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Pages 645 to 724. Mechanisms of Drug Interaction. Pharmacokinetic Reduced rate and/or completeness of absorption Altered bioavailabilty Reduced plasma protein binding Altered tissue distribution Altered hepatic metabolism Altered renal excretion Haemodynamic interactions Pharmacodynamic
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Mechanisms of Drug Interaction • Pharmacokinetic • Reduced rate and/or completeness of absorption • Altered bioavailabilty • Reduced plasma protein binding • Altered tissue distribution • Altered hepatic metabolism • Altered renal excretion • Haemodynamic interactions • Pharmacodynamic • Potentiation/antagonism at target receptor • Potentiation at non-target receptor • Alteration of fluid/electrolyte environment • Interference with transport mechanisms
Pharmacodynamic Interactions • Decreased effectiveness • Increased toxicity • Predictable within a class of drugs
Pharmacokinetic Interactions • Outcome direct effect of change in drug level • Chance of interaction occurring difficult to predict • Nature of interaction can be predicted
Drugs with low bioavailability due to high pre-systemic metabolism (First pass effect
Things to Remember • Interactions are easily forgotten when prescribing • Interactions are difficult to remember • Pharmacodynamic interactions can often be predicted across drug classes • Pharmacokinetic interactions can not be predicted – experiments needed • Many interactions probably remain undescribed – so look out for them • The chances of interaction are 60 times higher in a patient taking 5 drugs than in one taking 2.