Drug Interactions Practice Questions

Q: Rifampicin is a potent enzyme inducer. It is most likely to induce the metabolism of which of the following anti-retroviral drugs?

Nevirapine. **Explanation:** **Mechanism and Correct Answer:** Rifampicin is a classic "macro-inducer" of the hepatic **Cytochrome P450 (CYP3A4)** enzyme system. The metabolism of **Nevirapine**, a Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI), is heavily dependent on the CYP3A4 pathway. When co-administered with Rifampicin, the metabolism of Nevirapine is significantly accelerated, leading to sub-therapeutic plasma levels and a high risk of treatment failure or viral resistance. Therefore, dose adjustments or alternative regimens (like using Rifabutin or Efavirenz) are often required. **Analysis of Incorrect Options:** * **Tenofovir, Abacavir, and Zidovudine (Options A, C, D):** These drugs belong to the **NRTI (Nucleoside Reverse Transcriptase Inhibitor)** class. NRTIs are generally not metabolized by the CYP450 system. They undergo intracellular phosphorylation to become active and are primarily eliminated via renal excretion (Tenofovir) or glucuronidation (Zidovudine). Consequently, their plasma concentrations are not significantly affected by enzyme inducers like Rifampicin. **High-Yield Clinical Pearls for NEET-PG:** * **Rifampicin vs. Protease Inhibitors (PIs):** Rifampicin is contraindicated with most PIs (e.g., Lopinavir, Ritonavir) because it reduces their levels by over 80-90%. * **The "Rifa" Exception:** **Rifabutin** is preferred over Rifampicin in HIV patients on PIs because it is a much less potent enzyme inducer. * **Efavirenz:** Among NNRTIs, Efavirenz is the preferred choice to co-administer with Rifampicin (though the dose may need to be increased to 800mg in some patients). * **Mnemonic:** Rifampicin induces **"G-P-S"** (Griseofulvin, Phenytoin, Sulfonylureas) and **"W-O-C"** (Warfarin, Oral Contraceptives, Corticosteroids).

Q: Oral contraceptive pills (OCPs) are contraindicated in patients receiving which of the following medications?

Rifampicin. **Explanation:** **1. Why Rifampicin is the Correct Answer:** Rifampicin is a potent **inducer of hepatic microsomal enzymes**, specifically the Cytochrome P450 system (notably CYP3A4). When a patient takes Rifampicin alongside Oral Contraceptive Pills (OCPs), the drug-metabolizing enzymes in the liver are upregulated. This leads to the **accelerated metabolism** of the estrogen and progestogen components of the OCP, significantly reducing their plasma concentration. Consequently, the drug levels fall below the therapeutic threshold required to suppress ovulation, leading to **contraceptive failure** and unwanted pregnancy. **2. Why the Other Options are Incorrect:** * **Ethambutol, Streptomycin, and Pyrazinamide:** These are first-line antitubercular drugs (ATT) that do not possess enzyme-inducing or enzyme-inhibiting properties. They do not interfere with the metabolic pathway of steroid hormones; therefore, they do not reduce the efficacy of OCPs. **3. High-Yield Clinical Pearls for NEET-PG:** * **The "Rifampicin Rule":** Rifampicin is one of the most powerful enzyme inducers. Patients on OCPs starting Rifampicin must be advised to use an **alternative/barrier method** of contraception (e.g., condoms) during the treatment and for 4 weeks after stopping Rifampicin. * **Other Enzyme Inducers (Mnemonic: GPRS Cell Phone):** **G**riseofulvin, **P**henytoin, **R**ifampicin, **S**moking, **C**arbamazepine, **P**henobarbitone. All of these can cause OCP failure. * **Broad-spectrum Antibiotics:** Drugs like Ampicillin or Tetracycline can also decrease OCP efficacy, but via a different mechanism: they inhibit gut flora, preventing the **enterohepatic circulation** of estrogens.

Q: The action of theophylline is reduced by which of the following?

Smoking. **Explanation:** Theophylline is a methylxanthine bronchodilator with a narrow therapeutic index, primarily metabolized by the hepatic cytochrome P450 enzyme system, specifically the **CYP1A2** isoenzyme. **Why Smoking is Correct:** Cigarette smoke contains **polycyclic aromatic hydrocarbons**, which act as potent **inducers of CYP1A2**. Enzyme induction increases the rate of theophylline metabolism, leading to decreased plasma concentrations and reduced therapeutic action. Consequently, chronic smokers often require significantly higher doses of theophylline (up to 50-100% more) to achieve the same clinical effect as non-smokers. **Why Other Options are Incorrect:** * **Erythromycin & Cimetidine:** These are classic **enzyme inhibitors**. They inhibit CYP1A2 and CYP3A4, decreasing the clearance of theophylline. This leads to increased plasma levels and a high risk of theophylline toxicity (nausea, seizures, arrhythmias). * **Lithium:** Theophylline actually increases the renal excretion of Lithium by increasing the glomerular filtration rate (GFR). Therefore, theophylline reduces the action of Lithium, not the other way around. **High-Yield Clinical Pearls for NEET-PG:** 1. **Narrow Therapeutic Window:** The therapeutic range for theophylline is 10–20 µg/mL. Toxicity often starts above 20 µg/mL. 2. **Other Inducers (Reduce levels):** Phenytoin, Rifampicin, Phenobarbitone, and Carbamazepine. 3. **Other Inhibitors (Increase levels):** Ciprofloxacin, Clarithromycin, and Allopurinol. 4. **Smoking Cessation:** If a patient on theophylline stops smoking, the dose must be reduced immediately to prevent toxicity as the enzyme induction effect wears off.

Q: Which of the following drugs, when used with carbonic anhydrase inhibitors, can lead to the development of renal stones?

Topiramate. ### Explanation **Correct Option: D. Topiramate** **Mechanism and Rationale:** The development of renal stones (nephrolithiasis) is a known side effect of both **Carbonic Anhydrase Inhibitors (CAIs)** like acetazolamide and the antiepileptic drug **Topiramate**. Topiramate possesses weak carbonic anhydrase inhibitory activity. When CAIs are used, they inhibit the enzyme in the proximal renal tubule, leading to: 1. **Alkalinization of urine:** Reduced hydrogen ion secretion increases urinary pH. 2. **Hypercalciuria and Hypocitraturia:** Citrate normally keeps calcium in solution; its reduction, combined with alkaline urine, promotes the precipitation of **calcium phosphate stones**. Using Topiramate concurrently with other CAIs creates a synergistic effect, significantly increasing the risk of stone formation. **Analysis of Incorrect Options:** * **A. Valproic acid:** Primarily associated with hepatotoxicity, weight gain, and neural tube defects. It does not inhibit carbonic anhydrase. * **B. Carbamazepine:** Known for causing SIADH (hyponatremia), blood dyscrasias, and Stevens-Johnson Syndrome. It has no significant effect on urinary pH or stone formation. * **C. Gabapentin:** Primarily excreted unchanged by the kidneys. Its main side effects are sedation and peripheral edema; it does not influence renal stone pathophysiology. **NEET-PG High-Yield Pearls:** * **Zonisamide:** Another antiepileptic drug that inhibits carbonic anhydrase and carries a similar risk of renal stones. * **Ketogenic Diet:** Often used for refractory epilepsy, this diet also increases the risk of nephrolithiasis; combining it with Topiramate requires cautious monitoring. * **Clinical Advice:** Patients on Topiramate should be advised to maintain **vigorous hydration** to decrease the concentration of stone-forming salts in the urine.

Q: Which of the following drugs may enhance the effect of warfarin and increase the risk of bleeding?

Ketoconazole. **Explanation:** The interaction between drugs and **Warfarin** is a high-yield topic for NEET-PG, primarily revolving around the **Cytochrome P450 (CYP450)** enzyme system. Warfarin is metabolized mainly by CYP2C9. **1. Why Ketoconazole is Correct:** Ketoconazole is a potent **enzyme inhibitor**. By inhibiting the CYP450 enzymes responsible for Warfarin metabolism, it leads to decreased clearance and increased plasma concentrations of Warfarin. This enhances its anticoagulant effect, prolongs the Prothrombin Time (PT)/INR, and significantly increases the clinical risk of bleeding. **2. Analysis of Incorrect Options:** * **Phenobarbitone, Rifampicin, and Carbamazepine:** These are all classic **enzyme inducers**. They increase the synthesis of CYP450 enzymes, which accelerates the metabolism of Warfarin. This leads to *decreased* therapeutic levels of Warfarin, potentially causing treatment failure and increasing the risk of thrombosis (clotting) rather than bleeding. **3. High-Yield Clinical Pearls for NEET-PG:** * **Mnemonic for Enzyme Inhibitors (Increase Warfarin effect):** **VITAMINS K** – **V**erapamil, **I**soniazid, **T**rimethoprim, **A**miodarone, **M**etronidazole, **I**ndinavir, **N**eomycin, **S**ulfonamides, **K**etoconazole (and other azoles). * **Mnemonic for Enzyme Inducers (Decrease Warfarin effect):** **G P R S Cell Phone** – **G**riseofulvin, **P**henytoin, **R**ifampicin, **S**moking, **C**arbamazepine, **P**henobarbitone. * **Key Monitoring:** Always monitor **INR** (International Normalized Ratio) when adding or stopping any drug in a patient on Warfarin. * **Broad-spectrum antibiotics** can also enhance Warfarin's effect by killing gut flora that synthesize Vitamin K.

Q: Co-administration of which of the following drugs with Zidovudine is not preferred?

All of the above. **Explanation:** The primary concern when co-administering drugs with **Zidovudine (AZT)** is the potential for additive toxicity, specifically **bone marrow suppression** and interference with its metabolic pathway. Zidovudine is metabolized in the liver via **glucuronidation** (by the enzyme UDP-glucuronosyltransferase). * **Aspirin and Indomethacin (NSAIDs):** These drugs compete with Zidovudine for the same glucuronidation pathway in the liver. This competition inhibits the metabolism of Zidovudine, leading to increased plasma levels and a significantly higher risk of systemic toxicity, particularly severe anemia and neutropenia. * **Trimethoprim:** While often used in HIV patients for PCP prophylaxis (as Co-trimoxazole), Trimethoprim can cause additive hematological toxicity. Both Zidovudine and Trimethoprim are known to cause bone marrow suppression; their combined use increases the risk of leucopenia and megaloblastic changes. **Why "All of the above" is correct:** Each of these drugs either pharmacokinetically interferes with Zidovudine’s clearance (Aspirin, Indomethacin) or pharmacodynamically enhances its bone marrow toxicity (Trimethoprim). Therefore, their co-administration is generally avoided or monitored very closely. **High-Yield NEET-PG Pearls:** * **Dose-limiting toxicity of Zidovudine:** Anemia and Neutropenia. * **Other drugs to avoid with AZT:** Ganciclovir, Pyrimethamine, and Amphotericin B (due to additive myelosuppression or nephrotoxicity). * **Stavudine (d4T) Interaction:** Never combine Zidovudine with Stavudine because they compete for the same intracellular phosphorylation (activation) pathway, leading to antagonism. * **Drug of choice for preventing vertical transmission (Mother-to-child) of HIV:** Zidovudine (though now often part of HAART regimens).

Q: Which of the following drugs can cause a disulfiram-like reaction?

All of the above. ### Explanation The **disulfiram-like reaction** occurs when certain drugs inhibit the enzyme **aldehyde dehydrogenase (ALDH)**. When alcohol is consumed while taking these drugs, acetaldehyde (a toxic metabolite of ethanol) accumulates in the blood. This leads to distressing symptoms such as flushing, tachycardia, palpitations, nausea, vomiting, and hypotension. **Analysis of Options:** * **Griseofulvin (Option A):** An antifungal used for dermatophytosis. It is a well-known inducer of disulfiram-like reactions and patients are strictly advised to avoid alcohol during treatment. * **Procarbazine (Option B):** An alkylating agent used in Hodgkin’s lymphoma. Besides being a weak MAO inhibitor, it significantly inhibits ALDH, causing severe intolerance to alcohol. * **Chlorpropamide (Option C):** A first-generation sulfonylurea. It is the most notorious drug in its class for causing this reaction (often called "Chlorpropamide-alcohol flush"), mediated by both ALDH inhibition and increased prostaglandin levels. Since all three drugs interfere with acetaldehyde metabolism, **Option D (All of the above)** is the correct answer. ### High-Yield Clinical Pearls for NEET-PG To master this topic, remember the mnemonic **"G-C-P-M-C"** for common drugs causing disulfiram-like reactions: 1. **G**riseofulvin 2. **C**hlorpropamide (1st gen Sulfonylureas) 3. **P**rocarbazine 4. **M**etronidazole (The most commonly tested clinical example) 5. **C**ephalosporins (Those with the **MTT side chain**: Cefoperazone, Cefotetan, Cefamandole) * **Mechanism:** Inhibition of Aldehyde Dehydrogenase $\rightarrow$ $\uparrow$ Acetaldehyde. * **Treatment:** Management is primarily supportive (IV fluids and antiemetics); symptoms usually subside once the drug is cleared.

Question 1

Rifampicin is a potent enzyme inducer. It is most likely to induce the metabolism of which of the following anti-retroviral drugs?

Accepted Answer

Nevirapine

Answer

Tenofovir

Answer

Abacavir

Answer

Zidovudine

Question 2

Oral contraceptive pills (OCPs) are contraindicated in patients receiving which of the following medications?

Accepted Answer

Rifampicin

Answer

Ethambutol

Answer

Streptomycin

Answer

Pyrazinamide

Question 3

The action of theophylline is reduced by which of the following?

Accepted Answer

Smoking

Answer

Erythromycin

Answer

Cimetidine

Answer

Lithium

Question 4

Which of the following drugs, when used with carbonic anhydrase inhibitors, can lead to the development of renal stones?

Accepted Answer

Topiramate

Answer

Valproic acid

Answer

Carbamazepine

Answer

Gabapentin

Question 5

Which of the following drugs may enhance the effect of warfarin and increase the risk of bleeding?

Accepted Answer

Ketoconazole

Answer

Phenobarbitone

Answer

Rifampicin

Answer

Carbamazepine

Question 6

A patient being treated with ketoconazole develops Gastroesophageal Reflux Disease (GERD). Which of the following drugs should not be prescribed to him?

Accepted Answer

Cisapride

Answer

Itopride

Answer

Metoclopramide

Answer

Domperidone

Question 7

Co-administration of which of the following drugs with Zidovudine is not preferred?

Accepted Answer

All of the above

Answer

Indomethacin

Answer

Aspirin

Answer

Trimethoprim

Question 8

What is the effect of concomitant use of hydrochlorothiazide on serum lithium levels?

Accepted Answer

Serum lithium levels rise

Answer

Serum lithium levels decrease

Answer

Serum hydrochlorothiazide levels rise

Answer

Serum hydrochlorothiazide levels fall

Question 9

Why should a patient on verapamil not be given a beta-blocker?

Accepted Answer

Conduction block

Answer

Bronchospasm

Answer

Neurogenic shock

Answer

Anaphylaxis

Question 10

Which of the following drugs can cause a disulfiram-like reaction?

Accepted Answer

All of the above

Answer

Griseofulvin

Answer

Procarbazine

Answer

Chlorpropamide

Drug Interactions — MCQs

Drug Interactions — MCQs

On this page

Practice by Chapter

Want unlimited practice?