(Circulation. 1999;99:156-161.)
© 1999 American Heart Association, Inc.
Current Perspective |
Aminorex to Fen/Phen
An Epidemic Foretold
From the University of Pennsylvania Medical Center, Philadelphia, Pa.
Correspondence to Alfred P. Fishman, MD, 5 West Gates Pavilion, Hospital of the University of Pennsylvania, 3400 Spruce St, Philadelphia, PA 19104-4283. E-mail fishmana@mail.med.upenn.edu
Key Words: pharmacokinetics • drugs • anorexigens • neurotransmitters • obesity
Over the years, a variety of diets and drugs for the treatment of obesity have come and gone. More recently, newspapers, radio, and television have featured the rise and fall of the latest appetite-suppressants, dexfenfluramine and the combination of fenfluramine and phentermine (fen/phen). The rise occurred after approval of dexfenfluramine by the Food and Drug Administration (FDA); the fall was prompted by an unexpected outbreak of valvular heart disease related to the use of anorectic agents.1
The outbreak of valvular heart disease was unexpected. Even though alarms had been sounded of an impending epidemic of pulmonary hypertension that would follow the turning loose of the appetite suppressants by the FDA,2 3 previous experience with these medications had not foretold an epidemic of valvular heart disease.
In this article, the pathogenetic mechanisms involved in the pulmonary vascular and cardiac valvular disease are explored within the larger framework of dietary pulmonary hypertension.4 Insights into these mechanisms appear to be relevant to avoiding similar epidemics caused by anorectic agents and in developing future weight-losing medications.
Obesity as a Target
One major weakness in the war against overweight and obesity is
the blurred outlines of the targets. Although any degree of overweight
is undesirable, not all degrees of obesity call for the same type or
vigor of attack. For example, the goal of a 10% reduction in weight in
an individual who is mildly obese and at risk for systemic hypertension
and diabetes warrants more aggressive measures than does achieving the
same weight loss by an individual determined to
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