Drugs Acting on the Calcium Receptor: Calcimimetics and Calcilytics
2008
Publisher Summary Bne and mineral-related diseases are a heterogeneous group of disorders affecting nearly every major organ system in the body. By far the most common disorder is osteoporosis, a disease characterized by reduced bone density and an increased susceptibility to fractures. Less common, but also associated with altered bone metabolism, are primary and secondary hyperparathyroidism. Drugs that alter the circulating levels of parathyroid hormone (PTH) provide one means of treating hyperparathyroidism and possibly osteoporosis. The secretion of PTH from parathyroid glands can be influenced by a number of factors acting in endocrine or paracrine fashion but the most important is serum calcium. This chapter reviews the progress made in the discovery and development of calcimimetics and calcilytics, ligands that act as activators and inhibitors, respectively, of the calcium receptor. The most significant advance is the regulatory approval of the first calcimimetic for treating some forms of hyperparathyroidism: cinacalcet-HCl. Calcimimetic and calcilytic compounds permit the study of parathyroid physiology without changing the level of any of these serum factors and allow circulating levels of endogenous PTH to be altered at will. The most significant use of calcimimetics and calcilytics is therapeutic. Cinacalcet is an addition to the armamentarium used to manage secondary hyperparathyroidism in patients on dialysis. Cinacalcet is also the only medical treatment for parathyroid cancer. Yet the drug is not without its limitations and it has yet to be approved for treating patients not on dialysis or those with primary hyperparathyroidism not owing to carcinoma.
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