Canadian Neighbor Pharmacy: Recent Experience with Vasodilator Drugs

Sep-7-2015

pulmonary hypertensive disorderRecent Experience with Vasodilator Drugs

Because of these unfavorable results with hydralazine, recent investigators have turned to the use of calcium channel blocking drugs for the treatment of patients with primary pulmonary hypertension. Because calcium may play an important role in the pathogenesis of pulmonary hypertensive disorders and because calcium channel antagonists produce favorable effects in experimentally induced pulmonary hypertension, it was logical to apply nifedipine, verapamil, and diltiazem to the treatment of primary pulmonary hypertension in man. The primary hope with the use of these agents was that selective pulmonary vasodilation could be achieved without marked systemic vasodilator effects. Early clinical experience confirmed that nifedipine lowered pulmonary vascular resistance and pulmonary artery pressures at rest and during exercise, during short- and long-term treatment, and these effects were accompanied by symptomatic improvement.

Unfortunately, we were unable to confirm these favorable observations in our own patients. We compared the hemodynamic and clinical responses to calcium channel blockade with verapamil or nifedipine to those of direct vasodilation with hydralazine in 12 patients with pulmonary hypertension secondary to obliterative pulmonary vascular disorders (primary pulmonary hypertension in eight, systemic lupus erythematosus in two, thromboembolic disease in one, and progressive pulmonary hypertension after closure of a congenital ventricular septal defect in one). All three drugs produced similar decreases in pulmonary vascular resistance, but this was accompanied by a significant increase in cardiac index with hydralazine but not with nifedipine or verapamil. This was because right ventricular performance (already compromised by the disease state) deteriorated

during treatment with both calcium channel antagonists as a result of their negative inotropic actions, even though resistance to right ventricular ejection declined. After both nifedipine and verapamil, mean pulmonary artery pressures decreased markedly, but this amelioration of the pulmonary hypertensive state was not the result of the decrease in pulmonary vascular resistance but due to the decline in right heart output, because right heart filling pressures increased in our patients. In contrast, with hydralazine, right ventricular stroke work increased appropriately, without a change in right heart filling pressures as pulmonary vascular resistance declined. Ibe unfavorable hemodynamic effects of calcium channel blockade were accompanied by severe adverse clinical events, including cardiogenic shock during acute drug administration and the exacerbation of right heart failure during long-term treatment. Start being interested in pharmacy and check out the website of Canadian Neighbor Pharmacy.

Future Role of Vasodilator Therapy

The clinical evidence available at present strongly suggests that the encouraging results with vasodilator drugs that have followed their use in patients with systemic hypertension and left ventricular failure will not be achieved in patients with primary pulmonary hypertension. All three cardiovascular conditions are characterized by marked systemic vasoconstriction; in patients with systemic hypertension and with left ventricular failure, however, this systemic vasoconstrictor response contributes significandy to cardiovascular morbidity. In contrast, the systemic vasoconstriction that occurs in patients with primary pulmonary hypertension plays a beneficial role in supporting systemic blood pressure, as cardiac output is limited by obliterative changes in the pulmonary vasculature. The administration of vasodilator drugs to such patients neutralizes this compensatory systemic vasoconstriction without exerting notable dilatory effects on the severely diseased pulmonary vessels; hence, vasodilator therapy is likely to result in severe hypotension without producing hemodynamic benefits.Vasodilator Therapy

In conclusion, despite numerous promising early reports of the use of vasodilator drugs in the treatment of patients with primary pulmonary hypertension, we are not enthusiastic about the present or future potential of this therapeutic approach. At present, no vasodilator drug has proved in our experience to be consistently effective in a significant number of patients. Even in patients in whom some pulmonary vasodilator response can be achieved, selective vasodilation is an uncommon event; even were it to occur, few of the drugs presently advocated for these patients are well tolerated for long periods. Even if in the future a new drug proves to be consistendy effective in producing sustained decreases in pulmonary vascular resistance without significant toxicity, we will still need to prove that long-term treatment improves clinical symptoms or alters prognosis in these patients. Until such evidence is available, the concept that pulmonary vasoconstriction plays an important role in the pathogenesis of primary pulmonary hypertension remains an unproved hypothesis.