CYP450 & drug interactions flashcards
16 high-yield MRCP Part 1 cards from the Intellect Medicos Clinical Pharmacology & Toxicology course. Try to answer each question before you open it — then study them properly with spaced repetition, which brings each card back just before you would forget it.
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Chronic heavy alcohol use ______ cytochrome P450 enzymes, whereas an acute binge inhibits them.
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induces
Why? This is why chronic drinkers are at higher risk in paracetamol overdose (more NAPQI made), while binge drinking can raise levels of drugs such as warfarin.
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Chronic heavy alcohol use induces cytochrome P450 enzymes, whereas an acute binge ______ them.
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inhibits
Why? This is why chronic drinkers are at higher risk in paracetamol overdose (more NAPQI made), while binge drinking can raise levels of drugs such as warfarin.
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Which antifungal is a cytochrome P450 inducer, unlike the azoles?
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Griseofulvin.
Why? Azoles (ketoconazole, fluconazole) inhibit CYP450, whereas griseofulvin induces it and can make the combined pill unreliable.
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Which H2-receptor antagonist is a recognised cytochrome P450 inhibitor?
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Cimetidine.
Why? It inhibits several CYP enzymes, so it can raise levels of warfarin, phenytoin and theophylline.
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A 70-year-old man with atrial fibrillation is stable on warfarin. He is started on amiodarone. Two weeks later he has haematuria and an INR of 7. What is the mechanism of this interaction?
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Amiodarone inhibits CYP2C9, reducing warfarin metabolism and raising its effect.
Why? The warfarin dose usually needs reducing when amiodarone starts, with closer INR checks; amiodarone's long half-life means the effect lasts weeks.
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A 68-year-old woman with COPD takes oral theophylline. She is given ciprofloxacin for a chest infection and three days later has vomiting, palpitations and a seizure. What is the mechanism?
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Ciprofloxacin inhibits CYP1A2, reducing theophylline clearance and causing theophylline toxicity.
Why? Theophylline has a narrow therapeutic index. Clarithromycin and erythromycin cause the same problem (CYP1A2/CYP3A4 inhibition).
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Which fruit juice should patients on simvastatin avoid, and why?
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Grapefruit juice — it inhibits intestinal CYP3A4, raising simvastatin levels and the risk of myopathy.
Why? Simvastatin and atorvastatin are CYP3A4 substrates; rosuvastatin and pravastatin are much less affected.
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A man with HIV on a ritonavir-boosted regimen has used inhaled fluticasone for asthma for a year. He now has a moon face, striae and proximal weakness. What is the mechanism?
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Ritonavir strongly inhibits CYP3A4, so fluticasone accumulates, causing iatrogenic Cushing's syndrome (and adrenal suppression).
Why? Inhaled and intranasal steroids can reach systemic levels when their CYP3A4 metabolism is blocked.
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Why can naproxen cause methotrexate toxicity?
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NSAIDs reduce the renal excretion of methotrexate.
Why? Methotrexate is renally cleared; reduced clearance leads to myelosuppression, mucositis and hepatotoxicity.
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How does furosemide increase the risk of digoxin toxicity?
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It causes hypokalaemia, which increases digoxin binding to the Na+/K+ ATPase.
Why? Potassium competes with digoxin at the pump, so low potassium enhances digoxin's effect (pharmacodynamic interaction).
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What is the danger of giving IV verapamil to a patient taking a beta-blocker?
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Profound bradycardia, AV block, hypotension and asystole.
Why? Both drugs slow the AV node and reduce contractility; their effects add together.
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Which electrolyte problem results from combining ramipril with spironolactone?
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Hyperkalaemia.
Why? Both reduce potassium excretion (ACE inhibition lowers aldosterone; spironolactone blocks its receptor).
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A renal transplant recipient on ciclosporin has started a herbal remedy for low mood. His ciclosporin level has fallen and his creatinine is rising. Which remedy is most likely, and by what mechanism?
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St John's wort — it induces CYP3A4 (and P-glycoprotein), lowering ciclosporin levels and risking rejection.
Why? St John's wort also lowers levels of the combined pill (contraceptive failure) and warfarin (falling INR).
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Why should omeprazole be avoided in a patient taking clopidogrel?
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Omeprazole (and esomeprazole) inhibits CYP2C19, which is needed to convert the prodrug clopidogrel to its active form, so its antiplatelet effect falls.
Why? The MHRA discourages omeprazole and esomeprazole with clopidogrel; if a PPI is needed, lansoprazole or pantoprazole is usually chosen instead.
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By how much should the azathioprine dose be reduced if allopurinol is started, and why?
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To about a quarter of the usual dose, because allopurinol inhibits xanthine oxidase, which breaks down azathioprine (via mercaptopurine).
Why? Without dose reduction, thiopurine levels rise and cause severe bone marrow suppression.
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What happens to lamotrigine levels when sodium valproate is added, and what is the risk?
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Levels roughly double (valproate inhibits lamotrigine glucuronidation), raising the risk of serious rash including Stevens–Johnson syndrome.
Why? Lamotrigine must be started at a lower dose and titrated more slowly in patients taking valproate.
More Clinical Pharmacology & Toxicology topics
- Pharmacokinetics, receptors & pharmacogenetics
- Autonomic, dopamine, serotonin & antiemetic drugs
- Drug & therapeutic level monitoring
- Pregnancy, breastfeeding & contraception
- Antimicrobial mechanisms & toxicity
- Cardiovascular, immunosuppressant & anaesthetic drugs
- Overdose of common drugs
- Poisons, antidotes & recreational drugs
- Adverse drug reactions: drugs causing X