Drug Interactions Practice Questions

Q: All of the following are inducers of the microsomal enzyme system except?

Ticlopidine. ### Explanation The microsomal enzyme system, primarily the **Cytochrome P450 (CYP450)** family in the liver, is responsible for the metabolism of many drugs. **Enzyme Inducers** increase the synthesis of these enzymes, leading to faster metabolism and decreased plasma concentrations of co-administered drugs. **Why Ticlopidine is the Correct Answer:** Ticlopidine is an antiplatelet drug that acts as a **microsomal enzyme inhibitor**, specifically inhibiting CYP2C19. Unlike inducers, inhibitors decrease enzyme activity, which can lead to toxic levels of other drugs (e.g., phenytoin or theophylline) if administered concurrently. **Analysis of Incorrect Options (Inducers):** * **A. Carbamazepine:** A potent inducer of CYP3A4. It is unique because it is an **auto-inducer**, meaning it induces its own metabolism over time. * **B. Phenytoin:** A classic broad-spectrum inducer that affects multiple CYP isoforms, often leading to significant drug-drug interactions (e.g., reducing the efficacy of oral contraceptives). * **C. Phenobarbitone:** One of the most powerful known inducers. It increases the synthesis of glucuronyl transferase and CYP enzymes, and is clinically used in neonatal jaundice to accelerate bilirubin conjugation. **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. * **Mnemonic for Inhibitors (VITAMIN K):** **V**alproate, **I**soniazid, **T**iclopidine/Terfenadine, **A**miodarone, **M**acrolides (except Azithromycin), **I**ndinavir, **N**on-DHP CCBs (Verapamil/Diltiazem), **K**etoconazole (and other Azoles). * **Chronic Alcoholism** induces enzymes, whereas **Acute Alcohol intake** inhibits them. * **St. John’s Wort** is a notable herbal enzyme inducer often tested in exams.

Q: Warfarin therapy is prolonged by all except:

Rifampicin. The core concept behind this question is the modulation of **Cytochrome P450 (CYP450)** enzymes and the role of intestinal flora in Vitamin K synthesis. **1. Why Rifampicin is the correct answer:** Warfarin is metabolized primarily by the CYP2C9 enzyme. **Rifampicin** is a potent **microsomal enzyme inducer** [2]. By inducing these enzymes, it accelerates the metabolism of Warfarin, leading to decreased plasma levels and a **reduced** anticoagulant effect (shortened prothrombin time). Therefore, it does *not* prolong Warfarin therapy; it antagonizes it. **2. Why the other options are incorrect:** * **Erythromycin:** This is a known **enzyme inhibitor** [1]. It inhibits CYP450 enzymes, slowing down Warfarin metabolism, which increases its plasma concentration and **prolongs** its effect (increasing the risk of bleeding). * **Amoxicillin & Tetracycline:** Broad-spectrum antibiotics prolong Warfarin therapy through a different mechanism [3]. They eliminate **intestinal bacterial flora** that normally synthesize Vitamin K2 [3]. Since Warfarin works by inhibiting Vitamin K epoxide reductase, a reduction in endogenous Vitamin K levels potentiates Warfarin’s anticoagulant action. **Clinical Pearls for NEET-PG:** * **S-Warfarin** is 3-5 times more potent than R-Warfarin and is metabolized by **CYP2C9** [2]. * **Enzyme Inducers (Reduce Warfarin effect):** Phenytoin, Carbamazepine, Phenobarbitone, Rifampicin, Griseofulvin (Mnemonic: **GPRS Cell Phone**). * **Enzyme Inhibitors (Increase Warfarin effect):** Valproate, Ketoconazole, Cimetidine, Erythromycin, Isoniazid (Mnemonic: **Vitamins K, C, E, I**). * **Monitoring:** Warfarin efficacy is monitored using **PT/INR** (Extrinsic pathway) [3].

Q: All of the following cause inhibition of CYP3A except?

Saquinavir. ### Explanation The Cytochrome P450 (CYP) system, specifically the **CYP3A4** isoform, is responsible for the metabolism of over 50% of clinically used drugs. Understanding its inhibitors and inducers is a high-yield topic for NEET-PG. **Why Saquinavir is the correct answer:** While most Protease Inhibitors (PIs) are known to interact with the CYP system, **Saquinavir** is primarily a **substrate** of CYP3A4 rather than a potent inhibitor. In clinical practice, Saquinavir has such poor bioavailability that it must be "boosted" by another PI (Ritonavir) to reach therapeutic levels. Unlike Ritonavir, it does not significantly inhibit the metabolism of other drugs. **Analysis of Incorrect Options:** * **Ritonavir (Option B):** This is the **most potent inhibitor** of CYP3A4 among the protease inhibitors. It is used pharmacologically in "low doses" specifically to inhibit the metabolism of other PIs (like Lopinavir or Saquinavir), thereby increasing their plasma concentrations (PK boosting). * **Itraconazole (Option C):** Azole antifungals (especially Ketoconazole and Itraconazole) are classic, potent inhibitors of CYP3A4. They frequently cause drug-drug interactions with statins and warfarin. * **Erythromycin (Option D):** Macrolide antibiotics (except Azithromycin) are notorious CYP3A4 inhibitors. They can lead to toxicity of co-administered drugs like Theophylline or Carbamazepine. **NEET-PG High-Yield Pearls:** * **Mnemonic for CYP3A4 Inhibitors (VITAMIN G):** **V**erapamil, **I**traconazole (and other azoles), **T**elithromycin/Tetracycline, **A**miodarone, **M**acrolides (excluding Azithromycin), **I**nhibitors of HIV Protease (**Ritonavir**), **N**efazodone, **G**rapefruit juice. * **The "Azithromycin Exception":** Among macrolides, Azithromycin does not inhibit CYP enzymes and is the safest choice regarding drug interactions. * **Rifampicin** is the most potent universal **inducer** of CYP enzymes.

Q: A patient is taking ketoconazole for fungal infection develops a cold for which he is prescribed terfenadine. What is the likely drug interaction between terfenadine and ketoconazole?

Ketoconazole decreases the metabolism of terfenadine.. ### Explanation **1. Why Option A is Correct:** The interaction between ketoconazole and terfenadine is a classic example of **enzyme inhibition**. Ketoconazole is a potent inhibitor of the hepatic microsomal enzyme **CYP3A4**. Terfenadine is a pro-drug that is normally rapidly metabolized by CYP3A4 into its active, non-toxic metabolite (fexofenadine). When ketoconazole is co-administered, it blocks the metabolism of terfenadine, leading to significantly elevated plasma levels of the parent drug. **2. Why the Other Options are Incorrect:** * **Option B:** Terfenadine does not significantly affect the metabolic enzymes responsible for ketoconazole clearance; the interaction is unidirectional. * **Option C:** This is the opposite of the actual effect. Ketoconazole *increases* terfenadine levels by preventing its breakdown. * **Option D:** There is a major, life-threatening interaction between these two drugs, which led to the withdrawal of terfenadine from many markets. **3. Clinical Pearls & High-Yield Facts for NEET-PG:** * **Mechanism of Toxicity:** High levels of terfenadine (and astemizole) block the **delayed rectifier potassium channels (IKr)** in the heart. * **Clinical Outcome:** This leads to **QT interval prolongation**, which can progress to a life-threatening polymorphic ventricular tachycardia known as **Torsades de Pointes**. * **The "Safe" Alternative:** **Fexofenadine** (the active metabolite of terfenadine) is used clinically because it does not block potassium channels and does not cause cardiotoxicity, even in the presence of CYP3A4 inhibitors. * **Other CYP3A4 Inhibitors:** Be wary of similar interactions with Erythromycin, Clarithromycin, and Grapefruit juice.

Question 1

A 45-year-old man with bronchial asthma is on regular theophylline therapy. He develops a fungal infection and is started on ketoconazole. After 4 –5 days, he presents with nausea, vomiting, tremors, palpitations, and restlessness. His serum theophylline level is found to be elevated. What is the most likely reason for this toxicity?

Accepted Answer

Ketoconazole inhibits CYP450 enzymes, decreasing theophylline metabolism

Answer

Ketoconazole induces CYP450 enzymes, increasing theophylline metabolism

Answer

Theophylline induces ketoconazole metabolism

Answer

Additive pharmacodynamic effect of both drugs

Question 2

Nitrates are contraindicated with which of the following drug classes?

Accepted Answer

Phosphodiesterase-5 (PDE-5) inhibitors

Answer

Sulphonylureas

Answer

Immunomodulators

Answer

Selective Serotonin Reuptake Inhibitors (SSRIs)

Question 3

A diabetic female on Isoniazid (INH) and Rifampicin for tuberculosis developed Deep Vein Thrombosis (DVT). She was started on Warfarin, but her Prothrombin Time (PT) is not elevated. What is the next appropriate step in management?

Accepted Answer

Use Low Molecular Weight Heparin (LMWH)

Answer

Increase the dose of Warfarin

Answer

Replace Warfarin with Acenocoumarol

Answer

Switch Ethambutol for Rifampicin

Question 4

All of the following are inducers of the microsomal enzyme system except?

Accepted Answer

Ticlopidine

Answer

Carbamazepine

Answer

Phenytoin

Answer

Phenobarbitone

Question 5

Which drug may inhibit the cytochrome P450 metabolism of warfarin?

Accepted Answer

Cimetidine

Answer

Ethanol

Answer

Rifampicin

Answer

Procainamide

Question 6

Warfarin therapy is prolonged by all except:

Accepted Answer

Rifampicin

Answer

Amoxicillin

Answer

Erythromycin

Answer

Tetracycline

Question 7

All of the following drugs reduce the efficacy of combined oral contraceptive pills when used together, EXCEPT:

Accepted Answer

Penicillin

Answer

Rifampin

Answer

Griseofulvin

Answer

Carbamazepine

Question 8

All of the following cause inhibition of CYP3A except?

Accepted Answer

Saquinavir

Answer

Ritonavir

Answer

Itraconazole

Answer

Erythromycin

Question 9

A patient is taking ketoconazole for fungal infection develops a cold for which he is prescribed terfenadine. What is the likely drug interaction between terfenadine and ketoconazole?

Accepted Answer

Ketoconazole decreases the metabolism of terfenadine.

Answer

Terfenadine increases the levels of ketoconazole.

Answer

Ketoconazole decreases the levels of terfenadine.

Answer

There is no interaction between these drugs.

Question 10

A 50-year-old patient diagnosed with pulmonary tuberculosis is started on standard drug therapy. After 1.5 months, the patient develops fatigue, low-grade fever, muscle aches, bone pains, and body aches. The patient also complains of pleuritic chest pain. Sputum tests are negative for acid-fast bacilli. Further investigations reveal the patient is positive for anti-histone antibodies. Abnormality in which of the following metabolic processes is responsible for the patient's current condition?

Accepted Answer

Acetylation

Answer

Sulfation

Answer

Glucuronide conjugation

Answer

Hydroxylation

Drug Interactions — MCQs

Drug Interactions — MCQs

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