hapter40Katzung课程.pptVIP

* * * * * * * * * Hormones Hormone AntagonistsChapter 40 - Katzung Least toxic of anticancer drugs Highly selective Breast, endometrial, prostate cancers 5 Categories Androgens – Progestins Antiandrogens Gonadotropin-releasing hormone analogs Estrogens – Antiestrogens Aromatase inhibitors Hormone Synthesis Progesterone Aromatase Aromatase Androgens – Breast cancer Indications: palliative therapy in advanced disseminated breast cancer MOA: irreversible inhibitor of the enzyme steroid aromatase that is responsible for the synthesis of estrone from androstenedione Hepatic metabolism, contraindicated in male breast cancer Most commonly used androgen for breast cancer. Few or no androgenic side effects - hirsutism Adrenal estrogen depletion – post menopausal women Indications: palliative treatment of carcinoma of the breast or endometrium; off-label use: appetitie stimulant in HIV Not recommended during the first 4 months of pregnancy, must use at least 2 months of therapy to determine efficacy MOA: Anti-leutinizing effect mediated by the pituitary gland and marked changes in progestatinal agent movement into the endometrium Marked weight gain, thromboembolisms, USE contraception Indications: adjunctive and palliative treatment of inoperable metastatic recurrent endometrial cancer, advanced breast cancer and renal carcinoma, Other – long acting contraceptive via IM injection MOA: inhibits secretion of pituitary gonadotropin which prevents follicular maturation and ovulation, converts proliferative endometrium into secretory endometrium May cause hepatic failure, avoid use in first 4 months of pregnancy, thromboembolism Progestins - endometrium Indications: metastatic carcinoma of the prostate MOA: non-steroidal anti-androgen inhibits cellular uptake of androgen steroids and inhibits nuclear binding of androgens to their receptors - adrenal Used with LHRH (GnRH) agonists, photosensitivity, inform patients of urine color changes, hepatic metabolism