PHARM 2: Drugs used for Women's Reproductive Health

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Use of Tocolytics to Suppress Preterm Labor

'Toco' - contraction of the uterus 'lysis' - break down the contractions of the uterus GOAL for controlling preterm labor- is to only delay labor for 24 to 72 hours to treat the mom with antibiotics and the corticosteroids for the baby *steriods used to treat preterm* betamethasone (given in two doese in 24 hours apart) or dexamethasone (given in 4 doses 12 hours apart) -the goal in trying to control the uterine contractions is to hold off delivery until you have time to give all the doses of the steroids and to have 24 hours for the steroids to do what they need to do -for the fetus the steroids help to accelerate the maturation of the cells in the lungs also helps to speed up maturation in other body organs as well - *an adverse effect in the long run of these steroids is that when they are used to speed up maturation of the fetus the do this at the expense of some of the later growth of the fetus, (may actually slow down the growth of the fetus)* -if the fetus were to go to term when it is born it may be a little smaller than what it would have been, as a result these babies do much better than if they would not have had the steroids at all. -Monitor used to record maternal contractions to determine dosage and timing of medications -for the tocolytic drugs to work we want to stop uterine contractions, so need to use a drug that will either relax skeletal muscle, or give a drug that blocks the movement of calcium into the cells to prevent a uterine contraction (CCBs) -Tocolytics can generally delay labor for 24 to 72 hours -Pharmacotherapy currently includes calcium channel blockers and beta-adrenergic agonists; all are off-label for this use -*Magnesium sulfate (relax skeletal muscle)* -*Nifedipine (Adalat, Procardia)* calcium channel blocker, works very slowly, may have to start out with another drug to stop the contractions then use this one to maintain -*Terbutaline (Brethine)*

Prostaglandins

*Carboprost (Hemabate) & Dinoprostone (Cervidil, Prepidil, Prostin E2) & misoprostol (Cytotec)* -prostaglandins are synthesized in all tissues in the body but unlike other hormones in the body they act in the tissues they are made -play an important in the natural labor and delivery of a baby -also used to help get the cervix ready for induction of labor, will soften the cervical tissues by adding more water and breaking down the collagen -an unripened cervix has a firmness to it, but in order for labor to be successful the cervix needs to be pliable enough to allow it to dilate and do this by causing water to be retained in the tissue to break down in the tissue -can also be used in the postpartum pt to help control postpartum hemorrhage -can be used before and after labor and delivery -used the *misoprostol (Cytotec)* in the abortion to help expel the uterus of the products of pregnancy, very rare cases you may also be used to induce labor in pts, needs to be monitored very carefully -can make contractions so close together to cause complications with the babys breathing -misoprostol is a prostaglandin used mainly to help protect the GI tract from meds like NSAIDS and aspirin irritation -the other two prostaglandins are used not as much -another use for the prostaglandins is to help control postpartum bleeding -*Carboprost (Hemabate)* is a good drug for this, can control the bleeding very well with few side effects *given IM only* -helps the uterus to clamp down and contract and stay contracted so that when you do an assessment and feel the uterus after she has a baby you want it to stay contracted and stay hard so that it clamps off the open blood vessels that could bleed heavily on the inside, by getting the uterus to clamp down and contract this will control the bleeding -*Dinoprostone (Cervidil supp, Prepidil gel, Prostin E2)* used very often in the form of a gel, or in a suppository form that can be inserted under the cervix to help ripen the cervix before you induce labor -will place this in the evening in before they plan an induction so that they can sleep through the night as much as she can (sometime the prostaglandins can make her cramp and can trigger true labor in some cases if the woman was close to labor on her own) and begin the true induction with the Oxytocin the next morning

Drugs Similar to Oxytocin

*Carboprost (Hemabate)* -Induces abortion; controls postpartum bleeding -Equivalent to endogenous prostaglandin F2 alpha -Pregnancy category C *Dinoprostone (Cervidil, Prepidil, Prostin E2)* -Prostaglandin E2 -Prepares cervix for labor, aborts deceased fetus -Pregnancy category C *Methylergonovine (Methergine)* -Similar to ergonovine -Controls postpartum bleeding; restores uterine tone -Pregnancy category C -drugs used to clamp down the uterus to control postpartum bleeding *never give to a pt while she is still pregnant* can be given PO, IM, or IV IV in emergent cases, works rapid, even IM effects work within 5 min -keeps the uterus contracted and helps controls the bleeding by clamping off the uterus *can cause serious HTN and even stroke* check BP prior to admin and know for certain that the pts are normotensive and have a BP of 140/90 or less -med can be repeated Q2H PRN to control hemorrhage -if given Iv give slowly over 2 min to minimize the adverse effects -once the pt has got the drug instruct the pt that her uterus will contract and will be painful, medicate the pt before they start, be proactive and give pain med wither when giving the drug or right after -assess BP frequently after -treat N/V, headache -bradyycardia is rare with PO admin -bc it can cause HTN seizures are a possibility *NOT GIVEN TO A WOMEN WITH A FETUS IN HER UTERUS AND TYPICALLY GIVEN TO CONTROL POSTPARTUM HEMORRHAGE*

Hormone Replacement Therapy

*Effects of estrogen alone* -Increased risk of CVD and thromboembolic disorders -No increased risk for breast cancer or MI *Benefits of HRT* -Relief from menopausal symptoms -Prevention of osteoporosis-related fractures -May offer protection from colorectal cancer -Short-term use may be appropriate for women with no history of CVD or cancer -Topical preparations may bring relief for some symptoms

Mifepristone (Mifeprex)

*Indications* Terminating pregnancies with gestation of less than 49 days *Adverse effects* Bleeding most severe Cramping Nausea Diarrhea Headache Headache Dizziness Vomiting Fatigue Abdominal cramps *Serious adverse effects* Septic shock (rare) *Interventions* Conduct comprehensive health assessment Confirm pregnancy and that length of gestation is <49 days Ensure that medical support is available in case of excessive bleeding or partial abortion Assess for presence of IUD and use of anticoagulants or corticosteroids Instruct patient on expected adverse effects *Patient teaching* Follow therapeutic regimen exactly Attend follow-up appointments Immediately report heavy vaginal bleeding, prolonged vomiting, severe cramps, weakness or fever >100.4°F Do not take any other drugs without approval of health care provider *Contraindications/precautions* Long-term corticosteroids therapy Ectopic pregnancies Anticoagulant therapy Patients unable to understand implications of abortion *Drug interactions* Drugs that inhibit the hepatic CYP450 system (e.g., phenytoin, phenobarbital, carbamazepine) St. John's wort Grapefruit juice

Types of Estrogen-Progestin Combination Oral Contraceptives

*Monophasic* Constant dose of estrogen and progestin throughout the 21 day cycle *Biphasic* Estrogen constant rate in each pill Progestin may increased toward end of cycle to better nourish the uterine lining *Triphasic* Estrogen and progestin vary in three phases *Four-phase* - contains a synthetic estrogen and progestin, used to help pts with heavy menstrual bleeding

Uterine Stimulants: Oxytocics

*Oxytocics:* agents used to stimulate uterine contractions and induce labor -Oxytocin (Pitocin), made naturally in the body made by the hypothalamus and stored in the posterior pituitary to be secreted -oxytocin along with ADH are the two that are stored here, have very similar structure -oxytocin has a lot of characteristics similar to ADH, such as retention of water *need to keep in mind when thinking about side effect of long term use for oxytocin* -target organs for oxytocin are the uterus and the breasts -in the breast it stimulates the let down of milk but not the production helps with releasing milk -also known as the hormone of love, when a person is with someone that the love, the touching hugging and caressing is released by oxytocin -pts who are hospitalized or at risk for a true preterm labor (their cervix is dilating on its own before pregnancy reaches term) -these pts can be at risk if they have sexual relations actually triggering labor to occur, there are also some prostaglandins in semen so combining these two can put a woman at risk for preterm labor -the way that we use oxytocin as a med is in a way to make the contractions of the uterus so that we can deliver the fetus -this is a category X drug, bc if used in the wrong context can cause delivery of the fetus before it is viable or able to live on its own *Tocolytics:* agents used to inhibit uterine contractions during premature labor Most widely used oxytocic is the natural hormone oxytocin -Secreted by the posterior pituitary gland -Target organs: uterus and breast

Estrogen/Progesterone HRT - conjugated estrogen and medroxyprogesterone acetate (Prempro), transdermal (CombiPatch)

*Patient Instructions* • Report leg or chest pain, leg edema, sudden change in vision, severe headache, or shortness of breath. • Do not smoke. • Stop taking at least 4 weeks before any surgery that increases the risk of thromboembolic events. • Exercise regularly and follow a heathy, low-fat diet. • Take oral forms with food. • Take pill or apply transdermal patch at bedtime. • Obtain regular blood pressure checks. • Perform self-breast examination every month. • Obtain a mammogram and breast examination at the recommended intervals. • Report vaginal bleeding or spotting to the provider • Advise patient to report edema to provider *Contraindications* • History of or other risk for thromboembolic events • Suspected or confirmed breast, vaginal, cervical, or endometrial cancer • Liver disease • Undiagnosed vaginal bleeding *Precautions* • Hypertension • Gall bladder disease • Diabetes mellitus • Heart disease • Migraines • Kidney dysfunction *Interactions* • Rifampin (Rifadin), ritonavir (Norvir), phenobarbital, carbamazepine (Tegretol), primidone (Mysoline), phenytoin (Dilantin), and St. John's wort can reduce the effectiveness of hormone replacement therapy. • Hormone replacement therapy can reduce the effects of warfarin (Coumadin) and hypoglycemic drugs. • Hormone replacement therapy can increase levels of theophylline (Theo-Dur), diazepam (Valium), chlordiazepoxide (Librium), and tricyclic antidepressants. • Ketoconazole (Nizoral) may increase the adverse effects of progesterone.

Progesterone - medroxyprogesterone acetate (Provera)

*Patient Instructions* • Report leg or chest pain, leg edema, sudden change in vision, severe headache, or shortness of breath. • Do not smoke. • Stop taking at least 4 weeks before any surgery that increases the risk of thromboembolic events. • Perform self-breast examination every month. • Obtain a mammogram and breast examination at the recommended intervals. • Report any unusual breakthrough bleeding or spotting or changes in menstrual patterns. • Take oral forms with food. • Take at bedtime. • Report unusual weight gain. Make an apt to come back at the end of the 3 months to have a follow up injection if they wish to follow up with this form of BC, run a risk of becoming pregnant if missing the shot *Contraindications* • Pregnancy (risk category X) • History of or high risk for thromboembolic events • Undiagnosed vaginal bleeding • Liver disease • Cervical, uterine, vaginal, or breast cancer *Precautions* • Asthma • Seizures • Cerebrovascular accident • Migraines • Cardiac or kidney dysfunction *Interactions* • Rifampin (Rifadin), ritonavir (Norvir), phenobarbital (Luminal), carbamazepine (Tegretol), primidone (Mysoline), phenytoin (Dilantin), St. John's wort, and others can reduce the effectiveness of progesterones. • Progesterones may require adjustments in the dosage of hypoglycemic drugs.

Oral contraceptives - ethinyl estradiol and drospirenone (Yasmin)

*Patient Instructions* • Report leg or chest pain, leg edema, sudden change in vision, severe headache, or shortness of breath. • Do not smoke. • Stop taking at least 4 weeks before any surgery that increases the risk of thromboembolic events. • Report palpitations, paresthesias, weakness, or abdominal cramps. • Obtain regular blood pressure checks. • Report any unusual breakthrough bleeding or spotting or changes in menstrual patterns. • Perform self-breast examination every month. • Obtain a mammogram and breast examination at the recommended intervals. *Contraindications* • Pregnancy (risk category X) • History or other risk for thromboembolic events • Suspected or confirmed breast cancer • Altered liver function • Altered renal or adrenal function (estradiol and drospirenone) • Smokers above age 35 *Precautions* • Hypertension • Diabetes mellitus • Heart disease • Migraines *Interactions* • ACE inhibitors and other drugs that can elevate serum potassium can cause hyperkalemia (due to drospirenone). • Rifampin (Rifadin), ritonavir (Norvir), phenobarbital (Luminal), carbamazepine (Tegretol), primidone (Mysoline), phenytoin (Dilantin), and St. John's wort can reduce the effectiveness of oral contraceptives. • Oral contraceptives can reduce the effects of warfarin (Coumadin) and hypoglycemic drugs. • Oral contraceptives can increase levels of theophylline (Theo-Dur), diazepam (Valium), chlordiazepoxide (Librium), and tricyclic antidepressants.

Estrogen HRT - conjugated equine estrogen (Premarin), transdermal estradiol (Estraderm, Climara, FemPatch), intravaginal estradiol (Vagifem)

*Patient Instructions* • Take oral forms with food. • Take, apply, or instill at bedtime. • Report leg or chest pain, leg edema, sudden change in vision, severe headache, or shortness of breath. • Do not smoke. • Stop taking at least 4 weeks before any surgery that increases the risk of thromboembolic events. • Exercise regularly and follow a healthy, low-fat diet. • Obtain regular blood pressure checks. • Report persistent or recurrent vaginal bleeding. *Contraindications* • History of or other risk for thromboembolic events • Suspected or confirmed breast, vaginal, cervical, or endometrial cancer • Liver disease • Undiagnosed vaginal bleeding *Precautions* • Hypertension • Gall bladder disease • Diabetes mellitus • Heart disease • Migraines • Kidney dysfunction *Interactions:* • Rifampin, ritonavir (Norvir), phenobarbital, carbamazepine (Tegretol), primidone (Mysoline), phenytoin (Dilantin), and St. John's wort can reduce the effectiveness of estrogens. • Estrogens can reduce the effects of warfarin (Coumadin) and hypoglycemic drugs. • Estrogens can increase levels of theophylline (Theo-Dur), diazepam (Valium), chlordiazepoxide (Librium), and tricyclic antidepressants.

Pharmacotherapy of Infertility

*Pharmacotherapy* -drugs that Promotes maturation of ovarian follicles -drugs that Triggers ovulation -drugs that Promotes normal ovulation, prevents premature ovulation *Complications* -Ovarian hyperstimulation syndrome (OHS) -Endometriosis

Preterm Labor

*Preterm labor* Initiation of labor prior to 37 weeks' gestation *Most common causes of preterm labor* Premature rupture of membranes Infections of the chorion or uterus *Treatment of preterm labor* -Bed rest -give the mother corticosteroids to help for fetal lung maturity, so that when the baby is born they are not born with as much respiratory distress -Antibiotic (if uterine or chorionic infection) -sometimes the woman may come into the hospital and might not meet the criteria for preterm labor but is having contractions -very easy during pregnancy for a woman to become dehydrated -they will come into the L&D having contractions you look at the cervix and it looks okay but she is having contractions bc she is dehydrated -bc she is dehydrated the body is releasing ADH which is very similar to oxytocin, both are stored in the posterior pituitary sometimes the ADH will attach to the oxytocin receptor sites on the uterus and cause the uterus to contract -*treatment for this* - start an IV, give the pt an IV fluid bolus maybe over 30 min to an hour -sometimes they will give her a beta 2 agonist Terbutaline (given to pts with asthma) off label use will work to relax t he uterine muscle -stimulates the heart to have increase HR, tachycardia, chest pains, if used long term can cause risk for pulmonary edema -can cause tremors, hypokalemia (pt is not truly hypokalemic but when doing a blood sample looks this way bc the K+ moves into the cell, when the drug has worn off the K+ will move back into the bloodstream) -will cause the fetal HR to increase -typically given short term so other than the tremors and tachycardia you dont usually see a long term adverse effect of this drug -*hydrate and give a shot or two of Terbutaline usually you can get the contractions under control and the pt goes home*

Ergot alkaloids - methylergonovine (Methergine)

*Therapeutic Use* • Prevention and treatment of postpartum and post-abortion hemorrhage *Administration* • Check blood pressure prior to administration. Do not give if over 140/90 mm Hg. • Give orally for 2 to 7 days or IM every 2 hr as needed. • Give the drug IV only for emergency control of severe hemorrhage. • Administer IV doses slowly (over 1 min to minimize adverse effects). • Administer after the delivery of the placenta. • Monitor vital signs and uterine response. • Tell patients to expect some cramping. *Side/Adverse Effects* • Hypertension (rare with oral administration) • Nausea, vomiting (rare with oral administration) • Headache (rare with oral administration) • Bradycardia (rare with oral administration) • Seizures (rare with oral administration) *Interventions* • Monitor blood pressure. • Monitor for nausea and vomiting. • Monitor for headache and note any worsening of headache. • Monitor heart rate. • Monitor for signs of seizure activity. *Patient Instructions* • Report any nausea. • Report headache. • Report any weakness or palpitations. • Institute seizure precautions if indicated. *Contraindications* • Induction of labor • Threatened spontaneous abortion • Hypertension • Uterine sepsis • Cardiac disease *Precautions* • Diabetes mellitus • Liver disease • Renal failure *Interactions* • Other ergot alkaloids, parenteral sympathomimetics, and triptans increase the risk of hypertension can cause hypertension. • Protease inhibitors and itraconazole (Sporanox) increase the risk of toxicity.

Prostaglandin E analog - misoprostol (Cytotec)

*Therapeutic Use* • Prevention of gastric ulcers from long-term NSAID use *Administration* • Administer orally four times a day, with meals and again at bedtime. • Confirm nonpregnant state before initiating drug therapy, as this drug can cause spontaneous abortion. • Make sure women of childbearing age use effective contraception during drug therapy. *Side/Adverse Effects* • *Diarrhea, abdominal pain, nausea, dyspepsia, FEVER* (bc it is a prostaglandin) • Dysmenorrhea, uterine cramping, spotting (women) *Interventions* -bleeding can become life threatening if it becomes too heavy • Monitor for severe diarrhea and abdominal pain. • Monitor for excessive menstrual pain or midcycle bleeding. • Administer antidiarrheal agent, antiemetic, and acetaminophen ibuprofen as needed *Patient Instructions* • Report worsening diarrhea or abdominal pain. • Expect diarrhea to resolve after the first week of drug therapy. • Drink plenty of clear fluids. • Take the drug with food to minimize gastrointestinal effects. • Report menstrual changes. • Instruct to take antidiarrheal agent, antiemetic, and acetaminophen as needed *Contraindications* • Pregnancy risk category X • Hypersensitivity to the drug *Precautions* • Inflammatory bowel disease • Renal dysfunction • Children younger than 18 yr *Interactions* • Antacids that contain magnesium worsen diarrhea.

Oral contraceptives - ethinyl estradiol and drospirenone (Yasmin)

*Therapeutic Use* • Prevention of pregnancy • Reduction in fluid retention associated with premenstrual syndrome • Other benefits of oral contraceptives include decreased risk for: ◦◦uterine and ovarian cancers ◦◦pelvic inflammatory disease ◦◦benign breast disease ◦◦ovarian cysts *Administration* • Confirm negative pregnancy status before starting therapy. • Use an additional method of contraception during the first cycle. • Take pills at the same time each day. • Take according to the precise dosing schedule, typically 21 days of a drug-containing pill and 7 days of an inactive pill. • Follow the manufacturer's instructions for missed pills, typically taking one missed pill with the next pill, two pills for 2 consecutive days after 2 missed days, and after 3 missed days starting a new cycle 7 days later with alterative contraception in the interim. *Side/Adverse Effects* • Thromboembolism • Hyperkalemia (due to the drospirenone in this drug) • Hypertension (less likely with ethinyl estradiol and drospirenone than with other combination oral contraceptives) • Uterine bleeding • Increased growth of breast malignancies *Interventions* • Monitor for and report any indications of deep-vein thrombosis, pulmonary embolism, myocardial infarction, and cerebrovascular accident. • Encourage patients who smoke to quit. • Monitor potassium levels and ECG periodically. • Monitor blood pressure. • Monitor the pattern and amount of any reported bleeding. • Recommend mammograms and breast examinations at appropriate intervals. • Discontinue the drug for any indications of breast cancer.

LH and FSH stimulant - clomiphene (Clomid)

*Therapeutic Use* • Promotion of ovulation • Treatment of infertility *Administration* • Take orally, beginning 5 days after menstruation onset and continuing therapy for 5 days. (With amenorrhea, begin any time.) • Repeat the 5-day course at 30-day intervals as prescribed, depending on the occurrence of ovulation and conception. • Take the drug at the same time each day. • For a missed dose, take it as soon as possible. Double the next dose if not remembered until then. For two missed doses, consult the provider. • Stop taking the drug for any suspicion of pregnancy. *Side/Adverse Effects* • Vasomotor instability (hot flashes) • Breast engorgement • Nausea, abdominal discomfort • Blurred vision, flashes of light, dizziness. • *Ovarian hyperstimulation* - happens bc there are more than the normal amount of follicles being matured and as a result the pt may start to have symptoms of lower abdominal pain, pressure in the lower abdominal and retaining fluids and increasing in weight, *this can become life threatening* will need to be hospitalized and treated until resolved, will monitor the ovaries via ultrasound frequently • *Multiple gestation* - bc she is making more follicles, more than one might ovulate -usually as administered PO at the beginning of 5 days after the onset of menses -continues therapy for 5 days and repeat at 30 day intervals -if she thinks she might become pregnant stop taking -take same time every day, missed dose should be taken as soon as possible, doubled at the time of the next dose -if two doses are missed consult the Dr -will increase the estrogen and progesterone in the ovaries *Interventions* • Tell patients that this is a common effect. • Recommend comfort measures such as cold compresses and over-the-counter analgesics. • Monitor for worsening symptoms and vomiting. • Monitor for and report vision alterations. • Recommend an ophthalmology examination if symptoms occur. • Discontinue therapy if symptoms occur/persist. • Monitor for indications of ovarian enlargement. • Make sure patients understand that multiple gestation, usually twins, is not uncommon with clomiphene use. *Patient Instructions* • Expect hot flashes as a side effect of this therapy. • Apply cold compresses as needed and if helpful. • Take over-the-counter anti-inflammatory drugs as needed. • Wear a supportive bra. • Take the drug with food. • Report any visual disturbances., blurred vision • Do not engage in dangerous activities if symptoms occur. • Report pelvic pain. • Be aware of the possibility of twins. *Contraindications* • Pregnancy (risk category X) • Primary ovarian failure • Undiagnosed uterine bleeding • Liver disease • Uncontrolled thyroid disease • Thrombophlebitis *Precautions* • Polycystic ovarian enlargement *Interactions* • Tricyclic antidepressants, phenothiazines, and methyldopa (Aldomet) increase prolactin concentrations, thus interfering with fertility. • Black cohosh decreases effectiveness.

Estrogen/Progesterone HRT - conjugated estrogen and medroxyprogesterone acetate (Prempro), transdermal (CombiPatch)

*Therapeutic Use* • Relief of postmenopausal symptoms (vasomotor), and vulvar and vaginal atrophy • Prevention of postmenopausal osteoporosis *Administration* *Oral:* • Take according to the precise dosing schedule, typically continuously to avoid monthly bleeding. • Take pills at the same time each day. *Transdermal:* • Apply patches at the recommended interval, typically every 3 to 4 days. • Apply to clean, dry, intact skin on the abdomen or trunk (not breasts or waistline) and press firmly for 10 seconds. • Do not use the same site more than once per week. *Side/Adverse Effects* • Thromboembolism — Even greater risk with addition of progesterone than with estrogen alone • Nausea • Hypertension • Breast cancer • Breakthrough bleeding and other menstrual irregularities • Edema *Interventions* • Monitor for and report any indications of deep-vein thrombosis, pulmonary embolism, myocardial infarction, and cerebrovascular accident. • Encourage patients who smoke to quit smoking. • Plan for temporary use of HRT (3 to 4 years) for vasomotor symptoms. • Inform patients that this effect diminishes with time. • Monitor blood pressure. • Recommend mammograms and breast examinations at appropriate intervals. • Discontinue the drug for any indications of breast cancer. • Monitor the pattern and amount of any reported bleeding. • Monitor for edema and weight gain

Estrogen HRT - conjugated equine estrogen (Premarin), transdermal estradiol (Estraderm, Climara, FemPatch), intravaginal estradiol (Vagifem)

*Therapeutic Use* • Relief of severe menopausal symptoms (vasomotor) and vulvar and vaginal atrophy • Prevention of postmenopausal osteoporosis *Administration* *Oral:* • Take according to the precise dosing schedule, typically continuously to avoid monthly bleeding. • Take pills at the same time each day. *Transdermal estradiol patches:* • Apply patches at the recommended interval, typically once or twice per week. • Apply to clean, dry, intact skin on the abdomen or trunk (not breasts or waistline) and press firmly for 10 seconds. • Do not use the same site more than once per week. Intravaginal estradiol hemihydrates tablets (Vagifem) or vaginal cream (Estrace vaginal cream): • Use according to the precise dosing schedule, typically tablets are inserted once daily for 2 weeks, then twice per week • Insert tablet using provided applicator at bedtime. • Vaginal cream is applied using a reusable applicator to measure the precise dose; insert into vagina at bedtime. *Side/Adverse Effects* • Nausea • Thromboembolism — thrombophlebitis, pulmonary embolism, stroke, myocardial infarction • Hypertension • Endometrial hyperplasia, endometrial and ovarian cancer *Interventions* • Inform patients that this effect diminishes with time. • Monitor for and report any indications of deep-vein thrombosis, pulmonary embolism, myocardial infarction, and cerebrovascular accident. • Encourage patients who smoke to quit smoking. • Use HRT for no more than 3 to 4 years to treat vasomotor or genital symptoms of menopause. • Monitor blood pressure. • Monitor for vaginal bleeding. • Advise a yearly pelvic examination. • Check that patients who have an intact uterus are prescribed progesterone with their estrogen.

Progesterone - medroxyprogesterone acetate (Provera)

*Therapeutic Use* • Treatment of endometriosis • Treatment of dysfunctional uterine bleeding • Treatment of endometrial carcinoma *Administration* • Give orally daily or cyclically or via IM injection. • Expect amenorrhea and other menstrual irregularities. *Side/Adverse Effects* • Thromboembolism • Breast cancer • Breakthrough bleeding and other menstrual irregularities • Nausea • Edema *Interventions* • Monitor for and report any indications of deep-vein thrombosis, pulmonary embolism, myocardial infarction, and cerebrovascular accident. • Encourage patients who smoke to quit. • Recommend mammograms and breast examinations at appropriate intervals. • Discontinue the drug for any indications of breast cancer. • Monitor the pattern and amount of any reported bleeding. • Inform patients that this effect diminishes with time. • Monitor weight.

GnRH Agonist - leuprolide (Lupron)

*Therapeutic Use* • Treatment of endometriosis • Treatment of uterine fibroids • Treatment of advanced prostate cancer in males *MOA* - initially they work to cause the release of LH and FSH like it happens normally in the body, but over time these hormones levels will increase to the effect and this can cause suppression in the negative feedback and eventually suppresses the release of LH and FSH and in doing so you suppress the maturation of follicles and suppress ovulation -estrogen and progesterone is made during the menstrual cycle so you then effect the amount of these hormones which then causes the endometrial tissue to not develop like it normally does, so you have a very little amount of endometrial lining in the uterus and wherever it may be found in other parts of the body -then results in relief in about 3 to 6 months after starting the treatment and extend beyond the treatment period and if you can help the woman to achieve pregnancy then a lot of times it will reverse her problems *Administration* • Give via IM injection monthly or give depot form IM every 4 months. depot is more of a time released form • Rotate injection sites. • Refrigerate unopened vials. • Expect amenorrhea and other menstrual irregularities. *Side/Adverse Effects* bc you are suppressing estrogen the pt is at risk for: • Bone loss • Vasomotor instability (hot flashes) • Vaginal dryness • Headache she needs to be educated on these and recommend interventions that might offset these effects *pregnancy X* *Interventions* • Limit drug therapy to 6 months. • For longer-term therapy, monitor for bone loss via bone density scanning at recommended intervals. • Discuss complementary/alternative therapies. • Suggest vitamin B6 and vitamin E supplements. • Recommend water-soluble vaginal lubricants as appropriate. • Monitor for headache and other CNS effects. *Patient Instructions* • Perform weight-bearing exercise daily. • Consume adequate calcium and vitamin D. • Identify and avoid conditions that trigger hot flashes, such as fluctuations in glucose levels. • Consider alternative therapies with the provider's prescription. • Use vaginal lubricants if indicated. • Report headache, dizziness, or paresthesia. • Take over-the-counter analgesics to relieve headache. *Contraindications* • Pregnancy (risk category X) • Allergy to benzyl alcohol • Abnormal vaginal bleeding • Metastatic cerebral lesions *Precautions* • Osteoporosis • Advanced age *Interactions* • Estrogens reduce therapeutic effects. • Androgens reduce therapeutic effects.

Oxytocin - oxytocin (Pitocin)

*Therapeutic Use* • Uterine stimulation • Induction or enhancement of labor near or post term • Treatment of postpartum hemorrhage *Administration* • Administer IV via infusion pump. • Gradually increase the flow rate by 1 to 2 milliunits/min every 30 to 60 min until contractions last 1 min or less every 2 to 3 min. • Monitor blood pressure and pulse rate. • Monitor for uterine hyperstimulation (contractions lasting longer than 60 seconds, occurring more frequently than every 2 to 3 min, resting uterine pressure greater than 15 to 20 mm Hg). Stop the infusion and report hyperstimulation immediately. • Monitor fetal heart rate and rhythm, and report signs of fetal distress. • Stop the infusion for serious alterations in fetal heart rate or rhythm. *Side/Adverse Effects* • Uterine hyperstimulation • Hypertensive crisis • Water intoxication (rare at therapeutic doses) *Interventions* • Monitor risk factors such as multiple deliveries. • Monitor length, strength, and duration of contractions. • For indications of hyperstimulation, turn patients on their side, stop the infusion, and administer oxygen. • Be prepared to administer a uterine relaxant. • Monitor for headache, nausea, vomiting, and increasing blood pressure. • Monitor intake and output and level of consciousness. *Patient Instructions* • Report increasing duration or strength of contractions. • Report headache, palpitations, nausea, or chest pain. • Report drowsiness or headache. *Contraindications* • Unripe cervix • Placental abnormalities • Active genital herpes • Uterine surgery • Fetal distress • Lung immaturity • Cephalopelvic disproportion • Malpresentation • Prolapsed umbilical cord *Precautions* • Pre-eclampsia/hypertension • Multiparity (multiple fetuses) • Seizures • Polyhydramnios • Cardiac disease *Interactions* • Vasopressors, ephedra, and ma huang can cause hypertension. • Cyclopropane anesthesia causes hypotension, bradycardia, and dysrhythmias.

Prototype Drug: Mifepristone (Mifeprex)

*Therapeutic classification* Drug for abortion, synthetic steroid *Pharmacologic classification* Abortifacient, progesterone antagonist *Pregnancy category X* *Mechanism of action* -promotes abortion through the blockade of progesterone receptors (progesterone is the hormone that maintains pregnancy early on, keeps the uterus from contracting during the initial parts of pregnancy) -Progesterone and corticosteroid antagonist -*Blocks supportive effects of progesterone on uterine lining, causing the uterus to contract, preventing fertilized ovum from implanting in uterus* -can also promote cervical softening and dilation, setting up preterm labor so that the concepsus is delivered before it is viable -the pt is given the misoprostol in 36 to 48 hours after the Mifepristone -misoprostol is a prostaglandin to help further soften the cervix and cause it to dilate and help to evacuate the products of conception to complete the abortion -pretty effective and a lot safer than surgical abortion

Prototype Drug: Oxytocin (Pitocin)

*Therapeutic classification* Drug used to induce labor; uterine stimulant *Pharmacologic classification* Hormone, oxytocic *Pregnancy category X* *Mechanism of action* -binds to the receptor sites on the uterus and causes uterine contractions -Increases intensity and frequency of uterine smooth muscle contractions -binds with the receptor sites in the smooth muscle of the breast to cause contractions in breast tissue to contract, thus expelling breast milk -also used after the baby is delivered to prevent postpartum hemorrhage bc just like the prostaglandins is will cause the uterus to clamp down and decrease bleeding -if this bleeding becomes an issue after using Oxytocin (Pitocin) then you might move onto one of the prostaglandins (Carboprost (Hemabate) would probably be the best one) -could also use Methylergonovine (Methergine) -the only reason why you would choose Carboprost over Methylergonovine is bc Methylergonovine does cause a nincrease in BP -otherwise all are effective drugs for postpartum hemorrhage -when using oxytocin for induction of labor (meaning there is a fetus in the uterus) then you have to be very careful about the dosing, given is very tiny doses -administered on an IV pump diluted through a controlled pump at very small dosages and very carefully titrated to get the contraction pattern that you are looking for -*contraction patterns should be about 1 contraction every 3 to 4 min and anywhere from 30 to 60 seconds in length from the beginning to the end of each contraction* may be faster than this -while the pt is on oxytocin (Pitocin) we need to carefully monitor the pt and make sure that you monitor the fetus HR to ensure that the fetus is oxygenating well enough and prevent the uterus from contracting too much (hyperstimualtion) also monitor the mother for water retention usually not an issue unless the mother has been on this drug for a long time and a long induced labor then you worry about her retaining too much water to the point where she suffers from water intoxication and at this point her LOC would be altered her intake would be much more than her output and the would then start to suffer from the effects of water intoxication *life threatening* -*monitor intake and output and the LOC of the pt, another good assessment is to monitor lung sounds to make sure they are not filling up with water Q2H or Q4H for crackles -this is a drug that you have to really be careful about how much the pt gets when she still has a fetus in the uterus -but once the baby is born then you can open the IV fluid to a very fast bolus rate so that enough of the drug gets to the uterus to help clamp it down and prevent any postpartum bleeding *Indications* Inducing labor Reducing postpartum hemorrhage At higher doses, inducing abortion

Prototype Drug: Clomiphene (Clomid)

*Therapeutic classification* Infertility agent helps promote maturation of the follicles *Pharmacologic classification* Ovarian stimulant *Pregnancy category X* *Mechanism of action* -works by competing and blocking estrogen receptors in hypothalamus and pituitary, causing an increasing in LH (causes ovulation to occur) and FSH (promotes follicular maturation) sending message that estrogen levels are low -As a result, LH (luteinizing hormone) is secreted and ovaries are stimulated -FSH (follicle stimulating hormone) levels are also increased -this drug helps the ovaries -only works if the ovaries are able to respond to the hormones -in women who are good candidates will induce ovulation about 80% -with ppl with a condition in the pituitary ( not able to release the LH or FSH) they may need gonadotropin releasing hormones to help stimulate the release of FSH and LH *Indications* Female infertility Off-label: low sperm count

Prototype Drug: Nonoxynol-9

*Therapeutic classification* Intravaginal contraceptive *Pharmacologic classification* Spermicide *Pregnancy category C* *Mechanism of action* Inhibits ability of sperm to reach ovum *Indications* Preventing pregnancy -acts locally by inhibiting the ability of sperm to reach the ovum by disrupting the sperm's cell membrane, causing it to loose mobility and function. -The onset of action is immediate, and the furcation of action is 60 minutes, though when used in the contraceptive sponge its duration of action reaches 24 hours. -Spermicides rarely cause adverse effects, as there is minimal absorption and no metabolism. -Occasionally, vaginal irritation will result. -Spermicides should not be used by patients with uterine prolapse, cystocele, an allergy to nonoxynol-9, vaginitis, toxic shock syndrome, as well as those who are pregnant, post- abortion, or postpregnancy. -The patient should be taught to reapply spermicide prior to any act of sexual intercourse. -The patient should also be instructed to remove the contraceptive sponge 6 hours after sexual intercourse. -The patient should call the health care provider if she develops burning, inflammation, vaginal and vulvar itching, or vaginal discharge.

HRT

- Two types: 1) estrogen used alone 2) estrogen + progestin menopause usually begins around 50 for women, as early as 48 or late as 55 or later -Initial phases of premenopause: may have irregular cycles, or no periods (amenhorrhea) -Eventually the ovaries stop the production of estrogen woman has then been through her menopause and is not post menopause -Loss of estrogen has many effects on a woman, predominantly there are vasomotor symptoms: hot flashes, night sweets, urogenitial atrophy, vaginal dryness, itching and burning, bone loss, puts the woman at increases risks for fractures, alterations in lipid metabolism as a result will have increases levels of LDL and lowered levels of HDL which puts her in the same playing field as a male and puts at risk for CAD and MI -Sometimes in order to combat some of the vasomotor symptoms we may give a woman hormone replacement In the past HRT was used to prevent bone loss but not as much anymore -Used to help hot flashes, vaginal dryness, and sleep disturbances that go along with post menopause -One of the things to think about when choosing HRT is does she still have a uterus intact or has she had a hysterectomy, given an estrogen alone might be appropriate for women who have had a hysterectomy -You need to protect the uterus if they do still have one, if so you want to give HRT with estrogen and progesterone progesterone in the natural order in the menstrual cycle will stop the proliferation of the uterine lining and get it ready for pregnancy -So just like it stops the proliferation in the menstrual cycle it also stops the proliferation of the endrometrium for the woman given HRT and in doing so we help protect the uterine lining If you let it go and proliferate unchecked then there is a higher chance of endometrial cancer, this helps protect the woman -Progesterone's also increase the risk of estrogen induced cancers of the breast -Be careful when taking a Hx and family relatives of cancer of breast cancer -In this case the woman would not be a good candidate for HRT -HRT does have benefits in short term but in long term can put the women at risk for CV issues, not recommended for long term -Very important to screen candidates for HRT before they are started

Prototype Drug: Medroxyprogesterone (Provera)

-Available as Depo-Provera, depo-subQ-Provera, Provera, lasts for 3 months -Pt teaching come back in 3 months to continue treatment -*Therapeutic classification:* Hormone; drug for dysfunctional uterine bleeding -*Pharmacologic classification:* Progestin -*Pregnancy category X* -*Mechanism of action:* Inhibits GnRH, thus preventing LH surge and ovulation -*Indications:* Dysfunctional uterine bleeding, Secondary amenorrhea, Contraception

Prostaglandin Drugs for Pharmacologic Abortion

-Natural hormones that induce uterine contractions; used to expel implanted embryo -Three approved prostaglandins 1) Carboprost (Hemabate) 2) Dinoprostone (Cervidil, Prepidil, Prostin E2) 3) Misoprostol (Cytotec)

Drugs for Pharmacologic Abortion

-Pharmacologic (medical) abortion is removal of embryo by use of drugs after implantation occurs -Drugs used to induce abortion are called abortifacients -Several pharmacologic choices available -the termination of the pregnancy as well as the removal of the consepsis (all the products of the pregnancy) -to terminate pregnancy we use drugs known as abortifacients, differ from emergency contraceptive drugs as that these drugs terminate the pregnancy after it has been established -medical abortion drugs are a lot safer than the surgical method of abortions -the bleeding and infections are a lot lowered but can still happen when given the medications

ulipristal (Ella) - emergency contraception

-approved as a single dose product -mixture of progestrone antagonist and agonist -works by preventing ovulation -not OTC, prescription needed -advantages that this med does retain its effectiveness for up to 5 days after unprotected sex -after using use an alternative BC for up to 14 days -less effective for women with a BMI greater than 35 -okay for all women unless breast feeding

Spermicides

-chemical surfactants that destroy the cell membrane of the sperm -Available OTC -Creams, foams, jellies, suppositories -Nonoxynol-9 (prototype) and octoxynol-9 -Contraceptive sponge (Today Sponge) -Frequent use may increase risk of HIV transmission due to disruption of vaginal epithelium and anal mucosa -usually not a lot of serious side effects, no studies that show relation to birth defects -when used alone not very effective, commonly used with condoms or diaphragm can increase the efficacy -*Nonoxynol-9 (prototype)* can increase the risk of HIV transmission -*patient education* apply prior to sex but no more than one hour esp when used alone -if the container is a foam prep must be shaken -supp should be inserted at least 5 to 10 min before sex -should be reapplied each time sex is anticipated -douching should be postponed for at least 6 hours following sex to make sure the spermicide is not washed out -the contraceptive sponge that is on the market today appears like a sponge and impregnated with 1000mg of Nonoxynol-9 and inserted to cover the cervix and works by releasing the spermicide and absorb the seminal fluid and block the penetration of the sperm, may be more effective than just using the other formulations of the drug -unlike the spermicide the sponge can be left in place for 24 hours and does not need to be replaced no matter how many time sex happens -after 24 hour the sponge should be removed - the rate of unintended pregnancy is about 16% among women who have never have a baby before and about 32% with women who have have a baby -not the most effective but bc of low side effects can be used frequently

Copper T - Intrauterine devices

-does not contain any hormone, made with copper -inserted into the uterus -effective for up to 10 years -very good for a pt who knows for at least the next 10 years does not want to conceive -copper creates an inhospitable environment in the uterus so it prevents implantation should conception occur, also inhospitable to sperm as well so the chances of this happening are rare

Implanon - Subdermal implant

-inner aspect of the upper arm, single rod injected under the skin -Injected and releases under the skin lasts about 3 years of protection -Surgical procedure -Pts needs to come back after 3 years and have old one removed and a new one inserted -specially trained provider admins this

ParaGard, Progestasert, Mirena - Intrauterine devices

-inserted into the uterus -contains hormones, acts locally in the uterus to provide contraception Effective for about 5 years

Plan B One Step - Emergency contraceptive

-not intended to be used instead of another type of contraceptive -used for emergent cases only -can prevent pregnancy after unprotected sex -effective the sooner the pt takes it -current dosage is one dose -depends on where in the cycle the women is when they take it; may prevent or delay ovulation, may interfere with the fertilization of the egg, may prevent implantation of an egg in the uterus by altering its lining -not the same as the RU-486 pill (abortion pill) -plan B does not cause miscarriage or abortion, will not work if the pt is already pregnant when they take it -the pt typically takes within 72 hrs of unprotected sex can reduce the chance of pregnancy 89% if taken within the first 24 hrs can be up to 95% effective, after 72 hrs no guarantee it can be effective -not to be used as a regular contraceptive -has a very high concentration of hormone in it -not safe to be taken frequently -does not protect against STDs -can be purchased OTC without proof of age -stress to pts that bc of the dosage of this pill it if not to be taken frequently and not used as a regular BC method -provide this time to counsel the pt on types of BC methods if they do not currently use one -if the pt is already pregnant this will not cause an abortion -less effective for women who have a BMI above 25, may not work for women with a BMI greater than 30 -do not use if you have already used ella since your last menses

Endometriosis

-the occurrence of Endometrial tissue outside the uterus, can be attached anywhere, most of the time you find it outside the organs in the peritoneum, occasionally it can get into the bloodstream and migrate to other parts of the body RARE -no matter where the tissue is in the body it will react with the normal hormone fluctuation throughout the menstrual cycle bc it is reacting to the hormones it will proliferate become secretory and break down, when it does this outside uterus it can cause pain and infertility to the pt -about 25%-50% of the women are infertile bc of this -if they can get pregnant a lot of times it does correct the issue -for women who deiced to have treatment can be treated with GnRH agonists Common cause of infertility About 25-50% of infertile women have endometrosis *Drugs used to treat: GnRH (gonadotropin releasing hormone) agonists Leuprolide (Lupron) Nafarelin* May experience relief within 3-6 months of leuprolide therapy and relief may extend beyond the treatment period

Copper T (paraguard IUD)

-up to 5 days after unprotected sex -available for all women -inserted by a Dr. or nurse at a health center -provides very effective BC for up to 12 years

NuvaRing - vaginal route

2 inch diameter ring Contains estrogen and progesterone Provides 3 weeks of protection At the end of 3 weeks the ring is removed and at week 4 the pts has a breakthrough bleed and a new week is insereted during the 1st week of the next menses

Adverse Effects of Combined Oral Contraceptives

5% of women will develop HTN Breast tenderness Nausea Bloating Chloasma (darkened pigmentation on forehead, temples, cheeks, upper lip) Abnormal uterine bleeding Benign hepatic adenoma Multiple births Retinal disorders Melanoderma May pose slightly higher risk for breast cancer Slightly higher risk of cervical cancer

Prototype Drug: Conjugated Estrogens

Available as Cenestin, Enjuvia, and Premarin Therapeutic classification: Hormone Pharmacologic classification: Estrogen Pregnancy category X Mechanism of action: Bind to intracellular estrogen receptors that stimulate DNA and RNA to synthesize protein responsible for the biologic effects of estrogens Indications: Moderate to severe symptoms of menopause, Palliative treatment of inoperable prostate cancer

Ortho-Evra - transdermal patch

Contains estrogen and progesterone Applied and worn for 7 days and removed once a week and wear for 3 weeks A patch free week is the 4th week Not appropriate for all pts Women who are obese, the amount of drug in the alternative methods may not be enough Women that weigh more than 198lbs a transdermal patch may be ineffective

Estrogens

Estrogen is a general term for three steroid hormones: estradiol, estrone, and estriol Largest amount of estrogen present as estradiol Estrogen's effects on body Maturation of reproductive organs and secondary sex characteristics of females Decreases LDL, increases HDL in blood (good) bc of this estrogen is considered cardioprotective, women do not need to worry about this till after menopause Cardioprotective Strengthens bones - women who have gone through menopause have an increased risk for osteoporosis

Combination Oral Contraceptives

Extended-regimen OCs Seasonale (approved in 2003) Levonorgestrel and ethinyl estradiol Taken for 84 consecutive days followed by seven placebo tablets Allows a woman to go 3 months without a period Continuous contraceptive protection Four menstrual periods per year Extended regimen OCs Seasonique (approved in 2006) Instead of placebo: low dose estrogen Less bloating Less breakthrough bleeding --When a woman is taking hormones to prevent conception their not having the typical menses that would normally occur bc the hormones are being inhibited at the hypothalamus and pituitary level -What the woman is experiencing is a withdrawal of progesterone -once the body has been on birth control pills for a month or so the body begins to think that it is pregnant so you don't have a build up of the intrauterine lining like occurs in the natural cycles -so the women who are on esp the combo OCs their bleeding is very light -OC can be used for women who have very heavy menses to help control the amount of bleeding

Options and Choices for Birth Control

Factors that influence decisions: -Effectiveness -Adverse effects and safety -Age -Frequency of intercourse -Ease of use -Ability to adhere to regimen -Preexisting medical conditions -Cultural beliefs and practices -Determined by which drug might give the best protection with the least amount of side effects - Typically pill is admin on day 5 of menses, sometimes on the Sunday of the menses, take the pills for a 21 day pack, the remaining 7 days have placebo or no pill at all, resume taking the pills after the 7 days * If one dose is missed then take 2 doses at the next scheduled time.* And use adequate contraceptives for the next few days, if two doses in a row are missed in a row then take two tablets for the next two dosing times, use another contraceptive for at least 7 days after restarting the pills, if 3 or more pills are missed then stop taking the pills and resume with the next menses

Administration of Combination Oral Contraceptives

Initiated at lowest effective dose Starts on day 5 Continues for 21 days Placebo on other 7 days Common reason for treatment failure: forgetting to take daily dose - results in pregnancy -An oral contraceptive showing the daily doses and the different formulation taken in the last 7 days of the 28-day cycle.

Secondary Benefits of Combination Oral Contraceptives

Less painful menstruation Better-regulated menstrual flow Fewer outbreaks of acne Reduced incidence of: Ectopic pregnancy Pelvic inflammatory disease (PID) Ovarian and endometrial cancer Colorectal cancer Iron-deficiency anemia Benign breast diseases

Estrogen used to treat

Menopausal symptoms Female hypogonadism - females who do not have enough estrogen to develop the secondary sex characteristics Primary ovarian failure Prostate and breast cancers In replacement therapy, usually combined with progestin

Combination Oral Contraceptives

Most frequently used classes of drugs for contraception *Synthetic estrogens* Ethinyl estradiol Mestranol *Synthetic progestins* - once-daily dosing Norethindrone, norgestrel, desogestrel, levonorgestrel

Advantages of Combination Oral Contraceptives

Nearly 100% effective when taken daily Readily available and inexpensive Excellent method for healthy women with no contraindications Can be discontinued at any point without long-lasting adverse effects

Progestin-Only OC Products

Norethindrone-only products Aygestin Camila Errin Jolivette Nora-BE Ortho Micronor All above products are pregnancy category X Also approved, in higher doses, for amenorrhea, dysfunctional uterine bleeding, endometriosis

Newer Long-Term Contraceptive Delivery Methods

Not more effective than daily OCs Same types of contraindications Main benefit is ease of use and improved adherence Delivery methods Patches Vaginal inserts Injections Subdermal implants Intrauterine devices -Transdermal delivery Ortho-Evra Increased risk of thromboembolism -Vaginal delivery NuvaRing 3 weeks of protection -Depot injection Intramuscular medroxyprogesterone acetate (Depo-Provera) One dose; 3 months' protection - need to come back after 3 months and replace the injection to prevent the risk of pregnancy -Subdermal implant Implanon -Intrauterine devices ParaGard, Progestasert, Mirena Safe, reliable, effective

Benefits of Progestin-Only Oral Contraceptives

OC option for patients at high risk for estrogen-related adverse effects Unlike estrogens, progestins not associated with increased risk of Thromboembolic events Breast cancer *Have to stress to the pt to take it at a very regular time every day, sometimes forgetting to take it as much as an hour can effect the effectiveness of it, very important to take it the same time every day No make up to take this like there is with the combinations pills If they miss a pill then they need to do alternative contraceptives until they can start a new pack

Progestin-Only Oral Contraceptives

Often called "minipills" Less effective at preventing ovulation Prevent pregnancy by causing thick cervical mucous at entrance to uterus Discourage sperm penetration Inhibit implantation of fertilized egg Taken daily, no placebo Failure rate of 1% to 4% -Combination drugs will also do this but the primary MOA for combination drugs is that they prevent ovulation -progestin only or minipills may or may not prevent ovulation - the main MOA for them is the thickening of the cervical mucous

Action of Estrogen-Progestin Combination Oral Contraceptives

Prevent ovulation by Giving negative feedback to pituitary Suppressing secretion of luteinizing hormone (LH) Suppressing secretion of follicle-stimulating hormone (FSH) Without secretion of LH and FSH, follicle cannot mature; ovulation prevented -Also make the uterine endometrium less favorable to receive an embryo and reduces the likelihood of implantation - Can also be prescribed to promote regular timely menses and reduce the incidence of dysmenorria

Disadvantages of Progestin-Only Oral Contraceptives

Result in a higher incidence (than combo OCs) of irregular menstrual cycles, including Amenorrhea Prolonged bleeding Breakthrough spotting Higher risk (than with combo OCs) of ectopic pregnancy --minipills are less effective than combination pills

Progestins

Term refers to synthetic hormones with actions identical to natural endogenous progesterone -Drugs of choice for treating uterine abnormalities -Dysfunctional uterine bleeding; Often due to hormonal imbalance between estrogen and progesterone -Types of dysfunctional uterine bleeding Amenorrhea Endometriosis Oligomenorrhea Menorrhagia Breakthrough bleeding Premenstrual syndrome (PMS) Postmenopausal bleeding Endometrial carcinoma

Prototype Drug: Estradiol and Norethindrone (Ortho-Novum)

Therapeutic classification Combination oral contraceptive Pharmacologic classification Estrogen-progestin Pregnancy category X Mechanism of action Inhibits ovulation Indications Preventing pregnancy Off-label uses: Acne vulgaris Endometriosis Hypermenorrhea Dysfunctional uterine bleeding

Drugs Similar to Estradiol and Norethindrone

There are dozens of estrogen-progestin combinations All have same adverse effects, but those with higher doses may produce more adverse effects

Magnesium sulfate (relax skeletal muscle)

Tocolytics to Suppress Preterm Labor -used a lot as an immediate action - given IV on a pump, give a loading dose to get the blood levels up so that it starts working faster then switch to a maintenance dose at a constant IV drip -*MOA:* works bc it inhibits the release of Ach at the neuromuscular junction, where the nerve comes into the muscle to tell the muscle what to do -stops the muscle from contracting and relaxes all the muscles in the body, think about with respiratory muscles -monitor the breathing and count BPM, and note if they are having a decrease in the breathing, also assess DTR (deep tendon reflexes) at the patella, assess to make sure that the muscles at the level of the knee are still getting impulses from the brain to have a reflex, once they lose this reflex then you worry that they will lose the ability to breath monitor this Q2H and RR Q1H -along with this other adverse effects are hot flushes, and may be extremely hot, make the pt as comfortable as possible -may have water retention -assess I and O and kidney function, this drug is eliminated through the kidneys if the kidneys are working well then they are sometimes eliminating the drug as fast as it is going in, when they are retaining water they are retaining the drug as well -if the renal function is slowing down then they could overdose very quickly -assess I&O and lung sounds for fluid retention -*contraindications* pts with myasthenia gravis may further slow respiratory rate

Emergency Contraception

Treatment goal: immediate and effective contraception Drugs less effective when taken more than 72 hours after coitus Mechanism of action: prevents ovulation (does not cause abortion) Only two FDA-approved regimens in U.S. Plan B and ulipristal (Ella) Plan B available OTC for women 18+; by prescription for younger females Ulipristal by prescription only Not 100% effective Serious adverse effects uncommon

Hormonal Regulation of Female Reproductive Function

Two primary hormones of female reproductive system Estrogen Progesterone During childbearing years, most of these hormones are secreted by ovaries, with small amounts by other (nonreproductive) organs ex: adrenal glands In postmenopausal females, all estrogen and progesterone is secreted by the nonreproductive organs

Hormone Replacement Therapy (HRT)

Used to relieve symptoms of menopause -Two large studies: Women's Health Initiative (WHI) and Heart and Estrogen/Progestin Replacement Study (HERS) -Both studies disproved benefits of HRT -Effects of HRT (estrogen-progestin combination): Increased risk of MI, stroke, breast cancer, dementia, and venous thromboembolism, Decreased risk of hip fractures and colorectal cancer

Abortifacients

drugs that are used to terminate pregnancy. *Mifepristone (RU-486) and misoprostol (Cytotec)* are given together to terminate a pregnancy under 49 days (7 weeks). -This medical treatment requires three office visits to the healthcare provider. -*A single dose of mifepristone followed 36 to 48 hours later by a single dose of misoprostol is a frequently used regimen. *the mifepristone serves to disrupt the pregnancy and the misoprostol serves to evacuate the uterus -Mifepristone is a synthetic steroid that blocks progesterone receptors in the uterus. -Given within 3 days of intercourse, it is almost 100% effective at preventing pregnancy. (not used as often but can be used as an emergency contraceptive) -Given up to 9 weeks after conception, mifepristone aborts the implanted embryo. -*Misoprostol is a prostaglandin* that causes uterine contractions, increasing effectiveness of pharmacological abortion. -Pharmacologic abortion must be conducted under the close supervision of a health care provider. -*Methotrexate* (can also be used instead of Mifepristone) may be used in the ER for the removal for an ectopic pregnancy - an antineoplastic agent, is sometimes combined with intravaginal misoprostol. Treatment is 96% effective at causing abortion. -Prostaglandins may also be used to induce abortion. Three approved prostaglandins are dinoprostone, carboprost, and misoprostol. -Side effects are common with these medications. Vaginal bleeding may continue for several weeks. Most experience minor side effects. -Prostaglandins are used for pregnancy termination for second-trimester pregnancies. It causes nausea, vomiting, cramping, and fever. -Medications should not be used as a substitute for contraception.


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