Pharmacology and drug metabolism - cytochrome P450 and clinical consequences
This section summarises hepatic cytochrome P450 (CYP)-mediated drug metabolism, common mechanisms by which drugs alter CYP activity, and practical consequences for emergency medicine. It emphasises recognition of high‑risk interactions, immediate ED priorities and system processes to reduce harm (medicines reconciliation, targeted monitoring and safety reporting).
Key UK guidance: NICE NG5 (medicines optimisation) and MHRA Drug Safety Updates (examples cited below).
Why CYP interactions matter in the ED
- CYP enzymes perform Phase I hepatic metabolism for many drugs; changes in CYP activity commonly alter plasma concentrations and thus drug effect or toxicity.
- ED presentations often reflect CYP interactions: unexpected bleeding (anticoagulants), loss of seizure control, marked sedation, arrhythmia or drug toxicity after introduction or cessation of other medicines, OTC products, alcohol or smoking.
- Systems actions (timely medicines reconciliation, SmPC/interaction checks, and Yellow Card reporting) are essential to prevent and manage harm.
Core principles
Pharmacokinetic versus pharmacodynamic
- CYP interactions are pharmacokinetic: inhibition → reduced clearance and higher drug levels; induction → increased clearance and reduced drug levels.
- Pharmacodynamic interactions alter effect without changing concentration (for example, additive bleeding risk from NSAIDs plus anticoagulant).