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Transcript
Pages 645 to 724
Mechanisms of Drug Interaction
• Pharmacokinetic
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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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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.