The rationale for drug combinations in the therapy of arterial hypertension
Abstract
The therapeutic goal of antihypertensive drug combination is to improve the hypotensive effect with a possible reduction in incidence and severity of side effects. This goal can be reached by taking into account both pharmacokinetic and pharmacodynamic properties of single antihypertensive drugs. As far as pharmacokinetics is concerned, the rationale is to combine drugs which reach efficient concentrations with low interdose fluctuations and long duration of action. Drug combination with these pharmacokinetic properties allows efficient control of blood pressure with reduction in blood pressure variability and with a favourable trough to peak (T/P) ratio. Moreover these combinations can improve patient compliance to treatment through simplification of the dosing scheme, efficient blood pressure control throughout the dosage interval and reduction of incidence and severity of side effects. The pharmacodynamic rationale requires the combination of drugs with different mechanisms of action, whose biohumoral interactions must exert at least an additive antihypertensive effect and reduce the incidence and severity of side effects of one or of each antihypertensive drug. Finally, dosage should be chosen according to the therapeutic goal as follows: where the hypotensive effect is the primary target, drug doses near the plateau of the dose-response curve must be used, while lower, but effective doses should be used in order to improve tolerability.
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