BNF, Lexicomp and Stockley's Drug Interactions

What the book covers

10 high-yield topics. Each has the points most often examined and links to practise them.

1. 1How interactions happen

   • Most serious interactions are through CYP enzymes: inhibitors raise levels of the other drug, inducers lower them.
   • Strong inducers include rifampicin, carbamazepine, phenytoin and St John's wort.
   • Strong inhibitors include clarithromycin, ketoconazole, itraconazole, ritonavir and grapefruit juice.
   • Induction takes days to weeks to start and to wear off; inhibition is quick.
   Practise MCQsNotes: Drug InteractionsCheat sheet

2. 2High-risk interaction pairs

   • Warfarin with metronidazole, fluconazole, amiodarone or macrolides raises the INR.
   • Simvastatin with clarithromycin or itraconazole can cause rhabdomyolysis.
   • Methotrexate with trimethoprim or NSAIDs increases toxicity.
   • Nitrates with sildenafil cause severe hypotension.
   Practise MCQsNotes: Drug Interactions

3. 3QT-prolonging drugs

   • Common culprits are macrolides, fluoroquinolones, antipsychotics, methadone, ondansetron and amiodarone.
   • Low potassium or magnesium increases the risk.
   • Combining two QT-prolonging drugs is avoided where possible.
   • Torsades de pointes is treated with IV magnesium.
   Practise MCQsNotes: Adverse Drug Reactions

4. 4Serotonin syndrome and hyperkalaemia

   • Serotonin syndrome comes from combining SSRIs, SNRIs, tramadol, linezolid, triptans or MAO inhibitors.
   • It presents with agitation, clonus, sweating and fever.
   • Hyperkalaemia risk combines ACE inhibitors or ARBs, spironolactone, potassium supplements and trimethoprim.
   • Check potassium after starting any of these together.
   Practise MCQsNotes: Drug Interactions

5. 5Narrow therapeutic index drugs

   • Digoxin, lithium, phenytoin, theophylline, warfarin, aminoglycosides, vancomycin and tacrolimus need careful monitoring.
   • Brand switching of some, such as tacrolimus, should be avoided or monitored.
   • Sample timing matters: troughs just before a dose, digoxin at least 6 hours after.
   • Interpret phenytoin levels with albumin in mind.
   Practise MCQsNotes: Therapeutic Drug MonitoringCheat sheet

6. 6Liver disease

   • High-extraction drugs and those cleared by the liver accumulate in cirrhosis.
   • Sedatives and opioids can trigger hepatic encephalopathy.
   • Avoid NSAIDs in cirrhosis because of bleeding and kidney injury.
   • Paracetamol is acceptable at reduced doses in most liver disease.
   Practise MCQs

7. 7Children

   • Doses are calculated by weight or body surface area; check against the maximum adult dose.
   • Aspirin is avoided under 16 because of Reye's syndrome.
   • Codeine is avoided in young children because of variable CYP2D6 metabolism.
   • Tetracyclines stain teeth and fluoroquinolones are used only when needed.
   Practise MCQs

8. 8Prescription abbreviations and dosing terms

   • Error-prone abbreviations such as 'U' for units should be written out in full.
   • Weekly methotrexate dosing is a classic source of fatal error.
   • Check the strength and formulation on every liquid prescription.
   • Tenfold errors are the most dangerous paediatric dosing mistake.
   Practise MCQsNotes: Prescription Handling and DispensingCheat sheet

9. 9Kidney impairment

   • References give dose bands by creatinine clearance or eGFR; check which one the band uses.
   • Renally cleared drugs with narrow ranges (aminoglycosides, lithium, digoxin) need the closest attention.
   • Some drugs lose effect in poor kidney function, such as nitrofurantoin in moderate to severe impairment.
   • Nephrotoxic combinations (NSAID, ACE inhibitor or ARB, diuretic) raise the risk of acute kidney injury.
   Practise MCQsNotes: Therapeutic Drug MonitoringCheat sheet

10. 10Pregnancy and breastfeeding references

    • Check the trimester: risks such as organ malformation are highest in the first trimester.
    • Drug transfer into milk depends on protein binding, lipid solubility, half-life and oral bioavailability in the infant.
    • Drugs given safely to neonates directly are usually acceptable in breastfeeding.
    • Premature and newborn infants are most at risk from drugs passed in milk.
    Practise MCQs