Other Options are Incorrect:** * **Erythromycin:** This is a macrolide antibiotic that acts as a **CYP450 inhibitor**. It reduces the clearance of theophylline, thereby increasing its plasma concentration and risk of toxicity. * **Cimetidine:** A classic H2-receptor antagonist known for being a broad **enzyme inhibitor**. It significantly inhibits theophylline metabolism, leading to increased levels. * **Congestive Heart Failure (CHF):** In CHF, hepatic congestion and reduced liver blood flow impair the liver's ability to metabolize drugs. This decreased clearance results in **increased** theophylline levels. **High-Yield Clinical Pearls for NEET-PG:** 1. **Enzyme Inducers (Decrease Theophylline):** Rifampicin, Phenytoin, Phenobarbitone, and Smoking. 2. **Enzyme Inhibitors (Increase Theophylline):** Ciprofloxacin (potent), Erythromycin, Cimetidine, and Allopurinol. 3. **Disease States:** Liver cirrhosis and CHF increase theophylline levels due to reduced metabolism. 4. **Toxicity:** Watch for seizures and cardiac arrhythmias if levels exceed 20–30 µg/mL.

Question 12: Aspirin is contraindicated in a patient who is on treatment with which of the following medications?

A. Prednisolone
B. Warfarin (Correct Answer)
C. Theophylline
D. Oral contraceptives

Explanation: ### Explanation The correct answer is **Warfarin**. **1. Why Warfarin is the correct answer:** The interaction between Aspirin and Warfarin is a classic example of both **pharmacokinetic** and **pharmacodynamic** synergism, leading to a significantly increased risk of life-threatening hemorrhage [1, 2]. * **Pharmacokinetic:** Aspirin is highly plasma protein-bound. It displaces Warfarin from albumin binding sites, increasing the free (active) fraction of Warfarin in the blood [2]. * **Pharmacodynamic:** Aspirin inhibits platelet aggregation (via COX-1 inhibition) [3], while Warfarin inhibits the synthesis of clotting factors (II, VII, IX, X). Combining an antiplatelet with an anticoagulant creates a "double hit" on the hemostatic system [2]. Additionally, Aspirin can cause gastric mucosal erosions, providing a potential site for bleeding. **2. Why other options are incorrect:** * **Prednisolone:** While both drugs are ulcerogenic and their combination increases the risk of peptic ulcer disease, it is not an absolute contraindication. They are often used together in rheumatological conditions with PPI prophylaxis. * **Theophylline:** Aspirin does not significantly alter the metabolism or clearance of theophylline. * **Oral Contraceptives:** There is no major direct contraindication. In fact, OCPs are pro-thrombotic, whereas Aspirin is anti-thrombotic. **3. NEET-PG High-Yield Pearls:** * **NSAIDs and Lithium:** NSAIDs (except Aspirin and Sulindac) decrease the renal clearance of Lithium, leading to toxicity. * **Aspirin and Methotrexate:** Aspirin inhibits the renal tubular secretion of Methotrexate, increasing its toxicity. * **Triple Whammy:** The dangerous combination of an **ACE inhibitor/ARB + Diuretic + NSAID** which can precipitate acute renal failure. * **Reye’s Syndrome:** Aspirin is contraindicated in children with viral infections (Influenza/Varicella) due to the risk of fulminant hepatic failure and encephalopathy.

Question 13: Which of the following drug groups reacts unfavourably with lithium?

A. ACE inhibitors (Correct Answer)
B. Morphine
C. Valproate
D. Antipsychotics

Explanation: **Explanation:** **Lithium** has a narrow therapeutic index (0.6–1.2 mEq/L) and is primarily excreted by the kidneys. Its handling in the proximal tubule mimics that of sodium. **1. Why ACE Inhibitors are correct:** ACE inhibitors (e.g., Enalapril, Lisinopril) decrease the production of Aldosterone. This leads to increased sodium excretion (natriuresis) and a subsequent decrease in total body sodium. To compensate, the proximal tubule increases the reabsorption of sodium—and because the kidney cannot distinguish between the two ions—it also increases the **reabsorption of Lithium**. This leads to a significant rise in serum lithium levels, potentially causing **Lithium Toxicity**. **2. Analysis of Incorrect Options:** * **Morphine:** There is no significant pharmacokinetic interaction between opioids and lithium. * **Valproate:** Valproate is often used *with* lithium in the management of Bipolar Affective Disorder (BPAD) as a mood stabilizer. While they have additive side effects (like weight gain or tremors), they do not typically cause a toxic rise in lithium levels. * **Antipsychotics:** While combining lithium with high-dose antipsychotics (like Haloperidol) can rarely cause an encephalopathic syndrome, they do not directly interfere with lithium excretion in the same predictable, unfavorable manner as ACE inhibitors. **High-Yield Clinical Pearls for NEET-PG:** * **Drugs that INCREASE Lithium levels:** "The **D-A-N-T** mnemonic" — **D**iuretics (specifically Thiazides), **A**CE inhibitors/ARBs, **N**SAIDs (except Aspirin/Sulindac), and **T**etracyclines. * **Drugs that DECREASE Lithium levels:** Acetazolamide, Theophylline, Caffeine, and Sodium Bicarbonate (they increase lithium excretion). * **Thiazides** are the most common cause of drug-induced lithium toxicity in clinical practice.

Question 14: Which drugs are known to increase the level of theophylline?

A. Ciprofloxacin
B. Cimetidine
C. Allopurinol
D. All of these (Correct Answer)

Explanation: **Explanation:** Theophylline is a methylxanthine bronchodilator with a **narrow therapeutic index** (10–20 µg/mL). It is primarily metabolized in the liver by the **Cytochrome P450 (CYP1A2 and CYP3A4)** enzyme systems. Any drug that inhibits these enzymes will decrease the clearance of theophylline, leading to increased plasma levels and potential toxicity (seizures, arrhythmias). * **Ciprofloxacin:** A fluoroquinolone that is a potent inhibitor of CYP1A2. It significantly reduces theophylline clearance, often requiring a dose reduction of 30-50%. * **Cimetidine:** An H2-receptor antagonist known as a "pan-enzyme inhibitor." It inhibits multiple CYP isoforms, including those responsible for theophylline metabolism. * **Allopurinol:** Used in gout management, high doses of allopurinol can inhibit the hepatic metabolism of theophylline, leading to elevated serum concentrations. **Why "All of these" is correct:** All three drugs listed are **Enzyme Inhibitors**. Since theophylline relies heavily on hepatic metabolism for elimination, the co-administration of any of these agents increases the risk of theophylline toxicity. **High-Yield Clinical Pearls for NEET-PG:** 1. **Enzyme Inducers (The "Decreasers"):** Drugs like **Rifampicin, Phenytoin, Phenobarbitone, and Smoking** induce CYP enzymes, thereby *decreasing* theophylline levels and necessitating a dose increase. 2. **Toxicity Profile:** Early signs of toxicity include GI upset and tachycardia; severe toxicity manifests as **persistent vomiting, cardiac arrhythmias, and intractable seizures**. 3. **Erythromycin & Clarithromycin:** These macrolides are also frequent "distractors" in exams as they are potent CYP inhibitors that increase theophylline levels (Note: Azithromycin does not significantly inhibit CYP enzymes).

Question 15: Flushing with alcohol is seen in all EXCEPT:

A. Amoxicillin (Correct Answer)
B. Co-trimoxazole
C. Furazolidone
D. Chlorpropamide

Explanation: The question tests your knowledge of the **Disulfiram-like reaction**. This occurs when certain drugs inhibit the enzyme **Aldehyde Dehydrogenase (ALDH)**, leading to the accumulation of acetaldehyde in the blood after alcohol consumption. High levels of acetaldehyde cause symptoms like flushing, tachycardia, nausea, vomiting, and hypotension. ### **Explanation of Options:** * **Amoxicillin (Correct Answer):** Amoxicillin is a penicillin-group antibiotic. It does **not** interfere with alcohol metabolism or inhibit ALDH. Therefore, it does not cause flushing when taken with alcohol. * **Co-trimoxazole:** This sulfonamide combination is a well-known cause of disulfiram-like reactions. Patients are routinely advised to avoid alcohol during treatment. * **Furazolidone:** This is an antiprotozoal/antibacterial agent (often used for infectious diarrhea) that has significant MAO-inhibitory activity and consistently produces a disulfiram-like reaction with alcohol. * **Chlorpropamide:** This is a first-generation sulfonylurea used in diabetes. It is the classic example of a drug causing "Chlorpropamide-Alcohol Flushing" (CPF), a reaction mediated by the inhibition of ALDH. ### **High-Yield Clinical Pearls for NEET-PG:** * **Mnemonic for Disulfiram-like drugs:** "**C**an **F**lush **M**ore **G**roggy **P**eople" (**C**ephalosporins [Cefotetan, Cefoperazone], **F**urazolidone, **M**etronidazole/Tinidazole, **G**riseofulvin, **P**rocarbazine). * **Metronidazole** is the most frequently asked drug in this category. * **Cephalosporins** that cause this reaction usually contain a **methylthiotetrazole (MTT) side chain**. * **Treatment:** Management is primarily supportive (IV fluids and antihistamines); however, prevention through patient counseling is the gold standard.

Question 16: Ketoconazole should not be given to a patient being treated with astemizole because?

A. Ketoconazole induces the metabolism of astemizole.
B. Dangerous ventricular arrhythmias can occur. (Correct Answer)
C. Astemizole inhibits the metabolism of ketoconazole.
D. Astemizole antagonizes the antifungal action of ketoconazole.

Explanation: ### Explanation **1. Why the Correct Answer is Right:** The interaction between **Ketoconazole** and **Astemizole** (a second-generation antihistamine) is a classic example of **metabolic inhibition** leading to cardiotoxicity. * **Mechanism:** Astemizole is metabolized by the hepatic enzyme **CYP3A4**. Ketoconazole is a potent **inhibitor** of CYP3A4. * **Consequence:** Co-administration leads to toxic accumulation of astemizole in the plasma. High levels of astemizole block delayed rectifier potassium channels in the heart, prolonging the QT interval. This can trigger a life-threatening polymorphic ventricular tachycardia known as **Torsades de Pointes**. **2. Why the Incorrect Options are Wrong:** * **Option A:** Ketoconazole is an enzyme **inhibitor**, not an inducer. Enzyme induction would decrease drug levels, whereas here, levels increase to toxic limits. * **Option C:** The interaction is unidirectional in clinical significance; it is Ketoconazole that inhibits the metabolism of Astemizole, not vice versa. * **Option D:** There is no pharmacological antagonism between these two drugs; their primary therapeutic actions (antifungal vs. antihistaminic) do not interfere with each other. **3. Clinical Pearls & High-Yield Facts for NEET-PG:** * **The "Terfenadine/Astemizole" Rule:** Both drugs were largely withdrawn or restricted because of this interaction. **Fexofenadine** (the metabolite of terfenadine) is the safer alternative as it does not cause QT prolongation. * **Other CYP3A4 Inhibitors:** Erythromycin, Clarithromycin, and Ritonavir also cause similar dangerous interactions with Astemizole. * **ECG Hallmark:** Always associate the combination of "Macrolides/Azoles + Astemizole/Terfenadine/Cisapride" with **QT prolongation** and **Torsades de Pointes**.

Question 17: A patient on cisapride develops an upper respiratory tract infection and is prescribed erythromycin. What pharmacological interaction would be expected?

A. Decreased level of erythromycin and exacerbation of UI
B. Decreased effect of cisapride due to enzyme induction by erythromycin
C. Fatal ventricular arrhythmia (Correct Answer)
D. Hemorrhagic cystitis

Explanation: **Explanation:** The correct answer is **C. Fatal ventricular arrhythmia.** **Mechanism of Interaction:** This is a classic example of a **pharmacokinetic drug interaction** involving enzyme inhibition. Cisapride is a prokinetic agent metabolized primarily by the hepatic enzyme **CYP3A4**. Erythromycin is a potent **inhibitor of CYP3A4**. When co-administered, erythromycin inhibits the metabolism of cisapride, leading to toxic plasma levels of the drug. Cisapride has a known side effect of **prolonging the QT interval** by blocking the delayed rectifier potassium channels ($I_{Kr}$) in the heart. Elevated levels of cisapride significantly increase this risk, leading to a life-threatening polymorphic ventricular tachycardia known as **Torsades de Pointes (TdP)**, which can progress to fatal ventricular fibrillation. **Analysis of Incorrect Options:** * **Option A:** Erythromycin levels are not significantly affected by cisapride; rather, it is cisapride levels that rise. * **Option B:** Erythromycin is an enzyme **inhibitor**, not an inducer. An inducer (like Rifampicin) would decrease drug levels, whereas an inhibitor increases them. * **Option C:** Hemorrhagic cystitis is a classic side effect of Cyclophosphamide (due to acrolein), not related to this interaction. **High-Yield Clinical Pearls for NEET-PG:** * **The "QT-Prolonging" List:** Other drugs that prolong the QT interval include Class IA and III antiarrhythmics, Terfenadine, Astemizole, Fluoroquinolones, and Haloperidol. * **CYP3A4 Inhibitors (The "G-PACMAN" Mnemonic):** **G**rapefruit juice, **P**rotease inhibitors, **A**zole antifungals, **C**imetidine, **M**acrolides (except Azithromycin), **A**miodarone, and **N**on-DHP CCBs (Verapamil/Diltiazem). * **Regulatory Note:** Due to this fatal interaction, Cisapride and older antihistamines like Terfenadine have been withdrawn or strictly restricted in many markets.

Question 18: Toxicity of cycloserine is enhanced by?

A. Cycloserine
B. Amphotericin-B
C. Simvastatin
D. Alcohol (Correct Answer)

Explanation: **Explanation:** **Cycloserine** is a second-line antitubercular drug that acts by inhibiting cell wall synthesis (specifically the enzyme alanine racemase). Its clinical use is significantly limited by its **neurotoxicity**, which manifests as tremors, psychosis, and convulsions. **1. Why Alcohol is the Correct Answer:** The neurotoxic effects of cycloserine are significantly potentiated by **Alcohol**. Both substances cross the blood-brain barrier and affect the Central Nervous System (CNS). Alcohol consumption while on cycloserine therapy increases the risk and severity of **seizures** and psychotic episodes. Therefore, patients are strictly advised to avoid alcohol during treatment. **2. Analysis of Incorrect Options:** * **Amphotericin-B:** This is an antifungal known for nephrotoxicity and infusion-related reactions, but it does not have a specific synergistic interaction with cycloserine's neurotoxic profile. * **Simvastatin:** A statin used for dyslipidemia; its primary adverse effect is myopathy/rhabdomyolysis. It does not enhance cycloserine toxicity. * **Cycloserine (Option A):** This is the drug itself. While toxicity is dose-dependent, the question asks for an external factor that enhances its toxicity. **3. High-Yield Clinical Pearls for NEET-PG:** * **Mechanism of Action:** Structural analog of D-alanine; inhibits **L-alanine racemase** and **D-alanyl-D-alanine synthetase**. * **Antidote for Toxicity:** The neurotoxic side effects of cycloserine can be partially ameliorated or prevented by the co-administration of **Pyridoxine (Vitamin B6)**, usually at a dose of 100–150 mg/day. * **Contraindications:** History of epilepsy, depression, or severe psychosis. * **Mnemonic:** Remember the "Psych" in Cycloserine – it causes **Psych**osis and is worsened by Alcohol.

Question 19: Iron tablets should never be given along with which of the following?

A. Water
B. Lemon water
C. Milk (Correct Answer)
D. All of the above

Explanation: **Explanation:** The correct answer is **Milk**. The absorption of oral iron is highly sensitive to the pH of the stomach and the presence of specific dietary ligands. **1. Why Milk is the Correct Answer:** Milk and dairy products are rich in **calcium** and **phosphates**. Calcium competes with iron for absorption in the duodenum, while phosphates (and phytates) form insoluble complexes with iron, significantly reducing its bioavailability. Additionally, milk has a slight neutralizing effect on gastric acid; since iron (ferrous form) requires an acidic environment for optimal absorption, milk further hinders this process. **2. Why Other Options are Incorrect:** * **Water:** This is the ideal vehicle for taking iron tablets as it does not interfere with the chemical state or absorption of the drug. * **Lemon Water:** This is actually **beneficial**. Lemon water contains **Vitamin C (Ascorbic acid)**, which acts as a reducing agent. It maintains iron in the **Ferrous (Fe²⁺)** state, which is more soluble and more easily absorbed than the Ferric (Fe³⁺) state. **NEET-PG High-Yield Pearls:** * **The "Acid" Rule:** Iron absorption is enhanced by acidic environments (Vitamin C, Gastric acid) and inhibited by alkaline environments (Antacids, H2 blockers, PPIs). * **Food Interference:** Apart from milk, iron should not be taken with **tea or coffee** because they contain **tannins**, which bind iron and prevent absorption. * **Best Practice:** For maximum absorption, iron should be taken on an **empty stomach**. However, if gastric irritation occurs (a common side effect), it may be taken with a small amount of food, avoiding dairy and caffeine.

Question 20: Which of the following drugs is known to aggravate cyclosporine nephrotoxicity?

A. Amphotericin B (Correct Answer)
B. Itraconazole
C. Isoniazid
D. Lovastatin

Explanation: ### Explanation **Correct Option: A. Amphotericin B** The primary mechanism behind this interaction is **additive pharmacodynamic nephrotoxicity**. Cyclosporine causes renal vasoconstriction (primarily of the afferent arteriole), leading to decreased renal blood flow and glomerular filtration rate (GFR). Amphotericin B is inherently nephrotoxic as it causes direct tubular damage and further renal vasoconstriction. When used together, they synergistically increase the risk of acute kidney injury (AKI). **Analysis of Incorrect Options:** * **B. Itraconazole:** This is a potent **CYP3A4 inhibitor**. While it increases the plasma concentration of cyclosporine (increasing the *risk* of toxicity), it does not have the direct, additive nephrotoxic profile that Amphotericin B possesses. * **C. Isoniazid:** This is a **CYP450 enzyme inducer** (specifically in chronic use, though it can inhibit some isoforms). It typically *decreases* cyclosporine levels, potentially leading to graft rejection rather than aggravated toxicity. * **D. Lovastatin:** Cyclosporine inhibits the metabolism of statins (via CYP3A4 and OATP1B1). This interaction primarily increases the risk of **myopathy and rhabdomyolysis**, not direct nephrotoxicity. **High-Yield Clinical Pearls for NEET-PG:** * **Other Nephrotoxic Synergists:** Aminoglycosides, NSAIDs, Vancomycin, and Cisplatin also aggravate cyclosporine-induced renal damage. * **Gingival Hyperplasia:** A common side effect shared by Cyclosporine, Phenytoin, and Nifedipine. * **Monitoring:** Therapeutic Drug Monitoring (TDM) is mandatory for cyclosporine due to its narrow therapeutic index and extensive CYP3A4-mediated drug interactions. * **Mnemonic for Cyclosporine Toxicity:** The **6 H's** — **H**ypertension, **H**ypertrichosis (hirsutism), **H**yperplasia (gingival), **H**yperlipidemia, **H**yperkalemia, and **H**epatotoxicity (alongside Nephrotoxicity).

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