NR566 Final (Advanced Pharmacology for Care of the Family)with complete solutions

Anti-Androgens Finasteride (Propecia) Leuprolide (Eligard, Lupron, Lupron Depot) Spironolactone (Aldactone) Finasteride (Propecia, Proscar) blocks conversion of testosterone to dihydrotesterone Used to tx: -BPH -male pattern baldness 3 months of therapy need to see benefits Stopping, reverses effect w/in 12 months Adverse side effects: - Decreased libido -Impotence dutasteride (Avodart) 5-alpha reductase inhibitor used to tx: BPH Can stay in serum up to 6 mon after discontinuing can be absorbed through skin pregnant woman shouldn't handle capsules (fetal anomaly in male fetus) Adverse Effects decreased libido Impotence Leuprolide Acetate (Lupron) Luteinizing hormone - releasing agonist create reversible: -orchiectomy state -oophorectomy state Used to tx: - advanced prostatic cancer - Management of endometriosis - Uterine fibroids - polycystic ovarian disease - central precocious puberty in peds Flutamide (Eulexin, Euflex) Truly non-steroidal agent Used to tx: -Advanced prostate cancer -female androgen excess syndrome Adverse Effects in males - gynecomastia -reversible liver toxicity Black Box Warning -hepatic failure -hepatic encephalopathy Basline/monthly liver function test for 1st 4 months Spironolactone (Aldactone) aldosterone antagonist potassium sparing diuretic used for tx: -female hirsutism (abnormal growth of hair) -acne -relief of PMS/PMDD symptoms (25-50 mg/d) Adverse reactions - dose related + reversible when discont. -GI upset -Drowsiness -Gynecomastia -Impotence -Cutaneous (skin) eruptions - Urticaria Black Box Warning Tumorigenicity in animals Should not be used during pregnancy Androgen Testosterone most important adrogen in humans levels remain stable at 55yr 70 yrs men decrease in -strength, libido, muscle mass Transdermal application of testosterone Patch + gel can be applied to intact nonscrotal skin once daily not for use in woman men cannot have skin contact with pregnant woman or children Men need to wash hands after application + allow skin to dry Testopel Subcu Pellet produces testosterone for 3-6 months Contraindications for Testosterone Male breast cancer prostate cancer Pregnancy (X category) Lactation Complications of Testosterone - Edema w/or w/out congestive heart failure (use caution in pts w/ preexisting cardiac, renal, or hepatic disease) Increased risk for -prostatic hypertrophy -prostatic hyperplasia -prostatic carcinoma Hypogonadal men might experience sleep apnea This risk increases in men w/obesity or chronic lung disease. Refer to endocrinologist stimulating growth in boys with delayed puberty aging men to increase strength + muscle mass Adverse Reactions Androgens Prolonged high dose use = -life threatening hepatitis -hepatic neoplasms -Hepatocellular carcinoma Methyltestosterone + fluoxymesterone low dose: -cholestatic hepatitis -Jaundice All Patients -Nausea -vomiting -change in liver function - edema - Cholestatic jaundice -Suppression of clotting factors - Increased red blood cell production (Hemorrhage + Thrombus) Gender Specific side effects of testosterone Gynecomastia Reduced sperm levels Ance Baldness Decrease libido Depression Headache Scrotal pain Goin pain Changes in Urination Priapism (A sustained erection) Women: Menstrual irregularities Hypercalcemia Virilization Anabolic Steroids Peliosis (blood cysts in liver) liver tumors Testosterone Drug Interactions Diabetic agents Anticoagulants Corticosteroids Imipramine Cyclosporine Clinical use Androgens Hormone replacement for hypogonadal males or male climacteric (late onset hypogonadalism or testosterone deficiency syndrome) Endometriosis Refractory anemia Estrogen for osteoporosis + loss of libido Estrogen Endogenous Hormone maturation + function of the female reproductive system Effects of Estrogen on the reproductive Cycle -Maturation of reproductive organs -Development of secondary sexual characteristics -Regulation of the menstrual cycle -Endometrial regenerations postmenstration - Closure of long bones after puberty growth spurt -Maintenance of bone density by decreasing rate of bone absorption - Maintenance of normal structure of skin and blood vessels - Reduction of bowel motility -Alters production + activity of selected proteins -Enhances the coagulability of blood (produces fibrinogen) - Facilitates loss of intravascular fluid into extracellular space (RAA cycle) -Maintains the stability of thermoregulatory center in the brain. LH + FSH do what? Stimulate follicular development in the ovary Adequate estrogen + surge of LH causes? Ovulation Synthesized estrogens are used in the primary care setting for? -replacement after oophorectomy -natural menopause -hot flashes -vaginal atrophy -irregular menstrual bleeding Progesterone only pills were associated with what problem? Significant breakthrough bleeding Potency ratio of replacement estrogens to contraception estrogens 1:10 Dose of estrogen for contraception is higher than the dose needed for replacement therapy Advance practice nurses prescribe oral contraceptives for? -tx of dysmenorrhea -cycle control -acne management -amenorrhea -hirsutism associated with Polycystic Ovary Disease. Absolute Contraindications for Estrogen Therapy Current/Prior hx of estrogen dependent cancer Current pregnancy Undiagnosed dysfunctional uterine bleeding Deep vein thromboembolism Arterial Thromboemboli w/in the prior yr Clotting Disorders Severe Hepatic Disease Relative Contraindications to Estrogen Therapy Cardiovascular Disease Uncontrolled HTN Diabetes Mellitus Gallbladder Disease Obesity Endometriosis Seizure Disorder Migraines Women who experience these should not be prescribed estrogen Migraines with Aura = increased risk for stroke Intact Uterus = increased risk for hyperplasia + endometrial cancer Risk of non-estrogen dependent breast cancer? Not significant in short term use W/every 10 yr increment of use 14% rise in breast cancer. Estrogen Replacement therapy (ERT) + Estrogen plus progestin therapy (HRT) increases risk for? Coronary Heart Disease Stroke Thromboemboli Estrogens are Pregnancy Category X Teratogenicity high rate Ethinyl Estradiol Contraindicated in what pts Pts who smoke and are older than 35 yrs Adverse Reactions Estrogens Most reactions are dose-related Most are seen in oral contraceptives Cardiovascular + hematological MI HTN Alteration in clotting factors Thromboembolism (Leg pain, visual disturbances, + severe headache) Elevation of systemic BP Gallbladder disease Irregular bleeding Estrogen Drug Interactions Oral anticoagulants Fosamprenavir Benzodiazepines - rifampin Corticosteroids Dantrolene Anticonvulsants woman may experience impaired glucose tolerance and increased triglycerides with oral estrogens Conjugated Equine Estrogen (Premarin) Animal source Micronized Estradiol (Estrace, Gynodiol) Only bioidentical estrogen-alone product that is available in pill form. typical regimen 1mg taken daily Lower dose used for osteoporosis prevention Estrone-based Drugs Estrogens derived from plant sources Prevention + management Vulvovaginal Atrophy Low dose oral ERT w/estrogen from plant or animal sources Decrease vaginal PH Thickens/revascularizes the vaginal epithemlium reverses vaginal atrophy Vaginal Estrogen also produces these effects Contraception Estrogens Ethinyl Estradiol Mestranol (weaker of the 2) Transdermal Formulations Once or twice weekly application Also have skin irritation 20-40% Vaginal Instillation -For pts who cant tolerate oral form -Severe Uretheral +Urogenital Atrophy -Creams + rings have lower risk for endometrial hyperplasia than oral -creams nightly application -Rings + tablets can be less messy -Oral formulations retain the positive effects of ERT that accrue because of liver metabolism Monitoring Estrogen Therapy All pts should monitor BP Baseline blood test should be drawn including lipid panel Order mammograms prior to prescribing ERT or HRT Women should have annual mammograms pelvic evaluations Cardiovascular assessments Pt Administration Oral hormonal contraceptives + HRT need to take the drug daily at about the same time to avoid break through bleeding. Women may experience mild nausea and breast tenderness or midcycle spotting during first 2 months of therapy. Sometimes taking medication at bedtime can help the nausea Rotate site for transdermal, do not put on breast tissue Mifepristone (Mifeprex) - Is a progesterone receptor antagonist - Inhibits both endogenous + exogenous progesterone - Mifepristone + Misoprostol aborts pregnancys In the first 7 weeks. - Bleeding or spotting for an average of 9-16 days - Persistent heavy/moderate bleeding could mean an incomplete abortion -Available only through manufacturer and not licensed pharmacies - Very specific requirements associated with administration - Exhibits antiglucocorticoid + weak antiandrogenic activity - off label uses = tx of endometriosis, chushing's syndrome + uterine leiomyomata Progesterones Progesterone Medroxyprogesterone Norethrindrone Megestrol Acetate Most used in oral contraceptives & for HRT Some generations have been developed to - Address mood change - Break through bleeding - Sensitivity to progesterone agents Effects of Progestine on reproductive organs Thickening of the endometrium Thickening of cervical mucus Thinning of vaginal mucosa Relaxation of smooth muscles of uterus & fallopian tube During pregnancy progestin maintains the thickened endometrium relaxes myometrial muscles thickens the myometrium for labor develops the placenta prevents lactation until the fetus is born develops alveolobular what happens in the absence of pregnancy when production of estrogen and progestin is decreased? Shedding of the endometrium to produce menstruation Suppress the LH surge necessary for ovulation Progestin actions outside of reproductive system - Stimulates lipoprotein activity and seems to favor fat deposition - Increases basal insulin levels & insulin responses to glucose - Promotes glycogen storage in the liver; promotes ketogenesis - Competes with aldosterone in the renal tubule to decrease NA+ resorption - Increases body temp - Increases ventilatory response to CO2 Progestins Contraindications - Pts w/thromboembolic disease or hx of it should not use - Breast cancer may become worse under hormone influence - Impaired liver function - Depression associated w/long & short acting - Pts who use tobacco products Progestins Precautions Fluid retention Carefully observe pts affected negatively by excess fluid - epilepsy -migraine -asthma -congestive heart failure - renal dysfunction Decrease in glucose tolerance observed in small % on estrogen-progesterone combination drugs Diabetic pts increase glucose monitoring Pregnancy and progestins Progesterone is category D Norethindrone acetate is X Progesterone gel is used to support embryo implantation & maintain pregnancies. Lactation may be enhanced by Medroxyprogesterone, dont know what effects are on infants Progestin Adverse Reactions Most common - Irregular, break through vaginal bleeding Some experience amenorrhea Acne & Chloasma have occurred w/more androgenic progestin Increased breast tenderness Galactorrhea (excessive production of mik) Nausea Depression Weight gain Injectable & Implantable Progesterone for contraception is associated with? Weight change irregular menstrual bleeding IM progestin (Depo-Provera) - pts are at increased risk for osteoporosis b/c of low estrogen levels -BLACK BOX WARNING - dont use for longer than 2 yrs -bone density loss may extend beyond duration of tx - Delays to return to fertility may also occur with IM Progestins Drug Interactions Aminoglutethimide + Rifampin Decrease effectiveness = unplanned pregnancy Clinical Use of Progestins perimenopausal postmenopausal contraceptive alone & in combo with estrogen progestin only contraception Suppress LH surge necessary for ovulation Thickening of cervical mucus tubal motility slowed delaying transport of sperm & ovum Cause atrophy of endometrium Preventing implantation Progestin Administration Progestin only contraceptive = daily dosing Injectable form = administration every 12 weeks if outside 2 week window for shot... - use others from of protection for intercourse - repeat pregnancy test before restarting injections -women have to present to initial administration of injectable progesterone while actively menstruating & have (-) pregnancy test. Erectile Dysfunction Drugs phosphodiesterase type 5 inhibitors Sildenafil citrate (Viagra) Peak 60 min Duration 4 hrs Taken an hr before sexual activity reduced clearance in elderly Vardenafil shorter onset Duration 6hrs take hr before sex Tadalafil fastest acting + lasts longest 17-36 hrs Taken 15 min before sexual activity Daily use approved for ED and BPH pts complain of lower back pain Use of ED meds Originally used as vasodilator for use in angina Effective in pulmonary HTN as well high-altitude pulmonary edema Branded under different names (Revato, Staxyn & Adcirca) Produces smooth muscle relaxation in the penis = erection. No drug effect w/out sexual stimulation Also relaxes smooth muscle in bladder = benign prostatic enlargement if used daily