NR 566 Final Exam Study Guide (LATEST) Advanced Pharmacology

566 Final Exam Study Guide Week 5 Prevention of osteoporosis with hormone replacement therapy (p. 433) Hormone therapy (HT) reduces postmenopausal bone loss & thereby decreases the risk for o steoporosis & related fractures. Unfortunately, when HT is stopped, bone mass rapidly decreases by approximately 12%. Hence to maintain bone health, HT must continue lifelong. As a result, the risk for harm is increased. Accordingly, alternative treatments are preferred. Effective alternatives to HT include raloxifene (Evista) & bisphosphonates like alendronate (Fosamax), calcitonin (Miacalcin), & teriparatide (Forteo). All patients should practice primary prevention of bone loss by ensuring adequate intake of calcium & vitamin D, performing regular weight-bearing exercise, & avoiding smoking & excessive alcohol use. When and when not to use progestin for hormone replacement therapy and why (pp. 430-433) Goals for noncontraceptive uses of progestins are to counteract endometrial hyperplasia caused by unopposed estrogen during hormone therapy; management of dysfunctional uterine bleeding, amenorrhea, & endometriosis; & support of pregnancy in women with corpus luteum deficiency. Progestins are also used in in vitro fertilization cycles & to prevent prematurity in women at high risk for preterm birth. Progestins are contraindicated in the presence of undiagnosed abnormal vaginal bleeding. Relative contraindications include active thrombophlebitis or a history of thromboembolic disorders (DVT, CVA), active liver disease, & carcinoma of the breast. Progestins should not be prescribed for women who have undergone hysterectomy. Local vs. systemic estrogen options and why one would be chosen over the other (p. 428) Local estrogen options: Transdermal: Transdermal estradiol is available is 4 formulations: • Emulsion (Estrasorb): Applied once daily to the top of both thighs & the back of both calves. • Spray (Evamist): Applied once daily to the forearm. • Gels (EstroGel, Elestrin, Divigel): Applied once daily to one arm, from the shoulder to the wrist or to the thigh (Divigel). • Patches (Alora, Climara, Estraderm, Menostar, Vivelle-Dot): Applied to the skin of the trunk (but not the breast). Intravaginal: Estrogens for intravaginal administration are available as inserts, creams, & vaginal rings. All are used primarily for the treatment of vulval & vaginal atrophy associated with menopause. NOTE: Femring is also used for systemic effects to control hot flashes & night sweats. • Inserts (Imvexxy, Vagifem, Yuvafem) • Creams (Estrace Vaginal, Premarin Vaginal) • Vaginal rings (Estring, Femring) Systemic estrogen options: Oral: Owing to convenience, the oral route is used more than any other. The most active estrogenic compound— estradiol—is available alone & in combination with progestins. Parenteral: Although estrogens are formulated for IV & IM administration, use of these routes is rare. IV administration is generally limited to acute, emergency control of heavy uterine bleeding. Transdermal estrogen therapy has fewer adverse effects (p. 428) Compared with oral formulations, the transdermal formulations have 4 advantages: • The total dose of estrogen is greatly reduced (because the liver is bypassed). • There is less nausea & vomiting. • Blood levels of estrogen fluctuate less. • There is a lower risk for DVT, PE, & CVA. Management of oral contraceptives (OCs) -How to change patient from one combination oral contraceptive to another. (p. 441) When one combination OC is being substituted for another, 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) (p. 442) Most 28-day cycle products are taken in a repeating sequence consisting of 21 days of an active pill followed by 7 days on which either no pill is taken, an inert pill is taken, or an iron-containing pill is taken. The sequence is begun on either the first day of the menstrual cycle or the first Sunday after the onset of menses. With the first option, protection is conferred immediately, so no backup contraception is needed. With a Sunday start, which is done to have menses occur on weekdays rather than the weekend, protection may not be immediate, so an alternate form of birth control should be used during the first 7 days of the pill pack. With both options, each dose should be taken at the same time every day (with a meal or at bedtime). Successive dosing cycles should commence every 28 days even if there is breakthrough bleeding or spotting. Unlike combination OCs, whose administration is cyclic, progestin-only OCs are taken continuously. Use is initiated on day 1 of the menstrual cycle, & one pill is taken daily thereafter. A backup contraceptive method should be used for the first 7 days. -What teaching needs to be done? (p. 442) Educate patient on proper protocol for missed doses (depending on medication type & cycle): For products that use a 28-day cycle, the following recommendations apply: • If one or more pills are missed in the first week, take one pill as soon as possible & then continue with the pack. Use an additional form of contraception for 7 days. • If one or two pills are missed during the second or third week, take one pill as soon as possible & then continue with the active pills in the pack but skip the placebo pills & go straight to a new pack once all the active pills have been taken. • If three or more pills are missed during the second or third week, follow the same instructions given for missing one or two pills but use an additional form of contraception for 7 days. 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 the pills have been taken continuously for the prior 3 weeks. For progestin-only OCs, if one or more doses is missed or taken greater than 3 hours after the scheduled dose, the following guidelines apply: • If one pill is missed, it should be taken as soon as remembered & backup contraception should be used for at least 2 days. The pills should be resumed as scheduled on the next day. • If two pills are missed, the regimen should be restarted & backup contraception should be used for at least 2 days. • In addition, if two or more pills are missed & no menstrual bleeding occurs, a pregnancy test should be done. Effectiveness of oral contraceptives can be reduced with some medications, including certain common antibiotics. -What baseline data is needed? (p. 446) Assess for history of hypertension, diabetes, thromboembolism, cerebrovascular or cardiovascular disease, breast cancer. Urine pregnancy test. -Contraindications for OCs (p. 446) Contraindications to use include current pregnancy, history of thromboembolus, breast cancer, & women over 35 years of age who continue to smoke tobacco. Use with caution in women with diabetes, hypertension, & cardiac disease. How to achieve an extended cycle with oral contraceptives (p. 442) Many health care providers recommend taking combination OCs for an extended time rather than following the traditional 28-day cycle because doing so decreases episodes of withdrawal bleeding, with the associated menstrual pain, premenstrual symptoms, headaches, & other problems. Prolonged use of OCs is possible because these drugs suppress endometrial thickening, hence monthly bleeding is not required to slough off hypertrophied tissue. At this time, 14 products are packaged & marketed for prolonged use. It is important to note that there is nothing special about the estrogen/progestin combinations used in these extended- cycle products. In other words, we could get the same results with other combination OCs, provided they are monophasic. To achieve an extended schedule, the user would simply purchase four packets of a 28-day product (each of which contains 21 active pills) & then take the active pills for 84 days straight. What behaviors would make one birth control method more effective over another? (pp. 437-438) -Be able to evaluate a patient scenario and suggest an appropriate birth control method (type of prescribed contraception: OC, long-term methods, IUD, etc. With perfect use, the failure rate for OCs is only 0.3%. However, with typical use, the failure rate is significantly higher: about 8%. Among women of higher weight, efficacy is somewhat reduced. Possible reasons include decreased blood levels of the hormones, sequestration in adipose tissue, & altered metabolism. Combination OCs should be avoided by women with certain cardiovascular disorders & those older than 35 years who smoke. For women in these categories, an alternative method (diaphragm, progestin-only pill, or IUD) is preferable. Additional factors that bear on selecting a birth control method include family planning goals, age, frequency of sexual intercourse, & the individual’s capacity for adherence. If family planning goals have already been met, sterilization of either the male or female partner may be desirable. For women who engage in coitus frequently, OCs or a long-term method (Nexplanon, Depo-Provera, IUD) are reasonable choices. Conversely, when sexual activity is limited, use of a spermicide, condom, or diaphragm may be more appropriate. Because barrier methods combined with spermicides can offer some protection against STDs, these combinations may be of special benefit to individuals who have multiple partners. If adherence is a problem (as it can be with OCs, condoms, & diaphragms), use of a long-term method (vaginal contraceptive ring, IUD, Nexplanon, Depo-Provera) can confer more reliable protection. What effect does CYP450 inhibitors or inducers have on OCs? (p. 441) -Recall examples of CYP450 inhibitors and inducers from NR565 (Chapter 4 in textbook) -How does this impact prescribing of OCs? Products that induce hepatic cytochrome P3A4 can accelerate OC metabolism & thereby reduce OC effects. Common drugs that induce CYP450 are phenytoin, carbamazepine, rifampin, alcohol, & sulfonylureas. Women taking OCs in combination with any of these agents should be alert for indications of reduced OC blood levels, such as breakthrough bleeding or spotting. If these signs appear, it may be necessary to either: 1. Increase the estrogen dosage of the OC 2. Combine the OC with a second form of birth control (condom, etc.) 3. Switch to an alternative form of birth control OCs can decrease the benefits of warfarin & hypoglycemic agents. By increasing clotting factors, OCs can decrease the effectiveness of warfarin, an anticoagulant. By increasing levels of glucose, OCs can counteract the benefits of insulin & other hypoglycemic agents used in diabetes. Accordingly, when combined with OCs, warfarin & hypoglycemic agents may require increased dosage. OCs can impair the hepatic metabolism of several agents, including theophylline, tricyclic antidepressants, diazepam, & chlordiazepoxide. Because of reduced clearance, these drugs may accumulate to toxic levels. If signs of toxicity appear, the dosages of these drugs should be reduced. Benefits and drawbacks of progestin-only contraception (p. 442) Benefits: Because they lack estrogen, “minipills” do not cause thromboembolic disorders, headaches, nausea, or most of the other adverse effects associated with combination OCs. Drawbacks: Unfortunately, although slightly safer than combination OCs, the progestin-only preparations are less effective & are more likely to cause irregular bleeding (breakthrough bleeding, spotting, amenorrhea, inconsistent cycle length, variations in the volume & duration of monthly flow). Irregular bleeding is the major drawback of these products & the principal reason that women discontinue them. What are the most effective forms of contraception? (p. 437) The most effective methods are an etonogestrel implant (Nexplanon), an intrauterine device (IUD), & sterilization. OCs, medroxyprogesterone (Depo-Provera), the contraceptive ring, & the contraceptive patch are close behind. The least reliable methods include barrier methods, periodic abstinence, spermicides, & withdrawal. Testosterone replacement (pp. 450-453) -Administration • Oral: Only 2 androgens are approved for oral therapy—fluoxymesterone & methyltestosterone. Despite the advantage of cost &. Ease of administration, they are not first-line agents. The androgenic effects of oral androgens are erratic & pose a risk for hepatotoxicity, therefore they should not be used long term. • Transdermal patches: Androderm—applied once daily to the upper arm, thigh, back, or abdomen. • Transdermal gel: AndroGel, Testim, Fortesta, Vogelxo—applied once daily (preferably in the morning) to clean, dry skin of the shoulders, upper arms, or abdomen. Can be transferred to others by skin-to-skin contact. Wash hands with soap & water after every application, cover the application site with clothing once the gel has dried, wash the application site before skin-to-skin contact with another person, women & children should avoid skin- to-skin contact with application sites on gel users & wash contaminated skin immediately if accidental contact with gel application site occurs. • Transdermal topical solution: Axiron—dosing is done by pumping the liquid onto an applicator & then applying the liquid to clean, dry, intact skin of the underarm at the same time every morning. Patients should not swim or bathe for 2 hours after application. If an underarm deodorant/antiperspirant is used, it should be applied before applying the testosterone to avoid contaminating the product. • Transdermal nasal gel: Natesto—Pump should be primed before use & excess gel should be removed. Blow nose before administration. Insert pump into nostril with the tip aimed toward the lateral nostril wall. Depress pump slowly until it stops. As the tip is withdrawn, it should be wiped against the lateral nostril wall to ensure that any remaining gel is distributed to the nostril. After administration in both nostrils, the nose should be lightly massaged below the nasal bridge. The patient should avoid blowing or sniffing for at least 1 hour after administration. • Implantable pellets: Testopel—implanted subdermally in the hip area or abdominal wall lateral to the umbilicus. • Buccal tablets: Striant—tablets are applied to the gum area just above the incisor tooth & are designed to stay in place until removed. To ensure good adhesion, tablets should be held in place (with a finger over the lip) for 30 seconds. • Intramuscular esters: testosterone cypionate (Depo-Testosterone), testosterone enanthate (Delatestryl)—IM injection -Patient Teaching Topical testosterone: To minimize the risk for accidental skin-to-skin transfer, advise users of testosterone gel or testosterone topical solution to: • Wash their hands after every application • Cover the application site with clothing after the gel has dried • Wash the application site before anticipated contact with another person Also, warn women & children to avoid contact with the user’s skin where testosterone was applied & advise them to wash contaminated skin if accidental contact with an application site should occur. Androgens: Tell female patients about signs of virilization (deepening of the voice, acne, changes in body & facial hair, menstrual irregularities). Instruct them to report if these occur. Apprise patients of the signs of liver dysfunction (yellow tint to skin & eyes, fatigue, loss of appetite, nausea, dark- colored urine, light-colored stools). Advise them to report the occurrence of these changes. Inform patients that swelling of the extremities or unusual weight gain may be evidence of salt & water retention. Counsel them to report these events. Remind patients of child-bearing age that this drug can cause fetal malformations. If the patient is capable of becoming pregnant, emphasize the need for consistent use of reliable contraception. Treatment of delayed puberty -When is it appropriate to initiate androgen therapy (short course and long-term) (p. 448) In some boys, puberty fails to occur at the usual age (before 15 years old). Most often, this failure reflects a familial pattern of delayed puberty & does not indicate pathology. Puberty can be expected to occur spontaneously but later than usual. Hence treatment is not an absolute necessity. However, some providers will prescribe a limited course of androgen therapy off label if the psychologic pressure of delayed sexual maturation are causing a boy significant distress. In these cases, a limited course of androgen therapy is indicated. Both fluoxymesterone (Androxy, Halotestin) & methyltestosterone (Methitest) are approved for this purpose. If delayed puberty is the result of true hypogonadism, long-term replacement therapy is indicated. Androgen therapy -Effects: Therapeutic (pp. 448-449) • Male hypogonadism: A condition in which the testes fail to produce adequate amounts of testosterone. May be hereditary, or it may result from other causes, including pituitary failure, hypothalamic failure, & primary dysfunction of the testes. • Replacement therapy: When testicular failure occurs in adult males. Treatment restores libido, increases ejaculate volume, & supports expression of secondary sex characteristics. Treatment will NOT restore fertility. • Delayed puberty: If puberty fails to occur before age 15 years, some providers will prescribe a limited course of androgen therapy off label if the psychologic pressure of delayed sexual maturation are causing a boy significant distress. • Testosterone therapy in menopausal women: Can alleviate some menopausal symptoms, especially fatigue, reduced libido, & reduced genital sensitivity. • Cachexia: A wasting of the body associated with severe illnesses such as AIDS, severe trauma, & chronic systemic infections. Testosterone levels often decline in these patients, putting them at risk for wasting & loss of muscle mass. Testosterone therapy decreases this risk. • Anemias: Sometimes used in men & women to treat anemias that have been refractory to other therapy. Adverse (p. 450) • Virilization in women, girls, & boys: The most common complication of androgen therapy. When taken in high doses by women, androgens can cause acne, deepening of the voice, proliferation of facial & body hair, male-pattern baldness, increased libido, clitoral enlargement, & menstrual irregularities. Masculinization can also occur if taken by children (for sports performance enhancement). Boys may experience growth of pubic hair, penile enlargement, increased frequency of erections, & even priapism (persistent erection). Girls can have growth of pubic hair & clitoral enlargement. • Premature epiphyseal closure: When given to children, androgens can accelerate epiphyseal closure, decreasing adult height. To evaluate androgen effects, radiographic examination of the hand & wrist should be performed every 6 months. • Hepatotoxicity: Androgens can cause cholestatic hepatitis & other disorders of the liver. Clinical jaundice may occur but is rare. Androgens may also be carcinogenic: hepatocellular carcinoma has developed in some patients after prolonged use of these drugs. (Liver damage is associated primarily with the 17-