Pharmacology Chapter 34- Women's Health Drugs

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Types of oral contraceptives

*Biphasic*- two alternating doses, 1st dose is used for 10 days then changes for the remaining days. Estrogen dosage is fixed, progesterone dose changes. *Triphasic*- most closely resembles the natural female cycle; estrogen/progesterone dosages change three times during the cycle. *Monophasic*- estrogen/progesterone dosages are fixed.

Drug interactions with Contraceptives

*Drugs the reduce the effects of oral contraceptives*- - Rifampin - Isoniazid - Ritonavir - Several antiepileptics (barbiturates) - St. John's Wort - Antibiotics (penicillins and cephalosporins especially) *Drugs whose effects are reduced by oral contraceptives*- - Warfarin - Hypoglycemic agents *Drugs whose effects are increased by oral contraceptives*- - Theophylline: CV (tachycardia), CNS (seizures). - Tricyclic antidepressants: CV (tachycardia, angina). - Diazepam: CNS and respiratory depression.

Preparations and routes of Progestins

*Oral*- Medroxyprogesterone acetate (Provera). Megestrol (Megace). - primarily use for palliative treatment for endometrial or breast cancer. - also used as an appetite stimulant of anorexia or weight loss in patients with AIDS and patients with cancer. *Intramuscular*- Medroxyprogesterone acetate (Depo Provera). *Intravaginal*- Crinone (gel). Endometrin. *Vaginal ring*- NuvaRing (with estradiol).

Preparations and routes of Estrogens

*Oral*: used more than any other route, available alone and in combo products- - Premarin - Estratab - Menest - Estrace *Transdermal*- - Estrasorb - Evamist - EstroGel, Elestrin - Climara, Estraderm, Menostar *Intravaginal*- - Vagifem - Estrace vaginal - Premarin vaginal

Interactions with Estrogens

*Warfarin*- decreases anticoagulation effect. *Rifampin*- decreases estrogen effect. *Smoking*- decreases estrogen effect and increases risk for thrombosis. *Antibiotics*- decreases estrogen effect. *Grapefruit juice*- decreases metabolism of estrogen = increased adverse effects.

Drugs for Osteoporosis

- Calcitonin - Bisphosphonates - Selective Estrogen Receptor Modulators (SERMS) - Teriparatide - Denosumab

Women's health drugs

- Estrogens - Progestins - Osteoporosis drugs - Fertility drugs - Uterine stimulants - Uterine relaxants

Dosing schedule of Contraceptives

28 day cycle- 21 days of active pill, 7 days of either no pill, inactive pill, or iron pill. Extended and continuous cycle- no break from active pill.

A patient calls the clinic because she realized she missed one dose of an oral contraceptive. Which statement from the nurse is appropriate? (Select all that apply) A. "Go ahead and take the missed dose now, along with today's dose." B. "Don't worry, you are still protected from pregnancy." C. "Please come to the clinic for a re-evaluation of your therapy." D. "Wait 7 days, and then start a new pack of pills." E. "You will need to use a backup form of contraception concurrently for 7 days."

A. "Go ahead and take the missed dose now, along with today's dose." E. "You will need to use a backup form of contraception concurrently for 7 days."

When the nurse is teaching patients about postmenopausal estrogen replacement therapy, which statement is correct? A. "It is not recommended in patients with a history of endometrial cancer." B. "Use is recommended and beneficial in older women." C. "Estrogen therapy should be long term to prevent menopausal symptoms." D. "If estrogen is taken, supplemental calcium will not be needed."

A. "It is not recommended in patients with a history of endometrial cancer."

The nurse has provided patient education regarding therapy with the SERM raloxifene (Evista). Which statement from the patient reflects a good understanding of the instruction? A. "When I take that long flight to Asia, I will need to stop taking this drug at least 3 days before I travel." B. "I can continue taking this drug even when traveling as long as I take it with a full glass of water each time." C. "After I take this drug, I must sit upright for at least 30 minutes." D. "One advantage of this drug is that it will reduce my hot flashes."

A. "When I take that long flight to Asia, I will need to stop taking this drug at least 3 days before I travel."

A patient is beginning a new prescription of raloxifene (Evista). The nurse will teach the patient to expect which potential adverse effects? (Select all that apply) A. Leg cramps B. Loss of appetite C. Diarrhea D. Hot flashes E. Drowsiness

A. Leg cramps D. Hot flashes

When combination oral contraceptives are given to provide postcoital emergency contraception, the nurse must remember which fact? A. They are not effective if the woman is already pregnant. B. They should be taken within 12 hours of unprotected intercourse. C. They are given in one dose. D. They are intended to terminate pregnancy.

A. They are not effective if the woman is already pregnant.

Selective Estrogen Receptor Modulators (SERMs)

Activate estrogen receptors in some tissues and block them in others. Examples- - Raloxifene (Evista) - Tamoxifen (Nolvadex)

Pharmacokinetics of Alendronate (Fosamax)

Administered orally with very low bioavailability (absorption). If drug is taken with solid food, absorption is substantially decreased.

Contraindications to estrogen use

Allergy. Estrogen-dependent cancer. Undiagnosed abnormal vaginal bleeding. Pregnancy category X. Active thromboembolic disorder (stroke, thrombophlebitis, etc) or a history of such a disorder. Cardiovascular disease. Active liver disease. Cautious use: breastfeeding women.

Contraindications to the use of Contraceptives

Allergy. Pregnancy. Abnormal liver function. High risk for or history of thromboembolic events (such as myocardial infarction, pulmonary embolism, stroke).

Methylergonovine (Methergine)

Argot alkaloid. Stimulates uterine contraction, causes constriction of arterioles and veins = can decrease bleeding after childbirth. Monitor the patient's vital signs and uterine contractility. Reserved for patients who have not responded to oxytocin. Not to be used during labor. Given after delivery of the placenta. IV administration can lead to hypertension.

A pregnant woman is experiencing contractions. The nurse remembers that pharmacologic measures to stop contractions are used during which time frame? A. Before the 20th week of gestation. B. Between the 20th and 37th weeks. C. After the 37th week. D. At any time during the pregnancy if delivery is not desired.

B. Between the 20th and 37th weeks.

The most serious side effects of progestins include which of the following? A. Menopause B. Liver dysfunction C. Myocardial infarction D. Pancreatic insufficiency

B. Liver dysfunction

When teaching a patient who is taking oral contraceptive therapy for the first time, the nurse relates that adverse effects may include which of the following? A. Dizziness B. Nausea C. Tingling in the extremities D. Polyuria

B. Nausea

When reviewing the health history of a patient who wants to begin taking oral contraceptives, the nurse recalls that which conditions are contraindications to this drug therapy? (Select all that apply) A. Multiple sclerosis B. Pregnancy C. Thrombophlebitic disorders D. Hypothyroidism E. Estrogen-dependent cancers

B. Pregnancy C. Thrombophlebitic disorders E. Estrogen-dependent cancers

Terbutaline (Brethine)

Beta 2 agonist. Activates beta 2 receptors in the uterus: results in a decrease in the intensity and the frequency of contractions. Administered SQ for suppression of labor. *Adverse effects*- palpitations, tachycardia, hypertension, angina. Hold if maternal heart rate exceeds 120 beats per minute. Can be used to suppress preterm labor, not *prevent* preterm labor.

A woman comes into the emergency department. She says that she is pregnant and that she is having contractions every 3 minutes but she is "not due yet." She is very upset. While assessing her vital signs and fetal heart tones, what is the most important question the nurse must ask the patient? A. "What were you doing when the contractions started?" B. "Are you preregistered at this hospital to give birth?" C. "How many weeks have you been pregnant?" D. "Have you felt the baby move today?"

C. "How many weeks have you been pregnant?"

The nurse is discussing therapy with clomiphene (Clomid) with a husband and wife who are considering trying this drug as part of treatment for infertility. It is important that they be informed of which possible effect of this drug? A. Increased menstrual flow. B. Increased menstrual cramping. C. Multiple pregnancy (twins or more). D. Sedation

C. Multiple pregnancy (twins or more).

What patient teaching is appropriate for a patient taking alendronate (Fosamax)? (Select all that apply) A. Take with food. B. Take at night just before going to bed. C. Take with an 8-oz. glass of water. D. Take with a sip of water. E. Take first thing in the morning upon arising. F. Do not lie down for at least 30 minutes after taking.

C. Take with an 8-oz. glass of water. E. Take first thing in the morning upon arising. F. Do not lie down for at least 30 minutes after taking.

Nifedipine (Procardia)

Calcium channel blocker. Blocks calcium channels and inhibits the entry of calcium into myometrial cells. Can suppress preterm labor for at least 48 hours. Efficacy is equal to terbutaline, but safer. *Adverse effects*- tachycardia, facial flushing, headache, dizziness, nausea, hypotension in hypovolemic patients. To suppress preterm labor: initial loading dose of 30 mg orally, followed by 10 or 20 mg every 4-6 hours.

Oxytocin (Pitocin)

Can increase the force of uterine contractions, can cause milk ejection, and water retention. *Therapeutic use*- to induce labor, and for post-partum hemorrhage. *Requires continuous monitoring*- - Vital signs - Fetal heart beat - Contractions: goal is that the patient will have contractions every 2-3 minutes, 45-60 seconds in length. Administered IV/IM. *Precautions/Contraindications*- pregnancies with any concerns, active genital herpes.

Progestins

Compounds that have actions similar to progesterone. Acts prior to gestation to prepare the uterus for implantation of a fertilized ovum and helps maintain the uterus throughout pregnancy.

Therapeutic uses of Estrogens

Contraception (when combined with a progestin). Menopausal hormone therapy. Female hypogonadism. Atrophic vaginitis. Ovarian failure. Uterine bleeding. Osteoporosis. Breast/prostate cancer.

The nurse is reviewing the use of obstetric drugs. Which situation is an indication for an oxytocin (Pitocin) infusion? A. Termination of a pregnancy at 12 weeks. B. Hypertonic uterus C. Cervical stenosis in a patient who is in labor. D. Induction of labor at full term.

D. Induction of labor at full term.

Administration of Ibandronate (Boniva)

Dosage for prevention and treatment of osteoporosis is 150 mg/month, taken on the same day each month. Take on empty stomach in the morning. Swallow with a full glass of water. Stay upright for 60 minutes. IV- give slow IV push.

Mechanism of action/Drug effects of Progestins

Effects are the same as natural progesterone- Secretory changes in the endometrium. - diminished endometrial proliferation. Increase in basal body temperature. Thickening of vaginal mucosa. Relaxing uterine smooth muscle. Alterations in menstrual blood flow.

Contraindications to the use of Progestins

Estrogen-dependent breast cancer. History of thromboembolic disorder. Pregnancy. Undiagnosed vaginal bleeding.

Clomiphene (Clomid)

Fertility drug. Used to promote ovulation by blocking receptors for estrogen, which increases the pituitary secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) which then stimulate ovulation. *Adverse effects*- - hot flashes - nausea - abdominal discomfort - breast engorgement - multiple births (occurs in 8-10% of clomid facilitated pregnancies). Initial treatment: 50mg/day for 5 days.

Adverse effects of Alendronate (Fosamax)

Generally well tolerated. - Esophagitis - Musculoskeletal pain - Ocular inflammation - Necrosis of the jaw bone

Zolendronate (Reclast)

IV bisphosphonate with five approved indications- - postmenopausal osteoporosis - osteoporosis in men - Paget's disease - glucocorticoid-induced osteoporosis - hypercalcemia of malignancy Can cause fever, nausea, constipation, bone and joint pain, bone injury to the jaw, kidney damage. Administered once a year, or every 2 years. For Paget's disease, it's only administered once.

Calcitonin- Salmon (Miacalcin, Fortical)

Inhibits osteoclasts and increases calcium excretion in the urine. *Therapeutic uses*- - treatment of established post-menopausal osteoporosis (but not prevention). - Paget's disease. - hypercalcemia. *Adverse effects*- - Very safe. Includes nasal dryness and irritation. *Preparations*- - Intranasal spray. - Parenteral.

Mechanism of action of Contraceptives

Inhibits ovulation by inhibiting the release of gonadotropins and by increasing vaginal mucosal viscosity.

Magnesium sulfate

Inhibits the release of acetylcholine at neuromuscular junctions. Used for the prevention of seizures associated with preeclampsia and eclampsia. *Adverse effects*- hypotension, flushing, headache, dizziness, lethargy, dry mouth, feeling of warmth. Bolus followed by a continuous drip for 24 hours after delivery.

Therapeutic uses of Progestins

Menopausal hormone therapy: prevents endometrial overgrowth/hyperplasia. Dysfunctional uterine bleeding. Amenorrhea. Endometriosis. Contraception (when combined with an estrogen). Infertility. Prematurity prevention. Endometrial carcinoma and hyperplasia.

Uterine stimulants

Oxytocin (Pitocin) Methylergonovine (Methergine)

Indications for the use of Contraceptives

Prevention of pregnancy. Endometriosis. Hypermenorrhea. Amenorrhea. Acne. Emergency contraception. - should be taken within 72 hours of unprotected intercourse, with a follow up dose 12 hours after the initial dose.

Alendronate (Fosamax)

Suppresses resorption of bone by decreasing both the number and activity of osteoclasts. *Therapeutic uses*- - postmenopausal osteoporosis. - prevention of osteoporosis in postmenopausal women. - glucocorticoid osteoporosis. - Paget's disease. - osteogenesis imperfecta. - post-operative knee arthroplasty.

Administration of Alendronate (Fosamax)

Take in the morning before breakfast on an empty stomach. To avoid the risk of esophagitis, patients should- - take with a full glass of water. - remain upright for 30 minutes. - avoid chewing or sucking tablets. Available in tablets. Dosing varies with patient, 5mg daily or 35mg weekly for prevention.

Adverse effects of Progestins

Teratogenic effects. Liver dysfunction. Thromboembolic disorders. Gynecologic effects: amenorrhea, spotting. Breast tenderness, bloating, depression, weight gain.

Drugs for preterm labor management

Terbutaline (Brethine) Nifedipine (Procardia) Magnesium sulfate

Estrogens

Three major endogenous estrogens: estradiol, estrone, and estriol. All are synthesized from cholesterol.

Adverse effects of Contraceptives

Thromboembolic disorders. Cancer (can promote breast cancer growth in certain women). Hypertension. Abnormal uterine bleeding. Weight gain. Depression.

Adverse effects of Estrogens

Thromboembolic events (DVT, PE, CVA, MI). Nausea- most common undesirable effect. Endometrial hyperplasia and cancer. Breast and ovarian cancer. Chloasma (brown patches on the skin). Amenorrhea, bleeding. Breast tenderness. Liver dysfunction. Several black box warnings: cancer and cardiovascular. Hold estrogen products for up to a month before a surgery with prolonged immobilization.

Contraceptives

Two main categories- - Estrogen plus progestin (known as combination): more widely used. - Progestin only (mini pills).

Raloxifene (Evista)

Used for postmenopausal osteoporosis, breast cancer. Can lower cholesterol and LDL. *Adverse effects*- venous thromboembolism, hot flashes. Black box: CV risk (stroke, deep vein thrombosis). Clients should discontinue raloxifene 72 hours before prolonged immobilization. May decrease the effects of warfarin (requires an increased dose of warfarin).

Ibandronate (Boniva)

Used in the prevention and treatment of postmenopausal osteoporosis. Benefits derive from inhibiting osteoclast- mediated bone resorption. Can cause adverse GI effects, IV administration may cause renal damage (check BUN and creatinine before beginning therapy). P.O./IV. Dosing is daily, once a week, once a month, or every 3 months.

Tamoxifen (Nolvadex)

Used to treat and prevent breast cancer. *Adverse effects*- hot flashes, fluid retention, vaginal discharge, N/V, menstrual irregularities. Increased risk of thromboembolism, and risk of endometrial cancer because it acts as an estrogen agonist at receptors in the uterus. Women usually take 20mg/day for 5 years for both treatment and prevention of breast cancer.

Progestin only oral contraceptives

Used with moms who are breastfeeding (estrogen would dry up the milk supply). Less effective, more breakthrough bleeding. 28 day cycle, no breaks.

Mechanism of action/Drug effects of Estrogens

When estrogen binds to estrogen receptors, DNA, RNA, and proteins are synthesized (building blocks of all living tissues). Required at puberty for the development and maintenance of sexual characteristics: causes initiation of menses, breast development, body fat distribution, and skin softening. Effects are produced in tissues that have estrogen receptors- these include female genital organs, breasts, pituitary gland, and the hypothalamus.

Bisphosphonates

Work by inhibiting osteoclasts to increase bone mineral density. Drug examples- - *Alendronate (Fosamax)* - *Ibandronate (Boniva)* - *Zolendronate (Reclast)* - Risedronate (Actonel) - Tiludronate (Skelid) - Etidronate - Pamidronate (Aredia)


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