Enzymes, transporters and receptors that medicines modulate — what they are, what they do and how they explain interactions.
It is the most frequent target in interactions: drugs that inhibit it (e.g. ketoconazole, clarithromycin, grapefruit juice) raise substrate concentrations; drugs that induce it (e.g. rifampicin, carbamazepine, phenytoin) lower them and may cause loss of efficacy.
View details →CYP2D6 inhibition (e.g. fluoxetine, paroxetine) can double concentrations of substrates such as codeine, tramadol and metoprolol; in poor metabolisers, prodrugs activated by this enzyme (codeine → morphine) may have reduced effect.
View details →CYP2C9 inhibition (e.g. fluconazole, amiodarone, metronidazole, cotrimoxazole) is the central mechanism of interactions that raise INR with coumarins; induction (rifampicin) reduces the anticoagulant effect.
View details →CYP1A2 inhibition (e.g. ciprofloxacin + theophylline) increases the risk of theophylline toxicity (nausea, tachycardia, seizures); smokers who quit may accumulate substrates metabolised by this enzyme.
View details →CYP2C19 inhibition (e.g. omeprazole + clopidogrel) reduces formation of the active clopidogrel metabolite and may decrease antiplatelet protection; induction (rifampicin) accelerates substrate metabolism.
View details →CYP2C8 inhibition (e.g. gemfibrozil + repaglinide) raises substrate concentrations and the risk of hypoglycaemia; induction reduces the effect.
View details →CYP2B6 induction (e.g. rifampicin, phenobarbital) lowers efavirenz and bupropion concentrations; inhibition increases exposure.
View details →Chronic alcohol intake induces CYP2E1 and increases NAPQI formation from paracetamol, raising the risk of hepatotoxicity at therapeutic doses.
View details →COX-1 inhibition by NSAIDs and aspirin explains the gastrotoxic effects (ulcer, bleeding) and, with aspirin, the antiplatelet effect. It is the target of NSAID + anticoagulant/antiplatelet interactions.
View details →Selective COX-2 inhibitors spare COX-1 and have lower gastrointestinal risk, but retain cardiovascular (thromboembolic) and renal risk; interactions with anticoagulants remain relevant.
View details →Drugs that inhibit P-gp (e.g. amiodarone, clarithromycin, ketoconazole, verapamil, diltiazem) increase absorption and concentrations of substrates such as digoxin, dabigatran and tacrolimus; inducers lower them.
View details →BCRP inhibition increases exposure to substrates such as rosuvastatin, methotrexate and sulfasalazine; combination with inhibitors (e.g. ciclosporin) may require dose reduction.
View details →OATP1B1 inhibition (e.g. ciclosporin, clarithromycin) reduces hepatic uptake of statins and raises systemic concentrations, with risk of myopathy and rhabdomyolysis.
View details →MAO-A inhibition raises synaptic monoamines; combination with SSRIs, tramadol, pethidine or dextromethorphan can cause serotonin syndrome, and tyramine-rich food can cause a hypertensive crisis.
View details →Selective MAO-B inhibition at therapeutic doses has lower tyramine interaction risk, but combination with serotonergic drugs (SSRIs, pethidine) retains serotonin syndrome risk.
View details →Warfarin and acenocoumarol inhibit VKORC1, reducing synthesis of vitamin K-dependent factors; dietary vitamin K intake antagonises this effect and shifts the INR.
View details →Oxidant drugs can cause acute haemolysis in G6PD-deficient patients: primaquine, sulfonamides (cotrimoxazole), nitrofurantoin, dapsone, high-dose aspirin.
View details →Drugs that inhibit TPMT (e.g. allopurinol) increase azathioprine toxicity; allopurinol + azathioprine is the classic interaction and requires azathioprine dose reduction.
View details →Combining PDE5 inhibitors with nitrates (nitroglycerin, isosorbide) causes severe, potentially fatal hypotension, by potentiating nitric oxide; they also potentiate hypotension with alpha-blockers and riociguat.
View details →Statins (simvastatin, atorvastatin) are metabolised by CYP3A4 and transported by OATP1B1; inhibition by ketoconazole, clarithromycin, ciclosporin or amiodarone increases the risk of myopathy and rhabdomyolysis.
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