Physiological and Pharmacological Interactions of Antihypertensive Drugs

Abstract

The complex mechanisms that maintain the blood pressure can be interfered with at many points by drugs. A drug acting at one point may be potentiated by another which blocks a compensatory reflex minimizing the effect of the first. Many therapeutically useful drug combinations have a nonspecific mechanism of this kind although drugs that act upon different points in the sympathetic efferent vasomotor pathway have not been proved to have a useful additive effect. It is not easy to prove a synergistic action of two drugs unless it is large. The best supported examples are combinations of either a diuretic or a vasodilator with a sympathetic blocking drug. These combinations are the ones most widely used in treatment of hypertension. They allow the dose of each active substance to be reduced so that unwanted side-effects are decreased without losing the desired action on the blood pressure. Drug combinations have special risks besides their obvious advantages. Patients are more likely to become confused and take the wrong doses if their treatment regime is complicated. Two drugs which are individually nontoxic may have dangers when used together. Oliguria and a mounting blood urea may follow combined use of powerful modern diuretics. Toxic effects may be entirely unrelated to the main therapeutic action of the drug, as with the enhanced diabetogenic effect of diazoxide used with hydrochlorothiazide. Several potent cardiovascular drugs modify the response to drugs which might be given to raise the blood pressure in an emergency. No drug in common therapeutic use seriously reduces the response to injected noradrenaline but some, such as sympathetic blockers and monoamine oxidase inhibitors, greatly increase sensitivity. Pressor amines that act indirectly by noradrenaline release may be ineffective in the presence of drugs which deplete or insulate the stores of the transmitter in adrenergic nerve endings. The advantages and disadvantages of drug interactions deserve more thought and study than they usually receive.