SELECTIVE
ESTROGEN RECEPTOR MODULATORS (SERMs)
Selective ER modulators (SERMs) are nonhormonal pharmacological
agents that bind to ERs. A characteris-tic feature of the SERMs is that a given agent will
act as an estrogen agonist in one or more tissues and as an es-trogen
antagonist in one or more other estrogen target organs. Tamoxifen citrate (Nolvadex), clomiphene cit-rate (Clomid, Serophene) and raloxifene (Evista) are examples of nonsteroidal
SERMs. The best studied SERM is tamoxifen citrate, a drug formerly
character-ized as an antiestrogen.
Tamoxifen is a partial
estrogen agonist in breast and thus is used as a treatment and
chemopreventative for breast cancer. Tamoxifen is a full agonist in bone and
endometrium, and prolonged use of tamoxifen leads to a fourfold to fivefold
increase in the incidence of en-dometrial cancer.
Raloxifene (Evista) is a new SERM approved for use
in the treatment and prevention of osteoporosis be-cause it has estrogenic
activity in bone. Raloxifene is an estrogen antagonist in both breast and
endometrial tis-sues. The estrogenlike properties of raloxifene result in the
maintenance of a favorable serum lipid profile (de-creased low-density
lipoprotein levels with no change in either high-density lipoproteins or
triglycerides). Raloxifene is 95% bound to plasma proteins. Absorp-tion of
raloxifene is impaired by cholestyramine.
Tamoxifen, clomiphene, and
raloxifene are orally ac-tive. The primary route of excretion of all three
drugs is in the feces. The undesirable effects common to all three of these
SERMs are increased frequency of hot flashes and increased risk of
thromboembolism. Both effects are attributable to their estrogenic activity.
Faslodex (Fulvestrant) is a SERM with no known
agonist activity on the ER. It is administered as a monthly injection. In phase
III clinical trials faslodex showed good activity against advanced breast
cancer.
Related Topics
Privacy Policy, Terms and Conditions, DMCA Policy and Compliant
Copyright © 2018-2024 BrainKart.com; All Rights Reserved. Developed by Therithal info, Chennai.