Pharmacological properties of combination therapies for hypertension

Single drug therapy for the treatment of hypertension has traditionally been a standard of practice. More recently combination therapy as first-line treatment has gained acceptance both by the medical practice community and the US Food and Drug Administration. The advantages of combinations may be a synergistic or additive antihypertensive effect, metabolic improvement, or both. The combination of a thiazide-type diuretic and a potassium-sparing diuretic has been quite useful in the past to prevent the need for potassium supplementation. The combination of β-adrenoceptor blockade and a thiazide diuretic results in an additive antihypertensive effect that permits the effective use of very low thiazide doses. The mechanism of antihypertensive effects of each member of the combination are complimentary with increased sympathetic outflow and renin-angiotensin axis activation induced by the diuretic being blunted by β₁-adrenergic blockade. Combinations not used as first-line therapy, such as angiotensin converting enzyme inhibitors or angiotensin receptor blockade and a thiazide diuretic, have complimentary antihypertensive mechanisms and have been useful in treating patient groups who do not respond well to converting enzyme inhibitor monotherapy. The combination of a calcium antagonist with diuretic therapy has an additive hypertensive effect as well; however, the complimentary mechanisms are less obvious. Finally, the combination of angiotensin converting enzyme inhibition and calcium antagonist therapy has been useful in selected patients, but again the complimentary mechanisms are less obvious. As first-line therapy, combinations for diuretics and β₁-receptor blockers have been useful for achieving increased antihypertensive effect with decreased adverse drug effect.