Drug Interactions — MCQs

Drug Interactions Indian Medical PG Practice Questions and MCQs

Question 131: 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:

A. Summation
B. Additive effects
C. Synergism (Correct Answer)
D. Antagonism

Explanation: ***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.

Question 132: The effect of both drugs given together on the blood pressure of a patient was evaluated in comparison with the effect of individual drugs on BP. The following curve represents: (Recent NEET Pattern 2016-17)

A. Summation
B. Additive effects
C. Synergism (Correct Answer)
D. Antagonism

Explanation: ***Synergism*** - The graph shows that the effect of drugs A and B when given together (A+B) is significantly **greater than the sum of their individual effects**. - This amplified effect, where the combined response is more than the simple addition of individual responses, is the definition of **synergism** (also called potentiation or supra-additive effect). *Summation* - Summation occurs when the **combined effect** of two drugs is **equal to the arithmetic sum** of their individual effects. - In the depicted graph, the peak effect of A+B is clearly much higher than the sum of the peaks of A and B individually, ruling out simple summation. *Additive effects* - Additive effects are synonymous with summation, meaning the combined effect is precisely the sum of individual effects. - The graph demonstrates a response that **exceeds a simple additive effect**, indicating a synergistic interaction rather than mere additive action. *Antagonism* - **Antagonism** occurs when one drug reduces or blocks the effect of another drug, resulting in a combined effect that is **less than the sum** of individual effects. - In the depicted graph, the combined effect (A+B) clearly shows enhancement rather than reduction, ruling out antagonism.

Question 133: 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?

A. Diaphragm
B. Male condom
C. Depo-Provera injection (Correct Answer)
D. Combined oral contraceptive pill

Explanation: ***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

Question 134: Which one of the following vaccines is known to interfere with the Yellow Fever vaccine if administered within 3 weeks of each other?

A. Tetanus toxoid
B. Cholera vaccine
C. Typhoid vaccine
D. Measles vaccine (Correct Answer)

Explanation: ***Correct: Measles vaccine*** - **Measles vaccine (MMR)** is a **live attenuated viral vaccine** that can interfere with yellow fever vaccine immune response - Both are live viral vaccines and CDC/WHO guidelines recommend they be administered **simultaneously OR separated by ≥4 weeks** - When live viral vaccines are given too close together (but not simultaneously), immune interference can reduce antibody response to the second vaccine - This is due to **interferon production** from the first vaccine suppressing replication of the second vaccine virus *Incorrect: Typhoid vaccine* - While **oral typhoid vaccine (Ty21a)** is live attenuated, it is a **bacterial vaccine** and does not have the same viral interference pattern - Can generally be co-administered with yellow fever vaccine without significant spacing requirements - Main concern with oral typhoid is interference from **antibiotics and antimalarials**, not other vaccines *Incorrect: Tetanus toxoid* - **Inactivated vaccine** that does not interfere with live vaccines - Can be given simultaneously or at any interval with yellow fever vaccine - No immune competition with live viral vaccines *Incorrect: Cholera vaccine* - Currently available **oral cholera vaccines** (CVD 103-HgR or killed whole-cell vaccines) do not have documented interference with yellow fever - No specific spacing requirements with yellow fever vaccine - Can be co-administered or given at any interval **Note:** This question is from UPSC-CMS 2022. The original exam key may have listed typhoid, but current CDC and WHO immunization guidelines identify measles (MMR) as the primary vaccine requiring spacing with yellow fever due to live viral vaccine interference.

Question 135: The drugs which may interfere with the efficacy of oral contraceptives and increase the failure rates are all of the following EXCEPT

A. Ampicillin (Correct Answer)
B. Phenytoin
C. Barbiturates
D. Rifampicin

Explanation: ***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.

Question 136: Which one of the following drugs does NOT interfere with efficacy of oral contraceptive pills and increase the failure rates?

A. Barbiturates
B. Rifampicin
C. Ranitidine (Correct Answer)
D. Ampicillin

Explanation: ***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.

Question 137: 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?

A. 90 minutes
B. 60 minutes
C. 120 minutes (Correct Answer)
D. 30 minutes

Explanation: **_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.

Question 138: 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?

A. Stop the drug
B. Stop retigabine and start on carbamazepine
C. Increase the dose (Correct Answer)
D. Decrease the dose

Explanation: ***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 139: Which anti-asthma drug is avoided with erythromycin?

A. Ipratropium
B. Salbutamol
C. Theophylline (Correct Answer)
D. Terbutaline

Explanation: ***Theophylline*** - **Erythromycin** inhibits the **cytochrome P450 (CYP) enzymes** responsible for theophylline metabolism, leading to increased theophylline levels and potential toxicity. - Elevated theophylline can cause adverse effects such as **nausea**, **vomiting**, **arrhythmias**, and **seizures**. *Ipratropium* - **Ipratropium** is largely eliminated unchanged in urine, with minimal hepatic metabolism. - It does not interact significantly with **erythromycin** as its metabolism is not dependent on the CYP enzyme system. *Salbutamol* - **Salbutamol** is primarily metabolized by **sulfotransferase enzymes** in the liver and gut, not primarily by CYP enzymes. - Therefore, **erythromycin** has a negligible impact on salbutamol's metabolism and plasma levels. *Terbutaline* - **Terbutaline** is mainly metabolized by **conjugation reactions** (glucuronidation and sulfation) and excreted renally. - It also has limited interaction potential with **erythromycin** due to its distinct metabolic pathways.

Question 140: A lady has taken medication for amoebiasis infection. She drank alcohol on the same day. She has nausea, vomiting, and dizziness. Which anti-amoebic drug could have led to interaction with alcohol to produce these symptoms?

A. Nitazoxanide
B. Paromomycin
C. Metronidazole (Correct Answer)
D. Diloxanide

Explanation: ***Metronidazole*** - **Metronidazole** is well-known for causing a **disulfiram-like reaction** when consumed with alcohol. - This reaction leads to a rapid accumulation of **acetaldehyde**, manifesting as nausea, vomiting, flushing, headache, and dizziness. *Nitazoxanide* - **Nitazoxanide** is an oral anti-infective agent used for protozoal infections, but it is **not associated with a disulfiram-like reaction** with alcohol. - Its mechanism of action involves interfering with the **pyridoxine ferredoxin oxidoreductase enzyme**, which is distinct from alcohol metabolism. *Paromomycin* - **Paromomycin** is an aminoglycoside antibiotic primarily used for luminal amoebiasis and is **poorly absorbed from the GI tract**. - It does **not typically interact with alcohol** or cause disulfiram-like reactions. *Diloxanide* - **Diloxanide furoate** is a luminal amoebicide primarily used for asymptomatic cyst passers. - It is **not known to cause a disulfiram-like reaction** or significant interactions with alcohol.

Practice by Chapter

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Pharmacodynamic Interactions

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Clinically Significant Drug Interactions

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Management of Drug Interactions

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