Prostacyclin and PGE1 treatment of pulmonary hypertension.
Prostacyclin and PGE1 show promise in treatment of many forms of pulmonary hypertension. Their clinical use can be expected to increase as their pulmonary vasodilating effects become better known. There is as yet no unequivocal reason to choose one agent over the other, but several observations suggest that prostacyclin will eventually be preferred. First, prostacyclin appears to have a shorter half-life (1 to 2 min), which means that any drug-induced adverse effects will disappear more quickly. Although it is commonly said that up to 80% of PGE1 is metabolized with one passage through the lungs, in one study 34% of intravenously administered radiolabeled PGE1 remained in the bloodstream 20 min after administration. Second, prostacyclin causes less severe and less prolonged rebound platelet activation after discontinuation. Third, prostacyclin has been shown to reduce resting pulmonary vascular tone and hypoxic pulmonary vasoconstriction in virtually every published study in every species tested at every stage of development (fetal, newborn, and adult life); results with PGE1, although very impressive, have been less consistent. Nevertheless, there is little doubt that PGE1 is a powerful pulmonary vasodilator in most clinical situations complicated by pulmonary hypertension. Further, PGE1 is available for clinical use, while prostacyclin remains an investigational drug. Thus, it is likely that PGE1 will become the "nitroprusside" of the lesser circuit for intensive care use, a position PGE1 will hold alone at least until prostacyclin becomes available. Chronic infusions of prostacyclin may prove particularly useful in patients with primary pulmonary hypertension awaiting heart-lung transplantation. Eventually, orally available prostacyclin and PGE1 analogs will offer a new therapeutic avenue in many diseases complicated by chronic pulmonary hypertension.
Long
W A
WA
Rubin
L J
LJ
D000527:Alprostadil / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D011464:Epoprostenol / Q000627:therapeutic use*; D006333:Heart Failure / Q000188:drug therapy; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000209:etiology; D008173:Lung Diseases, Obstructive / Q000188:drug therapy; D008946:Mitral Valve Stenosis / Q000150:complications; D012128:Respiratory Distress Syndrome / Q000188:drug therapy
D011464:Epoprostenol; D000527:Alprostadil