Anorectic Drugs and the Vasculature

Abstract

The anorectics are drugs used to suppress appetite in patients treated for obesity. More than 3 million prescriptions were filled in 1997 alone for dexfenfluramine (dex), recently the most commonly prescribed anorectic drug (Voelkel et al., 1997). Their use has been associated with life-threatening diseases ranging from primary pulmonary hypertension (PPH) (Abenhaim et al., 1996), strokes (Schwitter et al., 1992), and heart attacks (Bailie, 1991; Evrard et al., 1990) to severe cardiac valvular disease (Connolly et al., 1997; Khan et al., 1988). Although dex is now withdrawn from the market, the interest of the scientific community in this drug remains strong for two main reasons. First, there are now new anorectic drugs, already approved for the treatment of obesity, such as sibutramine, with very similar structures and possibly similar mechanisms of action to dex (Heal et al., 1998; McNeely and Goa, 1998; Van Gaal et al., 1998), and thus physicians and scientists need to be alert to anorectic-related vascular complications. Second, dex might prove to be an excellent tool for establishing pulmonary and even systemic models of experimental hypertension. One of the main reasons that PPH remains a fatal disease with no cure is the lack of animal models. As will be discussed in this chapter, the complications caused by anorectic drugs are a “paradise” for the vascular biologist, because they involve the three most important cells involved in vascular disease: the vascular smooth muscle cell (SMC), the platelet, and the endothelium (Rubin, 1997). This chapter will summarize the evidence that suggests that K+ channel inhibition plays a critical role in the mechanism of action and the complications related to anorectic drug use.