Drug interactions

Drug interactions

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).

Drug-food interactions:
• 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)

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