Drug Interactions Practice Questions

Q: What is the primary reason that the therapeutic efficacy of antihypertensive drugs is reduced by NSAIDs?

Decrease the synthesis of vascular prostacyclin. ***Decrease the synthesis of vascular prostacyclin*** - NSAIDs **inhibit cyclooxygenase (COX)**, reducing the production of **vasodilatory prostaglandins** such as **prostacyclin (PGI2)** and **PGE2** [1]. This inhibition leads to **vasoconstriction** and **sodium retention**, counteracting the effects of antihypertensive medications [2].*Cause sodium retention* - While NSAIDs do cause **sodium retention**, this is a *consequence* of **prostaglandin inhibition**, not the primary mechanism of reducing antihypertensive efficacy. - **Sodium retention** contributes to increased blood volume and elevated blood pressure, but the foundational issue is the interruption of the **vasodilatory prostaglandin pathway** [3].*Inhibit the action of antihypertensive drugs* - NSAIDs do not directly **inhibit the action** of most antihypertensive drugs at their receptor sites or enzymatic targets. - Instead, they introduce a **counteracting physiological effect** (vasoconstriction and sodium retention) that *reduces the overall clinical efficacy* of the antihypertensive regimen.*Alter the pharmacokinetics of antihypertensive drugs* - NSAIDs generally do not significantly alter the **absorption, distribution, metabolism, or excretion** (ADME) of most antihypertensive drugs to a degree that would profoundly reduce their efficacy. - While some minor pharmacokinetic interactions might occur, the primary mechanism of interaction leading to reduced efficacy is **pharmacodynamic** (physiological counteraction).

Q: A 20-year-old nulliparous woman is taking oral contraceptive pills. Which anti-tuberculous drug decreases the effect of OCP?

Rifampicin. ***Rifampicin*** - **Rifampicin** is a potent **CYP450 enzyme inducer**, accelerating the metabolism of oral contraceptive pills [1]. - This increased metabolism leads to lower systemic levels of contraceptive hormones, thereby reducing the OCP's effectiveness and increasing the risk of **unintended pregnancy**. *INH (Isoniazid)* - Isoniazid is primarily metabolized by N-acetyltransferase and cytochrome P450, but it does **not significantly induce** the CYP450 enzymes responsible for OCP metabolism. - It has a much lower potential for drug-drug interactions with oral contraceptives compared to rifampicin. *Pyrazinamide* - Pyrazinamide's metabolism does **not involve significant CYP450 induction** or inhibition that would affect the efficacy of oral contraceptives. - Its mechanism of action and metabolic pathways do not typically interfere with hormonal contraception. *Ethambutol* - Ethambutol is largely excreted unchanged and has **minimal to no interaction with the cytochrome P450 system**. - It does **not affect the metabolism** or effectiveness of oral contraceptive pills.

Q: Lenalidomide co-administration with which other drug increases the risk of thrombosis?

Glucocorticoids. ***Glucocorticoids*** - Co-administration of **lenalidomide** with **dexamethasone** (a glucocorticoid) significantly increases the risk of **venous thromboembolism (VTE)** in patients with **multiple myeloma**. - This combination therapy, though effective, necessitates **thromboprophylaxis** to mitigate the heightened risk of blood clots. *Alcohol* - While alcohol can affect drug metabolism and contribute to bleeding risk, it is not specifically known to increase the **thrombotic risk** when co-administered with lenalidomide. - Its primary interactions with lenalidomide are not related to clotting. *Barbiturates* - **Barbiturates** are strong **CYP450 enzyme inducers**, which can alter the metabolism of many drugs by decreasing their plasma concentrations. - They are not directly associated with an increased **thrombosis risk** when combined with lenalidomide. *Antibiotics* - Some antibiotics can interact with coagulation pathways or affect vitamin K levels, but there is no specific evidence linking **antibiotic co-administration** with an increased **thrombotic risk** when taken with lenalidomide. - Any potential interactions are generally minor and not related to thrombosis risk.

Q: A factor that is likely to increase the duration of action of a drug that is partially metabolized by CYP3A4 in the liver is:

Chronic administration of cimetidine with the drug. ***Chronic administration of cimetidine with the drug*** - **Cimetidine** is a potent inhibitor of various **cytochrome P450 (CYP450) enzymes**, including **CYP3A4**. - By inhibiting the metabolism of a drug predominantly metabolized by **CYP3A4**, cimetidine will increase its plasma concentration and extend its **duration of action**. *Chronic administration of phenobarbital with the drug* - **Phenobarbital** is a strong **inducer of CYP450 enzymes**, including **CYP3A4**. - Induction would accelerate the metabolism of the drug, thus **decreasing its duration of action**, not increasing it. *Displacement from tissue binding sites by another drug* - Displacement from tissue binding sites would primarily increase the **free fraction of the drug in the plasma**, leading to a more rapid distribution to eliminating organs and potentially **shorter duration of action** if elimination is extraction-limited. - This mechanism does not directly impact the **metabolic rate** unless clearance is significantly altered through increased availability for metabolism. *Chronic administration of rifampicin* - **Rifampicin** is a potent **inducer of CYP3A4** and other CYP enzymes. - Its administration would lead to **increased metabolism** of the co-administered drug, thereby **reducing its duration of action**.

Q: Which drug should not be given with ketoconazole?

Indinavir. ***Correct: Indinavir*** - **Indinavir** is a **protease inhibitor (antiretroviral)** that is primarily metabolized by **CYP3A4** - **Ketoconazole** is a **potent CYP3A4 inhibitor** that significantly increases indinavir plasma concentrations - Co-administration leads to **increased risk of indinavir toxicity** including nephrolithiasis, hyperbilirubinemia, and hepatotoxicity - **Dose reduction of indinavir is required** if concurrent use is necessary (typically reduce to 600 mg q8h from 800 mg q8h) *Incorrect: Macrolide* - Many **macrolides** (erythromycin, clarithromycin) are CYP3A4 substrates and can interact with ketoconazole - While caution is advised due to **QT prolongation risk**, this interaction is less severe than with indinavir - Not an absolute contraindication but requires monitoring *Incorrect: Aminoglycoside* - **Aminoglycosides** (gentamicin, amikacin, tobramycin) are **NOT metabolized by CYP450 enzymes** - They are **hydrophilic** and eliminated **unchanged by renal excretion** - **No clinically significant interaction** with ketoconazole - Can be safely co-administered without dose adjustment *Key Learning Point* - Ketoconazole inhibits CYP3A4, affecting metabolism of many drugs including **protease inhibitors, calcium channel blockers, statins, and some macrolides** - Always check for CYP3A4 substrate drugs when prescribing azole antifungals

Q: Which of the following drugs has the least significant drug interaction with digoxin?

Amlodipine. ***Amlodipine*** - **Amlodipine** generally has a **minimal impact** on digoxin levels and rarely causes clinically significant interactions. - It works through a different mechanism (calcium channel blockade) and does not typically affect digoxin's absorption, distribution, metabolism, or excretion. *Cholestyramine* - **Cholestyramine** is an **ion-exchange resin** that can bind to digoxin in the gastrointestinal tract, significantly **reducing its absorption**. - This interaction can lead to **subtherapeutic digoxin levels** and reduced therapeutic efficacy. *Thiazide diuretics* - **Thiazide diuretics** can cause **hypokalemia**, which significantly **potentiates digoxin toxicity**. - Low potassium levels allow more digoxin to bind to the Na+/K+-ATPase pump, increasing its inotropic and arrhythmogenic effects. *Quinidine* - **Quinidine** can **increase serum digoxin concentrations** by inhibiting its renal and non-renal clearance and displacing it from tissue binding sites. - This can lead to **digoxin toxicity**, necessitating a reduction in digoxin dosage when co-administered.

Q: Concomitant treatment with which of the following can cause oral contraceptive failure?

Rifampicin. ***Rifampicin*** - **Rifampicin** is a potent inducer of **hepatic microsomal enzymes** (cytochrome P450 enzymes), particularly CYP3A4. - This enzyme induction leads to increased metabolism and faster clearance of the estrogen and progestin components of **oral contraceptives**, reducing their effectiveness and risking unintended pregnancy. *Enalapril* - **Enalapril** is an ACE inhibitor used to treat hypertension and heart failure; it does not significantly interact with **oral contraceptive metabolism**. - Its primary mechanism of action involves the **renin-angiotensin-aldosterone system**, which is distinct from the hepatic metabolism of sex hormones. *Ibuprofen* - **Ibuprofen** is a nonsteroidal anti-inflammatory drug (**NSAID**) used for pain and inflammation; it does not affect the metabolism of **oral contraceptives**. - Its mechanism involves inhibiting **prostaglandin synthesis**, and it is not an inducer of hepatic enzymes. *Metformin* - **Metformin** is an oral hypoglycemic agent used for type 2 diabetes; it does not have known significant interactions that would cause **oral contraceptive failure**. - Its primary action is to reduce **hepatic glucose production** and improve insulin sensitivity, with no impact on sex hormone metabolism.

Q: The dose of Digoxin should be reduced when given along with which medication?

Quinidine. ***Quinidine*** - **Quinidine** is known to increase **digoxin plasma concentrations** by inhibiting its renal and non-renal clearance and by displacing it from tissue-binding sites. - This interaction can significantly elevate digoxin levels, necessitating a **dose reduction** [1] to avoid **digoxin toxicity**. *Rifampicin* - **Rifampicin** induces hepatic enzymes, leading to an **increased metabolism** of many drugs, including digoxin. - This interaction would typically *decrease* digoxin levels, potentially requiring an **increase** in digoxin dose, not a reduction. *Indomethacin* - **Indomethacin** and other **NSAIDs** can impair renal function, which *may* indirectly affect digoxin clearance. - However, it does not have a direct, significant interaction with digoxin that would commonly require a primary dose reduction of digoxin for healthy kidneys. *Antacids* - **Antacids** can *reduce the absorption* of some drugs by altering gastric pH or adsorbing the drug. - While they can slightly decrease digoxin absorption if taken concurrently, this effect is usually not significant enough to necessitate a **digoxin dose reduction** in most clinical settings.

Q: Which of the following drugs should not be administered concomitantly with warfarin, as it decreases the effect of oral anticoagulants?

Oral contraceptive. ***Oral contraceptive*** - **Oral contraceptives** contain estrogen, which increases the synthesis of clotting factors (especially factors II, VII, IX, X), thereby **decreasing the anticoagulant effect of warfarin** and increasing the risk of thrombosis. - This interaction necessitates increased monitoring of **INR** and potential **warfarin dose adjustments** when co-administered. *Cimetidine* - **Cimetidine** is a potent inhibitor of **cytochrome P450 enzymes**, which are responsible for warfarin metabolism. - Co-administration with warfarin would **increase** its anticoagulant effect (by reducing warfarin clearance), leading to a higher risk of bleeding, not a decrease. *Aspirin* - **Aspirin** inhibits **platelet aggregation** through irreversible COX-1 inhibition and does not decrease the effect of warfarin. - It can, however, **increase the risk of bleeding** when combined with warfarin due to its antiplatelet properties, but it doesn't reduce warfarin's anticoagulant action. *Broad-spectrum antibiotic* - Many **broad-spectrum antibiotics** can **potentiate** the effect of warfarin by reducing vitamin K-producing gut flora or inhibiting warfarin metabolism. - This interaction typically leads to an **increased INR** and higher bleeding risk, not a decreased anticoagulant effect.

Question 1

Oral contraceptive failure occurs in a patient on rifampicin due to which of the following reasons?

Accepted Answer

Rifampicin induces the metabolism of contraceptive hormones.

Answer

Rifampicin stimulates gonadotropin release from the pituitary.

Answer

Rifampicin decreases the secretion of progestin.

Answer

Rifampicin antagonizes the action of oral contraceptives.

Question 2

What is the primary reason that the therapeutic efficacy of antihypertensive drugs is reduced by NSAIDs?

Accepted Answer

Decrease the synthesis of vascular prostacyclin

Answer

Cause sodium retention

Answer

Inhibit the action of antihypertensive drugs

Answer

Alter the pharmacokinetics of antihypertensive drugs

Question 3

A 20-year-old nulliparous woman is taking oral contraceptive pills. Which anti-tuberculous drug decreases the effect of OCP?

Accepted Answer

Rifampicin

Answer

INH

Answer

Pyrazinamide

Answer

Ethambutol

Question 4

Lenalidomide co-administration with which other drug increases the risk of thrombosis?

Accepted Answer

Glucocorticoids

Answer

Alcohol

Answer

Barbiturates

Answer

Antibiotics

Question 5

A factor that is likely to increase the duration of action of a drug that is partially metabolized by CYP3A4 in the liver is:

Accepted Answer

Chronic administration of cimetidine with the drug

Answer

Chronic administration of phenobarbital with the drug

Answer

Displacement from tissue binding sites by another drug

Answer

Chronic administration of rifampicin

Question 6

Which drug should not be given with ketoconazole?

Accepted Answer

Indinavir

Answer

Macrolide

Answer

All of the options

Answer

Aminoglycoside

Question 7

Which of the following drugs has the least significant drug interaction with digoxin?

Accepted Answer

Amlodipine

Answer

Cholestyramine

Answer

Thiazide diuretics

Answer

Quinidine

Question 8

Concomitant treatment with which of the following can cause oral contraceptive failure?

Accepted Answer

Rifampicin

Answer

Enalapril

Answer

Ibuprofen

Answer

Metformin

Question 9

The dose of Digoxin should be reduced when given along with which medication?

Accepted Answer

Quinidine

Answer

Rifampicin

Answer

Indomethacin

Answer

Antacids

Question 10

Which of the following drugs should not be administered concomitantly with warfarin, as it decreases the effect of oral anticoagulants?

Accepted Answer

Oral contraceptive

Answer

Aspirin

Answer

Cimetidine

Answer

Broad-spectrum antibiotic

Drug Interactions — MCQs

Drug Interactions — MCQs

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