Drug interactions

In a drug interaction one drug alters the effects of another, resulting in increased or decreased effects. Fluvoxamine inhibits the hepatic metabolism of warfarin and increases its anticoagulant effect, (2Z> whereas carbamazepine reduces the anticoagulant effect of warfarin by increasing its metabolism. (28>

1. Pharmaceutical interactions occur when there is a physicochemical interaction between two compounds in solution. Lists of such incompatibilities are too long to remember. To avoid pharmaceutical interactions, do not combine drugs in an infusion solution and use only saline or dextrose in drug infusions.

2. Pharmacokinetic interactions occur when one drug interferes with the disposition of another during absorption, distribution, or elimination.

• Sucralfate reduces the absorption of amitriptyline by about 50 per cent;(29) this might be of clinical importance, but drug absorption interactions are not usually important.

• Phenytoin is displaced from protein-binding sites by valproate (which also inhibits its metabolism).

• The metabolism of psychotropic drugs can theoretically be inhibited by drugs that inhibit metabolism via cytochrome P-450 in the liver ( T§.b..!e..1). Reports of such interactions appear frequently. Inhibitory drugs include cimetidine, antifungal imidazoles (such as fluconazole), and macrolides (such as erythromycin).

• MAO inhibitors inhibit the metabolism of dietary amines and of the noradrenaline that they release, resulting in hypertension. Avoid this combination.

• Diuretics inhibit the renal excretion of lithium; alter the dosage of lithium and monitor the serum concentration when starting a diuretic or changing the diuretic dosage.

3. Pharmacodynamic interactions occur when two drugs interact at the same site of action. Alcohol potentiates the actions of all psychotropic drugs; patients taking psychotropic drugs should be warned that even one alcoholic drink can impair their ability to drive or operate machinery. The combination of reuptake inhibitors with non-selective irreversible monoamine oxidase inhibitors can cause the serotonin syndrome, which is sometimes fatal. Flumazenil reverses the effects of benzodiazepines—a beneficial pharmacodynamic interaction.

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