Posted by SLS on January 9, 2007, at 13:47:33
Two Parkinson's Disease Drugs May Cause Valvular Dysfunction CME
Medscape
News Author: Steve Stiles--------------------------------------------------------------------------------
"January 8, 2007 — Two case-control studies published simultaneously in the January 4 issue of The New England Journal of Medicine provide some of the strongest evidence that treatment with the ergot-derived dopamine antagonists pergolide and cabergoline, commonly used in Parkinson's disease, can cause cardiac-valve dysfunction. They also suggest that the adverse effect is not caused by some other prescribed dopamine antagonists, especially those not derived from ergot.According to a perspective by Bryan L. Roth, MD, PhD, of the University of North Carolina in Chapel Hill, that accompanies the 2 studies, the findings support prior clinical and mechanistic evidence for a link between a histologically distinct fibrotic valvulopathy and treatment with drugs that block the serotonin receptor 5-hydroxytryptamine 2B (5-HT2B). Pergolide and cabergoline have that biochemical action in common, whereas the other studied dopamine antagonists do not have significant effects on 5-HT2B, writes Dr. Roth.
The 2 "very careful clinical studies" validate the earlier work and "nail down" 5-HT2B agonism as the mechanism behind the valvulopathy that has been associated with dopamine antagonists and some other drugs, Dr. Roth told heartwire. The observed effects were huge, he said. "They were not minor incidences for a side effect. When you consider that these drugs have been on the market now for decades, you wonder how this could possibly have been missed."
In his article, Dr. Roth describes how earlier research from his group and others had helped define the biochemical mechanisms behind 5-HT2B-related valvulopathy and determine that an active metabolite of fenfluramine is a potent agonist of the receptor. That drug in combination with phentermine constituted the diet pill "fen-phen," which was pulled from the market during the late 1990s after reports that fenfluramine and its isomer dexfenfluramine were a likely cause of valvular disease. The underlying biochemical processes were unrecognized at the time.
An association between 5-HT2B agonism and valve disease, Dr. Roth writes, "has now been seen with drugs for diverse indications.... Clearly, practitioners should avoid prescribing drugs that are potent 5-HT2B-receptor agonists, a growing list of medications that now includes ergot derivatives, dopamine agonists, and amphetamine derivatives" used to treat such disorders as migraines, obesity, and Parkinson's disease..."
http://www.medscape.com/viewarticle/550405_print
- Scott
poster:SLS
thread:720797
URL: http://www.dr-bob.org/babble/20070107/msgs/720797.html