NR_566_WEEK_6_study_guide. Must Read.

NR_566_WEEK_6_study_guide. Must Read. NR 566 Week 6 Study Guide Chapter 22: Drugs Affecting the Reproductive System  Know the pharmacodynamics, pharmacotherapeutics, clinical use, drug interactions, and ADRs for: Erectile dysfunction (ED) drugs, Estrogens and Progesterone, and Antiandrogen drugs  Androgen drugs o Testosterone is the primary male androgen o Responsible for:  Growth, maturation, and maintenance of male sex organs and secondary sexual characteristics  Skeletal growth spurt in adolescence and termination of linear growth by fusion of the epiphyseal growth plate  Activation of sebaceous glands (acne during puberty)  Enhances production of erythropoietic stimulating factor, increased RBCs production  Libido o Androgen Drugs: testosterone propionate (in oil, DepoTesterone), testosterone enanthate (in oil, Delatestryl), testosterone cypionate (in oil, Depo-Testosterone), methyltestosterone (Android, Methitest, Testred, Virilon), testosterone gel (AndroGel 1%, AndroGel 1.62%, Axiron, Testium), fluoxymesterone, TD testosterone (Testoderm, Androderm), and buccal testosterone (Striant)  Used to treat Indicated for the symptomatic Tx of  1) deficiency states in males associated with hypogonadism and  2) in both sexes for d/os such as CA and HIB, Tx libido, endometriosis, and postmenopausal symptoms in women, have been used illicitly to enhance athletic performance and increase muscle mass o Contraindicated: male breast CA, prostate CA, and Pregnancy (Category X), and lactation  Antiandrogens: several different categories o Androgen hormone inhibitors (5-alpha-reductase inhibitors)  Drugs: Finasteride (Propecia, Proscar) and dutasteride (Avodart)  MOA: Block conversation of testosterone to dihydrotesterone  Used to Tx BPH  PSA levels and digital prostate examination are required monitoring for men on these agents  Finasteride (Propecia, Proscar):  Extensive hepatic metabolism  BPH: 5mg/day, 6 to 12 months of therapy until therapeutic response o Regression of prostate size increased urinary flow, and improve BPH symptoms  Approved for Male pattern baldness: 1 mg/day, three months until results  Stopping the drugs reverses the effect within 12 months  ADRs: decreased libido, impotence (can occur at both doses)  Dutasteride (Avodart)  Inhibits both type 1 and 2 (5-alpha-reductase)  Peak clinical effect 6 to 12 months of therapy  Extensively metabolized in the liver (CYP3A4 and CYP3A5)  Used to Tx BPH  Absorbed through the skin, women who are pregnant or may become pregnant should not handle dutasteride capsules r/t risk of fetal anomaly to a male fetus  ADR: decreased libido and impotence o Gonadotropin-releasing hormone analogue: luteinizing hormone-releasing hormone antagonist  Leuprolide acetate (Lupron)  Create a reversible chemical orchiectomy state in males and an oophorectomy state in females  Used to Tx: advanced prostatic CA and for management of endometriosis and uterine leiomyomata (fibroids)  1 mg SC daily or IM every 3 months (depot formulation)  Increased suppression when used with flutamide (direct antiandrogen)  Peds: Tx central precocious puberty  Women: reducing uterine fibroids, endometriosis, and PCOS (pain relief, regain fertility) o Direct antiandrogens  Flutamide (Eulexin), bicalutamide (Casodex), and nilutamide (Nilandron)  Inhibit androgen uptake or nuclear binding of androgen at target tissues  Uses as part of combo therapy Tx of prostatic carcinoma  Flutamide: competitive antagonist at the androgen receptor site  Truly a nonsteroidal agent  ADRs: gynecomastia and reversible liver toxicity  Renal doses: less than 29 mL/min  BLACK BOX WARNING: hepatic failure, hepatic encephalopathy, and death o Usually within the first 3 months of therapy o Baseline and monthly LFTs for the first 4 months of therapy and periodically o D/c if any symptoms of hepatic injury or jaundice develop o Spironolactone (Aldactone): aldosterone antagonist and inhibitor of 5-alpha-reductase  used as a K sparing diuretic  Off label use for Tx of female hirsutism and acne due to antiandrogenic properties  50 to 200 mg/day  Competitive inhibitor of the dihydrotestosterone, aldosterone, and interferes with the androgen receptors in the prostate  Also reduces 17-alpha-hydroxylase activity: lowers plasma levels of testosterone and androstenedione  Metabolized by the liver  Short term use for primary hyperaldosteronism in patients preoperatively  Long term: for those who are not good candidates for Sx with idiopathic hyperaldosteronism  PMS/PMDD symptoms may be relieved by spironolactone (25 mg QID beginning on day 14 of the menstrual cycle)  ADRs: dose-related and reversible when the drug is d/c GI upset, drowsiness, gynecomastia, impotence, cutaneous eruptions, and urticaria  BLACK Box Warning: r/t animal chronic toxicity studies demonstrated tumorigenicity  Contraindications: pregnancy  Drug Interactions o Finasteride: Nevirapine: Combo induces hepatic metabolism of finasteride: monitor for effectiveness of finasterid