3. Pages 645 to 724

7. 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

8. Pharmacodynamic Interactions Decreased effectiveness Increased toxicity Predictable within a class of drugs

9. Pharmacokinetic Interactions Outcome direct effect of change in drug level Chance of interaction occurring difficult to predict Nature of interaction can be predicted

15. Drugs with zero order kinetics

18. Drugs with low bioavailability due to high pre-systemic metabolism (First pass effect

20. Interaction in the gut

23. Interaction in the liver

29. Haemodynamic drug interaction

32. Displacement from plasma protein binding sites

34. Interaction in the kidney

40. Interaction at the receptor NB MAOIs

44. 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.