Clinical Pharmacology of Prazosin and Phentolamine in Patients with Heart Failure

Abstract

In a controlled crossover study we assessed the effects of an initial single oral dose of 150 mg phentolamine or 2 mg prazosin on the haemodynamics and plasma concentrations of noradrenaline in 12 patients with mild to moderate cardiac dysfunction in cardiomyopathy (NYHA Classes I-III). Nine of these patients continued chronic oral treatment with either 300-450 mg phentolamine or 7.5-15 mg prazosin for a period of 4-6 weeks each in randomised order. The effects on both haemodynamics and plasma noradrenaline were essentially the same under the treatment with both drugs. The acute effect on reduction of exercise-induced elevation of diastolic pulmonary artery pressure was abolished after chronic treatment. However, significant increase in stroke volume—on average, from 83 ± 7.2 to 100 ± 6.0 ml (phentolamine) and 99 ± 6.7 ml (prazosin)—occurred only after chronic treatment. Increased sympathetic activity, as expressed in plasma noradrenaline concentrations, was similar under both phentolamine and prazosin. There was no direct evidence for the clinical relevance of the more pronounced presynaptic α-blockade with phentolamine as compared with the almost pure postsynaptic α-blocking properties of prazosin. Development of tolerance seemed to occur with both drugs; however, haemodynamic benefit in terms of increased stroke volume could only be achieved after chronic treatment.