Contraceptives PDF

Pharmacology CONTRACEPTIVES Lec 9 Pharmacology | CONTRACEPTIVES Contents : Introduction 3 Types of hormonal contraceptives 4 Mechanism of action Exogenously 19 ANDROGENS 24 Anti- androgens 39 Pharmacology | CONTRACEPTIVES Contraceptives may be hormonal or nonhormonal {for example, condom, diaphragm,...

Pharmacology CONTRACEPTIVES Lec 9 Pharmacology | CONTRACEPTIVES Contents : Introduction 3 Types of hormonal contraceptives 4 Mechanism of action Exogenously 19 ANDROGENS 24 Anti- androgens 39 Pharmacology | CONTRACEPTIVES Contraceptives may be hormonal or nonhormonal {for example, condom, diaphragm, contraceptive sponge, and copper intrauterine device). Pharmacology | CONTRACEPTIVES A. Types of hormonal contraceptives 1. Combination oral contraceptives: A combination of estrogen and progestin is the most common type of oral contraceptive. These preparations are highly effective in achieving contraception. Monophasic combination pills contain a constant dose of estrogen and progestin given over 21 to 24 days. Note: The most common estrogen in combination pills is ethinyl estradiol. The most common progestins are norethindrone, norethindrone acetate, levonorgestrel, desogestrel, norgestimate, and drospirenone. Pharmacology | CONTRACEPTIVES Triphasic oral contraceptive products attempt to mimic the natural female cycle and usually contain a constant dose of estrogen with increasing doses of progestin given over 21 days. With most oral contraceptives, active pills are taken for 21 to 24 days, followed by 4 to 7 days of placebo, for a total regimen of 28 days. Withdrawal bleeding occurs during the hormone-free (placebo) interval. Pharmacology | CONTRACEPTIVES Use of extended-cycle contraception (84 active pills followed by 7 days of placebo) results in less frequent withdrawal bleeding. A continuous oral contraceptive product (active pills taken every day) is also available. Pharmacology | CONTRACEPTIVES 2. Transdermal patch The contraceptive transdermal patch contains ethinyl estradiol and the progestin norelgestromin. During the 28-day cycle, one patch is applied each week for 3 weeks to the abdomen, upper torso, or buttock. No patch is worn during the 4th week, and withdrawal bleeding occurs. Pharmacology | CONTRACEPTIVES The transdermal patch has efficacy comparable to that of the oral contraceptives, but it is less effective in women weighing greater than 90 kg. Total estrogen exposure with the transdermal patch may be significantly greater than that seen with oral contraceptives. Pharmacology | CONTRACEPTIVES 3. Vaginal ring The contraceptive vaginal ring contains ethinyl estradiol and etonogestrel. The ring is inserted into the vagina and left in place for 3 weeks. After 3 weeks, the ring is removed, and withdrawal bleeding occurs during the 4th week. Pharmacology | CONTRACEPTIVES 4. Progestin-only pills Progestin-only pills (the "mini-pill") contain a progestin, usually norethindrone, and are administered daily to deliver a low, continuous dosage of drug. These preparations are less effective than combination oral contraceptives, and irregular menstrual cycles may be more frequent. Progestin only pills may be used in patients who are breast-feeding (unlike estrogen, progestins do not have an effect on milk production) or who have intolerance or contraindications to estrogen-containing products. Pharmacology | CONTRACEPTIVES 5. Injectable progestin Medroxyprogesterone acetate is a contraceptive that is administered via intramuscular or subcutaneous injection every 3 months. This product provides high sustained levels of progestin, and many women experience amenorrhea with medroxyprogesterone acetate. In addition, return to fertility may be delayed for several months after discontinuation. Pharmacology | CONTRACEPTIVES Weight gain is a common adverse effect. Medroxyprogesterone acetate may contribute to bone loss and predispose patients to osteoporosis and/or fractures. Therefore, the drug should not be continued for more than 2 years unless the patient is unable to tolerate other contraceptive options. Pharmacology | CONTRACEPTIVES 6. Progestin implants After subdermal placement in the upper arm, the etonogestrel implant offers contraception for up to 3 years. The implant is as reliable as sterilization, and the contraceptive effect is reversible when removed. Adverse effects include irregular menstrual bleeding and headaches. Note: Progestin implants and intrauterine devices are known as long-acting reversible contraceptives (LARC) Pharmacology | CONTRACEPTIVES The etonogestrel implant has not been studied in women who weigh more than 130% of ideal body weight and may be less effective in this population. Pharmacology | CONTRACEPTIVES 7. Progestin intrauterine device Various levonorgestrel-releasing intrauterine devices offer a highly effective method of contraception for 3 to 5 years. Note: This is a suitable method of contraception for women who desire long-term contraception. It should be avoided in patients with pelvic inflammatory disease or a history of ectopic pregnancy. The levonorgestrel intrauterine device is a highly effective treatment for heavy menstrual bleeding. The nonhormonal copper intrauterine device provides contraception for up to 10 years. Pharmacology | CONTRACEPTIVES Pharmacology | CONTRACEPTIVES 8. Postcoital contraception Postcoital or emergency contraception reduces the probability of pregnancy after intercourse without effective contraception to between 0.2% and 3%. The most common method of emergency contraception uses a single high dose of levonorgestrel. For maximum effectiveness, emergency contraception should be taken as soon as possible after unprotected intercourse and preferably within 72 hours. Pharmacology | CONTRACEPTIVES The levonorgestrel emergency contraceptive regimens are generally better tolerated than the estrogen-progestin combination regimens. An alternative emergency contraceptive is the progesterone agonist /antagonist ulipristal. It is indicated for emergency contraception within 5 days of unprotected intercourse. Pharmacology | CONTRACEPTIVES B. Mechanism of action Exogenously Exogenously administered estrogen in contraceptives provides negative feedback which blunts release of follicle-stimulating hormone (FSH) by the pituitary gland and progestin inhibits LH secretion, thus preventing ovulation. Progestin also thickens the cervical mucus, thus hampering the transport of sperm. Withdrawal of the progestin stimulates menstrual bleeding during the placebo week. Pharmacology | CONTRACEPTIVES C. Adverse effects The incidence of adverse effects with contraceptives is determined by the specific compounds and combinations used. The most common adverse effects with: Estrogens are breast fullness, fluid retention, headache, and nausea. Increased blood pressure may also occur. Pharmacology | CONTRACEPTIVES Progestins may be associated with depression, changes in libido, hirsutism, and acne. Although rare, thromboembolism, thrombophlebitis, myocardial infarction, and stroke may occur with use of estrogen-containing contraceptives. These severe adverse effects are most common among women who are over age 35 and smoke, and estrogen-containing contraceptives should be avoided in this population. Pharmacology | CONTRACEPTIVES Progestin-only products are preferred in older women who are smokers, due to a lower risk of severe adverse effects. The incidence of cervical cancer may be increased with hormonal contraceptives, because women are less likely to use barrier methods of contraception that reduce exposure to human papillomavirus, the primary risk factor for cervical cancer. Oral contraceptives are contraindicated in the presence of cerebrovascular and thromboembolic disease. Note: Oral contraceptives are associated with a decreased risk of endometrial and ovarian cancer. ANDROGENS Pharmacology | CONTRACEPTIVES ANDROGENS The androgens are a group of steroids that have anabolic and/or masculinizing effects in both males and females. Testosterone the most important androgen in humans, is synthesized by Leydig cells in the testes and, in smaller amounts, by thecal cells in the ovaries and by the adrenal gland in both sexes. Other androgens secreted by the testes are 5αdihydrotestosterone (DHT), androstenedione, and DHEA in small amounts. Pharmacology | CONTRACEPTIVES In adult males, testosterone secretion by Leydig cells is controlled by gonadotropinreleasing hormone from the hypothalamus, which stimulates the anterior pituitary gland to secrete FSH and LH. Testosterone or its active metabolite, DHT, inhibits production of these specific trophic hormones through a negative feedback loop and, thus, regulates testosterone production. Pharmacology | CONTRACEPTIVES The androgens are required for: 1. Normal maturation in the male. 2. Sperm production. 3. Increased synthesis of muscle proteins and haemoglobin. 4. Decreased bone resorption. Synthetic modifications of the androgen structure modify solubility and susceptibility to metabolism (thus prolonging the half-life of the hormone), and separate anabolic and androgenic effects. Pharmacology | CONTRACEPTIVES Mechanism of action Like the estrogens and progestins, androgens bind to a specific nuclear receptor in a target cell. Although testosterone itself is the active ligand in muscle and liver, in other tissues, it must be metabolized to derivatives, such as DHT. For example, after diffusing into the cells of the prostate, seminal vesicles, epididymis, and skin, testosterone is converted by 5α-reductase to DHT, which binds to the receptor. Pharmacology | CONTRACEPTIVES Therapeutic uses Androgenic steroids are used for males with primary hypogonadism (caused by testicular dysfunction) or secondary hypogonadism (due to failure of the hypothalamus or pituitary). Anabolic steroids can be used to treat chronic wasting associated with human immunodeficiency virus or cancer. An unapproved use of anabolic steroids is to increase lean body mass, muscle strength, and endurance in athletes and body builders. Note: Testosterone replacement should only be used for males with hypogonadism related to medical conditions and not low testosterone associated with aging Pharmacology | CONTRACEPTIVES Formulations of testosterone or its derivatives (for example, methyltestosterone) may be used in combination with estrogen for women with menopausal symptoms unresponsive to estrogen alone. Danazol : a weak androgen is used in the treatment of endometriosis and fibrocystic breast disease. Weight gain, acne, decreased breast size; deepening voice, increased libido, and increased hair growth are among the adverse effect. Note: Danazol also possesses antiestrogenic activity Pharmacology | CONTRACEPTIVES Pharmacokinetics Testosterone: This agent is ineffective orally because of inactivation by first-pass metabolism. Therefore, testosterone is administered via a transdermal patch, topical gel or solution, buccal tablet, or implantable pellet. Esters of testosterone (for example, testosterone cypionate or enanthate) are administered intramuscularly. Pharmacology | CONTRACEPTIVES The esterified formulations are more lipid soluble and have an increased duration of action up to several weeks. Inactive metabolites are excreted primarily in the urine. Pharmacology | CONTRACEPTIVES Testosterone and its esters demonstrate a: 1:1 relative ratio of androgenic to anabolic activity Testosterone derivatives :Alkylation of the 17a position of testosterone is associated with less hepatic metabolism and allows oral administration of the hormone. Pharmacology | CONTRACEPTIVES Methyltestosterone and fluoxymesterone [are examples of orally administered testosterone derivatives. Oxandrolone and oxymetholone are orally active 17a-alkylated derivatives of DHT. Oxandrolone has anabolic activity 3 to 13 times that of testosterone. Pharmacology | CONTRACEPTIVES Adverse effects In females : Androgens can cause masculinization, acne, growth of facial hair, deepening of the voice, male pattern baldness, and excessive muscle development. Menstrual irregularities may also occur. Testosterone should not be used by pregnant women because of possible virilization of the female fetus. Pharmacology | CONTRACEPTIVES In males: Excess androgen can cause priapism, impotence, decreased spermatogenesis, gynecomastia, and cosmetic changes such as those described for females. Androgens can also stimulate growth of the prostate. In children: Androgens can cause abnormal sexual maturation and growth disturbances resulting from premature closing of the epiphyseal plates. Pharmacology | CONTRACEPTIVES General effects Androgens can increase serum LDL and lower serum high-density lipoprotein levels. They may also cause fluid retention and peripheral edema. Testosterone replacement therapy has been associated with a possible increased risk of myocardial infarction and stroke. Pharmacology | CONTRACEPTIVES Hepatic adverse effects have been associated with the 17a-alkylated androgens. Local skin irritation is a common adverse effect with topical formulations. In athletes Use of anabolic steroids (for example, DHEA) by athletes can cause premature closing of the epiphysis of the long bones, which stunts growth and interrupts development. Pharmacology | CONTRACEPTIVES High doses taken by young athletes may result in reduction of testicular size, hepatic abnormalities, increased aggression ("roid rage"), major mood disorders, and other adverse effects described above. Pharmacology | CONTRACEPTIVES Anti- androgens Counter male hormonal action by interfering with the synthesis of androgens or by blocking their receptors. Antiandrogens, such as flutamide , bicalutamide , enzalutamide and nilutamide act as competitive inhibitors of androgens at the target cell and are effective orally for the treatment of prostate cancer. Pharmacology | CONTRACEPTIVES Finasteride and dutasteride inhibit 5a-reductase, resulting in decreased formation of dihydrotestosterone. These agents are used for the treatment of benign prostatic hyperplasia.