Drug Interactions Practice Questions

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

Metronidazole. ### Explanation The correct answer is **Metronidazole**. **Mechanism of Action:** A **disulfiram-like reaction** occurs when certain drugs inhibit the enzyme **acetaldehyde dehydrogenase**. Under normal circumstances, alcohol is metabolized into acetaldehyde and then into acetic acid. When this enzyme is inhibited, acetaldehyde accumulates in the blood, leading to symptoms such as flushing, tachycardia, palpitations, nausea, vomiting, and hypotension. Metronidazole is the classic example of a drug that triggers this reaction when consumed with alcohol. **Analysis of Options:** * **Metronidazole (Correct):** It is a nitroimidazole antibiotic that interferes with alcohol metabolism, making it a high-yield topic for forensic toxicology and pharmacology. * **Acamprosate (Incorrect):** This drug is used to maintain abstinence in alcohol-dependent patients by modulating glutamatergic neurotransmission. It does *not* cause a disulfiram-like reaction. * **Tetracycline (Incorrect):** While it is a broad-spectrum antibiotic, it does not inhibit acetaldehyde dehydrogenase. * **Digitalis (Incorrect):** A cardiac glycoside used for heart failure and arrhythmias; its toxicity involves gastrointestinal upset and visual disturbances (xanthopsia), but not alcohol-related reactions. **High-Yield Clinical Pearls for NEET-PG:** * **Other drugs causing Disulfiram-like reactions:** * **Antibiotics:** Cephalosporins (Cefoperazone, Cefotetan), Tinidazole, Griseofulvin. * **Sulfonylureas:** Chlorpropamide, Tolbutamide. * **Others:** Procarbazine (anticancer), Coprine (found in certain mushrooms). * **Treatment:** Management is primarily supportive (IV fluids and antiemetics). Fomepizole may be considered in severe cases. * **Patient Counseling:** Patients on Metronidazole must be advised to avoid alcohol during treatment and for at least **48–72 hours** after the last dose.

Q: A patient with rheumatoid arthritis is taking indomethacin and an ACE inhibitor for hypertension. What potential side effect is likely to be seen?

Hyperkalemia. ***Hyperkalemia*** - The co-administration of an **ACE inhibitor** and an **NSAID (indomethacin)** significantly increases the risk of **hyperkalemia** due to synergistic effects on renal potassium balance. - **ACE inhibitors** directly block aldosterone synthesis (leading to reduced potassium excretion), while **NSAIDs** reduce prostaglandin synthesis, impairing renin release, which also suppresses aldosterone effect. *Hypercalcemia* - This scenario is not associated with hypercalcemia; drugs notorious for causing hypercalcemia include **thiazide diuretics**, or conditions like **primary hyperparathyroidism**. - Neither ACE inhibitors nor NSAIDs directly impair calcium homeostasis leading to clinically significant increases. *Hypernatremia* - **ACE inhibitors** decrease aldosterone levels, which promotes sodium excretion, typically resulting in **hyponatremia** or normonatremia, not hypernatremia. - Although NSAIDs can cause fluid retention, this is largely due to increased water reabsorption leading to expansion of extracellular fluid, not an increase in serum sodium concentration. *Hyperphosphatemia* - **Hyperphosphatemia** is primarily seen in end-stage **chronic kidney disease (CKD)** because the kidneys cannot excrete phosphate effectively. - The combination of indomethacin and an ACE inhibitor does not directly impair phosphate excretion via the mechanisms needed to cause clinically significant hyperphosphatemia.

Q: Carbamazepine and erythromycin were given to a patient, and he presented with ataxia and dizziness. Which of the following is the reason for the symptoms?

Toxicity of carbamazepine. ***Toxicity of carbamazepine*** - Erythromycin is a potent inhibitor of the hepatic **CYP3A4 enzyme**, which is primarily responsible for the metabolism and subsequent clearance of carbamazepine. - Inhibition of carbamazepine metabolism leads to increased plasma concentration, resulting in **CNS side effects** such as **ataxia, dizziness**, nystagmus, and drowsiness. *Toxicity of erythromycin* - Erythromycin toxicity typically presents with **gastrointestinal symptoms** (e.g., nausea, vomiting, diarrhea) or cardiac issues like **QT prolongation**. - The described symptoms, ataxia and dizziness, are classic manifestations of **anticonvulsant toxicity**, not macrolide toxicity. *Erythromycin speeds up carbamazepine metabolism* - This statement is incorrect; erythromycin **inhibits** CYP3A4, thus slowing down carbamazepine metabolism and resulting in drug accumulation. - If metabolism were sped up (i.e., enzyme induction), the patient would likely experience sub-therapeutic carbamazepine levels, increasing the risk of **seizure recurrence**. *Sub-therapeutic carbamazepine levels causing seizures* - Recurrent seizures are caused by **sub-therapeutic levels** of carbamazepine, often due to enzyme induction (e.g., by phenytoin, carbamazepine itself) or non-compliance. - The symptoms of ataxia and dizziness indicate **supratherapeutic levels** (toxicity), which is the opposite of the low levels that cause breakthrough seizures.

Q: Imipramine and Diphenhydramine are given together to a patient. Why is this combination considered irrational?

Both have anticholinergic action. ***Both have anticholinergic action*** - Imipramine, being a **Tricyclic Antidepressant (TCA)**, possesses significant **anticholinergic properties** (Muscarinic receptor blockade). - Diphenhydramine, a first-generation antihistamine, is also a highly effective **anticholinergic agent**; their co-administration leads to severe, potentially fatal, additive anticholinergic effects (e.g., acute confusion, severe urinary retention, paralytic ileus). *Both cause serotonin syndrome* - While Imipramine is a weak **Serotonin-Norepinephrine Reuptake Inhibitor (SNRI)**, Diphenhydramine does not directly contribute significantly to **serotonin toxicity**. - The primary and most hazardous interaction is the severe risk of **anticholinergic crisis**, not Serotonin Syndrome. *Both cause hypotension* - Imipramine can cause **orthostatic hypotension** due to its **alpha-1 adrenergic blockade** effects. - Although side effects include hypotension, the combined risk of severe **anticholinergic side effects** (delirium, ileus) is the overwhelming reason this combination is irrational. *Both cause increased sedation* - Both drugs are highly sedating, which is a valid concern for driving and daily function, mediated by **H1 receptor antagonism**. - However, while increased sedation is a risk, the combination is specifically deemed irrational because of the risk of life-threatening **anticholinergic toxicity**, which is a more critical pharmacological interaction than simple additive sedation.

Q: Drug A is epinephrine and drug B is cocaine. The effect of both drugs given together on the blood pressure of a patient was evaluated in comparison with effect of individual drugs on BP. The following curve represents:

Synergism. ***Synergism*** - **Synergism** occurs when the combined effect of two drugs is significantly greater than the sum of their individual effects. In the provided graph, the peak blood pressure with drugs A+B is notably higher than the sum of the peaks for A and B administered separately. - Epinephrine (Drug A) is a **vasoconstrictor**, and cocaine (Drug B) **inhibits norepinephrine reuptake**, potentiating epinephrine's effects by increasing synaptic levels of catecholamines. This leads to a much stronger combined increase in blood pressure than expected from simple addition. *Summation* - **Summation** implies that the combined effect of two drugs is equal to the sum of their individual effects. - The graph clearly shows that the combined effect (A+B) produces a blood pressure response that is much greater than simply adding the individual responses of A and B, ruling out summation. *Additive effects* - **Additive effects** are a type of summation where the combined effect of two or more drugs is numerically equal to the arithmetic sum of their individual effects. - Similar to summation, this option is incorrect because the observed combined effect of A and B is significantly *more* than the mathematical sum of their separate effects, indicating potentiation rather than simple additivity. *Antagonism* - **Antagonism** occurs when one drug reduces or blocks the effect of another drug. - This is incorrect because the graph shows that the combined administration of epinephrine and cocaine produces a *greater* blood pressure response, not a reduced one. Antagonism would result in a combined effect less than expected or less than either drug alone.

Q: A 25-year-old newly married female on liver enzyme inducers is requesting contraceptive advice in family planning clinic. Which of the following would be the most reliable method of contraception for her?

Depo-Provera injection. ***Depo-Provera injection*** - Among the listed options, **Depo-Provera** (medroxyprogesterone acetate depot injection) is considered the most reliable for women on enzyme-inducing drugs - While **enzyme inducers do affect progestin-only injectables**, the effect is **less pronounced** than with combined oral contraceptives due to the **high dose and depot formulation** - Provides **long-acting contraception** (3 months) that is **not user-dependent**, eliminating issues with daily compliance - **Note:** Current guidelines suggest considering **shortened dosing intervals** (10-11 weeks instead of 12) or preferably **copper IUD** (non-hormonal, unaffected by drug interactions) as first-line, but among these options, this is most reliable *Combined oral contraceptive pill* - **Combined OCPs** contain both estrogen and progestin, which undergo **extensive hepatic metabolism** - **Enzyme-inducing drugs** (rifampicin, phenytoin, carbamazepine, phenobarbital, St. John's wort) significantly **increase metabolism**, reducing plasma levels by up to **50%** - This leads to **contraceptive failure** and unintended pregnancy - **Least suitable option** for this patient *Diaphragm* - A **barrier method** that is **unaffected by drug interactions** - However, has a **higher typical-use failure rate** (12% per year) compared to highly effective methods - Requires **proper fitting, insertion technique, and use with spermicide** - **User-dependent** effectiveness makes it less reliable than long-acting methods *Male condom* - **Barrier method** with **no drug interaction concerns** - **Typical-use failure rate** of approximately **13% per year** due to inconsistent or incorrect use - Effectiveness is **highly user-dependent** - Less reliable than long-acting hormonal methods for pregnancy prevention

Q: The drugs which may interfere with the efficacy of oral contraceptives and increase the failure rates are all of the following EXCEPT

Ampicillin. ***Ampicillin (Correct Answer)*** - While previously thought to reduce oral contraceptive efficacy, **current evidence shows ampicillin has NO significant interaction** with oral contraceptives. - The old theory suggested some antibiotics might alter gut flora and reduce **enterohepatic recirculation of estrogen**, but this has been largely **debunked for ampicillin and most antibiotics**. - **Unlike the enzyme inducers listed below**, ampicillin does not significantly affect OC metabolism or efficacy. *Phenytoin (Incorrect - DOES interfere)* - **Phenytoin is a potent enzyme inducer** (cytochrome P450 enzymes). - This induction enhances the metabolism of estrogen and progestin components, **reducing their plasma concentrations and effectiveness**. - Backup contraception is recommended when using phenytoin with oral contraceptives. *Barbiturates (Incorrect - DOES interfere)* - **Barbiturates are potent enzyme inducers**, similar to phenytoin. - They increase hepatic metabolism of oral contraceptive steroids, leading to **lower circulating hormone levels and increased risk of contraceptive failure**. - Alternative contraception should be considered. *Rifampicin (Incorrect - DOES interfere)* - **Rifampicin is one of the strongest inducers of hepatic microsomal enzymes**, particularly CYP3A4. - This leads to **rapid and substantial increase in metabolism of both estrogen and progestin**, drastically reducing OC efficacy. - **Non-hormonal contraception is strongly recommended** during rifampicin therapy.

Q: Which one of the following drugs does NOT interfere with efficacy of oral contraceptive pills and increase the failure rates?

Ranitidine. ***Ranitidine*** - **Ranitidine** is an H2 receptor antagonist that reduces stomach acid and does not interact with the **cytochrome P450 enzyme system**, which metabolizes oral contraceptives. - This means it does not significantly alter the **pharmacokinetics** of oral contraceptive pills, ensuring their efficacy is maintained. *Barbiturates* - **Barbiturates** are potent inducers of the **hepatic cytochrome P450 enzyme system**, specifically CYP3A4. - This induction accelerates the metabolism of estrogen and progestin components of oral contraceptives, leading to **lower serum levels** and reduced contraceptive efficacy. *Rifampicin* - **Rifampicin** is a strong inducer of the **hepatic cytochrome P450 enzyme system**, particularly CYP3A4, which is responsible for metabolizing steroid hormones. - This accelerated metabolism significantly reduces the serum concentrations of oral contraceptive hormones, thereby **decreasing their effectiveness** and increasing the risk of unintended pregnancy. *Ampicillin* - **Ampicillin**, and other broad-spectrum antibiotics, can theoretically interfere with oral contraceptive efficacy by disrupting the **enterohepatic recirculation** of estrogens. - This disruption leads to a decrease in the reabsorption of estrogen metabolites from the gut, resulting in **lower circulating estrogen levels** and potentially reduced contraceptive protection.

Q: A patient is on phenytoin for a seizure disorder. He was prescribed sucralfate 4 times a day for peptic ulcers. What should be the minimum duration of time between consumption of these drugs?

120 minutes. **_120 minutes_** - **Sucralfate** forms a protective barrier in the stomach and can **adsorb other medications**, significantly reducing their absorption. - A minimum separation of **2 hours (120 minutes)** is recommended between sucralfate and other oral medications to prevent drug interactions. *90 minutes* - While a longer interval is beneficial, **90 minutes** may not be sufficient to completely avoid the significant reduction in **phenytoin absorption** caused by sucralfate. - Given the narrow therapeutic index of phenytoin, a more conservative approach with a longer separation is preferred. *60 minutes* - A **60-minute interval** is generally considered too short to prevent the **adsorption of phenytoin** by sucralfate. - This short duration increases the risk of **subtherapeutic phenytoin levels** and potential seizure recurrence. *30 minutes* - A **30-minute interval** is entirely inadequate and would almost certainly lead to a significant **reduction in phenytoin absorption**. - This would place the patient at high risk of **seizure recurrence** due to insufficient drug levels.

Q: A patient who was diagnosed with epilepsy was put on retigabine TDS. Now phenytoin is being added. Which of the following changes should be made to retigabine?

Increase the dose. ***Increase the dose*** - **Phenytoin** is a potent **enzyme inducer** that induces hepatic enzymes including **UGT (glucuronidation) enzymes**. - **Retigabine** is primarily metabolized by **N-acetylation and glucuronidation** (not significantly by CYP450 enzymes). - Phenytoin induces UGT enzymes, which **increases retigabine metabolism and clearance**, leading to **decreased plasma concentrations**. - To maintain therapeutic levels and seizure control, the **dose of retigabine needs to be increased** when co-administered with phenytoin. *Stop the drug* - There is no clinical indication to completely **stop retigabine** simply because phenytoin is being added, as both can be used concurrently with dose adjustment. - Doing so might lead to a **loss of seizure control** if retigabine was providing effective seizure management. *Stop retigabine and start on carbamazepine* - This is an unnecessary and unindicated change; there is no medical reason to **switch from retigabine to carbamazepine** due to phenytoin addition. - Like phenytoin, **carbamazepine is also a strong enzyme inducer**, so similar drug interactions would occur. *Decrease the dose* - **Decreasing the dose** would be appropriate if phenytoin were an enzyme inhibitor, leading to higher retigabine levels. - Since phenytoin is an **enzyme inducer**, decreasing the dose would further reduce retigabine's therapeutic concentration, potentially leading to **breakthrough seizures**.

Question 1

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

Accepted Answer

Metronidazole

Answer

Acamprostate

Answer

Tetracycline

Answer

Digitalis

Question 2

A patient with rheumatoid arthritis is taking indomethacin and an ACE inhibitor for hypertension. What potential side effect is likely to be seen?

Accepted Answer

Hyperkalemia

Answer

Hypercalcemia

Answer

Hypernatremia

Answer

Hyperphosphatemia

Question 3

Carbamazepine and erythromycin were given to a patient, and he presented with ataxia and dizziness. Which of the following is the reason for the symptoms?

Accepted Answer

Toxicity of carbamazepine

Answer

Toxicity of erythromycin

Answer

Erythromycin speeds up carbamazepine metabolism

Answer

Sub-therapeutic carbamazepine levels causing seizures

Question 4

Imipramine and Diphenhydramine are given together to a patient. Why is this combination considered irrational?

Accepted Answer

Both have anticholinergic action

Answer

Both cause serotonin syndrome

Answer

Both cause hypotension

Answer

Both cause increased sedation

Question 5

Drug A is epinephrine and drug B is cocaine. The effect of both drugs given together on the blood pressure of a patient was evaluated in comparison with effect of individual drugs on BP. The following curve represents:

Accepted Answer

Synergism

Answer

Summation

Answer

Additive effects

Answer

Antagonism

Question 6

A 25-year-old newly married female on liver enzyme inducers is requesting contraceptive advice in family planning clinic. Which of the following would be the most reliable method of contraception for her?

Accepted Answer

Depo-Provera injection

Answer

Diaphragm

Answer

Male condom

Answer

Combined oral contraceptive pill

Question 7

The drugs which may interfere with the efficacy of oral contraceptives and increase the failure rates are all of the following EXCEPT

Accepted Answer

Ampicillin

Answer

Phenytoin

Answer

Barbiturates

Answer

Rifampicin

Question 8

Which one of the following drugs does NOT interfere with efficacy of oral contraceptive pills and increase the failure rates?

Accepted Answer

Ranitidine

Answer

Barbiturates

Answer

Rifampicin

Answer

Ampicillin

Question 9

A patient is on phenytoin for a seizure disorder. He was prescribed sucralfate 4 times a day for peptic ulcers. What should be the minimum duration of time between consumption of these drugs?

Accepted Answer

120 minutes

Answer

90 minutes

Answer

60 minutes

Answer

30 minutes

Question 10

A patient who was diagnosed with epilepsy was put on retigabine TDS. Now phenytoin is being added. Which of the following changes should be made to retigabine?

Accepted Answer

Increase the dose

Answer

Stop the drug

Answer

Stop retigabine and start on carbamazepine

Answer

Decrease the dose

Drug Interactions — MCQs

Drug Interactions — MCQs

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