Table of Contents
Mechanisms of drug interactions
Cytochrome P450 system interactions
The cytochrome P450 system is a collection of liver enzymes that make up a key pathway for drug metabolism. The system is a major source of important drug interactions.
Cytochrome P450 inducers
Reduce the concentration of drugs metabolised by the cytochrome P450 system.
CRAPS out drugs: Carbamazepine, Rifampicin, bArbituates, Phenytoin, St Johns wart
Cytochrome P450 inhibitors
Increase the concentration of drugs metabolised by the cytochrome P450 system.
Some Certain Silly Compounds Annoyingly Inhibit Enzymes, Grrrrrrr: Sodium valproate, Ciprofloxacin, Sulphonamides, Cimetidine, Antifungals, Amiodarone, Isoniazid, Erythromycin/clarithromycin/azithromycin, Grapefruit juice
Cytochrome P450 substrates
Drugs metabolised by the P450 system that are affected by cytochrome P450 inducers/inhibitors.
COWPATS: Ciclosporin, Carbamazepine, Citalopram, Oral contraceptive pill, Warfarin, Phenytoin, Protease inhibitors, Acetylcholinesterase inhibitors (e.g. donepezil), Theophylline, Statins, Steroids
High risk drugs
Always look for interactions in the BNF.
- Narrow therapeutic range drugs
- Examples (Guys With Large Dongles Totally Make Perfect Internet Connections): Gentamicin, Warfarin, Lithium, Digoxin, Theophylline, Methotrexate, Phenytoin, Insulin, Ciclosporin
- Interactions are particularly important for narrow therapeutic range drugs because small changes in their concentrations can cause severe toxicity
- Cytochrome P450 inducers/inhibitors
- Examples: see above
- Many interactions!
- Highly protein-bound drugs
- Examples (Protein Bound Drugs Normally Fight When Available Space is Sparse): Phenytoin, Benzodiazepines, Digoxin, NSAIDs, Furosemide, Warfarin, Amiodarone, Sulfonylureas/sulfonamides, Statins
- Often displace each other from protein binding sites, which increases the proportion of the displaced drug in its unbound (active) form
- Drugs affecting physiology
- Examples: antihypertensives, hypoglycaemics, anticoagulants
- Affect the physiological environment and are more likely to have interactions
