Drug Interactions Practice Questions

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).

Q: Which of the following pairs of drugs are metabolized by the same Cytochrome enzyme?

Omeprazole and Clopidogrel. **Explanation:** The correct answer is **A. Omeprazole and Clopidogrel**. Both drugs are primary substrates for the isoenzyme **CYP2C19**. **1. Why Option A is Correct:** Clopidogrel is a prodrug that requires activation by the CYP2C19 enzyme to its active thiol metabolite to exert its antiplatelet effect. Omeprazole is also metabolized by (and is a potent inhibitor of) CYP2C19. This shared pathway is clinically significant because omeprazole can competitively inhibit the activation of clopidogrel, potentially leading to reduced antiplatelet efficacy and an increased risk of cardiovascular events. **2. Analysis of Incorrect Options:** * **B. Phenytoin and Tacrolimus:** Phenytoin is primarily metabolized by **CYP2C9** (and 2C19), whereas Tacrolimus is a major substrate of **CYP3A4**. * **C. Paracetamol and Warfarin:** Paracetamol is mainly metabolized via glucuronidation and sulfation (with a small portion via **CYP2E1** to NAPQI), while Warfarin (specifically the more potent S-isomer) is metabolized by **CYP2C9**. * **D. Omeprazole and Warfarin:** As noted, Omeprazole uses **CYP2C19**, while Warfarin uses **CYP2C9**. **High-Yield NEET-PG Pearls:** * **CYP3A4:** The most abundant CYP enzyme; metabolizes ~50% of all drugs (e.g., Statins, CCBs, HIV Protease inhibitors). * **CYP2D6:** Shows significant genetic polymorphism; metabolizes Codeine, Metoprolol, and Haloperidol. * **Enzyme Inducers (GPRS Cell Phone):** **G**riseofulvin, **P**henytoin, **R**ifampicin, **S**moking, **C**arbamazepine, **P**henobarbitone. * **Enzyme Inhibitors (VITAMIN K):** **V**alproate, **I**soniazid, **T**rimethoprim, **A**miodarone, **M**acrolides (except Azithromycin), **I**ndinavir, **N**il (Cimetidine), **K**etoconazole.

Q: A 27-year-old man with epilepsy presents with complaints of persistent lethargy and occasional feelings of intoxication. He does not consume alcohol and is currently taking phenobarbital for the long-term management of tonic-clonic seizures. He was recently started on a medication for the treatment of gastroesophageal reflux disease. Which of the following agents was he most likely prescribed?

Cimetidine. **Explanation:** The patient is experiencing symptoms of **phenobarbital toxicity** (lethargy, ataxia, and "intoxication" feelings) due to a drug-drug interaction. Phenobarbital is a narrow therapeutic index drug metabolized by the hepatic cytochrome P450 (CYP450) enzyme system. **1. Why Cimetidine is Correct:** Cimetidine is a potent **non-specific inhibitor of the CYP450 enzyme system** (specifically CYP1A2, 2C9, 2D6, and 3A4). When added to a stable regimen of phenobarbital, cimetidine inhibits its metabolism, leading to increased plasma levels of the anticonvulsant and subsequent toxicity. **2. Why the Other Options are Incorrect:** * **Famotidine and Ranitidine:** These are also $H_2$ receptor antagonists used for GERD. However, unlike cimetidine, they have **negligible effects** on the CYP450 system and do not typically cause significant drug interactions with antiepileptics. * **Lansoprazole:** While some Proton Pump Inhibitors (PPIs) like Omeprazole can inhibit certain CYP isoforms (e.g., CYP2C19), Lansoprazole has a much lower potential for clinically significant interactions compared to the classic enzyme inhibitor, Cimetidine. **High-Yield Clinical Pearls for NEET-PG:** * **Cimetidine Side Effects:** Apart from enzyme inhibition, it has **anti-androgenic effects** (gynecomastia, galactorrhea, and decreased libido) because it displaces DHT from its receptors and inhibits the metabolism of estradiol. * **Mnemonic for Enzyme Inhibitors:** "**SICKFACES.COM**" (Sodium valproate, Isoniazid, Cimetidine, Ketoconazole, Fluconazole, Alcohol (acute), Chloramphenicol, Erythromycin, Sulfonamides, Ciprofloxacin, Omeprazole, Metronidazole). * **Phenobarbital:** It is a potent enzyme **inducer**, but in this scenario, it is the *substrate* being affected by the *inhibitor* (Cimetidine).

Q: In theophylline metabolism, drug interactions occur with all EXCEPT:

Tetracyclines. **Explanation:** Theophylline has a narrow therapeutic index and is primarily metabolized by the hepatic **Cytochrome P450 (CYP1A2 and CYP3A4)** enzyme system. Therefore, any drug that induces or inhibits these enzymes will significantly alter theophylline serum levels. **1. Why Tetracyclines is the Correct Answer:** Tetracyclines (like Doxycycline or Oxytetracycline) do not significantly inhibit or induce hepatic microsomal enzymes. Consequently, they do not interfere with theophylline clearance. It is a common "distractor" in exams because **Macrolides** (like Erythromycin and Clarithromycin) are potent inhibitors that *do* interact with theophylline, but Tetracyclines do not. **2. Analysis of Incorrect Options:** * **Cimetidine:** A well-known **Enzyme Inhibitor**. It reduces the metabolism of theophylline, leading to increased serum levels and potential toxicity (tachycardia, seizures). * **Phenobarbitone:** A potent **Enzyme Inducer**. It increases the synthesis of CYP enzymes, leading to faster metabolism of theophylline and decreased therapeutic efficacy. * **Rifampicin:** Another powerful **Enzyme Inducer**. Like Phenobarbitone, it enhances theophylline clearance, necessitating a dose increase to maintain bronchodilation. **High-Yield Clinical Pearls for NEET-PG:** * **Ciprofloxacin (Fluoroquinolone):** Frequently tested as a potent inhibitor of theophylline metabolism. * **Smoking:** Tobacco smoke induces CYP1A2, which *increases* theophylline clearance (smokers need higher doses). * **Theophylline Toxicity:** Early signs include GI upset and restlessness; severe toxicity leads to **cardiac arrhythmias** and **intractable seizures**. * **Mnemonic for Inducers:** "GPRS Cell Phone" (Griseofulvin, Phenytoin, Rifampicin, Smoking, Carbamazepine, Phenobarbitone).

Q: Which of the following drugs reduces the efficacy of combined oral contraceptive pills?

Griseofulvin. **Explanation:** The correct answer is **Griseofulvin**. **Mechanism of Interaction:** Combined Oral Contraceptive Pills (COCPs) are primarily metabolized in the liver by the **Cytochrome P450 (CYP450)** enzyme system, specifically the **CYP3A4** isoenzyme [1]. **Griseofulvin** is a potent hepatic enzyme inducer. When co-administered, it increases the rate of metabolism of estrogen and progesterone components of the pill. This leads to decreased plasma concentrations of these hormones, potentially falling below the therapeutic threshold required to suppress ovulation, thereby resulting in **contraceptive failure** [2]. **Analysis of Incorrect Options:** * **Diazepam:** It is a benzodiazepine that is metabolized by the liver but does not significantly induce or inhibit enzymes in a way that affects COCP efficacy. In fact, COCPs may actually inhibit the metabolism of diazepam, potentially increasing its sedation. * **Aspirin & Paracetamol:** These are non-opioid analgesics. They do not induce hepatic enzymes. While high doses of Vitamin C or Paracetamol can occasionally compete for sulfate conjugation (potentially increasing estrogen levels slightly), they do not reduce the efficacy of the pill. **High-Yield Clinical Pearls for NEET-PG:** * **Other Enzyme Inducers:** Remember the mnemonic **"GP Cell Phone"** or **"GPRS"** for drugs that reduce COCP efficacy: **G**riseofulvin, **P**henytoin, **R**ifampicin (the most potent), and **S**t. John’s Wort (herbal) [1], along with Carbamazepine [2] and Phenobarbitone. * **Rifampicin Alert:** Rifampicin is a classic "favorite" for NEET-PG; it is the only antibiotic with a proven, clinically significant reduction in COCP levels due to enzyme induction. * **Clinical Advice:** Patients on enzyme-inducers should be advised to use an alternative method of contraception (e.g., IUCD) or a barrier method during and for 28 days after stopping the inducer.

Q: Which of the following is an inducer of microsomal enzymes?

Phenobarbitone. ### Explanation **1. Why Phenobarbitone is Correct:** Phenobarbitone is a classic, potent **inducer of hepatic microsomal enzymes** (specifically the Cytochrome P450 system, such as CYP1A2, CYP2C9, and CYP3A4). Enzyme inducers work by increasing the synthesis of microsomal enzymes, leading to an accelerated metabolism of themselves (auto-induction) and other co-administered drugs. This typically results in decreased plasma concentrations and reduced therapeutic efficacy of the affected drugs (e.g., warfarin, oral contraceptives). **2. Why the Other Options are Incorrect:** * **Paracetamol:** It is a substrate for microsomal enzymes (metabolized into the toxic metabolite NAPQI) but does not act as an inducer or inhibitor of the system. * **Digoxin:** It is a cardiac glycoside primarily excreted unchanged by the kidneys (via P-glycoprotein). It does not significantly interact with hepatic microsomal enzymes. * **Penicillin:** Most penicillins are excreted unchanged in the urine via tubular secretion and do not modulate the CYP450 enzyme system. **3. High-Yield Clinical Pearls for NEET-PG:** * **Mnemonic for Enzyme Inducers (GPRS Cell Phone):** **G**riseofulvin, **P**henytoin, **R**ifampicin, **S**moking, **C**arbamazepine, **P**henobarbitone. * **Clinical Consequence:** If a patient on Warfarin starts Phenobarbitone, their INR will drop (due to increased metabolism of Warfarin), necessitating a dose increase. * **Non-Microsomal Enzymes:** Note that enzymes like **Alcohol dehydrogenase**, **Xanthine oxidase**, and **MAO** are non-microsomal and are generally *not* inducible. * **Phenobarbitone Special Use:** It is used in **Congenital Non-hemolytic Jaundice (Type II Crigler-Najjar syndrome)** because it induces the enzyme glucuronyl transferase, helping conjugate bilirubin.

Q: Which drug should not be given with Apomorphine?

Ondansetron. Apomorphine is a potent dopamine agonist used as "rescue therapy" for "off" episodes in Parkinson’s disease [1]. A major side effect of apomorphine is severe nausea and vomiting [2]. However, **5-HT3 antagonists (like Ondansetron)** are strictly contraindicated for managing this emesis. When used together, there is a risk of **profound hypotension and loss of consciousness**. The exact mechanism is not fully understood but is clinically significant enough to warrant a "Black Box Warning." To manage apomorphine-induced vomiting, the drug of choice is **Trimethobenzamide**. **2. Analysis of Incorrect Options:** * **A. Dopamine Agonists:** Apomorphine itself is a non-ergoline dopamine agonist [1]. While adding other agonists (like Pramipexole) requires dose monitoring for additive dopaminergic side effects (dyskinesia, hallucinations) [3], it is not a contraindication; in fact, apomorphine is often used as an adjunct to existing dopaminergic therapy. * **B. Spironolactone:** This is a potassium-sparing diuretic. There is no significant pharmacological interaction between spironolactone and apomorphine. * **C. Aspirin:** Aspirin is an NSAID/antiplatelet agent. It does not interfere with the dopaminergic pathways or the hemodynamic stability associated with apomorphine. **3. High-Yield Clinical Pearls for NEET-PG:** * **Drug of Choice for Apomorphine Emesis:** Trimethobenzamide (started 3 days prior to apomorphine). * **Avoid Domperidone/Metoclopramide:** While Domperidone is often used in Parkinson's, 5-HT3 antagonists (Ondansetron) are the specific "Never-Give" combination with Apomorphine due to the syncope/hypotension risk. * **Apomorphine Route:** Administered **subcutaneously**, not orally (due to high first-pass metabolism) [1]. * **Other Uses:** Historically used as an emetic in toxicology (now obsolete).

Q: A patient stabilized on warfarin for DVT is given phenobarbitone. Which of the following is the likely interaction between the two drugs?

Phenobarbitone increases the metabolism of warfarin. **Explanation:** The interaction between warfarin and phenobarbitone is a classic example of **pharmacokinetic drug antagonism** mediated by **enzyme induction** [1], [2]. **Why Option B is Correct:** Phenobarbitone is a potent inducer of the hepatic microsomal enzyme system, specifically the **Cytochrome P450 (CYP) enzymes** (primarily CYP2C9, which metabolizes warfarin) [1]. By inducing these enzymes, phenobarbitone increases the rate of warfarin metabolism [1]. This leads to decreased plasma concentrations of warfarin, a shorter half-life, and a reduced anticoagulant effect [1]. Clinically, this necessitates an increase in the warfarin dose to maintain a therapeutic International Normalized Ratio (INR) [1]. **Why Other Options are Incorrect:** * **Option A:** Phenobarbitone does not significantly affect the gastrointestinal absorption of warfarin. Warfarin is already rapidly and almost completely absorbed [3]. * **Option C:** While many drugs (like sulfonamides or NSAIDs) interact with warfarin via protein displacement, phenobarbitone does not [2]. Displacement would lead to an *increased* free fraction of warfarin and a higher risk of bleeding, which is the opposite of what occurs with phenobarbitone [1]. **High-Yield Clinical Pearls for NEET-PG:** 1. **G-P-R-S-Cell Phone:** A common mnemonic for **Enzyme Inducers**: **G**riseofulvin, **P**henytoin, **R**ifampicin, **S**moking, **C**arbamazepine, and **P**henobarbitone. 2. **Clinical Consequence:** If phenobarbitone is suddenly stopped in a patient on warfarin, the enzyme induction wears off, warfarin metabolism slows down, and the patient faces a high risk of **life-threatening hemorrhage** [1]. 3. **Warfarin Metabolism:** Warfarin is primarily metabolized by **CYP2C9** [2], [3]. Genetic polymorphisms in this enzyme can also affect a patient's dose requirements [3].

Q: Which of the following is a known inhibitor of microsomal enzymes?

Sodium valproate. **Explanation:** The correct answer is **Sodium valproate**. This question tests the fundamental pharmacological concept of **Microsomal Enzyme Induction vs. Inhibition**, a high-yield topic for NEET-PG. **1. Why Sodium Valproate is Correct:** Sodium valproate is a potent **microsomal enzyme inhibitor**. It binds to and inhibits the Cytochrome P450 (CYP450) system in the liver. By inhibiting these enzymes, it decreases the metabolism of co-administered drugs (e.g., phenobarbitone, lamotrigine), leading to increased plasma concentrations and potential toxicity. **2. Why the Other Options are Incorrect:** * **Phenobarbitone (A):** A classic, potent enzyme **inducer**. It increases the synthesis of microsomal enzymes, leading to faster metabolism of drugs like warfarin and oral contraceptives. * **Griseofulvin (B):** An antifungal agent known to be an enzyme **inducer**. * **Phenytoin (C):** A widely used antiepileptic that acts as a powerful enzyme **inducer**. **3. High-Yield Clinical Pearls for NEET-PG:** To quickly distinguish between inducers and inhibitors, use these popular mnemonics: * **Enzyme INDUCERS (GPRS Cell Phone):** * **G**riseofulvin * **P**henytoin * **R**ifampicin * **S**moking/St. John's Wort * **C**arbamazepine * **P**henobarbitone * **Enzyme INHIBITORS (VITAMIN K):** * **V**alproate * **I**soniazid * **T**ame (Cimetidine) * **A**miodarone * **M**acrolides (except Azithromycin) * **I**t rona (Ketoconazole/Azoles) * **N**ight (Ritonavir) * **K** (Grapefruit juice) **Key Concept:** Enzyme inhibitors act rapidly (within 24 hours), whereas enzyme induction takes 1–2 weeks to manifest as it requires the synthesis of new enzyme proteins.

Question 1

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

Accepted Answer

Amphotericin B

Answer

Itraconazole

Answer

Isoniazid

Answer

Lovastatin

Question 2

Which of the following pairs of drugs are metabolized by the same Cytochrome enzyme?

Accepted Answer

Omeprazole and Clopidogrel

Answer

Phenytoin and Tacrolimus

Answer

Paracetamol and Warfarin

Answer

Omeprazole and Warfarin

Question 3

Which antibiotic decreases the absorption of iron?

Accepted Answer

Tetracyclines

Answer

Sulfonamide

Answer

Erythromycin

Answer

Ciprofloxacin

Question 4

A 27-year-old man with epilepsy presents with complaints of persistent lethargy and occasional feelings of intoxication. He does not consume alcohol and is currently taking phenobarbital for the long-term management of tonic-clonic seizures. He was recently started on a medication for the treatment of gastroesophageal reflux disease. Which of the following agents was he most likely prescribed?

Accepted Answer

Cimetidine

Answer

Famotidine

Answer

Lansoprazole

Answer

Ranitidine

Question 5

In theophylline metabolism, drug interactions occur with all EXCEPT:

Accepted Answer

Tetracyclines

Answer

Cimetidine

Answer

Phenobarbitone

Answer

Rifampicin

Question 6

Which of the following drugs reduces the efficacy of combined oral contraceptive pills?

Accepted Answer

Griseofulvin

Answer

Diazepam

Answer

Aspirin

Answer

Paracetamol

Question 7

Which of the following is an inducer of microsomal enzymes?

Accepted Answer

Phenobarbitone

Answer

Paracetamol

Answer

Digoxin

Answer

Penicillin

Question 8

Which drug should not be given with Apomorphine?

Accepted Answer

Ondansetron

Answer

Dopamine agonist

Answer

Spironolactone

Answer

Aspirin

Question 9

A patient stabilized on warfarin for DVT is given phenobarbitone. Which of the following is the likely interaction between the two drugs?

Accepted Answer

Phenobarbitone increases the metabolism of warfarin

Answer

Phenobarbitone increases the absorption of warfarin

Answer

Phenobarbitone displaces warfarin from plasma protein binding sites

Answer

All of the above

Question 10

Which of the following is a known inhibitor of microsomal enzymes?

Accepted Answer

Sodium valproate

Answer

Phenobarbitone

Answer

Griseofulvin

Answer

Phenytoin

Drug Interactions — MCQs

Drug Interactions — MCQs

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