Reproductive System Drugs Rachel Picone MS APRN WHNPBC
Reproductive System Drugs Rachel Picone, MS, APRN, WHNP-BC
Objectives � Identify indications, mechanism of action (MOA), adverse effects (AE) for androgens, estrogens and progestins � Identify MOA, AE for medications used in erectile dysfunction � Identify indications, MOA, AE for selected medications used during pregnancy, labor and birth � Not responsible for Gn. RH analogs on the test!
Androgens: Uses � Male sex hormones testosterone androsterone � Induce masculinization by acting on target receptors in tissues � Synthetic androgens are indicated in the treatment of: ◦ Hypogonadism (congenital or acquired) ◦ FTM transgendered persons desiring to transition hormonally ◦ Palliative treatment of advanced breast cancer in women ◦ Severe fibrocystic breast disease
Androgens: Adverse Effects � Edema � Acne � Sexual changes � Decreased sperm production � Gynecomastia � Hirsutism � Liver dysfunction � Premature fusion of epiphyseal plates (stunting) � Mood changes � Increased LDL, decreased HDL � Insulin resistance � Illegal anabolic steroid use: psychosis, violence
Androgen Formulations � Danocrine (danazol) 100 -400 mg PO BID � Android, Testred (methyltestosterone) PO, buccal � Estratest (methylytestosterone w/ estrogen) PO � Oxandrin (oxandrolone) PO 2. 5 -20 mg/day divided doses � Depo-Testosterone (testosterone) IM, implant, buccal* � Androderm, Andro. Gel (testosterone) transdermal patch, gel* *used in transgender therapy
Phosphodiesterase (PDE) Inhibitors � Indicated in treatment of erectile dysfunction � MOA: smooth muscle relaxation, vasodilation Viagra (sildenafil) 50 mg po 1 h before sex Levitra (vardenafil) 10 mg po before sex or 2. 5 mg po daily Cialis (tadalafil) 10 mg po 1 h before sex Max frequency for all: once daily!
PDEs Adverse Effects: ◦ Headache, flushing, hearing and vision changes, dizziness, tinnitus, nasal congestion, back pain ◦ Cardiovascular events (less than 2%): angina, syncope, tachycardia, hypotension Caution in: � Concurrent use of nitrates, alpha-blockers � Patients with cardiovascular disease � Erection > 4 hrs is a medical emergency!
Estrogen Therapy � Female sex hormone responsible for feminization � Important in menstrual cycle and pregnancy � Important component in combined hormonal contraceptives � Used in menopausal therapy (including surgically or radiation-induced menopause) � MTF transgendered persons desiring to transition hormonally � Hypogonadism
Women’s Health Initiative (WHI) Landmark 2002 study � Postmenopausal estrogen therapy increases risk of heart attack, breast cancer, stroke and clot � Estrogen should not be used to prevent cardiovascular disease � Women with an intact uterus should not take systemic estrogen-only therapy due to risk of uterine cancer � Women should take the smallest effective dose for the shortest possible time and annually review the decision with a provider
Estrogen: Adverse Effects � Nausea � Acne � Increased triglycerides � Liver abnormalities � Changes in vaginal bleeding � Increased headaches � Visual changes � Mood changes � Breast tenderness � Increased risk of gallbladder disease � Increased risk of clot/VTE, stroke, MI � Endometrial hyperplasia, cancer
Estrogen Formulations See contraceptive presentation! For relief of vasomotor sx and vaginal atrophy associated w/ menopause: � Premarin (conjugated estrogen) PO � Prempro, Premphase (conjugated estrogen w/ medroxyprogesterone) � Combi. Patch (estradiol/norethindrone) transdermal � Estrace* (micronized estrogen) tablet or intravaginal cream � Femring, Estring (estradiol) vaginal rings � Estrasorb, Estro. Gel (estradiol) topical gel � Vagifem (estradiol) intravaginal tablet � Climara, Vivelle (estradiol) transdermal patches *used in transgender care
Progestins � Used to treat abnormal uterine bleeding � Important component in combined hormonal contraception, or may be used alone for contraception � Some use in postmenopausal therapy � Breast and uterine cancer treatment � Adjuvant therapy in cancer and AIDS as an appetite stimulant
Progestin: Adverse Effects � Menstrual irregularities � Weight gain � Edema � Nausea � Breast tenderness, nipple discharge � Headache � Mood changes � Clot/VTE � Decreased bone density with prolonged use
Progestin Formulations � See contraceptive presentation! � Depo-Provera IM or SC � Megace (megestrel) oral suspension
Drugs for Pregnancy, Labor & Birth
FDA Pregnancy Risk Categories Category A Adequate and well-controlled studies have failed to demonstrate a risk to the fetus in the first trimester of pregnancy (and there is no evidence of risk in later trimesters). Category B Animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women. Category C Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks. Category D There is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks. Category X Studies in animals or humans have demonstrated fetal abnormalities and/or there is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience, and the risks involved in use of the drug in pregnant women clearly outweigh potential benefits. FDA Pregnancy Risk Categories. http: //chemm. nlm. nih. gov/pregnancycategories. htm
Oxytocin Pitocin (oxytocin) IV or IM � Used to induce labor � Stimulates uterine contractions � In uterine atony or subinvolution, helpts uterus to contract and stop hemorrhage � Risks include uterine rupture, placental abruption, fetal hypoxia and trauma, fetal death, amniotic fluid embolism, cervical laceration
Prostaglandins � Prostin E 2, Cervidil, Prepidil (dinoprostone, prostaglandin E 2) � Cytotec (misoprostol, prostaglandin E 1 analog) : off label use, FDA-approved as a stomach ulcer treatment � Used for cervical ripening in the induction of labor � Used to stimulate uterine contractions in elective or therapeutic abortions
Mifepristone (RU-486) � “the abortion pill” � Antiprogesterone used with misoprostol in medication abortions before 9 weeks � Blocks the action of progesterone, which supports placenta and maintains pregnancy � FDA-approved up to 49 days gestation (7 wks) for medication abortion with misoprostolrequires 3 visits � High-quality clinical studies show that use up to 63 days (9 wks) with misoprostol taken at home is more efficacious with fewer side effectsrequires only 2 visits
Methylergonivine � Methergine®, oral or injectable, IV � Ergot alkaloid used in prevention and treatment of postpartum and postabortion hemorrhage � MOA: uterine stimulant � Not recommended prior to delivery of placenta, may cause retained placenta � SE: nausea, vomiting, dizziness, headache, dyspnea, cardiac symptoms
Terbutaline � Tocolytic � Classified as a bronchodilator, used off-label in preterm labor � MOA: sympathomimetic action inhibits uterine contractions via smooth muscle relaxation � Used in preterm labor with varying success � May be used to buy more time for maternal betamethasone injections to enhance fetal lung maturity � SE: tremors, tachycardia, headache, nausea
Magnesium Sulfate � Treatment of preeclampsia or eclampsia for prevention or control of seizures � MOA: CNS depressant, blocks neuromuscular transmission, vasodilator, lowers BP � AE: CNS depression, flaccid paralysis, circulatory collapse, severe hypotension, respiratory paralysis � Contraindicated in heart block! � Antidote: calcium gluconate IV
Resources � Centers for Disease Control U. S. Medical Eligibility for Contraceptive Use (CDC US MEC) http: //www. cdc. gov/reproductivehealth/Uninte nded. Pregnancy/USMEC. htm � Drugs and Lactation Database (Lact. Med) http: //toxnet. nlm. nih. gov/cgibin/sis/htmlgen? LACT
References American College of Obstetrics and Gynecologists (ACOG). (2005). Medical management of abortion. National Guideline Clearinghouse. Accessed at www. guidelines. gov Woodrow, R. , Colbert, B. , & Smith, D. (2011). Essentials of pharmacology for health occupations. Clifton Park, NY: Delmar Cengage Learning. U. S. Department of Health and Human Services. (2008). FDA pregnancy risk categories. Accessed at http: //chemm. nlm. nih. gov/pregnancycategories. ht m
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