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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 zero order kinetics

Drugs with low bioavailability due to high pre-systemic metabolism

(First pass effect

Interaction in the gut

Interaction in the liver

Haemodynamic drug interaction

Displacement from plasma protein binding sites

Interaction in the kidney

Interaction at the receptor

NB MAOIs

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.