NR 566 Final Exam Study Guide Complete Solution

Menopause 1. is the associated loss of estrogen which typically begins 2. During the initial phase, the menstrual cycle becomes 3. Eventually, ovulation and menstruation 1. at approximately age 51 to 52 years, with 95% of women entering menopause between the ages of 45 and 55 years. 2. irregular, anovulatory cycles may occur, and periods of amenorrhea may alternate with menses 3. cease entirely Physiologic Alterations Accompanying Menopause 1. Vasomotor Symptoms; hot flashes and night sweats) develop in approximately 2. Genitourinary Syndrome of Menopause; the urethra and vagina have the highest 3. Mental Changes; Many women report 4. Bone Loss; In the absence of estrogen, bone resorption accelerates, leading 5. Altered Lipid Metabolism; studies have shown increases in 6. Female Sexual Interest-Arousal Disorder 1. 70% of postmenopausal women. Episodes are characterized by sudden skin flushing, sweating, and a sensation of uncomfortable warmth. These episodes can occur at night, resulting in drenching sweats 2. concentrations of ERs; when estrogen levels decline during menopause, these structures begin to atrophy resulting in urge incontinence and urinary frequency; Urethritis and UTIs can also occur 3. cognitive changes such as difficulty in problem solving and short-term memory loss. Others experience depression or an increase in anxiety 4. to a 12% loss of bone density leading to Osteoporosis which can cause compression fractures of the vertebrae causing a decrease in height and produce a hump. In osteoporotic women, fractures of the hip and wrist can result from minimal trauma 5. LDL cholesterol & decreases in HDL cholesterol. which play a role in the increase in CV disease after menopause. 6. more common during this stage of life Estrogen Therapeutic Uses: 1. Menopausal hormone therapy- When estrogen is used for this purpose, 2. Female hypogonadism-In the absence of ovarian estrogens, 3. Acne-Estrogens, in the form of 4. Cancer palliation-sometimes used for palliative therapy 5. Gender-affirmation therapy-for 1. it is usually accompanied by the use of progestins 2. pubertal transformation will not take place. (variety of causes see pg 428) This treatment promotes breast development, maturation of the reproductive organs, and pubic and axillary hair. This tx regimen consists of continuous low-dose therapy (for approx a year) followed by cyclic administration of estrogen in higher doses 3. oral contraceptives, can help control acne. Tx is limited to patients at least 14-15 years old who want contraception 4. in management of advanced prostate CA in men and in a select type of metastatic breast CA in men& women 5. transgender women; not approved by the FDA) but prescribed off-label Forms of Estrogen 1. Estrogen is available in conjugated and esterified forms. Esterified estrogens 2. Until mid-2016, synthetic conjugated estrogens A (Cenestin) and B (Enjuvia) were available; however, 3. Phytoestrogens (plant-based compounds)-commonly used by women as a 4. Phytoestrogens are not as potent as estradiol, but they carry some of the same risks. 5. Selective estrogen receptor modulators (SERMs) are drugs that activate ERs in some tissues and block them in others. These drugs were developed in an effort 1. are plant based; conjugated estrogens are natural preparations derived from the urine of pregnant horses. 2. the manufacturer has withdrawn them from the market 3. "natural" way to manage symptoms associated with menopause 4. Women should not use phytoestrogens if they have a history of thromboembolic events or a personal or family history of breast, uterine, or ovarian cancer. 5. to provide the benefits of estrogen (e.g., protection against osteoporosis, maintenance of the urogenital tract, reduction of LDL cholesterol) while avoiding its drawbacks (e.g., promotion of breast cancer, uterine cancer, and thromboembolism) Estrogen-Adverse Effects 1. principal concerns with estrogen therapy are the potential for 2. endometrial hyperplasia and endometrial cancer can be resolved 3. Estrogens have been associated with what common SE 4. menopause may produce or uncover 5. Nausea is the most 6. (blank) a patchy brown facial discoloration, though not dangerous, may cause significant distress 1. endometrial hyperplasia, endometrial cancer, breast cancer, and cardiovascular thromboembolic events 2. by prescribing a progestin 3. Fluid retention with edema, gallbladder disease, jaundice, and headache; especially migraine headache 4. gallbladder disease. Jaundice may develop in women with preexisting liver dysfunction, especially those who experienced cholestatic jaundice of pregnancy 5. frequent undesired response to the estrogens 6. Chloasma, Contraindications of Estrogen 1. Estrogens should not be taken by patients with a history of 2. They should not be prescribed to women who 3. Patients with a hx of 1. DVT, pulmonary embolus, or conditions such as stroke or MI that occurred secondary to a thromboembolic event. 2. are pregnant or who have vaginal bleeding without a known cause. 3. liver disease, estrogen-dependent tumors, or breast cancer (except when indicated for management) also should not take estrogens. Estrogen-Interactions 1. Estrogens are major substrates of 2. In addition, they may decrease the effectiveness of some 3. Estrogens can also interact with 1. CYP1A2 and CYP3A4; inducers/inhibitors of these isoenzymes may raise/lower estrogen levels 2. antidiabetic drugs and thyroid preparations. 3. anticoagulants and other drugs that affect clotting. Local vs. systemic estrogen options and why one would be chosen over the other 1. Oral-Owing to convenience, the oral route is used 2. Transdermal estradiol is available in four formulations: 3. Compared with oral formulations, transdermal formulations have four advantages: 4. Intravaginal options come as inserts, creams, and vaginal rings & 5. The other vaginal ring (Femring) is used for systemic effects to 6. Parenteral; is used only for emergencies d/t 1. more than any other. estradiol—is available alone and in combination with progestin 2. Emulsion (Estrasorb), Spray, Gels & Patches 3a. The total dose of estrogen is greatly reduced 3b. There is less nausea and vomiting. 3c. Blood levels of estrogen fluctuate less. 3d. There is a lower risk for DVT, pulmonary embolism, and stroke. 4. are used only for local effects, primarily treatment of vulval and vaginal atrophy associated with menopause. 5. control of hot flashes and night sweats as well as local effects-Tx of vulval and vaginal atrophy 6. acute, emergency control of heavy uterine bleeding Clinical Practice Guidelines for menopause Not all women who experience distressing symptoms of menopause should be treated with oral estrogen or combination estrogen/progestin therapy. Key points include: 1. intravaginal preparations are most useful for treating sx associated 2. transdermal estrogen preparations have fewer adverse effects, use lower doses of estrogen, and have 3. progesterone is contraindicated in women who have undergone a 1. with local estrogen deficiency such as vaginal and vulvar atrophy; these preparations are assoc with a lower risk of systemic effects 2. less fluctuation of estrogen levels than do oral preparations 3. hysterectomy but required in women with an intact uterus who undergone hormone replacement therapy Summary of Key Prescribing Considerations -Estrogens 1. Therapeutic Goal: Management of symptoms and structural changes associated 2. Baseline Data: Heart rate, blood pressure, weight. Pregnancy test, thyroidstimulating hormone (TSH), & 3. Monitoring: Blood pressure, weight. Serum triglycerides, TSH if thyroid replacement required, & 4. Identifying High-Risk Patients: Estrogen therapy should not be prescribed for patients with: 5. Evaluating Therapeutic Effects: Therapeutic effects depend on the reason prescribed. 1. with decreased endogenous estrogen. (Other uses include palliation of metastatic breast cancer in selected cases.) 2. serum triglyceride (or full lipid panel). Screening for breast CA and CV disease. Gynecologic exam, if indicated. 3. Regular breast and pelvic exams as recommended for age. Schedule endometrial biopsy for unscheduled bleeding that continues for 6 months. 4. Abnormal vaginal bleeding of unknown cause • Estrogen-dependent cancer or breast cancer (except when used as treatment for certain metastatic cancers) • History of DVT or pulmonary embolism • Stroke, MI, or other arterial thromboembolism occurring within the past year • Abnormal liver function or disease • Pregnancy 5. For menopausal HT, patients report relief of symptoms and the vagina is pink and moist on gynecologic exam. 6. Minimizing Adverse Effects of Estrogen: • Nausea is common early in treatment. Advise patients that this adverse effect 6. diminishes with time. In the meantime, avoidance of cooking odors and warm, stuffy environments may help. Dry foods and raw fruits and vegetables help as well as Guided imagery with muscle relaxation, yoga, and music therapy • Menopausal HT with estrogen alone increases the risk for endometrial carcinoma. Adding a progestin lowers this risk to the pretreatment level. • Adverse effects similar to those caused by OCs (abnormal vaginal bleeding, hypertension, benign hepatic adenoma, reduced glucose tolerance) Black Box Warning for Estrogen Therapy 1. Endometrial cancer risk is increased in women with a 2. Estrogen may increase the risk for 3. Estrogen is not indicated for 1. uterus who take unopposed estrogen. 2. deep vein thrombosis and stroke. 3. cardiovascular disease or dementia and may increase the risk for dementia in women aged 65 years and older. Patient Education Estrogens From textbook 1. Inform the patient that nausea can be reduced by 2. Remind patients that estrogens present a small risk of 3. To minimize risk of undetected breast cancer, remind patients of the need to receive 4. To reduce cardiovascular risk, advise women to avoid smoking, perform regular exercise, 1. taking estrogens with food and by dosing at night. Explain that nausea diminishes over time. 2. breast cancer and endometrial cancer. 3. periodic mammograms. Instruct the patient to report any persistent or recurrent vaginal bleeding, to r/o endometrial carcinoma 4. decrease intake of saturated fats, and take appropriate drugs for HTN, DM, and high cholesterol Patient-Centered Care Across The Life Span Estrogens 1. Children 2. Pregnant women 3. Breastfeeding women 4. Older adults-Beers Criteria include estrogens among 1. Estrogens are not indicated for prepubertal children. 2. Estrogens are contraindicated during pregnancy. 3. Estrogens may affect infant development and may decrease both the quantity and quality of milk produced. 4. those identified as potentially inappropriate for use in geriatric patients. 65 (may increase dementia risk) Patient Education about Estrogen SE from lecture 1. Nausea is common early in treatment but. 2. Menopausal HT with this hormone alone increases the risk for . 3. adverse effects include abnormal 1. diminishes with time. To reduce nausea: avoid cooking odors and warm, stuffy environments, consume dry foods and raw fruits and vegetables, use guided imagery with muscle relaxation, yoga, and music therapy 2. endometrial carcinoma 3. vaginal bleeding, hypertension, benign hepatic adenoma, and reduced glucose tolerance) Summary of Key Prescribing Considerations-Progestins 1. Therapeutic Goal: Goals for noncontraceptive uses are to counteract 2. Baseline Data: Heart rate, blood pressure, and weight. 3. Monitoring: Blood pressure. Assessment for fluid retention, including weight. Consider referral for 4. Identifying High-Risk Patients: Progestins are contraindicated in the presence of 5. Minimizing Adverse Effects: Progestins can cause breakthrough bleeding, spotting, and amenorrhea. Warn patients that 1a. endometrial hyperplasia caused by unopposed estrogen during HR 1b. management of dysfunctional uterine bleeding, amenorrhea, and endometriosis 1c. support of pregnancy in women with corpus luteum deficiency & also used in in vitro fertilization cycles and to prevent risk for preterm birth. 2. Pregnancy test. Screening for breast and cardiovascular disease. Pelvic exam as indicated for age. 3. transvaginal ultrasound or hysteroscopy for occurrence of undx'ed bleeding for 6 months. 4. undx'ed vaginal bleeding, active thrombophlebitis or a hx of thromboembolic disorders, active liver disease, breast CA & women who've had a hysterectomy 5. this may occur, and instruct them to report any abnormal or prolonged vaginal bleeding. Black Box Warning Estrogen and Progestin Therapy 1. Estrogen plus progestin may increase the risk for 2. Estrogen plus progestin is not indicated for 3. Estrogen plus progestin may increase the risk for 1. thromboembolic events such as DVT, stroke, myocardial infarction, and pulmonary embolism. 2. CV disease or dementia and may increase the risk for dementia in women aged 65 years and older. 3. breast cancer Patient-Centered Care Across The Life Span Progestins 1. Children 2. Pregnant women-High-dose therapy during the first 4 months of pregnancy has been associated 3. Breastfeeding women 4. Older adults-Progestins are only indicated if the patient is taking 1. Progestins are not indicated for prepubertal children. 2. with an increased incidence of birth defects (limb reductions, heart defects, masculinization of the female fetus). 3. Progestins may contribute to neonatal jaundice. 4. estrogen and has a uterus. Transgender Woman (male phenotype) HT 1. Goals 2. Treatment 3. Monitoring needs 4. Risks 1. Stimulate dev of female secondary sex characteristics; requires medication to decrease testosterone levels 2. estrogen, antiandrogens, gonadotropin-releasing hormone (GnRH) agonists, or others 3. Estradiol, Testosterone, Prolactin, Triglycerides & Potassium if spironolactone used as antiandrogen 4. HT risks are the same as for HR pts. For estrogen, thromboembolic events remain the greatest risk factor Patient Education about Progestin SE from lecture 1. breakthrough (blank, blank & blank) may occur 2. report abnormal or 1. bleeding, spotting, and amenorrhea 2. prolonged vaginal bleeding 6mo Transgender Man (female phenotype) HT 1. Goals 2. Treatment 3. Monitoring needs 4. Risks 1. Stop menstruation, Stimulate development of male secondary sex characteristics 2. testosterone as would be done in hypogonadism 3. Serum testosterone levels every 3 months until optimal, then 1-2 times a year, Hb/Hct, cholesterol 4. Acne, possible male-pattern hair loss, Polycythemia Hypercholesterolemia, Liver impairmentThromboembolic disorders with increased risk of MI and stroke Selecting the Right Birth Control method 1. Effectiveness 2. Safety 3. Personal Preferences 4. Other Factors 1. Most Effective are subdermal implants, Intramuscular medroxyprogesterone acetate (Depo-Provera), Sterilization & Intrauterine device (IUD) - Reasonably effective are: Oral contraceptives (OC), Contraceptive ring, & Contraceptive Patch 2. OC contraindications: thrombus concerns, 35 years who smokers, & those with hx of breast carcinoma - OCs can cause significant side effects & Benefit/Risk analysis required 3. Improves consistent and correct use, Education increases consistent and correct use 4. Family planning goals, Age, Frequency of sexual activity Capacity for adherence - cost -access - developmental What behaviors would make one birth control method more effective over another? 1. personal preference is a major factor in providing the motivation needed for consistent implementation of a birth control method. 2. If family planning goals have already been met 3. For women who engage in coitus frequently, 4. Conversely, when sexual activity is limited, 5. Because barrier methods combined with spermicides can offer some protection against STDs 6. If adherence is a problem (as it can be with OCs, condoms, and diaphragms), 1a. even the best form of contraception will be less effective if improperly practiced, 1b. Practitioners should take pains to educate patients about the contraceptive methods available so that selection and use can be based on understanding 2. sterilization of either the male or female partner may be desirable. 3. OCs or a long-term method (e.g., Nexplanon, Depo-Provera, IUD) are reasonable choices 4. use of a spermicide, condom, or diaphragm may be more appropriate. 5. these combinations may be of special benefit to individuals who have multiple partners. 6. use of a long-term method (e.g., vaginal contraceptive ring, IUD, Nexplanon, Depo-Provera) can confer more reliable protection. Factors to consider when selecting birth control-Diagram Prototype Drugs Drugs for Birth Control 1. Combination Oral Contraceptive 2. Progestin-Only Oral Contraceptive 3. Long-Acting Contraceptives 1. Ethinyl estradiol/norethindrone 2. Norethindrone-aka "minipills" 3. Subdermal etonogestrel implant (Nexplanon), Depot medroxyprogesterone acetate (Depo-Provera) Mechanism of Action of OC 1. Combination OCs reduce fertility primarily 2. The estrogen in combination OCs suppresses, 3. progestin in combination OCs acts in the 1. by inhibiting ovulation. 2. release of FSH from the pituitary (and thereby inhibits follicular maturation) 3. hypothalamus and pituitary to suppress the midcycle luteinizing hormone surge, which normally triggers ovulation Summary of Key Prescribing Considerations Combination Oral Contraceptives 1. Therapeutic Goal: 2. Baseline Data: Assess for 3. Monitoring: 4. Identifying High-Risk Patients: Contraindications to use include 5. Evaluating Therapeutic Effects: If combination oral contraceptives are being used for menstrual symptoms, 6a. Minimizing Adverse Effects: Educate patients on proper protocol for missed doses 6b. Effectiveness of oral contraceptives can be reduced with 1. Prevention of unwanted pregnancy. 2. hx of HTN, DM, thromboembolism, cerebrovascular or cardiovascular disease, breast CA. UA pregnancy test 3. No routine monitoring required. 4. current pregnancy, hx of thromboembolus, breast CA, and women over 35 years of age who continue to smoke tobacco. Use with caution in women with diabetes, hypertension, and cardiac disease. 5. it is important to evaluate for decrease in cramping, menstrual flow, or duration of menses. 6a. (depending on medication type and cycle). 6b. some medications, including certain common antibiotics. Baseline assessment Considerations for OCs 1. If the history reveals an absolute contraindication to OC use 2. In women with relative contraindications 3. A full examination with pelvic exam is Some states in the United 4. States are allowing pharmacists to 1. OCs should not be prescribed. 2. OCs should be used with caution. 3. not needed to prescribe OCs. 4. prescribe OCs, thus eliminating the need for a healthcare visit. Absolute Contraindications to the Use of Combination Oral Contraceptives 1. Thrombophlebitis, thromboembolic disorders, cerebral vascular disease, coronary occlusion, or a past history of these conditions, or a predisposition 2. Abnormal liver function 3. Known or suspected breast cancer 4. Undiagnosed abnormal vaginal bleeding 5. Known or suspected pregnancy 6. Smokers older than 35 years Relative Contraindications to the Use of Combination Oral Contraceptives Hypertension Cardiac disease Diabetes History of cholestatic jaundice of pregnancy Gallbladder disease Uterine leiomyoma Epilepsy Migraine SE of OCs- Thromboembolic disorders. 1. Major factors that increase the risk for thromboembolism are 2. Several measures can help minimize thromboembolic phenomena: 2a. The estrogen dose in OCs should be 2b. OCs containing drospirenone or desogestrel should 2c. OCs should not be prescribed for 2d. OCs should be discontinued at least 1. heavy smoking, a history of thromboembolism, and thrombophilias 2a. no greater than required for contraceptive efficacy. In past hx OCs contained 100 μg of ethinyl estradiol Today's OCs contain no more than 50 μg 2b. generally be avoided because they may pose a higher risk for developing VTE. 2c. heavy smokers, women with a history of thromboembolism, or those with other risk factors for thrombosis. 2d. 4 weeks before surgery in which postoperative thrombosis might be expected. Patient Education-Thrombosis and Thromboembolism 1. Women should be informed about the symptoms of thrombosis and thromboembolism (e.g.,.... Black Box Warning-Oral Contraceptive Pills 2. Cigarette smoking increases the risk of 1. leg tenderness or pain, sudden chest pain, shortness of breath, severe headache, sudden visual disturbance) and instructed to consult the prescriber if these occur. 2. serious cardiovascular side effects from combination oral contraceptive pills. SE of OCs- Cancer. 1. OCs present no known risk for cancer—with the important exception of 2. OCs protect against (blank & blank) CA and have no effect on (blank), which is caused by human papillomaviruses. 3. OCs do increase risk of breast CA for some women, specifically 4. estrogens can promote the growth of 1. promoting (not causing) breast cancer growth 2. ovarian and endometrial; cervical cancer 3. women who have the BRCA1 gene mutation BUT not the BRCA2 mutation 4. existing breast carcinoma; which is why this is a absolute contraindication SE of OCs-Hypertension 1/2. f hypertension develops and OCs are determined to be the cause, two options are open: SE of OCs-Abnormal uterine bleeding 3. Spotting and bleeding can also occur with monthly cycle OCs, most often during 4. If a woman misses her period while taking monthly cycle OCs, . (1) discontinue the OC (2) continue the OC and manage the hypertension with drugs. 3. the first 3 months when low-estrogen OCs are used. 4. the possibility of pregnancy should be assessed OC Use in pregnancy and lactation 1. Combination OCs enter breast milk and. 2. In contrast, progestin-only OCs have Stroke in women with migraine. 3. When used by women who experience migraine headaches 4. B/c of the low risk of stroke, contraindications for women with migraines are 1. reduce milk production, especially in the early stages of lactation (so they're contraindicated) 2. little or no effect on milk production and hence are preferred for contraception during lactation 3. OCs may increase the risk for thrombotic stroke 4. 35 years, smokers, and those with HA that are preceded by a visual change known as an aura SE of OCs-Glucose intolerance. 1. OCs can elevate blood glucose levels. This diabetogenic effect is caused by 2. Glucose intolerance is most likely in patients who are 1. the progestin in OCs. 2. already diabetic or have experienced gestational diabetes Effects related to estrogen or progestin imbalance. 1. Effects that can result from an excess of estrogen include 2. Progestin excess can increase 3. A deficiency in either hormone can cause 4. For women who experience androgenic effects (e.g., acne, hirsutism)-caused by progestin, switching to 5. When one combination OC is being substituted for another, 1. nausea, breast tenderness, and edema. 2. appetite and cause fatigue and depression. 3. menstrual irregularities. 4. an OC that has drospirenone or dienogest can help 5. the change is best made at the beginning of a new cycle How to initiate treatment (when in the cycle is it best to start- may vary based on type of contraceptive) 1. With only one exception, combination OCs are 2. Most 28-day cycle products are taken in a repeating sequence consisting of 3. The sequence is begun on either 4. With the first option, protection is 5. With a Sunday start, which is done to have menses occur on weekdays rather than the weekend, protection 6. With both options, each dose 7. Successive dosing cycles should 1. dosed in a cyclic pattern. 2. 21 days of an active pill followed by 7 days on which either (1) no pill is taken, (2) an inert pill is taken, or (3) an iron-containing pill is taken. 3. the first day of the menstrual cycle or the first Sunday after the onset of menses. 4. conferred immediately; hence no backup contraception is needed. 5. may not be immediate; hence an alternate form of birth control should be used during the first 7 days of the pill pack. 6. should be taken at the same time every day (e.g., with a meal or at bedtime). 7. commence every 28 days How to achieve an extended cycle with oral contraceptives 1. To achieve an extended schedule, the user would simply purchase 2. Many health care providers recommend taking combination OCs for an extended time rather than following the traditional 28-day cycle because 1. four packets of a 28-day product (each of which contains 21 active pills) and then take the active pills for 84 days straight. 2. doing so decreases episodes of withdrawal bleeding, AND the assoc sx that come with that ie: menstrual pain, premenstrual symptoms, headaches etc. What to Do If Doses Are Missed for products that use a 28-day cycle 1. If one or more pills are missed in the first week, 2. If one or two pills are missed during the second or third week, 3. If three or more pills are missed during the second or third week What to Do If Doses Are Missed for extended cycle products 5. For combination OCs that use an extended or continuous cycle, up to 7 days can be missed with little or no increased risk for pregnancy provided that 1. take one pill as soon as possible and then continue with the pack. Use an additional form of contraception for 7 days. 2. take one pill as soon as possible and then continue with the active pills in the pack but skip the placebo pills and go straight to a new pack once all the active pills have been taken. 3. follow the same instructions given for missing one or two pills but use an additional form of contraception for 7 days. 4. the pills had been taken continuously for the prior 3 weeks. Benefits and drawbacks of progestin-only contraception Pros 1. Because they lack estrogen, minipills do not cause 2. progestin-only OCs have little or no effect on breastmilk Cons 3. progestin-only preparations are less effective and 4. Irregular bleeding is the major drawback of these products and 1. thromboembolic disorders, HAs, nausea, or most of the other adverse effects associated with combination OCs, making it an alternative for women with high risk of thromboembolic disorders 2. and can be used during lactation 3. are more likely to cause irregular bleeding 4. the principal reason that women discontinue them. MOAs of progestin-only contraception 1. minipills are weak inhibitors of ovulation; henceforth 2. Under the influence of progestins, cervical glands produce a thick, 3. Progestins also modify the endometrium, making it 1. this is not their primary MOA for preventing pregnancy 2. sticky mucus that acts as a barrier to penetration by sperm. 3. less favorable for implantation. Patient Education with progestin-only contraception 1. taking the pill at the same time every day is important to their effectiveness for instance, 2. progestin-only OCs are taken continuously. Use is initiated on If one or more doses is missed or taken greater than 3 hours after the scheduled dose, the following guidelines apply: 3. If one pill is missed, it should be taken as soon as remembered and 4. If two pills are missed, the regimen should be restarted and backup contraception should be used 1. Taking a pill even 3 hours late can reduce their efficacy and use of back up protection or emergency contraception is recommended if unprotected sexual intercourse occurred 2. day 1 of the menstrual cycle, and one pill is taken daily thereafter 3. backup contraception should be used for at least 2 days. The pills should be resumed as scheduled on the next day. 4. for at least 2 days. In addition, if two or more pills are missed and no menstrual bleeding occurs, a pregnancy test should be done. What effect does CYP450 inhibitors or inducers have on OCs? 1. inducers of hepatic cytochrome P3A4 can accelerate OC 2. Women taking OCs in combination with any of these agents should be alert for indications of reduced OC blood levels, such as 3. If these signs appear, it may be necessary to either 1. metabolism and thereby reduce OC effects 2. breakthrough bleeding or spotting. 3. (1) increase the estrogen dosage of the OC, (2) combine the OC with a second form of birth control (e.g., condom), or (3) switch to an alternative form of birth control. How does this impact prescribing of OCs? Drugs whose effects are reduced by oral contraceptives 1. OCs can decrease the benefits of warfarin 2. By increasing levels of glucose, OCs can counteract the benefits of 3. Accordingly, when combined with OCs, warfarin and hypoglycemic agents may require 1. By increasing levels of clotting factors, OCs can decrease the effectiveness of warfarin 2. insulin and other hypoglycemic agents used in diabetes 3. increased dosage. How does this impact prescribing of OCs? Drugs whose effects are increased by oral contraceptives. 1. OCs can impair the hepatic metabolism of several agents, including 2. Because of reduced clearance, these drugs may accumulate to toxic levels. If signs of toxicity appear, 1. theophylline, TCAs, diazepam, and chlordiazepoxide (Librium) 2. the dosages of these drugs should be reduced How to change patient from one form of contraceptive to another Switching to the Transdermal Contraceptive Patch ie: Xulane 1. For women not currently using OCs, the first patch should be 2. For women switching from OCs, the first patch should be applied 1. applied during the first 24 hours of the menstrual period. 2. on the first day of withdrawal bleeding. What are the most effective forms of contraception? 1. A subdermal system (Nexplanon) for delivery of etonogestrel 2. Nexplanon consists of a single 4-cm rod implanted subdermally in the groove between 3. Etonogestrel then diffuses slowly and continuously, providing Drug Interactions 4. Agents that induce hepatic enzymes—(including blank)—may reduce the efficacy of Nexplanon. Accordingly, Nexplanon should not be used by women taking these drugs. 1. is available for long-term reversible contraception 2. the biceps and triceps in the nondominant arm. 3. blood levels sufficient for contraception for 3 years 4. such as barbiturates, phenytoin, rifampin, carbamazepine, topiramate, HIV protease inhibitors, and St. John's wort What are the most effective forms of contraception? 1. Depot medroxyprogesterone acetate (DMPA) is given by injection 2. It protects against pregnancy for 3. When injections are discontinued, return of fertility is delayed 4. DMPA poses a risk for reversible 1. intramuscularly or subcutaneously. 2. three months or longer by inhibiting the secretion of gonadotropin 3. by an average of 9 months 4. bone loss, but this risk does not outweigh the benefits of treatment. IUDs 1. Intrauterine Devices; Historically, due to the wicking ability of the old IUD strings, 2. The risk for PID is highest during the 3. Two main classes of intrauterine devices are currently in use: 4. The TCu380A can be used for up to 5. levonorgestrel containing IUDs can be used for 1. increased risk of pelvic inflammatory disease related to IUD use was a concern (but is no longer) 2. first 20 days after insertion; screening for Gonorrhea and chlamydia infection should be done prior to insertion 3. a hormone-free copper IUD (TCu380A or Paragard) and a levonorgestrel containing IUD 4. 10 years and likely longer. 5. (3 to 7) years depending on the dose form. hierarchy of Contraceptives diagram Ch 52 Androgens Testosterone is the prototype of the androgen hormones. Biosynthesis and Secretion 1. Testosterone synthesis in males is promoted by two hormones of 2. In women, preandrogens (precursors of testosterone) are secreted 3. preandrogens by the adrenal glands is regulated by 1. the anterior pituitary: follicle-stimulating hormone (FSH) and luteinizing hormone (LH) 2. by the adrenal cortex and ovaries 3. adrenocorticotropic hormone, whereas synthesis of preandrogens by the ovaries is regulated by LH Physiologic and Pharmacologic Effects of Testosterone 1. testosterone promotes the transformations that signal 2. In males Androgens are also necessary for 1. puberty in males: testes enlarge, scrotum/penis enlarge. Pubic and axillary hair appears, and hair on the trunk, arms, and legs assumes adult male patterns. growth of bone and skeletal muscle, causes height and weight to increase rapidly. Testosterone accelerates epiphyseal closure, causing bone growth to cease within a few years. The larynx enlarges, Sebaceous glands increase (skin to becomes oily; acne results) The final pubertal change is beard development. 2. Spermatogenesis Physiologic and Pharmacologic Effects of Testosterone 1. endogenous androgens have only moderate effects in females. 2. Anabolic Effects; testosterone promotes 3. Erythropoietic Effects; Testosterone promotes synthesis of 1. promotion of clitoral growth and, perhaps, maintenance of normal libido. 2. growth of skeletal muscle. 3. erythropoietin, a hormone that acts on bone marrow to increase production of erythrocytes Therapeutic Uses for Testosterone include Hypogonadism (Male) Replacement Therapy (Male) Delayed Puberty (Male) Therapy in Menopausal Women Catabolic States (cachexia) Anemias Drug Therapy for Transgender Men Treatment of hypogonadism 1. Hypogonadism is a condition in which the testes fail to 2. Benefits of testosterone therapy include 3. principal drugs employed for testosterone replacement 4. The routes used for Tx are 1. produce adequate amounts of testosterone. causes may be hereditary, pituitary failure, hypothalamic failure, and primary dysfunction of the testes. 2. treatment restores libido, increases ejaculate volume, and supports expression of secondary sex characteristics; Tx does NOT restore fertility 3. are testosterone itself and two testosterone esters: testosterone enanthate and testosterone cypionate 5. oral tablets, IM injection, buccal, transdermal, gel, nasal and implants (or implantable pellets) Treatment of delayed puberty 1. If puberty fails to occur at the usual age (15 years). 2. The DOC for short course therapy are 3. When is it appropriate to initiate androgen therapy (short course vs long-term 1. a familial pattern of delayed puberty; thus tx is NOT req but some providers will prescribe a short-term course of androgen therapy off label 2. Oral tabs: fluoxymesterone (Androxy, Halotestin) and methyltestosterone (Methitest) 3. If delayed puberty is caused by hypogonadism (pituitary, hypothalamic, or testicular failure) then lifelong tx will ensue Androgen therapy Therapeutic Effects 1. Testosterone Therapy in Menopausal Women can 2. When prescribed off label for this use, it must be prescribed at 3. Cachexia, which occurs in severely immunocompromised pts testosterone can 4. The DOC for cachexia, a anabolic steroid is 5. The Blackbox warning for Oxandrolone (Oxandrin) 1. alleviate some menopausal symptoms, especially fatigue, reduced libido, and reduced genital sensitivity 2. doses lower than men. The goal is to mimic premenopausal testosterone production—about 300 μg/day 3. decrease the risk for wasting and loss of muscle mass 4. Oxandrolone (Oxandrin) 5. Oxandrolone can cause peliosis hepatitis, a condition in which blood-filled cysts form in the liver, leading to liver failure; it also carries an increased risk for atherosclerosis increasing LDL and decreasing HDL. Role of androgens in treating anemia 1. Androgens are sometimes used in men and women to treat anemias that have been refractory to other therapy. Anemias most likely to respond include 2. Androgens help relieve anemia by promoting synthesis of 3. When women are given testosterone, the Hb levels increase by an average of 1. aplastic anemia, anemia associated with renal failure, Fanconi anemia, and anemia caused by cancer chemotherapy. 2. EPO, the renal hormone that stimulates the production of red blood cells, WBCs and platelets. 3. 4.3 g/dL. In contrast, because men have high testosterone levels, to begin with, the increase in plasma Hb is smaller—only 1 g/dL. Adverse Effects of Testosterone 1. Virilization in Women, Girls, and Boys in characterized by 2. In young boys Virilization can cause 3. Other adverse effects include 1. acne, deepening of the voice, proliferation of facial and body hair, male-pattern baldness, increased libido, clitoral enlargement, and menstrual irregularities. Clitoral growth, hair loss, and lowering of the voice may be irreversible 2. growth of pubic hair, penile enlargement, increased 3. Premature Epiphyseal Closure, Hepatotoxicity, elevated Cholesterol Levels, Prostate Cancer, Abuse Potential (all androgens are sched 3), Risk for Thromboembolic Events including stroke, MI, DVT, and pulmonary embolism Summary of Key Prescribing Considerations Androgens 1. Therapeutic Goal: To manage 2. Baseline Data: Serum testosterone concentration, 3. Monitoring: Serum testosterone concentration, 4. Identifying High-Risk Patients: Androgens are contraindicated for 5. Evaluating Therapeutic Effects: Development of 1. hypogonadism and subsequent testosterone deficiency through testosterone supplementation. 2. CBC, lipid panel, liver function, prostate specific antigen (PSA). 3. lipids, liver function, and PSA after 1 year (refer to urologist if 4.0 ng/mL or 1.4 ng/mL above baseline) 4. pregnant women, for men who have prostate cancer or breast cancer, and for enhancing athletic performance. 5. secondary sex characteristics and restoration of energy, libido, and other symptoms of testosterone deficiency. Summary of Key Prescribing Considerations Androgens 6. Minimizing Adverse Effects: 6a. (blank) may occur in women who want to avoid this affect. . 6b. Accelerated bone maturation in children can decrease 6c. The 17-α-alkylated androgens can cause 6d. (blank & blank) may result in edema. 6e. Androgens can cause masculinization of the female fetus. 6a. Virilization; Assess for deepening voice, chest and facial hair, acne, and menstrual irregularities at each clinical encounter. Irreversible changes may be avoided if androgens are withdrawn early 6b. attainable adult height. Monitor effects on epiphyses with radiographs of the hand and wrist twice yearly. 6c. cholestatic hepatitis, jaundice. Rarely, liver CA develops. Monitor for sx of liver dysfunction such as jaundice, fatigue, and malaise. Obtain periodic AST/ALT. Liver function normalizes after the cessation of drug use. Avoid longterm use of 17-α-alkylated preparations. 6d. Salt and water retention; Assess for edema and weight gain at each clinical encounter. Consider androgen withdrawal or use of a diuretic. 6e. R/O pregnancy before androgen use. Ensure that female patients of childbearing age are using adequate contraception Administration methods for transdermal preparations 1. Testosterone is available in three transdermal formulations: 2. patches (Androderm) are indicated for 3. the gels have three advantages over patches: they 4. Black Box Warning-Testosterone Gel and Topical Solution 5. Why is secondary exposure a problem with gels? 1. patch, gel, and liquid 2. male hypogonadism; applied once daily to the upper arm, thigh, back, or abdomen; adverse effect is rash at the site of application 3. (1) cause less local irritation, (2) cannot fall off, and (3) produce more consistent testosterone levels. 4. Secondary exposure to testosterone gel on uncovered skin and on unwashed clothing has resulted in virilization in children & female partners 5. only 10% of an applied dose is absorbed; the other 90% remains on the skin after the gel dries Administration methods for transdermal preparations 1. AndroGel is supplied in a metered-dose pump & a 2. The gel is applied once 3. Patients should be instructed to squeeze the entire contents 4. patients should wait 5 to 6 hours before 5. testosterone should be measured 6. Testim is available in 5-g tubes; it is applied 7. To prevent the transfer of testosterone to others, patients should 1. and in unit-dose foil packets 2. daily (in am) to clean, dry skin of the shoulders, upper arms, or abdomen but not the genitalia 3. of the packet into the palms and then immediately apply the gel to the skin and rub it in. 4. showering or swimming 5. 14 days after the initiation of therapy and periodically thereafter. 6. once daily to skin of the shoulders or upper arms but not to the abdomen or scrotum 7. wash their hands and, after the gel has dried, keep the treated area covered with clothing How to prevent secondary exposure with gels 1. Gel users should wash their hands with soap and warm water after 2. Gel users should cover the application site with 3. Gel users should wash the application site before 4. Women and children should avoid skin-to-skin contact 5. Women and children who make accidental contact with a gel 1. every application. 2. clothing once the gel has dried. 3. skin-to-skin contact with another person. 4. with application sites on gel users. 5. application site should wash contaminated skin immediately Administration methods for transdermal preparations 1. The principal difference for Topical Solution is the application site: 2. Axiron is supplied as an alcohol-based solution 3. Axiron is applied to each axilla at the same time every morning. After 1. Axiron liquid is formulated specifically for application to the axilla 2. in a metered-dose pump; Rx doses are per actuation 3. 14 days or longer, blood levels of testosterone are measured and dosage is adjusted up/down as needed Considerations for other Testosterone Routes 1. nasal gel (Natesto); patients with nasal disorders or abnormalities 2. There has not been adequate testing for interactions 3. pellets are implanted subdermally in the 4. buccal tablets (Striant), are approved for 5. buccal Tablets are applied to the 6. Intramuscular testosterone esters; Unfortunately these 1. (e.g., chronic sinusitis, a severely deviated nasal septum) should not take this drug. 2. with other nasally administered drugs 3. hip area or abdominal wall lateral to the umbilicus 4. male hypogonadism, 5. gum area just above the incisor tooth 6. preparations produce testosterone blood levels that vary widely; As a result, patients may experience significant variations in libido, energy, and mood Ch 52 Men's health: ED & BPH 1. Drugs for ED fall into two major groups: oral and nonoral. The oral agents include 2. The nonoral agents include 3. Four PDE-5 inhibitors are available: 4. MOA of PDE-5 inhibitors causes selective inhibition of PDE-5. By doing so, 5. Benefits of PDE-5 inhibitors can 1. PDE-5 inhibitors—are by far the most common treatments for ED. 2. include papaverine plus phentolamine & alprostadil 3. sildenafil, tadalafil, vardenafil, and avanafil. All are considered first-line therapy for ED. 4. it increases and preserves cGMP levels in the penis, thereby making the erection harder and longer lasting. 5. help a wide range of patients, including those with diabetes, spinal cord injury, and transurethral prostate resection as well as ED of no known physical cause Patient-Centered Care Across the Life Span Drugs for Erectile Dysfunction 1. Pregnant women-It is recommended that men taking Alprostadil 2. Older adults-Consider lower dosing 1. drugs use a condom if their partner is a pregnant woman. 2. when prescribing for adults age 65 and older. 1. List the Adverse effects for PDE-5 inhibitors 2. What are the most COMMON adverse effects 1. - Hypotension-especially when combined with alpha blockers - Priapism: (painful erection lasting more than 6 hours) - Nonarteritic ischemic optic neuropathy: resulting in irreversible blurring or loss of vision. The cause is blockage of blood flow to the optic nerve - Sudden hearing loss. 2. headache, flushing, and dyspepsia, may also cause nasal congestion, diarrhea, rash, and dizziness. About 3% of patients experience mild transient visual disturbances (a blue tinge to vision, increased sensitivity to light, blurring) Drug Interactions of PDE-5 inhibitors 1. Nitrates are contraindicated for within 24 hrs of 2. α blockers are contraindicated for 3. CYP3A4 ie: ketoconazole, itraconazole, erythromycin, cimetidine, saquinavir, ritonavir, grapefruit juice; can suppress the metabolism of all 4 thereby 4. Class I and III antidysrhythmic drugs should NOT be used 1. Sildenafil & Vardenafil, 48 hrs within Tadalafil (Cialis), & 12 hrs of Avanafil, 2. Tadalafil (Cialis) & Vardenafil, use with caution in Sildenafil & Avanafil as they can result in symptomatic postural hypotension 4. increasing there levels, all req dosage reductions 5. with Vardenafil as it prolongs the QT interval 1. Preferred administration route of alprostadil and why Because of the inconvenient method of dosing, these drugs are second-line agents for ED. 1. Alprostadil has the same chemical structure as prostaglandin E1, which causes vasodilation When injected into the Intracavernous penile tissue it causes relaxation of smooth muscle (arterial, venous, and trabecular), causing a rapid inflow of arterial blood. The blood fills the vascular sinusoidal spaces of the corpus cavernosum, resulting in an erection Summary of Key Prescribing Considerations Phosphodiesterase-5 Inhibitors 1. Therapeutic Goal: PDE-5 inhibitors are used to 2. Baseline Data: Heart rate, blood pressure. Thorough 3. Monitoring: Heart rate, blood pressure. Eye examination to include 4. Identifying High-Risk Patients: PDE-5 inhibitors are contraindicated for men taking 1. enhance both the hardness and duration of erection in men with ED. 2. eye examination. Assess hearing. Evaluate pts for CV disorders, including stroke, hypo OR hypertension, HF, unstable angina, MI, and recent hx of severe dysrhythmia. 3. visual acuity, assessment of color vision, pupillary response, and fundoscopic exam. Assess for tinnitus, vertigo, and hearing loss. Assess for sx of pulmonary edema. 4. nitrates (ie: NTG) and should be avoided in men on α blockers. Avoid vardenafil—but not sildenafil or tadalafil—in men taking class I or class III antidysrhythmic drugs. For men with preexisting CV disease, consider carefully the risk assoc with sexual activity before prescribing a PDE-5 inhibitor or any drug for ED. Use PDE-5 inhibitors with caution in men taking CYP3A4 inhibitors and in those with NAION (blurred vision/blindness), coronary heart disease, and other CV disorders. Summary of Key Prescribing Considerations Phosphodiesterase-5 Inhibitors 2a. Minimizing Adverse Effects: Variability in response can be a problem if diet and timing are not considered. High-fat meals will delay 2b. Stress the importance of having an examination for development of 2a. absorption of avanafil, sildenafil, or vardenafil (but not tadalafil). Avanafil should be taken approximately 15-30 min before sexual activity. All other PDE-5 inhibitors should be taken about 1 h before sexual activity. Only tadalafil is approved for daily dosing. 2b. vision or hearing changes. Explain that prolonged priapism lasting longer than 4 h is a surgical emergency; go to the ED right away if this occurs. 1. BPH is a common condition that develops in more than 2. BPH is a nonmalignant prostate enlargement cells 3. Overgrowth of epithelial cells causes 1. 50% of men by age 60 years and 90% by age 85 years. 2. caused by excessive growth of epithelial (glandular) cells and smooth muscle 3. mechanical obstruction of the urethra, whereas overgrowth of smooth muscle causes dynamic obstruction of the urethra. BPH signs & symptoms 1. Signs and symptoms of BPH include urinary hesitancy, urinary urgency, increased 2. There is no direct correlation between symptoms and 3. Long-term complications of BPH include 1. frequency of urination, dysuria, nocturia, straining to void, postvoid dribbling, decreased force and caliber of the urinary stream, and a sensation of incomplete bladder emptying 2. prostate size; therefore substantial enlargement may have no symptoms 3. obstructive nephropathy, bladder stones, and recurrent urinary tract infections Overview of Tx BPH 1. BPH can be managed in three ways: 2. The goal of therapy is to 3. 5-α-reductase inhibitors are most appropriate for men with very 4. α blockers are preferred for men with 1. invasive treatments, drug therapy, and "watchful waiting 2. relieve bothersome urinary symptoms and delay disease progression 3. large prostates (mechanical obstruction) 4. relatively small prostates (dynamic obstruction) Know examples of drugs in each major drug class & Adverse effects 1. 5-α-Reductase Inhibitors examples include 2. MOA of 5-α-Reductase Inhibitors 3. Adverse effects of 5-α-Reductase Inhibitors include 4. Selective α1-a Blockers examples include 5. MOA α1-a Blockers 6. Adverse effects of α1-a Blockers include 1. Dutasteride & Finasteride (Proscar) 2. Reduce dihydrotestosterone (DHT) production, which causes the prostate to shrink, reducing mechanical obstruction of the urethra. May also delay BPH progression. Benefits take months to develop. 3. Decreased ejaculate volume and libido. Teratogenic to the male fetus. 4. Silodosin & Tamsulosin (Flomax) 5. relaxes smooth muscle in the bladder neck, prostate capsule/urethra, thereby decreases dynamic obstruction of the urethra. Benefits develop rapidly. 6. Abnormal ejaculation (ejaculation failure, reduced ejaculate volume, retrograde ejaculation). Risk of floppy-iris syndrome during cataract surgery. Know examples of drugs in each major drug class & Adverse effects 1. Nonselective α1 Blockers examples include 2. MOA of Nonselective α1 Blockers 3. Adverse effects of Nonselective α1 Blockers include 4. Phosphodiesterase-5 Inhibitor examples include 5. MOA of Phosphodiesterase-5 Inhibitors 6. Adverse effects of Phosphodiesterase-5 Inhibitors 7. α1-a Blocker/5-α-Reductase Inhibitor examples include 8. MOA of α1-a Blocker/5-α-Reductase Inhibitor 9. Adverse effects of α1-a Blocker/5-α-Reductase Inhibitor include 1. Alfuzosin & Doxazosin & Terazosin 2. same as α1-a Blockers Benefits develop rapidly 3. Hypotension, fainting, dizziness, somnolence, and nasal congestion (from blocking α1 receptors on blood vessels) 4. Tadalafil (Cialis) 5. Smooth muscle relaxation in the bladder, prostate, and urethra Initial improvement is seen in 2 weeks 6. Hypotension, priapism 7. Tamsulosin/dutasteride 8. Same as 5-α-reductase inhibitors and selective α1-a blockers the α blocker can provide rapid symptomatic relief (by relaxing prostate-related smooth muscle) while, over time, the 5-α-reductase inhibitor can provide additional symptomatic relief (by shrinking the prostate) and may also delay disease progression. 9. Decreased libido and abnormal ejaculation (ejaculation failure, reduced ejaculate volume, retrograde ejaculation) Summary of Key Prescribing Considerations-5-α Reductase-Inhibitors 1. Therapeutic Goal: Reduction in 2. Baseline Data: 3. Monitoring: Repeat 4. Identifying High-Risk Patients: Do not prescribe for patients 5. Evaluating Therapeutic Effects: 6. Minimizing Adverse Effects: The most common adverse effect is sexual dysfunction. Because these changes can be permanent, 1. prostate size relieves symptoms of bladder outlet obstruction 2. PSA 3. PSA at 6 months; if there is no decrease, evaluate for prostate cancer. Repeat PSA periodically. 4. suspected to have prostate cancer 5. Anticipate symptom improvement after 6–12 months. 6. the patient should return for possible dosage adjustment or change in medications if this concerns the patient. Patient-Centered Care Across the Life Span Drugs for BPH 1. Pregnant women-Finasteride and dutasteride are teratogens; 2. Breast-feeding women-It is not known if 5-α-reductase inhibitors are 3. Older adults-Beers Criteria includes the 1. they cause feminization of the male fetus. Because these drugs can be absorbed through the skin, pregnant women should not handle finasteride or dutasteride tablets that have been broken or crushed. Men taking finasteride or dutasteride should not donate blood to avoid the risk of exposing a pregnant recipient. 2. excreted in breast milk. Women taking these drugs for off-label uses (e.g., hirsutism) should not breastfeed. 3. peripheral α-1 blockers doxazosin and terazosin among its listing of potentially inappropriate medications for patients age 65 and older. Ch 82 Drug Therapy for Sexually Transmitted Diseases Treatment of STIs/STDs-Chlamydia 1. Adults and adolescents 2. Children 2a. 45 kg 2b. ≥45 kg but 8 year old 2c. ≥8 year old 3. Pregnant women 4. Newborns: ophthalmia or pneumonia 1. (Rx on exam) Azithromycin, 1 g PO once or Doxycycline PO × 7 days 2a. (Rx on exam) Erythromycin base/ethylsuccinate, 12.5 mg/kg PO 4 times/day × 14 days 2b. Azithromycin, 1 g PO once 2c. Azithromycin, 1 g PO once or Doxycycline PO × 7 days 3. Azithromycin, 1 g PO once 4. Erythromycin base/ethylsuccinate, 12.5 mg/kg PO 4 times/day × 14 days Treatment of STIs/STDs-Uncomplicated gonococcal urethritis 1. Urethritis, cervicitis, proctitis 2. If a patient is allergic to azithromycin 1. Ceftriaxone, 250 mg IM once, plus azithromycin, 1 g PO once 2. a 7-day course of doxycycline may be substituted. Treatment of STIs/STDs-Bacterial Vaginosis 1 of 3 options 1. Metronidazole 2. Metronidazole gel (0.75%) 3. Clindamycin cream (2%), 1. 500 mg PO 2 times/day × 7 days 2. 1 full applicator (5 g) intravaginally once/day × 5 days 3. full applicator (5 g) intravaginally at bedtime × 7 days Treatment of STIs/STDs-Trichomoniasis 1. Metronidazole, 2 g 2. Tinidazole (Rx on exam) 1. PO once 2. 2 g PO once Treatment of STIs/STDs-Herpes Simplex Virus 1. First episode, genital herpes (med on exam) 2. Severe infection 3. Recurrent episodes 4. Daily suppressive therapy 5. Neonatal herpes 1. Acyclovir, 400 mg PO 3 times/day × 7-10 days (or longer) or Acyclovir, 200 mg PO 5 times/day× 7-10 days 2. Acyclovir, 5-10 mg/kg IV every 8 h for 2-7 days then PO acyclovir to complete at least 10 days 3. Acyclovir, 800 mg PO 2 times/day × 5 days or Acyclovir, 400 mg PO 3 times/day × 5 days 4. Acyclovir, 400 mg PO 2 times/day 5. Acyclovir, 20 mg/kg IV every 8 h × 14 days (for skin or mucous membrane infection) or × 21 days (for CNS infection) Treatment of STIs/STDs-Syphilis 1. Primary, secondary, & early latent syphilis 1a. Children 1b. Adults 2. Late latent syphilis or latent syphilis of unk duration, or Tertiary 2a. children 2b. adults 3. Neurosyphilis 4. Congenital syphilis 1a. (Rx on exam) Benzathine PCN G, 50,000 units/kg IM once 1b. Benzathine PCN G, 2.4 million units IM once 2a. Benzathine PCN G, 50,000 units/kg IM once/week for 3 weeks 2b. Benzathine PCN G, 2.4 million units IM once/week for 3 weeks 3. Aqueous crystalline PCN G, 18-24 million units IV daily for 10-14 days 4. Aqueous crystalline PCN G, 50,000 units/kg IV every 12 h for the first 7 days of life, followed by 50,000 units/kg every 8 h for the next 3 days OR Procaine PCN G, 50,000 units/kg IM once daily for 10 days Week 2 Ch 19 Parkinson's Disease The Pathophysiology Underlying Motor Symptoms in PD 1. Motor symptoms result from damage to the extrapyramidal system, 2. When extrapyramidal function is disrupted, dyskinesias 3. dyskinesias that characterize PD are 4. In severe PD, bradykinesia may progress to 5. In PD, there is an imbalance between 6. imbalance results from degeneration of the neurons in the substantia nigra that supply 7. In the absence of dopamine, the excitatory influence of acetylcholine goes unopposed, causing excessive 1. a complex neuronal network that helps regulate movement 2. (disorders of movement) result 3. tremor at rest, rigidity, postural instability, and bradykinesia (slowed movement). 4. akinesia, the complete absence of movement 5. dopamine and acetylcholine 6. dopamine to the striatum. 7. stimulation of GABAergic neurons which contributes to the motor symptoms that characterize PD. Therapeutic Goal of Drugs for PD 1. Drugs can only provide symptomatic relief; 2. Furthermore, there is no convincing proof that any current drug 3. Given the neurochemical basis of parkinsonism—too little striatal dopamine and too much acetylcholine—the approach to treatment is 4. two types of drugs are used: 1. they do not cure PD 2. can delay disease progression 3. give drugs that can restore the functional balance between dopamine and acetylcholine. 4. (1) dopaminergic agents (i.e., drugs that directly or indirectly activate dopamine receptors) and (2) anticholinergic agents ie, Benztropine (rarely used) Overview of drug therapy amantadine is not 1st line agent Management of PD Early stages 1. For patients with mild symptoms, treatment can begin with an 2. For patients with mild or moderate symptoms, Management of PD in moderate-late stages 3. For patients with more severe symptoms, treatment should begin with either 4. levodopa is the most effective agent BUT 5. Hence the choice must be tailored to the patient: if improving motor function is the primary objective, then 6. However, if drug-induced dyskinesias are a primary concern, then 1. MAO-B inhibitor. MAO-B inhibitors confer mild symptomatic benefit. 2. DA agonists are the drugs of first choice; Pramipexole may be used alone or in combo with levodopa in early stages of PD 3. levodopa (combined with carbidopa) or a dopamine agonist. 4. long-term use carries a higher risk for disabling dyskinesias. 5. levodopa is preferred. 6. a dopamine agonist would be preferred. Management of PD in advanced stages 1. Apomorphine is a nonergot dopamine agonist approved for the 2. the drug is not given by mouth it is 1. acute treatment of hypomobility during off episodes in patients with advanced PD. 2. admin subcut; The most common SE are injection-site reactions, hallucinations, yawning, drowsiness, dyskinesias, rhinorrhea, and nausea and vomiting rare but serious CV effects: MI & sudden death Levodopa 1. Therapeutic teaching 2. MOA 1. although the drug is highly effective, beneficial effects diminish over time; sx may be well controlled during the first 2 years of treatment, by the end of year 5, the ability to function may deteriorate to pretreatment levels-reflects disease progression and not the development of tolerance to levodopa. 2. Levodopa reduces symptoms by increasing dopamine synthesis in the striatum; As dopamine, levodopa helps restore a proper balance between dopamine and acetylcholine. Levodopa Adverse Effects 3a. N/V 3b. Dyskinesias 3c. Cardiovascular effects. 3d. Psychosis. 3e. Central nervous system effects 3a. Dopamine triggers the CTZ of the medulla; N/V can be reduced by admin low initial doses or with food: low fat/protein meals 3b. 80% dev dyskinesias ranging from annoying (head bobbing, tics, grimacing), to disabling (ballismus, a rapid jerking or flinging of proximal muscle groups, or choreoathetosis, a slow involuntary writhing) can be tx'ed with amantadine 3c. Postural hypotension which can lead to falls, is common early in treatment; increasing salt/water intake may help or an α-adrenergic agonist 3c. Dopamine can induce visual hallucinations, vivid dreams or nightmares, and paranoia. Two sec-gen antipsychotics—clozapine and quetiapine—have been can manage levodopa-induced psychosis. 3e. Can range from anxiety and agitation to memory and cognitive impairment. Insomnia and nightmares are common. Some experience impulse control problems, ie promiscuity, gambling, binge eating, or alcohol abuse Medications used to treat “off” times including “wearing off” experiences assoc with Levodopa 1. Gradual loss—“wearing off”—develops near the end of the dosing interval and simply indicates that drug levels have declined to a subtherapeutic value. Wearing off can be minimized in three ways: 2. Abrupt loss of effect, often referred to as the “on-off” is a 3. Drugs that can help reduce off times are 4. Over the course of treatment, "off periods" are likely to 1. (1) shortening the dosing interval, (2) giving a drug that prolongs levodopa's plasma half-life-COMT-I ie: entacapone, and (3) giving a direct-acting dopamine agonist. 2. phenomenon, can occur at any time during the dosing interval—even while drug levels are high. 3. COMT inhibitor, MAO-B inhibitor & DA agonist 4. increase in both intensity and frequency Major Drug Interactions of Levodopa Drugs that increase beneficial effects of levodopa 1. Carbidopa 2. Entacapone, tolcapone 3. Amantadine 4. Anticholinergic drugs Drugs that decrease beneficial effects of levodopa 5. First-generation Antipsychotic drugs Drugs that increase levodopa toxicity 6. MAO inhibitors (especially nonselective MAO inhibitors) 1. Inhibits peripheral decarboxylation of levodopa 2. Inhibit destruction of levodopa by COMT in the intestine and peripheral tissues 3. Promotes release of dopamine 4. Block cholinergic receptors in the CNS; help restore balance between dopamine and ACh 5. Block dopamine receptors in the striatum 6. Inhibit MAO; increase risk for severe levodopa-induced HTN Summary of Key Prescribing Considerations Levodopa Combinations 1. Therapeutic Goal: To maintain or improve the patient's ability 2. Baseline Data: HR & BP and general cardiovascular (especially if apomorphine or cabergoline are being considered) and neuro/motor assessment. ie: 3. Monitoring: Orthostatic VS must be assessed at each 4. Identifying High-Risk Patients: Caution must be exercised in dealing with patients who have 1. to carry out activities of daily living. 2. bradykinesia, akinesia, postural instability, tremor, rigidity—should be assessed as well as the extent to which these interfere with ADLs (e.g., ability to work, dress, bathe, walk). Some studies suggest that levodopa can activate malignant melanoma, so a careful skin assessment should also be performed. 3. clinic visit. If the patient reports palpitations or if dysrhythmias are suspected, an ECG may be indicated. Motor function must be evaluated and compared with baseline. 4. cardiac disease or psychiatric disorders and in those taking selective MAO-B inhibitors. Summary of Key Prescribing Considerations Levodopa Combinations 6. Minimizing Adverse Effects 6a. N/V—Medications are best taken with 6b. If Dyskinesias develop 6c. Orthostatic hypotension—Patients should be advised to change 6d. Psychosis—(blank&blank) may be beneficial. 6e. Acute loss of effect—Off times can be reduced by combining 6a. a nonfat, nonprotein snack (e.g., fruit) for N/V 6b. A reduction in dosage may be needed. Amantadine may help with dyskinesias. 6c. from supine or sitting to standing slowly. Fall precautions must be implemented if a patient is hospitalized. 6d. Clozapine or quetiapine 6e. levodopa/carbidopa with a dopamine agonist- pramipexole, a COMT inhibitorentacapone, or a MAO-B inhibitor-rasagiline. Patient Education-Levodopa/Carbidopa 1. So that expectations may be realistic, inform patients that benefits of levodopa may be delayed for 2. Forewarn patients about possible abrupt loss of therapeutic effects during 3. Inform patients that N/V can be reduced by taking levodopa with 4. Counsel patients about possible levodopa-induced movement disorders ie 1. weeks to months. This will facilitate adherence. 2. off times and instruct them to notify you if this occurs. Avoiding high-protein meals may help. 3. low-fat, low-protein foods such as fruits and vegetables. In addition high fat meals can reduce absorption reducing therapeutic effects. Instr pts to notify you if N/V persist or becomes severe. 4. (tremor, dystonic movements, twitching) and instruct them to make an appointment for follow-up if these develop. Patient Education-Levodopa/Carbidopa 5. Patients may require assistive devices for opening medication containers. Ask the pharmacist to avoid 6. Inform patients about signs of excessive 7. Explain that hypotension with associated dizziness and lightheadedness may occur. Advise patients to 8. Inform patients about possible levodopa-induced psychosis ie; 9. Patients should be educated on dopamine dysregulation syndrome (DDS) which can manifest as: 10. Levodopa may darken 5. using childproof containers, which c