Appetite Suppressants and Pulmonary Hypertension

Overview

Anorectics (appetite-suppresant drugs) are frequently requested by patients. Their usage, however, can haveserious, life-threatening side effects, such as pulmonary hypertension and valve defects. The association of anorexigenuse with pulmonary hypertension was first detected at the end of the sixties. Back than, the incidence of pulmonaryhypertension, diagnosed as primary, increased soon after an anorexigen, aminorex was introduced. After aminorexwas recalled several years latter, the incidence of the disease returned to the usual low levels. A recent epidemiologicalstudy proved that a newer anorexigen, fenfluramine (or its stereoisomer, dexfenfluramine) considerably increasesthe risk of pulmonary hypertension. Currently, it is unclear how the anorectics contribute to the development ofpulmonary hypertension. One possibility may be the increase in plasma serotonin concentration. Serotonin isa pulmonary vasoconstrictor in many species. However, even if this mechanism plays any role in humans, it cannotcompletely explain the influence of anorectics on the pulmonary circulation. The anorectics cause membranedepolarization of the pulmonary vascular smooth muscle cells by inhibiting potassium channel activity. Thedepolarization activates voltage-operated calcium channels, thus increasing intracellular calcium ion concentration,which is the well-known stimulus for vasoconstriction. The increase in vascular tension can be especially significantwhen there is a deficiency in mechanisms acting against vasoconstriction, such as endothelial production of nitricoxide (NO). Such pre-existing defects may be the reason why only a fraction of patients using anorectics actuallydevelop pulmonary hypertension.

Key words:
appetite suppressants, aminorex, fenfluramine, pulmonary hypertension.