Summary:
Anorectics (appetite-suppresant drugs) are frequently requested by patients. Their usage, however, can have
serious, life-threatening side effects, such as pulmonary hypertension and valve defects. The association of anorexigen
use with pulmonary hypertension was first detected at the end of the sixties. Back than, the incidence of pulmonary
hypertension, diagnosed as primary, increased soon after an anorexigen, aminorex was introduced. After aminorex
was recalled several years latter, the incidence of the disease returned to the usual low levels. A recent epidemiological
study proved that a newer anorexigen, fenfluramine (or its stereoisomer, dexfenfluramine) considerably increases
the risk of pulmonary hypertension. Currently, it is unclear how the anorectics contribute to the development of
pulmonary hypertension. One possibility may be the increase in plasma serotonin concentration. Serotonin is
a pulmonary vasoconstrictor in many species. However, even if this mechanism plays any role in humans, it cannot
completely explain the influence of anorectics on the pulmonary circulation. The anorectics cause membrane
depolarization of the pulmonary vascular smooth muscle cells by inhibiting potassium channel activity. The
depolarization 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 significant
when there is a deficiency in mechanisms acting against vasoconstriction, such as endothelial production of nitric
oxide (NO). Such pre-existing defects may be the reason why only a fraction of patients using anorectics actually
develop pulmonary hypertension.
Key words:
appetite suppressants, aminorex, fenfluramine, pulmonary hypertension.
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