FRCA Notes

Drug Interactions

Drug interactions occur when a patient's response to a drug is modified by the action of another drug
Sometimes this an intended clinical effect e.g. sugammadex and rocuronium, other times it is deleterious to the action of either or both drugs
They can be classified as:

Pharmaceutical incompatibilities
Pharmacokinetic interactions
Pharmacodynamic interactions

Two drugs are physically or chemically incompatible
The reaction can occur inside or outside the body

Classification of pharmaceutical incompatibilities

Neutralisation e.g. protamine and heparin
Precipitation e.g. thiopentone and suxamethonium mixing in the same syringe, flucloxacillin and gentamicin
Chelation e.g. sugammadex and rocuronium, citrate and calcium, penicillamine and copper
Absorption e.g. halothane in rubber, paraldehyde and plastic syringes

Absorption

Activated charcoal can reduce the absorption of poisons
Prokinetics (metoclopramide) and reduced motility (muscarinic antagonists) will affect GA absorption
Adrenaline will affect the absorption of LA if it is co-administered
Nitrous oxide's second gas effect

Distribution

Any drug that affects cardiac output will influence distribution e.g. beta blockers
Drugs that compete for protein binding sites e.g. amiodarone and warfarin

Metabolism

Many effects e.g. enzyme inducers and inhibitors of the CYP450 system
Drugs with high extraction ratio are dependent on hepatic blood flow e.g. lidocaine - increased flow will increase metabolism

Excretion

E.g. doxapram increases MV and will therefore increase excretion of volatile agents
E.g. changing urinary pH using sodium bicarbonate to increase excretion of aspirin or tricyclic antidepressants

UK Perioperative Handbook advice is to stop all herbal medicines at least two weeks pre-operatively

Substance	Proposed Benefits	Pharmacological Effect	Perioperative Considerations
Echinacea	↑ immune system	Modulates cytokines Stimulates Mφ and NK cells	Avoid hepatotoxic drugs Associated with ↓ wound healing
Ephedra	CNS stimulant Weight loss	Sympathomimetic	Caution with sympathomimetics May ↑ tachyphylaxis
Garlic	Treatment of CVS disease	Antiplatelet effect	↑ bleeding risk; avoid NSAIDs
Ginger	Anti-inflammatory Anti-emetic	Serotonergic inhibitor Antiplatelet effect	↑ bleeding risk; avoid NSAIDs
Ginkgo bilboa	Neuroprotection Improved blood flow	Free radical scavenger Antiplatelet effect	↑ bleeding risk; avoid NSAIDs
Ginseng	Mood enhancer Aphrodisiac	Sympathomimetic	↑ bleeding risk; avoid NSAIDs Caution with sympathomimetics Can cause hypoglycaemia
St. John's Wort	Antidepressant	MAO-inihibitor CYP3A4 and 2C9 inhibitor	Reduces efficacy of multiple drugs Can cause serotonergic crisis
Valerian	Anxiolytic Hypnotic	CNS depression via GABA-ergic potentiation	Reduced anaesthetic requirements