Drug Interactions Practice Questions

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

Dangerous ventricular arrhythmias can occur.. ### 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 Clinical Pearls & High-Yield Facts for NEET-PG:** * **The "Terfenadine/Astemizole" Rule:** Both drugs were largely withdrawn or restricted because of this interaction.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**.

Q: A patient with HIV disease is on Highly Active Anti-Retroviral Therapy (HAART). The patient develops tuberculosis. Which one of the following anti-tubercular drugs interferes with HAART?

Rifampicin. **Explanation:** The correct answer is **Rifampicin**. **1. Why Rifampicin is correct:** Rifampicin is a potent **inducer of the Cytochrome P450 (CYP450) enzyme system**, specifically the CYP3A4 isoenzyme. Most Protease Inhibitors (PIs) and Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) used in HAART are substrates of this same enzyme system. By inducing these enzymes, Rifampicin significantly increases the metabolism of antiretroviral drugs, leading to sub-therapeutic plasma levels, treatment failure, and the development of drug-resistant HIV strains. **2. Why other options are incorrect:** * **Isoniazid (A):** While Isoniazid is a CYP450 inhibitor, it does not have the profound inducing effect that compromises HAART efficacy [1]. Its primary interaction concern is peripheral neuropathy, which can be additive if used with Stavudine (d4T). * **Ethambutol (B) and Pyrazinamide (C):** These drugs do not significantly induce or inhibit the hepatic microsomal enzyme system and do not have major pharmacokinetic interactions with antiretroviral agents. **3. NEET-PG Clinical Pearls & High-Yield Facts:** * **Rifabutin:** In patients on HAART (especially those on PIs), **Rifabutin** is the preferred alternative to Rifampicin because it is a much weaker inducer of the CYP3A4 system. * **Integrase Inhibitors:** If Rifampicin must be used with Dolutegravir, the dose of Dolutegravir must be increased (doubled to 50mg BD). * **IRIS:** Be alert for Immune Reconstitution Inflammatory Syndrome (IRIS) when starting HAART in a TB patient; typically, TB treatment is started first, followed by HAART within 2–8 weeks [2]. * **Mnemonic:** Rifampicin "Ramps up" enzymes (Inducer); Isoniazid "Inhibits" enzymes.

Q: Statin-induced myopathy is NOT exacerbated by which of the following drugs?

Enalapril. **Explanation:** Statins (HMG-CoA reductase inhibitors) are primarily metabolized by the cytochrome P450 system (specifically **CYP3A4**). The most significant adverse effect of statins is skeletal muscle toxicity, ranging from myalgia to life-threatening **rhabdomyolysis**. This risk increases when statins are co-administered with drugs that either inhibit their metabolism or share similar toxic profiles. **1. Why Enalapril is the correct answer:** Enalapril is an **ACE inhibitor** used for hypertension and heart failure. It does not inhibit the CYP3A4 enzyme system, nor does it possess intrinsic muscle toxicity. Therefore, it does not increase the plasma concentration of statins or exacerbate myopathy. **2. Why the other options are wrong:** * **Erythromycin (Option C):** This is a potent **CYP3A4 inhibitor**. It slows down the metabolism of statins (like Simvastatin and Lovastatin), leading to toxic plasma levels and a significantly higher risk of myopathy. * **Clofibrate & Nicotinic Acid (Options D & A):** Both are lipid-lowering agents. Fibrates (especially Gemfibrozil and Clofibrate) and Niacin have independent risks of causing myopathy. When combined with statins, they exert a **synergistic toxic effect** on muscles. Fibrates also inhibit the glucuronidation of statins, further increasing their levels. **High-Yield Clinical Pearls for NEET-PG:** * **Gemfibrozil** is the fibrate with the highest risk of causing myopathy when combined with statins; **Fenofibrate** is considered safer. * **Pravastatin and Rosuvastatin** are not primarily metabolized by CYP3A4, making them safer choices when a patient must take a CYP3A4 inhibitor. * **Checkpoints:** Always monitor **Serum Creatine Kinase (CK)** levels in patients on statins who complain of muscle pain or weakness. Statins should be discontinued if CK levels exceed **10 times** the upper limit of normal.

Q: A patient suffering from AIDS is on Zidovudine, Lamivudine, and Indinavir therapy. He develops pulmonary tuberculosis for which treatment is started. Which of the following antitubercular drugs should be avoided in him?

Rifampicin. ### Explanation The correct answer is **Rifampicin (Option D)**. **1. Why Rifampicin is avoided:** The patient is on a HAART (Highly Active Antiretroviral Therapy) regimen containing **Indinavir**, which is a **Protease Inhibitor (PI)**. Rifampicin is a potent **microsomal enzyme inducer** (specifically Cytochrome P450 3A4). It significantly increases the metabolism of Protease Inhibitors and Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs), leading to sub-therapeutic plasma levels of these drugs [1]. This can result in treatment failure and the development of drug-resistant HIV strains. **2. Why other options are incorrect:** * **Isoniazid (INH), Ethambutol, and Pyrazinamide:** These drugs do not have significant induction or inhibition effects on the CYP450 enzyme system. They do not interfere with the pharmacokinetics of Indinavir, Zidovudine, or Lamivudine and are considered safe to use in standard doses in HIV-TB co-infection [1]. **3. High-Yield Clinical Pearls for NEET-PG:** * **Rifabutin vs. Rifampicin:** In patients on Protease Inhibitors, **Rifabutin** is the preferred substitute for Rifampicin [1]. It is a much weaker enzyme inducer and has less impact on PI levels [2]. * **Integrase Inhibitors:** If a patient is on **Dolutegravir**, the dose must be doubled (50mg BD instead of OD) if Rifampicin is co-administered. * **Indinavir Side Effect:** Remember that Indinavir is notorious for causing **nephrolithiasis** (kidney stones) and crystalluria; patients must stay well-hydrated. * **Zidovudine Side Effect:** Monitor for **anemia/neutropenia**, as it causes bone marrow suppression. * **Lamivudine:** It is the safest NRTI and is also active against the Hepatitis B virus (HBV).

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

Fatal ventricular arrhythmia. **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.

Q: Toxicity of cycloserine is enhanced by?

Alcohol. **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.

Q: A patient with AIDS is receiving therapy with Zidovudine, Lamivudine, and Indinavir. The patient develops pulmonary tuberculosis and requires treatment initiation. Which of the following medications should be avoided in this patient?

Rifampicin. **Explanation** The core concept in this question is the **drug-drug interaction** between Rifampicin and Protease Inhibitors (PIs) like Indinavir. **1. Why Rifampicin is the Correct Answer:** Rifampicin is a **potent inducer of the Cytochrome P450 (CYP3A4) enzyme** system in the liver. Indinavir, a Protease Inhibitor, is a substrate for the same enzyme. When co-administered, Rifampicin significantly accelerates the metabolism of Indinavir, leading to a **marked reduction (up to 80-90%) in its plasma concentration**. This results in sub-therapeutic levels of the ARV drug, leading to treatment failure and the development of drug-resistant HIV strains. Therefore, Rifampicin is contraindicated in patients taking PI-based regimens. **2. Why Other Options are Incorrect:** * **Isoniazid (B), Ethambutol (C), and Pyrazinamide (D):** These are standard first-line anti-tubercular drugs (ATT) that do not have significant metabolic interactions with Zidovudine, Lamivudine, or Indinavir [1]. They can be safely used in HIV-TB co-infected patients. **3. High-Yield Clinical Pearls for NEET-PG:** * **Alternative:** If a Rifamycin must be used with a Protease Inhibitor, **Rifabutin** is the preferred choice because it is a much weaker inducer of CYP3A4 compared to Rifampicin. * **Efavirenz (NNRTI):** Unlike PIs, Efavirenz can be used with Rifampicin, though a dose adjustment (increasing Efavirenz to 800mg) was previously suggested (current guidelines often maintain 600mg). * **Integrase Inhibitors:** If a patient is on **Dolutegravir**, the dose must be increased to **50mg twice daily** (instead of once daily) if Rifampicin is co-administered. * **Rule of Thumb:** Rifampicin "Ramps up" enzymes (inducer); Cimetidine/Ketoconazole "Kicks them down" (inhibitors).

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

Amphotericin B. ### 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).

Question 1

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

Accepted Answer

Dangerous ventricular arrhythmias can occur.

Answer

Ketoconazole induces the metabolism of astemizole.

Answer

Astemizole inhibits the metabolism of ketoconazole.

Answer

Astemizole antagonizes the antifungal action of ketoconazole.

Question 2

A patient with HIV disease is on Highly Active Anti-Retroviral Therapy (HAART). The patient develops tuberculosis. Which one of the following anti-tubercular drugs interferes with HAART?

Accepted Answer

Rifampicin

Answer

Isoniazid

Answer

Ethambutol

Answer

Pyrazinamide

Question 3

Statin-induced myopathy is NOT exacerbated by which of the following drugs?

Accepted Answer

Enalapril

Answer

Nicotinic acid

Answer

Erythromycin

Answer

Clofibrate

Question 4

In a chronic alcoholic patient, all of the following drugs should be avoided except?

Accepted Answer

Beclomethasone

Answer

Cefamendole

Answer

Metronidazole

Answer

Chlorpropamide

Question 5

What is the primary adverse effect of the combination use of beta-blockers and calcium channel blockers?

Accepted Answer

Heart block

Answer

Hypertension

Answer

Hypotension

Answer

All of the above

Question 6

A patient suffering from AIDS is on Zidovudine, Lamivudine, and Indinavir therapy. He develops pulmonary tuberculosis for which treatment is started. Which of the following antitubercular drugs should be avoided in him?

Accepted Answer

Rifampicin

Answer

Isoniazid (INH)

Answer

Ethambutol

Answer

Pyrazinamide

Question 7

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

Accepted Answer

Fatal ventricular arrhythmia

Answer

Decreased level of erythromycin and exacerbation of UI

Answer

Decreased effect of cisapride due to enzyme induction by erythromycin

Answer

Hemorrhagic cystitis

Question 8

Toxicity of cycloserine is enhanced by?

Accepted Answer

Alcohol

Answer

Cycloserine

Answer

Amphotericin-B

Answer

Simvastatin

Question 9

A patient with AIDS is receiving therapy with Zidovudine, Lamivudine, and Indinavir. The patient develops pulmonary tuberculosis and requires treatment initiation. Which of the following medications should be avoided in this patient?

Accepted Answer

Rifampicin

Answer

Isoniazid

Answer

Ethambutol

Answer

Pyrazinamide

Question 10

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

Accepted Answer

Amphotericin B

Answer

Itraconazole

Answer

Isoniazid

Answer

Lovastatin

Drug Interactions — MCQs

Drug Interactions — MCQs

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