Drug Interactions Practice Questions

Q: Zidovudine toxicity is increased by all except?

Azithromycin. **Explanation:** Zidovudine (AZT), a Nucleoside Reverse Transcriptase Inhibitor (NRTI), is primarily metabolized in the liver via **glucuronidation** (by UGT enzymes) and is known for its significant **bone marrow toxicity** (anemia and neutropenia). **1. Why Azithromycin is the correct answer:** Azithromycin is a macrolide antibiotic that, unlike Erythromycin or Clarithromycin, **does not inhibit Cytochrome P450 enzymes** or interfere with the glucuronidation pathway of Zidovudine. It has no significant myelosuppressive effects. Therefore, it does not increase the toxicity of Zidovudine. **2. Why the other options are incorrect:** * **Probenecid:** It inhibits the hepatic glucuronidation of Zidovudine and reduces its renal excretion. This leads to increased plasma levels of Zidovudine, significantly raising the risk of toxicity. * **Cisplatin & Cyclophosphamide:** These are potent chemotherapeutic agents. Zidovudine’s dose-limiting toxicity is **myelosuppression**. When co-administered with other bone marrow depressants like Cisplatin or Cyclophosphamide, there is an additive/synergistic effect on hematotoxicity, increasing the risk of severe anemia and leukopenia. **High-Yield Clinical Pearls for NEET-PG:** * **Drug of Choice:** Zidovudine is used for the prevention of **mother-to-child transmission (MTCT)** of HIV during pregnancy and labor. * **Adverse Effects:** The most common side effect is **anemia** (macrocytic) and **neutropenia**. It can also cause nail hyperpigmentation and myopathy. * **Drug Interactions:** Apart from Probenecid, drugs like **Paracetamol (Acetaminophen)** can also increase Zidovudine toxicity by competing for glucuronidation. **Stavudine** should never be combined with Zidovudine as they compete for the same phosphorylation pathway (antagonism).

Q: Which of the following is a CYP-450 inducer?

DDT. The Cytochrome P450 (CYP450) enzyme system is the primary pathway for drug metabolism in the liver. **Enzyme Inducers** are substances that increase the synthesis and activity of these enzymes, leading to faster metabolism and decreased plasma levels of co-administered drugs [1]. **Why DDT is correct:** **DDT (Dichlorodiphenyltrichloroethane)**, an organochlorine insecticide, is a potent, long-acting inducer of hepatic microsomal enzymes. Although its clinical use is banned, it remains a classic pharmacological example of an environmental pollutant that stimulates the CYP450 system. Other common inducers include Rifampicin, Phenytoin, Carbamazepine, Phenobarbitone, and Chronic Alcoholism. **Why the other options are incorrect:** * **Cimetidine (A):** A classic H2-receptor blocker and a potent **CYP-inhibitor** [2]. It often leads to toxic levels of drugs like Warfarin and Theophylline. * **Ketoconazole (B):** An antifungal agent that is a well-known **CYP-inhibitor** (specifically CYP3A4) [1, 2]. * **Erythromycin (C):** A macrolide antibiotic that acts as a **CYP-inhibitor** [2]. (Note: Azithromycin is the exception among macrolides as it does not significantly inhibit CYP enzymes). **High-Yield Clinical Pearls for NEET-PG:** * **Mnemonic for Inducers (GPRS Cell Phone):** **G**riseofulvin, **P**henytoin, **R**ifampicin, **S**moking, **C**arbamazepine, **P**henobarbitone (and DDT). * **Mnemonic for Inhibitors (VITAMIN K):** **V**alproate, **I**soniazid, **T**urmeric, **A**miodarone, **M**acrolides, **I**ndinavir, **N**etupitant, **K**etoconazole (and Cimetidine/Grapefruit juice). * **Clinical Impact:** Inducers can lead to **therapeutic failure** (e.g., failure of oral contraceptives), while inhibitors can lead to **drug toxicity**.

Q: Magnesium sulfate potentiates the hypotensive action of which drug?

Nifedipine. **Explanation:** The correct answer is **Nifedipine**. **Mechanism of Interaction:** Magnesium sulfate ($MgSO_4$) acts as a physiological calcium channel blocker. It inhibits the entry of calcium into cells and antagonizes calcium-dependent processes. **Nifedipine** is a dihydropyridine Calcium Channel Blocker (CCB). When used concurrently, they exert a synergistic effect on vascular smooth muscle relaxation. This potentiation can lead to profound vasodilation, resulting in severe, unpredictable hypotension and potentially neuromuscular blockade. This interaction is clinically significant in the management of pre-eclampsia and eclampsia, where both drugs may be considered. **Analysis of Incorrect Options:** * **A. Methyldopa:** A centrally acting $\alpha_2$ agonist. While used in pregnancy-induced hypertension (PIH), it does not share a common pathway with magnesium’s calcium-antagonizing properties. * **C. Enalapril:** An ACE inhibitor. Its hypotensive effect is mediated through the renin-angiotensin-aldosterone system (RAAS). It is also contraindicated in pregnancy due to teratogenicity (renal dysgenesis). * **D. Hydralazine:** A direct-acting vasodilator. While it causes hypotension, its mechanism (primarily involving $K^+$ channels or $IP_3$ inhibition) is not directly potentiated by magnesium in the same synergistic manner as CCBs. **High-Yield Clinical Pearls for NEET-PG:** * **Drug of Choice:** $MgSO_4$ is the drug of choice for the treatment and prophylaxis of seizures in **Eclampsia**. * **Toxicity Sign:** The first sign of Magnesium toxicity is the **loss of deep tendon reflexes (patellar reflex)** (at 7–10 mEq/L). * **Antidote:** The specific antidote for Magnesium toxicity is **10% Calcium Gluconate** (10 mL IV over 10 mins). * **Monitoring:** Always monitor urine output, respiratory rate, and knee jerk when a patient is on $MgSO_4$.

Q: Oral contraceptive pill failure is associated with the use of which of the following medications?

Valproate. **Explanation:** The core concept behind oral contraceptive pill (OCP) failure is the induction of **Cytochrome P450 (CYP450) enzymes** in the liver. These enzymes accelerate the metabolism of estrogen and progesterone, reducing their serum concentrations below the therapeutic threshold required to inhibit ovulation. **Why Valproate is the Correct Answer (in the context of this question):** Unlike most older antiepileptics, **Sodium Valproate is an enzyme inhibitor**, not an inducer. Therefore, it does **not** increase the metabolism of OCPs and is **not** associated with OCP failure. In the context of "except" type questions or identifying the outlier in a list of drugs that cause failure, Valproate stands out because it maintains (or even slightly increases) the efficacy of the pill. **Analysis of Incorrect Options (Enzyme Inducers):** * **Rifampicin:** The most potent inducer of CYP3A4. It significantly lowers OCP levels and is the most common cause of drug-induced OCP failure. * **Phenobarbitone & Phenytoin:** These are classic hepatic enzyme inducers. They increase the clearance of synthetic steroids, necessitating a higher dose of estrogen (at least 50μg) or an alternative form of contraception. **High-Yield Clinical Pearls for NEET-PG:** * **Enzyme Inducers (Cause OCP Failure):** Rifampicin, Phenytoin, Carbamazepine, Phenobarbitone, Griseofulvin, and St. John’s Wort. * **Enzyme Inhibitors (Safe with OCPs):** Valproate, Sodium Valproate, and Levetiracetam. * **Clinical Management:** If a patient must take enzyme-inducing drugs, the WHO recommends using a Long-Acting Reversible Contraceptive (LARC) like an **IUCD** or **Injectable Medroxyprogesterone Acetate (DMPA)**, as these are not affected by first-pass hepatic metabolism.

Q: Which of the following anti-tuberculosis drugs should not be given to an AIDS patient?

Rifampicin. ### Explanation The correct answer is **Rifampicin**. **Why Rifampicin is avoided in certain AIDS patients:** The primary concern in treating a patient with both HIV and Tuberculosis (TB) is **drug-drug interactions**. Rifampicin is a **potent inducer of the Cytochrome P450 (CYP3A4) enzyme system**. Most Protease Inhibitors (PIs) and Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs), which are cornerstones of Highly Active Antiretroviral Therapy (HAART), are metabolized by this same enzyme system. When Rifampicin is administered, it significantly accelerates the metabolism of these antiretroviral drugs, leading to sub-therapeutic plasma levels, treatment failure, and the development of drug resistance. In clinical practice, **Rifabutin** is often used as a substitute because it is a much weaker enzyme inducer. **Why the other options are incorrect:** * **Ethambutol:** It does not interfere with the CYP450 system and has no significant interactions with HAART. Its main side effect is optic neuritis. * **Streptomycin:** An aminoglycoside that is excreted renally. It does not interact with the hepatic metabolism of antiretroviral drugs. * **Pyrazinamide:** It is a key component of the short-course intensive phase and does not have major metabolic interactions with HIV medications. **NEET-PG High-Yield Pearls:** * **Drug of Choice:** If a patient is on a PI-based regimen, **Rifabutin** is preferred over Rifampicin. * **Efavirenz Exception:** Rifampicin can be used if the patient is on an **Efavirenz-based** regimen (though the dose of Efavirenz may need adjustment). * **IRIS:** Be alert for **Immune Reconstitution Inflammatory Syndrome**, which occurs when the immune system recovers and reacts aggressively to the TB bacilli. * **Mnemonic:** Rifampicin **"Ramps up"** enzymes (Inducer); Cimetidine/Ketoconazole **"Cuts down"** enzymes (Inhibitors).

Q: All of the following are microsomal enzyme inhibitors except?

Glucocorticoids. **Explanation:** The correct answer is **Glucocorticoids** because they are **microsomal enzyme inducers**, not inhibitors. **1. Why Glucocorticoids are the correct answer:** Microsomal enzymes (primarily Cytochrome P450 enzymes in the liver) are responsible for the metabolism of various drugs. **Enzyme Inducers** increase the synthesis of these enzymes, leading to faster metabolism and decreased plasma levels of co-administered drugs. Glucocorticoids (like Dexamethasone) act as inducers, whereas the question asks for the "exception" among inhibitors. **2. Analysis of Incorrect Options (Enzyme Inhibitors):** * **Cimetidine:** A classic, potent H2-receptor antagonist known for inhibiting multiple CYP isoforms (CYP1A2, 2C9, 2D6, 3A4). It frequently causes drug interactions (e.g., increasing Warfarin or Theophylline levels). * **Ciprofloxacin:** A Fluoroquinolone that specifically inhibits **CYP1A2**, which can lead to toxicity of drugs like Theophylline. * **Isoniazid (INH):** A primary anti-tubercular drug that inhibits microsomal enzymes, notably increasing the levels of Phenytoin and Carbamazepine. **3. Clinical Pearls & High-Yield Facts for NEET-PG:** To remember these for the exam, use these popular mnemonics: * **Enzyme Inhibitors (VITAMIN K):** **V**alproate, **I**soniazid, **T**ame (Cimetidine), **A**miodarone, **M**acrolides (except Azithromycin), **I**ndinavir, **N**eferodone, **K**etoconazole (and other Azoles), plus **Ciprofloxacin** and **Grapefruit juice**. * **Enzyme Inducers (GPRS Cell Phone):** **G**riseofulvin, **P**henytoin, **R**ifampicin, **S**moking, **C**arbamazepine, **P**henobarbitone. Note: **Glucocorticoids** and **Chronic Alcoholism** also fall into this category. **Key Concept:** Inhibition is usually rapid (starts within 24 hours), whereas Induction is a slower process as it requires new protein synthesis.

Q: Disulfiram-like reaction is commonly caused by which of the following?

Metronidazole. **Explanation:** **Metronidazole** is the correct answer because it inhibits the enzyme **aldehyde dehydrogenase**. Under normal conditions, alcohol is metabolized into acetaldehyde, which is then converted into acetic acid by aldehyde dehydrogenase. When this enzyme is inhibited, acetaldehyde accumulates in the blood, leading to a "Disulfiram-like reaction." [2] Symptoms include intense flushing, tachycardia, palpitations, nausea, vomiting, and hypotension. Patients must be advised to avoid alcohol during and for at least 48–72 hours after completing metronidazole therapy. **Analysis of Incorrect Options:** * **A. Penicillin:** These are beta-lactam antibiotics that inhibit cell wall synthesis. They are not associated with alcohol metabolism interference. * **C. Tetracycline:** These inhibit the 30S ribosomal subunit. While they have several side effects (e.g., photosensitivity, teeth discoloration), they do not cause disulfiram-like reactions. * **D. Erythromycin:** A macrolide that inhibits the 50S subunit. It is a potent CYP450 inhibitor but does not affect aldehyde dehydrogenase. [1] **Clinical Pearls for NEET-PG:** * **Other drugs causing Disulfiram-like reactions:** * **Cephalosporins:** Specifically those containing the **Methylthiotetrazole (MTT) side chain** (e.g., Cefotetan, Cefoperazone, Cefamandole). * **Sulfonylureas:** First-generation agents like Chlorpropamide. * **Others:** Procarbazine (anticancer), Griseofulvin (antifungal), and Tinidazole. * **Mnemonic:** "Many Compounds Can Cause Terrible Reactions" (Metronidazole, Chlorpropamide, Cephalosporins, Cefotetan, Tinidazole, Retinoids/Griseofulvin).

Q: A 54-year-old man, currently taking erythromycin for bronchitis and another medication for gastroesophageal reflux disease (GERD), is brought to the emergency department after experiencing several syncopal episodes. If an electrocardiogram reveals torsades de pointes, what medication is the patient most likely taking for his reflux disease?

Cisapride. ### Explanation **Correct Option: A. Cisapride** The clinical presentation of syncopal episodes and **Torsades de Pointes (TdP)** on ECG indicates a drug-induced prolongation of the QT interval. **Mechanism:** Cisapride, a prokinetic agent used for GERD, is metabolized by the hepatic enzyme **CYP3A4**. Erythromycin is a potent **CYP3A4 inhibitor**. When taken together, erythromycin inhibits the metabolism of cisapride, leading to toxic plasma levels. Elevated cisapride levels block the delayed rectifier potassium channels ($I_{Kr}$) in the heart, resulting in delayed repolarization, QT prolongation, and life-threatening ventricular arrhythmias like Torsades de Pointes. Due to this high risk of cardiotoxicity, cisapride has been withdrawn or strictly restricted in many markets. **Why other options are incorrect:** * **B. Famotidine:** An $H_2$ receptor antagonist. It does not significantly inhibit CYP enzymes nor is it associated with QT prolongation. * **C. Lansoprazole:** A Proton Pump Inhibitor (PPI). While PPIs can affect the absorption of some drugs, they do not cause TdP when combined with erythromycin. * **D. Metoclopramide:** A D2 receptor antagonist used as a prokinetic. Its primary side effects are extrapyramidal (e.g., dystonia, parkinsonism) rather than cardiac arrhythmias. **High-Yield NEET-PG Pearls:** * **QT Prolonging Drugs (Mnemonic: ABCDE):** **A**ntiarrhythmics (Class IA, III), **B**iotics (Macrolides, Fluoroquinolones), **C**ant Psychotics (Haloperidol), **D**epressants (TCAs), **E**metics (Ondansetron). * **CYP3A4 Inhibitors:** Macrolides (except Azithromycin), Ketoconazole, Grapefruit juice, Ritonavir, and Cimetidine. * **Management of TdP:** The immediate drug of choice for hemodynamically stable Torsades de Pointes is **Intravenous Magnesium Sulfate**.

Q: Which of the following anti-tubercular drugs is avoided in an HIV-positive patient on zidovudine, lamivudine, and indinavir therapy who develops TB?

Rifampicin. The correct answer is **Rifampicin**. The core medical concept here is **drug-drug interactions** mediated by the Cytochrome P450 (CYP450) enzyme system. **Why Rifampicin is avoided:** Rifampicin is a **potent inducer of CYP3A4** and other microsomal enzymes. Indinavir is a Protease Inhibitor (PI) that is metabolized by CYP3A4. When co-administered, Rifampicin significantly decreases the plasma concentration of Indinavir (by up to 90%), leading to sub-therapeutic levels, risk of treatment failure, and development of HIV drug resistance [1]. In clinical practice, **Rifabutin** is preferred over Rifampicin in patients on PIs because it is a much weaker enzyme inducer [1]. **Why other options are incorrect:** * **Pyrazinamide (A), Isoniazid (B), and Ethambutol (C):** These are standard first-line anti-tubercular drugs (ATT) that do not significantly induce or inhibit the metabolism of Protease Inhibitors or Nucleoside Reverse Transcriptase Inhibitors (NRTIs) like Zidovudine and Lamivudine [1]. They can be safely used in this regimen. **High-Yield Clinical Pearls for NEET-PG:** * **Rifampicin & PIs:** Never combine Rifampicin with Protease Inhibitors (except ritonavir-boosted lopinavir in specific doses, though Rifabutin remains the drug of choice). * **NRTIs:** Drugs like Zidovudine and Lamivudine do not undergo CYP metabolism; therefore, Rifampicin does not affect their levels. However, Zidovudine and Isoniazid both cause anemia/sideroblastic changes, requiring monitoring. * **Rifabutin:** The preferred substitute for Rifampicin in HIV patients on PI-based or NNRTI-based HAART [1]. * **Efavirenz:** If a patient is on an NNRTI-based regimen, Efavirenz is the preferred agent to use alongside Rifampicin (dose adjustment may be needed).

Question 1

Zidovudine toxicity is increased by all except?

Accepted Answer

Azithromycin

Answer

Probenecid

Answer

Cisplatin

Answer

Cyclophosphamide

Question 2

Which of the following is a CYP-450 inducer?

Accepted Answer

DDT

Answer

Cimetidine

Answer

Ketoconazole

Answer

Erythromycin

Question 3

Magnesium sulfate potentiates the hypotensive action of which drug?

Accepted Answer

Nifedipine

Answer

Methyldopa

Answer

Enalapril

Answer

Hydralazine

Question 4

Oral contraceptive pill failure is associated with the use of which of the following medications?

Accepted Answer

Valproate

Answer

Rifampicin

Answer

Phenobarbitone

Answer

Phenytoin

Question 5

Which of the following anti-tuberculosis drugs should not be given to an AIDS patient?

Accepted Answer

Rifampicin

Answer

Ethambutol

Answer

Streptomycin

Answer

Pyrazinamide

Question 6

Aspirin is not given to a patient who is already on heparin because aspirin causes:

Accepted Answer

Platelet dysfunction

Answer

Aspirin inhibits the action of heparin

Answer

Enhanced hypersensitivity to heparin

Answer

Therapy of heparin cannot be monitored

Question 7

All of the following are microsomal enzyme inhibitors except?

Accepted Answer

Glucocorticoids

Answer

Cimetidine

Answer

Ciprofloxacin

Answer

Isoniazid

Question 8

Disulfiram-like reaction is commonly caused by which of the following?

Accepted Answer

Metronidazole

Answer

Penicillin

Answer

Tetracycline

Answer

Erythromycin

Question 9

A 54-year-old man, currently taking erythromycin for bronchitis and another medication for gastroesophageal reflux disease (GERD), is brought to the emergency department after experiencing several syncopal episodes. If an electrocardiogram reveals torsades de pointes, what medication is the patient most likely taking for his reflux disease?

Accepted Answer

Cisapride

Answer

Famotidine

Answer

Lansoprazole

Answer

Metoclopramide

Question 10

Which of the following anti-tubercular drugs is avoided in an HIV-positive patient on zidovudine, lamivudine, and indinavir therapy who develops TB?

Accepted Answer

Rifampicin

Answer

Pyrazinamide

Answer

Isoniazid

Answer

Ethambutol

Drug Interactions — MCQs

Drug Interactions — MCQs

On this page

Practice by Chapter

Want unlimited practice?