Occurs when one drug alters or modifies the response to another drug – this can be desired/beneficial/intended or undesired/harmful/unintended (it can increase or decrease the effect of the drug). Alteration in response may be due to a prescribed drug, over the counter drug, alcohol, food, smoking, environmental pollutants etc
Has been estimated in a number of studies to occur in from 9 to 70% of hospitalised patients. Clinically significant drug interactions are <1%. It is also assumed that those on >6 drugs can have an 80% chance of a drug interaction (those that are more unwell appear to have a greater risk).
Most common drugs involved in interactions are carbamazepine, cyclosporine, lithium, digoxin, oral contraceptives, monoamine oxidase inhibitors, rifampicin, phenytoin, theophylline, warfarin.
Pharmacological basis of drug interaction:
1) Incompatible – chemical or physical reactions occur between two or more drugs – both drugs are usually rendered inactive. Can occur in patient or when mixed together in same container prior to administration.
2) Pharmacodynamic interaction – both drugs act on the target site of clinical effect - they are in direct conflict. Synergistic effect – combination of drugs causes a greater effect. Antagonistic effect – combination of drugs causes a lessor effect.
3) Pharmacokinetic interaction – the drugs interact remotely from the target site alter clinical effect. (eg probenecid can be used with penicillin to delay renal excretion prolongs the effect of penicillin). The drug interaction can alter the absorption (eg delayed absorption may not achieve high plasma concentrations rapidly; drugs can affect GI tract absorption by changing pH, affecting the normal flora, induce vomiting, or altering motility/peristalsis); distribution (interacts with other drugs during process of distribution, especially drug displacement interaction from plasma protein binding); metabolism (one drug affect the metabolism of another); elimination (alteration in glomerular filtration rate, tubular secretion, pH alter elimination).
• food alters drug availability by affecting the rate or extent of absorption (may decrease extent of absorption); first pass metabolism (ie food generally increases liver blood flow increased extent of availability of drugs that are subjected to first pass metabolism); drug clearance (may be enhanced by foods involved with enzyme induction, eg high protein diets); grapefruit juice (inhibits the CYPSA4 enzyme that metabolises many drugs); drug effect alteration (can be agonist or antagonist; eg liquorice antagonistic to antihypertensives; eg alcohol causes respiratory depression with CNS depressant drugs)
• drugs also have effects on food (eg diuretics electrolyte loss)