CAOP Drug Interactions and Contraindications 2 — Questions and Answers
Question 1: A patient stabilised on lithium for bipolar disorder is prescribed naproxen for arthritis. What is the most likely outcome?
- Lithium levels decrease due to increased renal clearance
- Lithium levels increase due to reduced renal prostaglandin-mediated excretion (Correct answer)
- Naproxen levels increase due to lithium-mediated protein binding displacement
- No clinically relevant interaction is expected
Correct answer: Lithium levels increase due to reduced renal prostaglandin-mediated excretion
NSAIDs reduce renal prostaglandin synthesis, decreasing renal blood flow and lithium excretion, which can increase lithium plasma levels into the toxic range.
Question 2: Beta-blockers are contraindicated in patients with which of the following respiratory conditions?
- Mild seasonal allergic rhinitis
- Reactive airway disease / bronchial asthma (Correct answer)
- Obstructive sleep apnoea
- Pulmonary hypertension
Correct answer: Reactive airway disease / bronchial asthma
Non-selective beta-blockers block beta-2 receptors in bronchial smooth muscle, causing bronchoconstriction and potentially fatal bronchospasm in asthmatic patients.
Question 3: Concomitant use of clopidogrel and omeprazole is clinically significant because:
- Omeprazole induces CYP2C19, increasing clopidogrel activation
- Omeprazole inhibits CYP2C19, reducing conversion of clopidogrel to its active metabolite (Correct answer)
- Clopidogrel increases omeprazole bioavailability through P-gp inhibition
- Both drugs compete for the same platelet receptor binding sites
Correct answer: Omeprazole inhibits CYP2C19, reducing conversion of clopidogrel to its active metabolite
Clopidogrel is a prodrug requiring CYP2C19 for activation; omeprazole's CYP2C19 inhibition reduces formation of the active thiol metabolite, diminishing antiplatelet efficacy.
Question 4: Oral tetracyclines should not be taken with dairy products because calcium:
- Increases gastric acid, inactivating the antibiotic
- Forms insoluble chelate complexes with tetracyclines, reducing absorption (Correct answer)
- Competes with tetracyclines at intestinal efflux pumps
- Accelerates renal excretion of tetracyclines
Correct answer: Forms insoluble chelate complexes with tetracyclines, reducing absorption
Calcium (and other divalent/trivalent cations) chelates tetracyclines to form insoluble complexes in the gut, significantly reducing oral bioavailability by up to 50–80%.
Question 5: Oral fluoroquinolones (e.g., ciprofloxacin) should be administered at least 2 hours before or 6 hours after antacids primarily because antacids:
- Inhibit CYP3A4, increasing fluoroquinolone systemic exposure
- Chelate fluoroquinolones via magnesium/aluminium ions, reducing absorption (Correct answer)
- Alkalinise the urine, promoting fluoroquinolone crystallisation in renal tubules
- Accelerate gastric emptying, reducing fluoroquinolone contact time
Correct answer: Chelate fluoroquinolones via magnesium/aluminium ions, reducing absorption
Magnesium and aluminium in antacids form insoluble chelate complexes with fluoroquinolones in the gastrointestinal tract, markedly reducing their oral absorption.
Question 6: Co-prescribing methotrexate with NSAIDs increases the risk of methotrexate toxicity primarily because:
- NSAIDs induce DHFR, partially reversing methotrexate's mechanism of action
- NSAIDs reduce renal clearance and tubular secretion of methotrexate, increasing plasma levels (Correct answer)
- NSAIDs displace methotrexate from tissue binding sites, causing redistribution
- NSAIDs inhibit thymidylate synthase, potentiating bone marrow toxicity
Correct answer: NSAIDs reduce renal clearance and tubular secretion of methotrexate, increasing plasma levels
NSAIDs reduce renal prostaglandin synthesis, decreasing renal blood flow and inhibiting organic anion transporters involved in tubular secretion of methotrexate, leading to dangerous accumulation.
Question 7: Ciprofloxacin co-administered with theophylline is likely to cause which outcome?
- Subtherapeutic theophylline levels due to CYP1A2 induction
- Theophylline toxicity due to CYP1A2 inhibition by ciprofloxacin (Correct answer)
- Ciprofloxacin toxicity due to theophylline-mediated CYP3A4 inhibition
- Additive nephrotoxicity requiring dose reductions of both agents
Correct answer: Theophylline toxicity due to CYP1A2 inhibition by ciprofloxacin
Ciprofloxacin is a potent CYP1A2 inhibitor; since theophylline is primarily metabolised by CYP1A2, co-administration can reduce theophylline clearance by up to 30–50%, causing toxicity (seizures, arrhythmias).
CAOP Drug Interactions and Contraindications 2
A patient stabilised on lithium for bipolar disorder is prescribed naproxen for arthritis.
What is the most likely outcome?