Drug Affecting the Reproductive System PDF

Drug Affecting the Female and Male Reproductive System  The Female Reproductive System functions in a cyclical fashion, not in the steady-state fashion seen with much of the rest of the endocrine system. Introduction Altering any compo...

Drug Affecting the Female and Male Reproductive System  The Female Reproductive System functions in a cyclical fashion, not in the steady-state fashion seen with much of the rest of the endocrine system. Introduction Altering any component of this cycle or the system can have a wide variety of effects on the entire body. Hormones and hormonal-like agent. Sites of action of drugs affecting the female reproductive system  Estrogens Progestins estradiol desogestrel estrogen, conjugated drospirenone Sex Hormones estrogen, esterified etonogestrel & Estrogen estropipate levonorgestrel medroxyprogesterone Receptor norethindrone Modulator acetate Sex Hormone norgestrel progesterone ulipristal Estrogen raloxifene Receptor Modulator toremifene  cetrorelix chorionic gonadotropin chorionic gonadotropin alpha clomiphene Fertility Drug follitropin alfa follitropin beta ganirelix menotropins urofollitropin  Oxytocics methylergonovine oxytocin Uterine Motility Drugs Abortifacients carboprost dinoprostone mifepristone  Female sex hormones can be used to replace hormones that are missing or to Sex Hormones act on the control mechanisms of the endocrine system to decrease the & Estrogen release of endogenous hormones. Receptor Modulator Drugs that act like estrogen, particularly at specific estrogen receptors are used to stimulate the effects of estrogen in the body with fewer of the adverse effects.  estrogen and progestins (the endogenous female hormone progesterone and its various derivatives) estradiol (Estrace, Climara, and others) conjugated estrogens (Premarin), esterified estrogen (Menest), and estropipate (Ogen) Sex drospirenone (Yasmin, Yaz), etonogestrel Hormone (Implanon), levonorgestrel (Mirena), medroxyprogesterone (Provera), norethindrone (Aygestin), norgestrel (generic), progesterone (Prometrium), desogestrel (found in many contraceptive combinations), and ulipristal (Ella) used as a postcoital contraceptive.  Estrogen 1. Used for hormone replacement therapy (HRT). 2. Used as palliation for the discomforts of menopause. Therapeutic 3. Treat female hypogonadism and ovarian Actions and failure. Indications 4. Prevent postpartum breast engorgement. 5. As part of combination contraceptives. 6. Slow bone loss in osteoporosis. 7. Palliation in certain cancers that have know receptor sensitivity.  Estrogen 1. Important for the development of the FRS and secondary sex characteristics. 2. Affect the release of pituitary FSH and LH; Therapeutic 3. Capillary dilatation, fluid retention, and protein anabolism and thin cervical mucus Actions and 4. Conserve calcium and phosphorus and Indications encourage bone formation 5. Inhibit ovulation 6. Prevent postpartum breast discomfort. 7. Proliferation of the endometrial lining  An absence or decreased in estrogen produces the s/sx of menopause in the uterus, vagina, breast, and cervix. NOTE: Estrogen produce a wide variety of systemic effects, including protecting the heart from atherosclerosis, retaining calcium in the bones, and maintaining the secondary female sex characteristics.  Progestin 1. Used as contraceptives Therapeutic 2. Treat primary and secondary amenorrhea Actions and and functional uterine bleeding and as part Indications of fertility program. 3. Useful in treating specific cancers with specific receptor site sensitivity.  Progestin 1. Transform the proliferative endometrium into Therapeutic a secretory endometrium. Actions and 2. Inhibit the secretion of FSH and LH Indications 3. Prevent follicle maturation and ovulation 4. Inhibit uterine contraction 5. Have some anabolic and estrogenic effects.  When they are used as contraceptives the exact mechanism of action is not known, but it is thought that circulating progestins and estrogens “trick” the NOTE: hypothalamus and pituitary and prevent the release of GnRH, FSH, and LH, thus preventing follicle development and ovulation.  Estrogen 1. Absorbed through the GIT and undergo extensive hepatic Pharmacokinetics metabolism. 2. Excreted in the urine. 3. Cross the placenta and enter breast milk  Progestins 1. Well absorbed, undergo hepatic metabolism, excreted in the urine. Pharmacokinetics 2. Cross the placenta and enter breast milk  Estrogen 1. In the presence of any known allergies to estrogen. 2. Patients with idiopathic vaginal bleeding, breast cancer, or any estrogen-dependent cancer. Contraindications and Cautions 3. History of thromboembolic (blood vessel clot) disorders including CVA, or with heavy smokers 4. Hepatic dysfunction 5. During pregnancy 6. Avoided during BF  Estrogen 1. Metabolic bone disease Contraindications and Cautions 2. Renal insufficiency 3. Hepatic impairment 4. Breast feeding  Progestins 1. PID, STD, endometriosis, or pelvic Contraindications surgery. and Cautions 2. Drospirenone – risk for hyperkalemia (renal disorders, liver disease, adrenal dysfuction)  Progestins 1. Epilepsy Contraindications 2. Migraine Headaches and Cautions 3. Asthma 4. Cardiac or Renal dysfuction  Estrogen GUT (bleeding, menstrual irregularities, dysmenorrhea, amenorrhea, and changes in libido. Adverse Effects Systemic (fluid retention, electrolyte disturbances, headache, dizziness, mental changes, weight changes, and edema) GI (N/V, abdominal cramps & bloating, colitis)  Progestin Systemic (Similar to estrogen) Dermal patch contraceptives are associated with the same systemic effects, as well as local skin irritation. Adverse Effects Vaginal gel (headache, nervousness, constipation, breast enlargement, and perineal pain) Intrauterine system (abdominal pain, endometriosis, abortion, PID, and expulsion of the IUD. Vaginal gel (local irritation and swelling) Estrogen Two available ERM are raloxifene Receptor (Evista) and toremifene (Fareston). Modulator  ERM are not hormones but affect specific estrogen receptor sites, Therapeutic stimulating some, and blocking others. Actions and Produce some of the positive effects of Indications estrogen replacement while limiting the adverse effects  Administer orally raloxifene - absorbed from the GIT and is metabolized in the liver. Pharmacokinetics Excretion (feces) Cross the placenta and enter into breast milk.  1. Allergy to raloxifene 2. During pregnancy and lactation Contraindications and Cautions Caution should be used in patients with a history of venous thrombosis or smoking.  1. GI upset and N/V 2. Changes in fluid balance (headache, dizziness, visual changes, and mental Adverse Effects changes) 3. Hot flashes, skin rash, edema, and vaginal bleeding 4. Venous thromboembolism  Stimulate the FRS cetrorelix (Cetrotide), chorionic gonadotropin (Pregnyl), chorionic Fertility gonadotropin alpha (Ovidrel), Drugs clomiphene (Clomid), foliitropin alfa (Gonal-F), follitropin beta (Follistim AQ), ganirelix (generic), menotropins (Pergonal), and urofollitropin (Bravelle)  1. Stimulate follicles and ovulation or stimulate the hypothalamus to increased FSH and LH levels. 2. Treat infertility in women with Therapeutic functioning ovaries whose partners are fertile. Actions and 3. Stimulate multiple follicle development Indications for the harvesting of ova for in vitro fertilization. 4. Menotropins – stimulate spermatogenesis in men with low sperm counts  5. Cetrorelix – inhibits premature LH surges in women undergoing controlled ovarian stimulation by acting as a GnRH antagonist. 6. Chorionic gonadotropin – stimulates ovulation by acting like GnRH and affecting the FSH and LH release. Therapeutic 7. Follitropin alfa and follitropin beta are FSH Actions and molecules; injected to stimulate follicular Indications development in the treatment of infertility and for harvesting of ova for in vitro fertilization. 8. Menotropin – stimulates spermatogenesis 9. Urofollitropin – used to stimulate follicle development and induce ovulation.  Drugs are well absorbed and are Pharmacokinetics treated like endogenous hormones within the body, undergoing hepatic metabolism and renal excretion.  1. Presence of primary ovarian failure 2. Thyroid or adrenal dysfunction Contraindications 3. Ovarian cysts and Cautions 4. Pregnancy 5. Idiopathic uterine bleeding 6. Allergy to any fertility drug  1. Cautions should be used in women Contraindications who are breastfeeding. and Cautions 2. Those with thromboembolic disease 3. With respiratory diseases  1. Increased risk of multiple births and birth defects 2. Ovarian overstimulation (abdominal pain, distention, ascites, pleural effusion) 3. Headache 4. Fluid retention Adverse Effects 5. Nausea 6. Bloating 7. Uterine bleeding 8. Ovarian enlargement 9. Gynecomastia 10. Febrile reactions  Stimulate uterine contractions to assist labor (oxytocics) or induce abortion (abortifacients) Uterine Tocolytics – drugs used to slow uterine Motility activity Drugs Terbutaline – beta2-selective adrenergic agonist (used widely off-label as tocolytic agent to relax the gravid uterus to prolong pregnancy)  Stimulate contraction of the uterus, much like the action of the hypothalamus hormone oxytocin, Oxytocics stored in the posterior pituitary. Methylergonovine (Methergine), oxytocin (Pitocin)  1. Directly affect neuroreceptor site to stimulate contraction of the uterus. Therapeutic 2. Stimulate the lacteal glands in the Actions and breast to contract. Indications 3. Indicated for the prevention and treatment of uterine atony after delivery.  Rapidly absorbed after parenteral or oral administration. Metabolized in the liver Excreted in the urine and feces Cross the placenta and enter breast milk Pharmacokinetics Administered IM or IV Methylergonovine – administered as such directly after delivery and then continued in the oral form to promote uterine involution. Oxytocin– used in nasal form to stimulate mill “let down” in lactating women.  1. Allergy to oxytocics 2. Cephalopelvic disproportion, unfavorable Contraindications fetal position, complete uterine atony, or and Cautions early pregnancy  1. Patients with coronary disease and HPN Contraindications 2. Previous CS births and Cautions 3. Hepatic or Renal impairment  1. Related to excessive effects (uterine hypertonicity and spasm, uterine rupture, postpartum hemorrhage, decreased FHR) 2. GI upset (nausea, headache, and dizziness) Adverse 3. Methylergonovine – ergotism (n/v, BP Effects changes, weak pulse, dyspnea, chest pain, numbness and coldness in extremities, confusion, delirium and even coma) 4. Severe water intoxication with coma and maternal death  Used to evacuate uterine content via intense uterine contractions. Abortifacients carboprost (Hemabate), dinoprostone ( Cervidil, Prepidil Gel, Prostin E2), mifepristone (RU-486, Mifeprex)  1. Stimulate uterine activity, dislodging any implanted trophoblasts and Therapeutic preventing implantation of any Actions and fertilized egg Indications 2. Approved for use to terminate pregnancy at 12 to 20 weeks from the date of the LMP  Well absorbed when administered. Metabolized in liver and excreted in the urine. Mifepristone – administered orally and takes 5 – 7 days to produce the desired effect. Pharmacokinetics Carboprost – IM injection, onset of 15 minutes and a duration of 2 hours. Dinoprostone – intravaginal suppository, onset of effects in 10 minutes and a duration of effects of 2 hours.  1. Allergy to abortifacients or prostaglandin 2. After 20 weeks from the last menstrual Contraindications period and Cautions 3. Active PID or acute CV, hepatic, renal, or pulmonary disease. 4. Not recommended during lactation.  1. Caution should be used with any history of asthma, HPN, or adrenal Contraindications disease. and Cautions 2. With acute vaginitis or scarred uterus.  1. Abdominal cramping 2. Heavy uterine bleeding Adverse 3. Perforated uterus Effects 4. Uterine rupture 5. Headache, n/v, diarrhea, diaphoresis, backache, and rash,  Drugs that are used to affect the MRS include androgens (male steroid hormones), anabolic steroids, and drugs Introduction that act to improve penile dysfunction. The male steroids are produced in the testes and affects the entire male RS  danazol fluoxymesterone Androgen methyltestosterone testosterone Anabolic oxandrolone Steroids oxymetholone Drugs for alprostadil Treating avanafil Penile sildenafil Erectile tadalafil Dysfunction vardenafil  male sex hormone and includes testosterone and androgens testosterone (Durates, Testoderm, and others), the primary natural androgen used for replacement therapy in cases of hypogonadism and to treat certain Androgen breast cancers. Testosterones are all class III controlled substance. danazol (generic), fluoxymesterone (Android), and methyltestosterone (Testred)  1. responsible for growth and development of male sex organ 2. maintenance of secondary male sex characteristics 3. act to increase the retention of nitrogen, Therapeutic sodium, potassium, and phosphorus and to Actions and decreased the urinary excretion of calcium Indications 4. testosterone increased protein anabolism and decreased protein catabolism 5. increase the production of RBC 6. Danazol: used to treat endometriosis, fibrocystic breast disease (in females) and hereditary angioedema.  Depot (deep, slow-release) injections, buccal system, topical gels, topical sprays, urethral pellets, and a dermal patch. Danazol: synthetic androgen (long acting) available only in oral form. Pharmacokinetics Methyltestosterone and fluoxymesterone: long half-lives and available in the oral form. Well absorbed and widely distributed throughout the body. Metabolize in the liver and excreted in the urine.  1. Any known allergy to the drug or ingredients in the drug Contraindications 2. During pregnancy and lactation and Cautions 3. Presence of prostate or breast cancer in men  1. Presence of any liver dysfunction or cardiovascular disease. 2. The topical forms of testosterone have a black box warning alerting the user to the risk of virilization in children who come in contact with the drug from Contraindications touching the clothes and skin of the and Cautions man using the drug. 3. Danazol: has black box warning regarding the risk for thromboembolic events, fetal abnormalities, hepatitis, and intracranial HPN.  Androgenic effects 1. acne 2. edema 3. hirsutism Adverse 4. deepening of the voice Effects 5. oily skin and hair 6. weight gain 7. decreased in breast size 8. testicular atrophy  Antiestrogen effects 1. flushing Adverse 2. sweating Effects 3. vaginitis 4. nervousness 5. emotional lability  Common Effects 1. headache 2. dizziness Adverse 3. sleep disorders Effects 4. fatigue 5. rash 6. altered serum electrolytes  Potentially Life-threatening Effect Adverse 1. Hepatocellular Cancer Effects 2. Cardiovascular events: MI and stroke and venous embolic events (DVT and PE  analogues of testosterone that have been developed to produced the Anabolic tissue-building effects of testosterone Steroids with less androgenic effects. oxandrolone (Oxadrin), oxymetholone (Anadrol-50)  1. promote body tissue-building processes 2. reverse catabolic or tissue-destroying Therapeutic processes Actions and 3. increase Hgb and RBC mass Indications 4. used to treat anemias, certain cancers, and angioedema 5. promote weight gain and tissue repair 6. protein anabolism  Note: AS are also known to be used illegally for Therapeutic the enhancement of athletic Actions and performance by promoting increased Indications muscle mass, increased hct, and theoretically an increase in strength and endurance.  available orally well absorbed and widely distributed Pharmacokinetics throughout the body metabolized in the liver and excreted in the urine  1. in the presence of any known allergy to the drug 2. during pregnancy and lactation Contraindications 3. presence of liver dysfunction and Cautions 4. coronary disease 5. prostate and breast cancer  1. Pre-pubertal: Virilization (phallic enlargement, hirsutism, increased skin pigmentation) 2. Post-pubertal: inhibition of testicular function, gynecomastia, testicular Adverse atrophy, priapism, baldness and Effects change in libido 3. Women: hirsutism, hoarseness, deepening of the voice, clitoral enlargement, baldness, and menstrual irregularities.  4. Androgen, serum electrolyte changes, liver dysfunction, insomnia, and weight gain Adverse 5. Black box warnings: liver tumor, Effects hepatitis, and blood lipid changes (CAD) 6. Increased prostate problems, especially in geriatric patients.  7. Cardiomyopathy, hepatic carcinoma, Adverse personality changes, and sexual Effects dysfunction: excessive and off-label use of anabolic steroids  Penile erectile dysfunction – condition in which the corpus cavernosum does Drugs for not fill with blood to allow for penile erection Treating 2 types of drugs Penile prostaglandin alprostadil (Caverject, Muse) Erectile phosphodiesterase type 5 (PDE5) receptor Dysfunction inhibitors sildenafil (Viagra, also available as Revatio: for tx of PHPN), tadalafil (Cialis also available as Adcirca), and vardenafil (Levitra)  1. alprostadil acts locally to relax the vascular smooth muscle and allow filling of the corpus cavernosum Therapeutic 2. PDE5 inhibitors are taken orally and act to Actions and increase nitrous oxide levels in the corpus Indications cavernosum. 3. prevent breakdown of cGMP by phosphodiesterase, leading to increased cGMP levels and prolonged smooth muscle relaxation  5. PDE5 inhibitors have the advantage of being oral drugs that can be timed in coordination with sexual activity, based on the drug’s Therapeutic onset. Actions and 6. Sildenafil (Revatio) and tadalafil (Adcirca) Indications are also approved for the treatment of pulmonary arterial HPN – available in oral tablet or suspension and in IV form. 7. Tadalafil: approved for daily use in men who are very active sexually.  alprostadil: metabolized to inactive compounds in the lungs and excreted in the urine. PDE5 anhibitors: well absorbed from the GI tract, metabolized in the liver, Pharmacokinetics excreted in the feces. Note: The differences among the three PDE5 inhibitors lie in their onset and duration of action.  Sildenafil: median onset of 27 mins and a duration of 4 hrs Verdenafil: mean onset of action of 26 mins and a duration of 4 hrs Pharmacokinetics Tadalafi: has an onset of action of 45 mins and a duration of 2-3 hrs treat Pulmonary HPN  1. In the presence of any anatomical obstruction or condition that might predispose to priapism Contraindications 2. They cannot be used with penile and Cautions implants, and they are not indicated for use to improve sexual performance in woman.  1. Caution should be used in patients with bleeding disorders. 2. The PDE5 inhibitors should also be used cautiously in patients with CAD, active Contraindications peptic ulcer, retinitis pigmentosa, and Cautions optic neuropathy, hypotension, or severe HPN, congenital prolonged QT interval, or severe hepatic or renal disorders  1. Alprostadil: local effects-pain at the injection site, infection, priapism, fibrosis, and rash. Adverse 2. PDE5 inhibitors: associated with more systemic effects (headache, flushing, Effects dyspepsia, UTI, diarrhea, dizziness, optic neuropathy, 8th CN toxicity and loss of hearing, increased risk of melanoma and rash.