Selective estrogen receptor modulators drugs

The second drug is the selective estrogen receptor modulating drug, raloxifene (Figure 7.5) , which is used for the treatment of postmenopausal osteoporosis. The in vitro bioactivation of raloxifene by human liver microsomal CYP3A4 results in mechanism-based inactivation of this enzyme. The inactivation is attenuated by the CYP3A4-selective inhibitor ketoconazole (10 xM), is quenched minimally ( 15%) by GSH (5 mM), and is characterized by K, and partition... 

Idoxifene is another of the newer selective estrogen receptor modulators (SERMs), and preclinical data show that it has greater antiestrogenic activity than tamoxifen but lower estrogenic activity. It is not yet clear whether this affects its degree of usefulness or safety when it is used, for example, in cases of metastatic breast cancer. In comparisons of the two drugs in such patients the desired effects were similar and the incidence of adverse effects was essentially the same (14). 

Drugs currently used to treat osteoporosis are classified into those that inhibit osteoclastic bone resorption (including bisphos-phonates, denosumab, and selective estrogen receptor modulators) and those that stimulate bone formation by osteoblasts (parathyroid hormone and derivatives, such as teriparatide). Strontium ranelate may have a dual effect. Other drugs being tested in clinical trials include inhibitors of cathepsin K (an osteoclastic enzyme critical for bone resorption) and of sclerostin (a negative modulator of the Wnt pathway) [21],... 

Calcitonin therapy results in decreased bone resorption. Osteoclasts have calcitonin receptors and calcitonin inhibits their activity. Sodium fluoride stimulates bone formation by unknown mechanisms. In women with osteoporosis, fluoride therapy produced an increased bone mineral density but no reduction in the rate of vertebral fractures. Other drugs known as selective estrogen receptor modulators (raloxifene, droloxifene, idoxifene, and levormeloxifene) may provide an alternative to estrogen replacement therapy (Chapter 34). Administration of low doses of PTH [or recombinant PTH( 1 -34)] does not affect serum calcium concentration, promotes bone formation, and increases mineral density. This anabolic action of PTH is probably mediated by decreasing osteoblast apoptosis. 

Mountfield, R.J., Kiehr, B. and John, B.A. (2000) Metabolism, disposition, excretion, and pharmacokinetics of levormeloxifene, a selective estrogen receptor modulator, in the rat. Drug Metabolism and Disposition, 28,... 

Selective Estrogen Receptor Modulators Raloxifene (EVISTa) acts as an estrogen agonist on bone and liver, is inactive on the uterus, and acts as an estrogen antagonist on the breast. In postmenopausal women, raloxifene modestly increases bone mineral density and has been shown to reduce the risk of vertebral compression fractures in this setting, it is approved for both the prevention and treatment of osteoporosis. The major adverse effect is worsened vasomotor symptoms the drug also increases the incidence of deep venous thrombosis. 

Raloxifene is a selective estrogen receptor modulator (SERM). Its characteristic properties make the drug MOST suitable for treatment of a female patient who... 

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