Antiandrogens flutamide

Grzywacz, M.J., Yang, J.M. and Hait, W. N. (2003) Effect of the multidrug resistance protein on the transport of the antiandrogen flutamide. Cancer Research, 63, 2492-2498. 

Leuprolide is a potent LH-RH agonist for the first several days to a few weeks after initiation of therapy, and therefore, it initially stimulates testicular and ovarian steroidogenesis. Because of this initial stimulation of testosterone production, it is recommended that patients with prostatic cancer be treated concurrently with leuprolide and the antiandrogen flutamide (discussed earlier). Leuprolide is generally well tolerated, with hot flashes being the most common side effect. 

Antiandrogens Flutamide Bicalutamide Nilutamide Cyproterone acetate Progesterones 5-Of-Reductase inhibition Finasteride ... 

Three antiandrogens, flutamide, bicalutamide, and nilutamide, are currently available (Table 128-5). 

Examples of activated double bond electrophiles include a, 3-unsaturated carbonyl compounds, quinones, quinoneimines, quinonemethides and diiminoquinones as shown in Fig. 10.32B. These electrophilic intermediates are highly polarized and can react with nucleophiles in a 1,4-Michael-type addition at the more electrophilic or 3-oarbon of the activated double bond intermediate to the addition product (Fig. 10.32A). Specific examples of activated double bond electrophiles that have been proposed for the anticancer drug leflunamide, the food antioxidant butylated hydroxytoluene, acetaminophen, the antiandrogen flutamide, the anticonvulsant felbamate and the cytotoxic cyclophosphamide as shown in Fig. 10.32C. The bioinaotivation pathways for these electrophilic intermediate can involve either direct addition, with or without transferases, depending upon the degree of polarization and reactivity of the electrophilic intermediate (hard vs soft electrophiles). 

Liao S, Howell DK, Chang TN. Action of a nonsteroidal antiandrogen, flutamide, on the receptor binding and nuclear retention of 5a-dihydrotestosterone in rat ventral prostate. Endocrinology 1974 94 1205-1209. 

Flutamide -nonsteroidal antiandrogen -endocrine effects -hot flashes -decreased libido -gynecomastia -impotence -galactorrhea -diarrhea -nausea and vomiting -myalgias -elevated liver function tests... 

Monotherapy with flutamide, bicalutamide, and nilutamide is no longer recommended due to decreased survival as compared with patients treated with LHRH agonist therapy or orchiectomy. Antiandrogens are indicated for advanced prostate cancer only when combined with an LHRH agonist (flutamide and bicalutamide]) or orchiectomy (nilutamide). In combination, antiandrogens can reduce the LHRH agonist-induced flare. 

The adverse effects of antiandrogens are gynecomastia, hot flushes, GI disturbances, liver function test abnormalities, and breast tenderness. GI disturbances consist of diarrhea for flutamide and bicalutamide and nausea or constipation for nilutamide. Flutamide is also associated with methemoglobinemia, whereas nilutamide causes visual disturbances (impaired dark adaptation), alcohol intolerance, and interstitial pneumonitis. 

Bicalutamide, flutamide and nilutamide are nonsteroidal antiandrogens that are used for the treatment of prostatic carcinoma. They act as competitive antagonists at the androgen receptor. Hutamide also inhibits the formation of dihydrotestosterone from testosterone. 

The non-steroidal antiandrogens include flutamide, bicalutamide and nilutamide. By binding to the androgen receptor they inhibit translocation of the receptor from the cytoplasm to the nucleus. Flutamide also inhibits the formation of the active di-hydrotestosteron from testosteron. These agents are... 

B. Finasteride is a 5a-reductase inhibitor, which essentially makes dihydrotestosterone unavailable to the prostate but does not reduce serum testosterone levels. The decreased prostatic levels of dihydrotestosterone frequently result in a size regression of the prostate, while the relatively normal testosterone levels minimize a depressed libido. Flutamide and spironolactone exhibit antiandrogen effects by competing for the androgen receptor ketoconazole inhibits testosterone synthesis and stanozolol is an oral anabolic androgen preparation. 

Antiandrogens such as cyproterone acetate (5.54) or the nonsteroidal flutamide (5.55, a substituted anilide) are competitive antagonists on the cytosol receptor. They do not prevent DHT formation rather, they inhibit the nuclear retention of DHT in the prostate. They cause feminization in male fetuses and decrease libido in males. Cyproterone is also an active progestogen. In men, antiandrogens are used commonly in the treatment of prostatic cancer and uncommonly to inhibit sex drive in hypersexuality in women, antiandrogens are used to treat virilization. Bicalutamide (5.56) and nilutamide (5.57) are potent, orally active antiandrogens that may be used in the treatment of metastatic prostate carcinoma. 

Antiandrogens bicalutamide cyproterone acetate flutamide nilutamide... 

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