Drug Interactions Flashcards
What is the main feature of drugs which may experience interactions?
narrow TW
Are drug interactions always adverse?
no can be beneficial
What increases drug interactions?
- polypharmacy
- conditions such as renal impairment
What else should you be aware of when thinking about drug interactions?
- not just drug-drug but also drugs-food
- beware of OTC
What is a pharmacokinetic mechanism affecting absorption?
- 2 drugs may interact to alter rate of uptake
- eg. tetracycline + Fe2+ salts or Ca2+ milk
What is a pharmacokinetic mechanism affected by pH?
- absorption of many drugs is pKa dependent
- weak acids can be absorbed in stomach because of acidic environment
- weak bases don’t tend to be absorbed in stomach because they tend to be in the charged state
- passive absorption of drugs best in uncharged form, governed by pKa value
- rises in pH (antacids, H2 antagonists, PPIs) may influence absorption of other drugs
- separate by several hours
What are the 2 possible interaction mechanisms in CYP-mediated metabolism?
- inhibition
- induction
What is enzyme induction metabolism?
incr. quantity/activity of metabolising enzymes
Name 5 common enzyme inducers?
- Rifampicin
- Phenytoin
- Ethanol
- Carbamazepine (autoinduction)
- St John’s Wort
What does the enzyme inducing interaction do (OC)?
- reduce plasma conc of other drugs by incr. the metabolism
- eg. barbiturates, carbamazepine, rifampicin incr. metabolism of OCs: becomes ineffective
- may take a week or 2 for effect but effect can persist after stopping inducer
What is the most common example of enzyme inhibition?
Cy P450 inhibition:
- erythromycin/clarithromycin
- psoralen (from grape fruit juice)
rapid onset: 1-2 days
often reverse quickly on stopping
What is simvastatin contraindicated with?
macrolides
What does simvastatin interact with?
- amlodipine
- verapamil
- diltiazem
incr. risk of myopathy
What is the maximum dose of simva[statin] + amlodipine?
pravastatin does not interact
20mg
What happens around the drug interaction of renal elimination?
- presence of weak acid and base transporters in PCT (non-selective and site of drug interaction)
- competition for transports
- aspirin and methotrexate (used in rheumatoid arthritis, psoriasis, anti-cancer) compete for renal elimination, methotrexate not eliminated as effectively plasma conc rises
- counsel pts taking methotrexate NOT to take OTC ibuprofen or aspirin
- NSAIDs prescribed with care in RA
What are the fluid and electrolyte interactions?
- diuretics: lead to volume depletion when adding an ACEi incr. risk of severe first dose hypertension (take before bed?)
- diuretics: loops and thiazide cause hypokalaemia - so incr. toxicity of digoxin
What is the K-sparing diuretic interaction?
eg. spironolactone, amiloride
- increase K
- may be a problem if the pt takes K supplements or ACEIs (which also increase K): risk of hyperkalaemia
What are pharmacological interactions and give examples?
- actions oppose or augment
- eg. b-blockers block effects of salbutamol
eg. b-blockers and rate-limiting calcium channel blockers: - eg. b-blockers and verapamil: risk of bradycardia/asystole (potentially fatal/avoid)
- eg. beta-blockers and diltiazem may interact (avoid/extreme caution)
- much less of a problem w dihydropyridines
What are the warfarin interactions?
- narrow therapeutic window
- many interactions:
– enzyme inducers lead to failure of therapy
– enzyme inhibitors lead to incr. bleeding - increased bleeding with aspirin (+NSAIDs)
What measures blood clotting?
- monitored by INR (prothrombin time) with a specific target value and the dose is adjusted
- many drug interactions:
– may be potentiated by a range of drugs
– many be reduced by enzyme inducers
What are the consequences of increased action of warfarin?
- gastric
- cerebral
- haemoptysis
- blood in faeces
- blood in urine
- easy bruising
What has increasingly replaced warfarin more recently?
- DOACs
eg. Rivaroxaban - Direct Oral Anticoagulants
- Factor X inhibitor
- Fewer interactions
- No requirement to monitor
What is the interaction between clopidogrel and PPIs?
- omeprazole makes clopidogrel less effective: AVOID omeprazole or esomeprazole
- due to both being biotransformed by same Cyt P450
- clopidogrel is no longer converted to active metabolite
What PPIs do not interact with Cyt450?
-pantoprazole does not affect CytP450 and evidence suggests that it does not interact
- current advice use another PPI or H2RA (not cimetidine)
What should you avoid with the enzyme inducer St John’s Wort?
- oral contraceptives
- antiepileptics
- some HIV drugs
- Ciclosporin
- Warfarin
- Simvastatin
can enhance serotonergic syndrome: avoid with MAOIS and SSRIs
What are some food interactions?
- Cranberry juice thought to potentiate warfarin leading to fatalities
- grapefruit juice interacts with simvastatin and some ca-antagonists
What drugs interact with alcohol?
- labels 2 & 4 (avoid if affected or avoid)
- mostly CNS depressant / sedating factors enhanced (eg. TCAs, sedating antihistamines, benzodiazepines)
- few antibiotics actually interact (metronidazole leads to disulfiram-like effect)
- gastric affects (avoid aspirin containing products for hangover)
Warfarin and NSAIDs can lead to?
enhanced bleeding
Warfarin and antibiotics can lead to?
enhanced bleeding
(esp erythromycin and ciprofloxacin)
NSAIDs and methotrexate can lead to?
methotrexate toxicity
ACE inhibitors and potassium/potassium sparing diuretics can lead to?
risk of hyperkalaemia
Verapamil and beta-blockers can lead to?
risk of asystole
Digoxin and amiodarone can lead to?
risk of digoxin toxicity
digoxin and verapamil can lead to?
risk of digoxin toxicity
oral contraceptives and certain inducing agents can lead to?
eg. rifampicin, carbamazaepine and phenytoin
risk of failure of contraception
statins and macrolides can lead to?.
risk of myopathy
