Skip to main content
Sign in Create a free account
Varsity Tutors
Sign in

Pharmacology - NAPLEX

  1. A 39-year-old female (weight 72 kg) with major depressive disorder is started on phenelzine; 10 days later she presents with severe headache, palpitations, and BP 198/110 mmHg after eating aged cheese and pepperoni. Current meds: phenelzine 15 mg PO TID, multivitamin; labs: SCr 0.8 mg/dL, LFTs normal; allergy: none. Which mechanism of action explains this side effect?
    Answer: Inhibition of monoamine oxidase leading to decreased tyramine breakdown and excess catecholamines This question tests the pharmacodynamic interaction of monoamine oxidase inhibitors (MAOIs) like phenelzine with tyramine-rich foods, leading to hypertensive crisis. The key patient-specific factor is recent phenelzine initiation and ingestion of aged cheese/pepperoni, which contain tyramine that MAOIs prevent from being metabolized. Inhibition of monoamine oxidase leading to decreased tyramine breakdown and excess catecholamines is the correct mechanism, explaining the headache, palpitations, and hypertension. Dopamine D2 blockade or COMT inhibition do not involve tyramine, and GABA activation causes sedation, not sympathetic overactivity. Clinically, counsel patients on tyramine-restricted diets when starting MAOIs to avoid crises. In practice, consider MAOI washout periods and emergency treatments like phentolamine for similar interactions.
  2. A 55-year-old female (68 kg) with bipolar disorder is taking lithium carbonate 300 mg PO TID. She presents with nausea, coarse tremor, and confusion after starting ibuprofen 600 mg PO TID for back pain 5 days ago; allergies: none. Labs: lithium level 1.9 mEq/L (therapeutic 0.6–1.2), SCr 1.6 mg/dL (0.6–1.1), Na 136 mEq/L (135–145). Which monitoring strategy is most appropriate for this treatment?
    Answer: Obtain a 12-hour post-dose (trough) lithium level and monitor renal function closely This question tests lithium monitoring principles in the setting of drug-induced toxicity. The key patient-specific factors are the toxic lithium level (1.9 mEq/L), acute kidney injury (SCr 1.6 mg/dL), and recent NSAID initiation. Obtaining a 12-hour post-dose trough level and monitoring renal function (B) is correct - lithium levels must be drawn 12 hours post-dose for accurate interpretation, and renal function monitoring is crucial as lithium is 100% renally eliminated. Random levels 1 hour post-dose (A) are not standardized and will be falsely elevated. Liver function monitoring (C) is incorrect as lithium undergoes no hepatic metabolism. INR monitoring (D) is irrelevant as lithium doesn't affect coagulation. The clinical framework is that NSAIDs reduce renal lithium clearance by 20-60% through prostaglandin inhibition; lithium toxicity presents with GI, neurologic, and renal symptoms; management includes holding lithium and NSAIDs, IV hydration, and serial lithium levels every 6-12 hours.
  3. A 60-year-old female (weight 82 kg) with chronic pain and CKD stage 4 is prescribed gabapentin for neuropathy. Current meds: insulin glargine, acetaminophen 650 mg PO TID PRN; labs: SCr 2.6 mg/dL, estimated CrCl 22 mL/min; LFTs normal; allergy: codeine (nausea). What dose adjustment is required based on these lab values for gabapentin immediate-release?
    Answer: Use a reduced total daily dose with extended dosing interval (e.g., 300 mg PO once daily to BID) This question tests the pharmacokinetic adjustment of gabapentin in renal impairment, as it is primarily renally excreted unchanged. The key patient-specific factor is the patient's CKD stage 4 with CrCl 22 mL/min, which reduces gabapentin clearance and increases toxicity risk. Using a reduced total daily dose with extended dosing interval (e.g., 300 mg PO once daily to BID) is the best choice to maintain efficacy while preventing accumulation and side effects like sedation. No adjustment is incorrect as it ignores renal dosing guidelines, and avoiding gabapentin due to hepatic clearance is wrong since it is renally cleared; increasing the dose would worsen toxicity. Clinically, calculate CrCl and consult renal dosing resources for gabapentin, typically reducing to 100–300 mg daily for CrCl <30 mL/min. In practice, monitor for CNS side effects and titrate slowly in CKD patients to optimize neuropathy management.
  4. A 66-year-old female (weight 68 kg) with a mechanical mitral valve is stable on warfarin 4 mg PO daily (INR goal 2.5–3.5). She starts rifampin 600 mg PO daily for latent TB and returns 2 weeks later with INR 1.4 (normal 0.8–1.2) and no bleeding; SCr 0.9 mg/dL; LFTs normal; allergy: none. What is the best approach to manage this drug interaction?
    Answer: Increase warfarin dose with very frequent INR monitoring during rifampin therapy This question tests the pharmacokinetic induction of warfarin metabolism by rifampin, a potent CYP3A4 and CYP2C9 inducer, reducing anticoagulant effect. The key patient-specific factor is the subtherapeutic INR of 1.4 after 2 weeks of rifampin in a patient with a mechanical valve requiring higher INR goals. Increasing warfarin dose with very frequent INR monitoring during rifampin therapy is the best approach to restore therapeutic anticoagulation and prevent thrombosis. Decreasing warfarin is incorrect as it would further lower INR, and continuing unchanged or adding fluconazole ignores the induction effect. Clinically, anticipate up to 2–3 fold warfarin dose increases with rifampin, monitoring INR weekly initially. In practice, consider alternative anticoagulants like DOACs if induction interactions are unavoidable to maintain efficacy.
  5. A 45-year-old male (weight 90 kg) with epilepsy is stable on phenytoin; he presents with nystagmus and ataxia after starting trimethoprim-sulfamethoxazole for cellulitis 5 days ago. Meds: phenytoin 300 mg PO nightly, TMP-SMX DS 1 tab PO BID; labs: albumin 2.5 g/dL (normal 3.5–5), total phenytoin 14 mcg/mL (therapeutic 10–20), SCr 1.0 mg/dL; allergy: none. Which monitoring strategy is most appropriate for this treatment?
    Answer: Obtain a free phenytoin concentration (or adjust for albumin) and assess for toxicity This question tests the monitoring of phenytoin in the context of hypoalbuminemia and drug interactions, where total levels may not reflect free (active) drug. The key patient-specific factor is low albumin (2.5 g/dL) and recent TMP-SMX initiation, which displaces phenytoin from protein binding and inhibits its metabolism, increasing free levels and toxicity symptoms like nystagmus. Obtaining a free phenytoin concentration (or adjusting for albumin) and assessing for toxicity is the best strategy to accurately evaluate active drug exposure. Relying only on total levels is incorrect as they underestimate free drug in hypoalbuminemia, while INR or potassium monitoring is irrelevant to phenytoin toxicity. Clinically, use the Winter-Tozer equation to correct total phenytoin: corrected = total / [(0.2 x albumin) + 0.1]. In practice, always measure free levels in altered protein states or interactions to guide dosing and prevent adverse effects.
  6. A 50-year-old male (weight 79 kg) with depression is switched from paroxetine 40 mg PO daily to tamoxifen 20 mg PO daily after a new diagnosis of ER+ breast cancer (male breast cancer). After 3 months, his oncologist is concerned about reduced tamoxifen effectiveness. Labs: SCr 0.9 mg/dL, LFTs normal; allergy: none. What is the best approach to manage this drug interaction?
    Answer: Switch paroxetine to an antidepressant with less CYP2D6 inhibition (e.g., venlafaxine) if appropriate This question tests the pharmacokinetic interaction where strong CYP2D6 inhibitors like paroxetine reduce tamoxifen activation to endoxifen. The key patient-specific factor is concurrent use in a patient with ER+ breast cancer, potentially decreasing therapeutic efficacy. Switching paroxetine to an antidepressant with less CYP2D6 inhibition (e.g., venlafaxine) if appropriate is the best approach to preserve tamoxifen's anti-estrogen effects. Continuing paroxetine reduces active metabolites, adding omeprazole is irrelevant, and increasing tamoxifen lacks evidence and increases side effects. Clinically, screen for CYP2D6 inhibitors in tamoxifen users and consider genotyping. In practice, prefer weak inhibitors like citalopram for depression to optimize oncology outcomes.
  7. A 34-year-old male (82 kg) with generalized anxiety disorder is started on propranolol 20 mg PO TID for performance anxiety. He has a history of asthma controlled with albuterol HFA 2 puffs q4–6h PRN; allergies: none. Vitals today: HR 58 bpm, BP 112/70 mmHg; labs: SCr 0.9 mg/dL (0.6–1.3). Which mechanism of action explains the most clinically important risk in this patient?
    Answer: Nonselective β blockade inhibiting β2-mediated bronchodilation, potentially worsening bronchospasm This question tests understanding of beta-blocker receptor selectivity and contraindications. The key patient-specific factor is the history of asthma requiring albuterol use in a patient started on propranolol. Nonselective β blockade inhibiting β2-mediated bronchodilation (B) is correct - propranolol blocks both β1 and β2 receptors, antagonizing β2-mediated bronchodilation and potentially triggering severe bronchospasm in asthmatic patients. Selective β1 blockade causing reflex tachycardia (A) is incorrect as propranolol is nonselective and actually causes bradycardia. α1 agonism (C) and muscarinic antagonism (D) are not mechanisms of propranolol. The clinical framework is that nonselective beta-blockers (propranolol, nadolol, timolol) are contraindicated in asthma and COPD; if beta-blockade is necessary for anxiety in asthmatic patients, highly β1-selective agents like atenolol or metoprolol at low doses may be cautiously tried with close monitoring.
  8. A 62-year-old male (weight 86 kg) with type 2 diabetes is started on empagliflozin 10 mg PO daily. One week later he reports increased urination and thirst; fingerstick glucoses are improving. Current meds: empagliflozin 10 mg daily, metformin 1000 mg BID, lisinopril 10 mg daily; labs: Na 140 mEq/L, SCr 1.0 mg/dL; allergy: none. Which mechanism of action explains this side effect?
    Answer: Inhibition of SGLT2 in the proximal tubule causing glucosuria and osmotic diuresis This question tests the diuretic side effects of SGLT2 inhibitors like empagliflozin, promoting urinary glucose excretion. The key patient-specific factor is type 2 diabetes with recent empagliflozin start, causing polyuria and thirst from osmotic diuresis. Inhibition of SGLT2 in the proximal tubule causing glucosuria and osmotic diuresis is the correct mechanism, explaining the symptoms despite improving glucose control. DPP-4 blockade or PPAR-γ activation cause different effects like edema, not diuresis; insulin stimulation does not directly cause water loss. Clinically, counsel on transient volume depletion and monitor for dehydration. In practice, assess electrolytes and encourage hydration to manage SGLT2i side effects in diabetes care.
  9. A 49-year-old male (weight 88 kg) with hyperlipidemia is taking simvastatin 40 mg PO nightly. His provider prescribes clarithromycin 500 mg PO BID for pneumonia; 6 days later he reports severe muscle pain and dark urine. Labs: CK 3200 U/L (normal 30–200), SCr 1.6 mg/dL (baseline 1.0), AST 90 U/L; allergy: none. What is the best approach to manage this drug interaction?
    Answer: Hold simvastatin during clarithromycin therapy and use an alternative antibiotic if possible This question tests the pharmacokinetic interaction where clarithromycin inhibits CYP3A4, increasing simvastatin levels and rhabdomyolysis risk. The key patient-specific factor is concurrent use leading to elevated CK and myopathy symptoms in a patient with infection. Holding simvastatin during clarithromycin therapy and using an alternative antibiotic if possible is the best approach to prevent further muscle damage. Continuing both or adding coenzyme Q10 ignores the severe interaction, increasing dose worsens toxicity, and adding gemfibrozil compounds myopathy risk. Clinically, limit simvastatin to 10 mg with strong inhibitors or hold during short courses. In practice, check for CYP interactions and consider pravastatin alternatives to manage lipids safely during antibiotics.
  10. A 64-year-old male (weight 92 kg) with gout and CKD stage 3 is prescribed allopurinol 300 mg PO daily. Current meds: azathioprine 100 mg PO daily for ulcerative colitis, allopurinol 300 mg daily (new), prednisone 5 mg daily; labs: SCr 1.7 mg/dL, AST/ALT normal; allergy: none. What is the best approach to manage this drug interaction?
    Answer: Reduce azathioprine dose substantially and monitor CBC closely This question tests the pharmacokinetic interaction where allopurinol inhibits xanthine oxidase, reducing azathioprine metabolism and increasing myelotoxicity. The key patient-specific factor is CKD stage 3, which may further impair clearance and heighten bone marrow suppression risk in ulcerative colitis. Reducing azathioprine dose substantially and monitoring CBC closely is the best approach to maintain immunosuppression without severe toxicity. Continuing unchanged or increasing dose risks pancytopenia, and adding probenecid is irrelevant. Clinically, reduce azathioprine by 75% with allopurinol and monitor TPMT genetics if available. In practice, co-prescribe cautiously with frequent hematologic monitoring to balance efficacy and safety in gout and immunosuppression.
  11. A 63-year-old male (weight 74 kg) with heart failure with reduced ejection fraction and atrial fibrillation presents with nausea, anorexia, and yellow-tinged vision. Meds: digoxin 0.25 mg PO daily, furosemide 40 mg PO BID, carvedilol 12.5 mg PO BID; labs: K 3.1 mEq/L (normal 3.5–5.0), SCr 1.5 mg/dL, digoxin level 2.4 ng/mL (therapeutic 0.5–0.9 for HF). Which monitoring strategy is most appropriate for this treatment?
    Answer: Hold digoxin, correct electrolytes, and recheck a trough digoxin level (≥6 hours post-dose) This question tests digoxin toxicity monitoring, focusing on trough levels and electrolyte influences. The key patient-specific factor is hypokalemia (K 3.1 mEq/L) and elevated digoxin level (2.4 ng/mL), exacerbating toxicity symptoms like nausea and visual changes in heart failure. Holding digoxin, correcting electrolytes, and rechecking a trough level (≥6 hours post-dose) is the best strategy to confirm and manage toxicity while preventing arrhythmias. Continuing without change ignores toxicity, and checking 30 minutes post-dose measures peak, not trough; switching to IV increases risk without benefit. Clinically, digoxin toxicity is potentiated by hypokalemia, so replete potassium and monitor levels 5–7 days after changes. In practice, use lower doses (0.125 mg) in renal impairment and educate on toxicity signs for safe digoxin use in HF and AF.
  12. A 67-year-old male (88 kg) with a mechanical aortic valve is maintained on warfarin 5 mg PO daily (goal INR 2.5–3.5). He starts trimethoprim-sulfamethoxazole (TMP-SMX) DS 1 tablet PO BID for 7 days for cellulitis; allergies: none. Three days later, labs show INR 5.8 (0.8–1.2) and Hgb 13.9 g/dL (13.5–17.5) with no bleeding. What is the best approach to manage this drug interaction?
    Answer: Hold warfarin doses and arrange prompt INR recheck; consider alternative antibiotic if feasible This question tests management of a significant warfarin drug interaction. The key patient-specific factor is the dangerously elevated INR of 5.8 (goal 2.5-3.5) after starting TMP-SMX, without active bleeding. Holding warfarin and arranging prompt INR recheck (B) is correct - TMP-SMX inhibits CYP2C9, reducing warfarin metabolism and dramatically increasing INR, requiring immediate dose adjustment to prevent bleeding. Continuing both drugs (A) risks major bleeding with INR 5.8. Increasing warfarin (C) would worsen the supratherapeutic INR. Adding aspirin (D) would increase bleeding risk without addressing the elevated INR. The clinical framework is that TMP-SMX typically increases INR by 2-3 fold within 3-5 days through CYP2C9 inhibition; proactive warfarin dose reduction by 25-50% when starting TMP-SMX, with INR checks every 2-3 days, can prevent this dangerous interaction.
  13. A 77-year-old female (weight 50 kg) with CKD stage 4 and chronic knee pain is prescribed morphine sulfate immediate-release 15 mg PO every 4 hours PRN. After 2 days, family reports marked sedation and confusion. Current meds: morphine as above, amlodipine 5 mg daily; labs: SCr 2.9 mg/dL, estimated CrCl 18 mL/min; LFTs normal; allergy: none. What dose adjustment is required based on these lab values?
    Answer: Avoid or reduce morphine and consider an alternative opioid with less renally cleared active metabolites This question tests opioid dosing adjustments in renal impairment, where morphine's active metabolite (M6G) accumulates, causing toxicity. The key patient-specific factor is CKD stage 4 with CrCl 18 mL/min, leading to sedation and confusion from metabolite buildup. Avoiding or reducing morphine and considering an alternative opioid with less renally cleared active metabolites is the best choice to ensure safe analgesia without prolonged effects. No adjustment ignores accumulation risks, increasing dose worsens toxicity, and switching to ER form does not mitigate metabolite issues. Clinically, prefer opioids like fentanyl or hydromorphone in severe CKD due to hepatic metabolism. In practice, assess CrCl before opioid selection and monitor for CNS depression to guide therapy in renal patients.
  14. A 59-year-old female (weight 66 kg) with bipolar disorder is on lithium carbonate 300 mg PO TID and is started on hydrochlorothiazide 25 mg PO daily for HTN. One week later she reports tremor, diarrhea, and confusion. Labs: lithium 1.9 mEq/L (therapeutic 0.6–1.2), Na 132 mEq/L (normal 135–145), SCr 1.2 mg/dL; allergy: none. What is the best approach to manage this drug interaction?
    Answer: Stop hydrochlorothiazide and reduce lithium dose with repeat lithium level monitoring This question tests the pharmacokinetic interaction where thiazides like hydrochlorothiazide reduce lithium clearance via sodium depletion, increasing levels. The key patient-specific factor is recent HCTZ addition leading to toxicity symptoms and elevated lithium (1.9 mEq/L) in bipolar disorder. Stopping hydrochlorothiazide and reducing lithium dose with repeat level monitoring is the best approach to resolve toxicity and maintain mood stability. Continuing both or adding NSAIDs worsens toxicity, increasing lithium ignores reduced clearance, and switching thiazides does not avoid the class effect. Clinically, monitor lithium levels weekly after diuretic changes and adjust doses by 25–50%. In practice, prefer alternative antihypertensives like ACEIs in lithium users to prevent similar interactions.
  15. A 58-year-old male (92 kg) with type 2 diabetes and hypertriglyceridemia presents with new-onset facial flushing and itching 30 minutes after taking his first dose of immediate-release niacin 500 mg. Current medications include metformin 1000 mg PO BID, atorvastatin 40 mg PO daily, and aspirin 81 mg PO daily; allergies: penicillin (rash). Labs: AST 28 U/L (10–40), ALT 30 U/L (7–56), fasting glucose 148 mg/dL (70–99), TG 410 mg/dL (<150). Which mechanism of action explains this side effect?
    Answer: Prostaglandin-mediated vasodilation from increased PGD2/PGE2 release in the skin This question tests understanding of niacin's mechanism for causing flushing, a common side effect. The key patient-specific factor is the timing of symptoms (30 minutes after first dose) and the characteristic presentation of facial flushing and itching. Prostaglandin-mediated vasodilation from increased PGD2/PGE2 release in the skin (B) is the correct mechanism - niacin activates GPR109A receptors on epidermal Langerhans cells, triggering prostaglandin release and cutaneous vasodilation. Competitive inhibition of HMG-CoA reductase (A) describes statins' mechanism, not niacin's side effect profile. Bile acid chelation (C) describes bile acid sequestrants like cholestyramine. PPAR-α activation (D) describes fibrates' mechanism of action. The clinical takeaway is that pre-treatment with aspirin 325 mg 30 minutes before niacin can reduce flushing by inhibiting prostaglandin synthesis, and extended-release formulations cause less flushing than immediate-release.
  16. A 28-year-old male (weight 75 kg) with asthma is started on propranolol 40 mg PO BID for performance anxiety and soon develops wheezing and shortness of breath. Current meds: albuterol HFA 2 puffs PRN, fluticasone/salmeterol 250/50 mcg 1 inhalation BID, propranolol; labs: SCr 0.9 mg/dL; allergy: none. Which mechanism of action explains this side effect?
    Answer: Nonselective beta blockade inhibiting beta-2 mediated bronchodilation This question tests the pharmacodynamic contraindication of nonselective beta-blockers like propranolol in asthma, blocking bronchodilation. The key patient-specific factor is asthma history, where propranolol exacerbates wheezing by inhibiting beta-2 receptors. Nonselective beta blockade inhibiting beta-2 mediated bronchodilation is the correct mechanism, explaining the acute respiratory symptoms. Beta-2 agonism would improve breathing, muscarinic antagonism dries secretions but not constricts, and leukotriene inhibition is unrelated. Clinically, use cardioselective beta-blockers like metoprolol in asthma if needed. In practice, screen for respiratory conditions before nonselective agents and educate on rescue inhaler use for potential exacerbations.
  17. A 52-year-old male (weight 76 kg) with schizophrenia is on clozapine 350 mg/day and presents with fever, sore throat, and malaise. Current meds: clozapine 200 mg PO at bedtime + 150 mg PO in the morning, docusate 100 mg PO BID; labs: ANC 420/mm3^3 (normal 1500–8000), WBC 1.8 x103^3/mm3^3 (normal 4–11), SCr 0.9 mg/dL; allergy: none. Which monitoring strategy is most appropriate for this treatment?
    Answer: Stop clozapine and follow ANC monitoring per protocol due to severe neutropenia This question tests clozapine's risk of agranulocytosis, requiring strict ANC monitoring per REMS protocols. The key patient-specific factor is the severely low ANC of 420/mm³ with symptoms like fever, indicating agranulocytosis in schizophrenia treatment. Stopping clozapine and following ANC monitoring per protocol due to severe neutropenia is the best strategy to prevent life-threatening infections. Continuing or reducing dose ignores guidelines mandating discontinuation below 1000/mm³, and switching to lithium is inappropriate without addressing neutropenia. Clinically, monitor ANC weekly for 6 months, then biweekly, and hold for ANC <1500/mm³. In practice, rechallenge only after hematology consult and consider alternatives like olanzapine for psychosis if clozapine is discontinued.
  18. A 55-year-old male (weight 100 kg) with chronic hepatitis C-related cirrhosis (Child-Pugh C) is prescribed zolpidem 10 mg PO at bedtime for insomnia and experiences profound next-day sedation and falls. Current meds: spironolactone 100 mg daily, furosemide 40 mg daily, lactulose 20 g TID; labs: albumin 2.8 g/dL, total bilirubin 3.2 mg/dL (normal 0.1–1.2), INR 1.8 (normal 0.8–1.2), AST/ALT elevated; allergy: none. What is the pharmacokinetic parameter affecting this dose?
    Answer: Reduced hepatic metabolism increasing bioavailability and decreasing clearance This question tests pharmacokinetic changes in cirrhosis, where reduced hepatic metabolism and low albumin alter drug disposition. The key patient-specific factor is Child-Pugh C cirrhosis with hypoalbuminemia, increasing zolpidem's free fraction and prolonging effects like sedation. Reduced hepatic metabolism increasing bioavailability and decreasing clearance is the correct parameter, explaining profound next-day effects. Increased renal clearance or gastric pH would reduce exposure, and volume changes do not directly increase binding. Clinically, reduce zolpidem to 5 mg or avoid in severe liver disease. In practice, assess liver function and start low/go slow with sedatives to minimize falls in cirrhosis patients.
  19. A 64-year-old male (80 kg) with heart failure with reduced ejection fraction and hypertension is started on lisinopril. His current medications include furosemide 40 mg PO daily and spironolactone 25 mg PO daily; allergies: sulfa (hives). Baseline labs: K 5.6 mEq/L (3.5–5.0), SCr 1.4 mg/dL (0.6–1.3), eGFR 52 mL/min/1.73m2^2; BP 128/76 mmHg. What is the best approach to manage this drug interaction?
    Answer: Avoid adding lisinopril until hyperkalemia is corrected and/or spironolactone is reduced/held This question tests understanding of the dangerous drug interaction between ACE inhibitors and potassium-sparing diuretics. The key patient-specific factor is the baseline hyperkalemia (K 5.6 mEq/L) in a patient already on spironolactone, a potassium-sparing diuretic. Avoiding lisinopril until hyperkalemia is corrected (C) is the safest approach because adding an ACE inhibitor to spironolactone significantly increases hyperkalemia risk through dual mechanisms of reducing potassium excretion. Starting lisinopril with potassium supplementation (A) would dangerously worsen hyperkalemia. Reducing furosemide (B) is inappropriate as it helps promote potassium excretion and ACE inhibitor cough is unrelated to diuretic dose. Increasing spironolactone (D) would further elevate potassium levels. The clinical framework is to always check baseline potassium before starting ACE inhibitors/ARBs in patients on potassium-sparing diuretics, and consider temporarily holding or reducing the potassium-sparing agent when initiating RAAS blockade.
  20. A 58-year-old female (weight 60 kg) with rheumatoid arthritis takes methotrexate 15 mg PO once weekly with folic acid 1 mg PO daily. She develops severe mouth sores and fatigue after starting omeprazole 40 mg PO daily for GERD 3 weeks ago. Labs: SCr 1.3 mg/dL (baseline 0.9), AST 55 U/L (normal 10–40), ALT 62 U/L (normal 7–56); allergy: NSAIDs (GI bleed). What is the best approach to manage this drug interaction?
    Answer: Switch omeprazole to an H2-receptor antagonist and monitor for methotrexate toxicity This question tests the pharmacokinetic interaction where PPIs like omeprazole reduce methotrexate clearance by inhibiting renal tubular secretion. The key patient-specific factor is elevated SCr (1.3 mg/dL) indicating reduced clearance, contributing to methotrexate toxicity symptoms like mouth sores and fatigue. Switching omeprazole to an H2-receptor antagonist and monitoring for methotrexate toxicity is the best approach as H2 blockers have less impact on methotrexate excretion. Continuing both ignores the interaction, increasing toxicity risk; increasing methotrexate worsens exposure, and stopping folic acid reduces protection against side effects. Clinically, avoid PPIs with high-dose methotrexate and prefer H2 antagonists or antacids. In practice, monitor renal function and symptoms weekly when combining acid suppressants with methotrexate to prevent severe adverse effects.

Start this quiz