Potential benefit of combination therapy with diuretics and beta blockers having intrinsic sympathomimetic activity

When combining a beta blocker with a diuretic in patients with hypertension, consideration should be given to the potential advantages of intrinsic sympathomimetic activity (ISA). During long-term administration of a beta blocker without ISA, total peripheral resistance stabilizes at or slightly above the pretreatment level. Since cardiac output is decreased, blood pressure falls. Thus, beta blockers without ISA may exacerbate the underlying haemodynamic abnormality of long-standing hypertension, increased systemic resistance. In contrast, the reduction in pressure which occurs with a beta blocker possessing a high degree of ISA, such as pindolol, is associated with a reduction in total peripheral resistance and little change in cardiac output. Thiazide diuretics and most beta blockers without ISA also have an adverse impact on the blood lipid profile, potentially increasing cardiovascular risk. With the exception of oxprenolol, monotherapy with beta blockers which possess ISA have generally had no adverse blood lipid changes. Indeed, pindolol has been shown to increase HDL-cholesterol and to reduce the ratio of total cholesterol to HDL-cholesterol. Pindolol administered in combination with several diuretics has not increased the adverse lipid effects of these agents and, in some studies, evidence suggests that pindolol may counteract some or all of these changes. The clinical significance of these differences between beta blockers with and without ISA remains uncertain. Nevertheless, the potential haemodynamic and metabolic benefit of agents with ISA mandate that they receive careful consideration when selecting a beta blocker to administer with a diuretic.