Therapeutic Agents for the Reproductive System

Transcription

1 Therapeutic Agents for the Reproductive System Chapter 22 1 Female Reproductive System Produces and transports ova from ovary through fallopian tube into uterus, where fertilized ovum is housed After puberty, female ovary matures one egg per month; all eggs found in ovary at birth Eggs not produced but matured A girl is born with almost one million eggs at birth. By puberty, about half of those remain. During a woman s reproductive life, about 400 eggs are released. Palliative means that which brings relief but does not cure. The male and female reproductive systems interdependently operate with other systems such as the endocrine system and the urinary system. 2 Female Reproductive System (Cont.) Mature egg gathered by fimbriated ends of infundibulum of fallopian tubes In ovulation, oocyte is propelled into fallopian tube where fertilization takes place Ovum only viable for 24 to 48 hours Uterus houses fertilized ovum No fertilization: Endometrial layer sloughs off as menses Menstrual cycle begins with puberty; continues for 40 years until menopause For couples trying to conceive, intercourse shortly before or at the time of ovulation is more effective than intercourse after ovulation. Perimenopause is the term given to the years immediately prior to menopause, when symptoms such as hot flashes and irregular or skipped periods generally begin. 3

2 Anatomy of the Female Reproductive System Notice the uterus s proximity to the urinary bladder and the rectum. This physiology is responsible for two side effects of pregnancy: The enlarged womb puts pressure on both structures, resulting in the frequent need to urinate and, often, hemorrhoids. 4 Female Reproductive Hormones Gonadotropin-releasing hormone (GnRH) from anterior pituitary secretes hormones necessary for ovulation Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) stimulate ovaries to secrete estrogen and progesterone Major female hormones: Estrogen and progesterone secreted from anterior pituitary gland Some women experience pain in the lower abdomen at the time of ovulation. This pain is called mittelschmerz, from German for middle pain. It normally requires no treatment; OTC pain medicines can be used if needed. Ovulation predictor kits detect the surge in LH immediately before ovulation. The principal medications that affect the female reproductive system are hormones. Female hormones can be used for conditions such as abnormal uterine bleeding, abnormal ovulation, and even infertility. Combination oral contraceptives consist of estrogen and progestin to inhibit ovulation. Hormonal therapies can improve body image and fertility in some forms of female hypogonadism. Hormone treatment is most commonly used to treat infertility. Agents such as clomiphene (Clomid) and progesterone can be used. Another treatment that may help with infertility is assisted reproductive technology (ART), which uses in vitro fertilization, embryo transfer, and both egg and sperm transfer. 5 Mammary Glands Did you know that some medications are excreted in breast milk? (Answers will vary.) Often the pregnancy category given to a medication.indicates the drug's nonuse of such excretion occurs. Mammary glands or breasts (tissue) are regulated by hormonal secretions At puberty: Increase in estrogen stimulates development of glandular tissue Progesterone stimulates development of duct system to be used during production of milk 6

3 Conditions Affecting the Female Reproductive System Female hormones are used in treating conditions of male reproductive tract; prostate and testicular cancer Male hormones are used to treat endometrial or breast cancer, endometriosis, and fibrocystic disease in females Estrogen is dominant form of medical therapy Treats hormone replacement, abnormal uterine bleeding, abnormal ovulation, and infertility What is fibrocystic disease? (Fibrocystic disease is a common condition in females in which the breasts are lumpy and often uncomfortable, especially right before menstruation.) Estrogen replacement therapy can be compounded from a prescription for a particular patient. Estrogen is available orally, transdermally (patch), and as inserts (vaginal ring). 7 Estrogen Estrogen can be administered in depot, injectable, oral, or transdermal (patch) form. Its main use is oral contraception Affects bone and cardiovascular function Reduces levels of low-density lipoproteins Raises levels of high-density lipoproteins Lowers risks of cardiac disease Supports development and maintenance of reproductive organs 8 Estrogen (Cont.) Promotes retention of calcium, phosphorus for bone production In females: Treats hypogonadism, postpartum breast engorgement or lactation, symptoms of menopause, dysmenorrhea, endometriosis, and dysfunctional uterine bleeding In males: Used for inoperable prostate and testicular cancers Adverse effects: Aggravates asthma, epilepsy, migraines, heart disease, urinary tract diseases, and symptoms of diabetes mellitus What are some common symptoms of menopause? (Hot flashes, irregular or missed periods, and vaginal dryness) Many women experience increased numbers of headaches immediately before and during their periods. These headaches can usually be treated with nonsteroidal antiinflammatory drugs (NSAIDs), triptans, or both, such as naproxen and/or sumatriptan (Imitrex). In women, estrogens are used for a multitude of purposesñtreating hypogonadism, increasing the possibility of contraception, and relieving symptoms of menopause (natural or surgical). The primary oral estrogen products clinically in use are conjugated estrogens and estradiol. 9

4 Female Hypogonadism Maintaining an ideal body weight, eating a healthy diet, refraining from smoking, and adhering to an exercise regimen may improve infertility. Estrogen and progestin are used for hormone replacement and may help ovarian stimulation; low-dose testosterone may increase sex drive. Lack of production of estrogen in the ovaries Symptoms: Loss of menstruation, hot flashes, loss of body hair, loss of libido, infertility, and early menopause Treatment: Deter causes of these conditions Drug treatments: Hormone replacement therapies 10 Infertility Fertility drugs tend to increase the occurrence of multiple pregnancies; this is less of a risk with oral clomiphene than with some injectable fertility drugs. Prognosis depends on age, cause of condition, and treatment methods Hormone treatment is the most common; drugs such as Clomid, Pergonal, and other hormones can be used to increase ovulation Fertility agents: Given to promote maturation of graafian follicle and production of ovulation 11 Oral Contraceptives Relatively safe for nonsmokers of normal cardiovascular function Combination of estrogen and progestin inhibits ovulation Progestin-only called minipills Combinations most frequently prescribed; almost 100% effective It is very important to take progestin-only pills at the same time every day to maximize their effectiveness. Of the different methods of birth control, oral contraceptives have the highest incidence of side effectsñfrom nausea and vomiting to menstrual abnormalities to thrombotic complications. Concurrent cigarette smoking increases the risk of serious cardiovascular effects with oral contraceptives. 12

5 Oral Contraceptives (Cont.) Combinations include: Monophasic: Daily doses of estrogen and progestin remain constant throughout menstrual cycle Biphasic: Estrogen remains constant; progestin dose increased in second half of cycle Triphasic: Menstrual cycle divided into three phases; amount of progestin is constant but estrogen gradually increased throughout cycle Refer to Table 22-3 (p. 560). Side effects include thromboembolism, increased myocardial infarctions, and strokes. Contraceptives may also increase the blood sugar level; be precursors to gallbladder disease; and cause acne and hirsutism. 13 Effectiveness of Oral Contraceptives Menstruation normally occurs sometime during the last 7 days of the pill cycle, when inactive pills (or no pills) are taken. A form of oral contraceptive is now available that is taken on a 3-month cycle. Each package contains 12 weeks of active pills and 1 week of inactive pills. Medication started on fifth day of menstrual cycle and should be taken at same time of day for 21 days If single dose is missed, the chance of ovulation is small Risk of pregnancy increases with each dose missed 14 Available Forms Oral contraceptives: Tablets Seasonale Transdermal patches * Injections: 3 months NuvaRing Mirena Paragard An advantage of some nonoral products is that they can help individuals who may have trouble remembering to take a pill every day. The current recommendation for contraceptive transdermal patches, such as Ortho Evra, is to apply the patch to the upper arms, back, abdomen, or buttocks. The patch should be applied, worn for 1 week, and then removed. A new patch should be applied on the same day of the week that the first patch was applied. The fourth week should be patch free. 15

6 Other Contraceptive Products Intrauterine devices (IUDs) (Mirena) and NuvaRing are other types of contraceptives available. Spermicides: Active ingredient nonoxynol-9 Available as foam, jelly, gel, cream, suppository, and vaginal film Correct usage essential for contraceptive efficiency Must be applied before coitus 16 Other Contraceptive Products (Cont.) Lamb-intestine condoms are reported to be less effective for preventing sexually transmitted diseases (STDs) than are latex or polyurethane condoms. Barrier devices include male and female condoms, cervical caps, and diaphragms Male condom is most frequently used Made of three materials: Latex, polyurethane, and lamb intestine Female condom is loose-fitting polyurethane pouch 17 Emergency Contraceptives The Plan B One-Step emergency pill is a large dose of levonorgestrel and is in a single dose tablet. Plan B OTC is for women 17 years and older; its use in younger women requires a prescription. Morning-after pill First dose of morning-after pill is taken within 72 hours of unprotected intercourse Second dose is taken 12 hours after first dose 18

7 Emergency Contraceptives (Cont.) RU-486: Mifepristone (Mifeprex) Abortion pill; antiprogestin Antagonist to progesterone; prevents maintenance of pregnancy Used within first 9 weeks of pregnancy for safety Must be administered by qualified health care professional These are controversial and up to the pharmacist to dispense. Progesterone, naturally occurring as progestin, is the female hormone secreted from day 14 through day 28 of the menstrual cycle. The side effects associated with progestins include weight gain, stomach pain and cramping, swelling of the face and legs, headaches, mood swings, anxiety, weakness, rashes, acne, and insomnia. 19 Side Effects of Emergency Contraceptives Emergency contraception products do have some risk associated with them and should not be used as a regular means of birth control. Morning-after pill is high-dose contraceptive: Progestin only or in combination with estrogen Progestin requires only one tablet: Plan B Can lead to infertility, breast tenderness, chest pain, shortness of breath, blurred vision, and jaundice 20 Menopause Menopause is loss of the production of hormones normally produced by the ovaries Not a disease, but medication is used to treat side effects Lifestyle changes can lessen symptoms Use of neuropathic treatments Hot flashes are often side effects for which women seek medication. Menopause is a natural loss of the production of hormones normally synthesized by the ovaries, which occurs with age. Although menopause is not a disease, the symptoms associated with menopause, such as hot flashes, can lead women to seek hormone replacement therapy (HRT). 21

8 Drug Treatment for Menopause Estradiol is a major natural estrogen produced by ovaries; combined with progestins Protects women against coronary and vascular disease Risks include thromboembolitic diseases and neoplasms Considered the most effective treatment for menopausal symptoms, such as hot flashes, mood swings, and night sweats Hormone replacement therapy (HRT): Use as shortterm therapy for the most severe menopausal symptoms All estrogens are Pregnancy Category X and cannot be used by anyone of childbearing age. Soy (or soy isoflavone extracts) and black cohosh are plant-based remedies used by some women as alternatives to HRT. More research is needed to fully understand the benefits and risks of these preparations. The use of HRT for menopausal symptoms is particularly controversial. Although it is effective in treating menopausal symptoms such as hot flashes, mood swings, and night sweats, HRT has been shown to increase a women s risk of developing breast cancer, stroke, blood clots, and heart disease. Recommendations are that the smallest dose be given for the shortest length of time. 22 Pelvic Inflammatory Disease Inflammation of female reproductive organs; may occur due to STD Risk factors: History of pelvic inflammatory disease (PID), age, and multiple sexual partners Drug treatment: Antimicrobials and oral medications PID is a severe inflammation of the uterine lining, fallopian tubes, or ovaries that can cause chronic pain and permanent infertility. Symptoms include abnormal or increased vaginal discharge, bleeding between periods, painful menstruation, painful urination/bowel movements, fever, painful intercourse, and pain in the upper right abdomen. Anabolic steroids are schedule C-III controlled substances because of their potential for abuse. PID is a female-only disease most common in those 15 to 25 years of age. Women who have multiple sex partners or whose partner has had multiple sex partners have an increased risk of contracting PID. 23 Male Reproductive System Closely tied to urinary system Urethra passes through penis and is surrounded by prostate gland Testicles are responsible for production and storage of sperm after puberty Sperm production continues throughout life Sperm forms à passes through epididymis (matures) à vas deferens à proximal portion à ejaculatory duct (through prostate and bulbourethral glands) à urethra à penis à ejaculation (sexual intercourse) Why are the testicles located outside the body (in the scrotum) rather than inside the abdomen? (The optimum temperature for sperm production is lower than the core body temperature. Having the testicles outside the body keeps them at the appropriate temperature.) How long do sperm remain viable in the female reproductive tract? (Sperm remain viable in the female reproductive tract for about 72 hours.) What is the difference (if any) between sperm and semen? (Sperm refers to the male reproductive cells themselves. Semen contains the sperm cells plus other substances that nourish and protect the sperm.) Sperm production begins before the age of puberty and decreases with age, although most men produce sperm throughout their lifetime. 24

9 Male Reproductive System (Cont.) The sperm and fluids pass through the urethra in the penis for ejaculation during sexual intercourse. Prostate is size and shape of walnut Encircles part of urethra Functions are to secrete fluids to the sperm to enhance motility and viability and to provide alkaline environment that will endure acidic environment of vagina 25 Reproductive System of the Male What is this diagram missing? (The figure shows a circumcised penis; the foreskin has been excised from the glans [head]). 26 Male Sex Hormones Stimulated by gonadotropin-releasing hormone (GnRH) of anterior pituitary gland Stimulates formation of LH (or interstitial cellstimulating hormone) and FSH Interstitial cells of testes then stimulated to secrete testosterone Most abundant androgen is testosterone In puberty, androgens stimulate formation of secondary male characteristics, which are building muscle mass, deepening of voice, and facial hair growth Collectively, male hormones are referred to as androgens. The production of testosterone from the testes is responsible for the growth of the prostate gland, seminal vesicles, vas deferens, and others. Testosterone is also responsible for secondary sex characteristics such as changes in voice pitch as a boy enters puberty and increased muscle development. Follicle-stimulating hormone (FSH) is released as puberty begins and causes the stored immature sperm cells to divide and mature. 27

10 Male Hypogonadism The increase in the sperm count is achieved through increased secretion of testosterone, FSH, and interstitial cell stimulating hormone. Androgens provide a sense of well-being, mental stability, and energy to those with male hypogonadism. Testosterone also provides the body with a resistance to fatigue. Body cannot produce enough testosterone Can occur in fetus, during puberty, or in adulthood Treatment: Stress reduction Drug treatment: Androgens and natural testosterone Medication delivery systems may promote development of secondary sex characteristics 28 Benign Prostatic Hypertrophy Enlargement of prostate gland Enlargement won't spread Symptoms: Urinary hesitancy, decreased urine stream, frequency of urination, and nocturia Treatment: Avoid smoking, alcohol, caffeine, and OTC antihistamines; surgery Drug treatment: 5-Alpha reductase inhibitors and alpha-blockers The prostate gland is positioned between the bladder and urethra and encircles the urethra. When the prostate becomes enlarged, it makes urination difficult. 5-Alpha reductase inhibitors reduce the size of the prostate, although it can take up to 6 months to achieve maximum effectiveness. Often the two medication classes are used concurrently to obtain the best results. Alpha-blockers used in the treatment of benign prostatic hyperplasia (BPH) work selectively to inhibit alpha-1 receptor sites. Some of these agents such as terazosin (Hytrin) and doxazosin (Cardura) are less selective for prostate tissue and are also used for the treatment of hypertension. Other alphablockers such as tamsulosin (Flomax) have more targeted activity for the tissues of the prostate. Benign means noncancerous. 5-Alpha reductase inhibitors block the conversion of testosterone to a more active androgen (5-alpha dihydrotesterone [DHT]) that is known to increase the growth of cells, thus reducing the growth of the prostate tissue. Avodart is a 5-alpha reductase inhibitor, which may cause birth defects; therefore a woman who is pregnant or trying to become pregnant should avoid contact with crushed or broken tablets because the active drug can penetrate through the skin Alpha Reductase Inhibitors and Alpha-Adrenergic Blockers Some of these agents (e.g., terazosin) are less selective for prostate tissue and are also used for the treatment of hypertension. 5-Alpha inhibitors block the conversion of testosterone to a more active androgen More active one is known to increase cell growth Alpha-adrenergic blockers Inhibit alpha-1 receptor sites 30

11 Erectile Dysfunction Lack of blood flowing to penis Conditions that can affect the prostate gland include diabetes, atherosclerosis, high blood pressure (BP), and cardiovascular diseases Persistent erectile dysfunction (ED) can be a sign of a possible problem with an underlying undiagnosed condition Using nitroglycerin and medications for erectile dysfunction are prohibited. ED is the inability of the man to achieve or maintain an erection, commonly referred to as impotence, attributable to a lack of blood flowing to the penis, rather than a lack of desire. Patients taking nitrates should not concurrently take sildenafil or related drugs because of the potential for dangerous decreases in blood pressure that can occur when these agents are combined. The following conditions can lead to ED: prostatism, prostatitis, prostatocystitis, nerve damage, substance abuse, low testosterone levels, depression, anxiety, cigarette smoking, and medication use. The generic name for Cialis is tadalafil; sildenafil is the generic name for Viagra; vardenafil is the generic name for Levitra and Staxyn; and alprostadil is the generic name for Caverject. Alprostadil (Caverject) is available as an intracavernous injection, and alprostadil (Muse) is available as a urethral suppository. 31 Drug Treatment for Erectile Dysfunction Refer to Table 22-8 (p. 572). Sildenafil (Viagra) introduced in 1998 to treat impotence Side effects: Headaches, flushing of skin, gastrointestinal (GI) symptoms, nasal congestion, and diarrhea Patients on nitrates: Do not take sildenafil; could cause dangerous decrease in BP 32 Prostate Cancer Cells grow at an uncontrollable rate in patients with cancer. African Americans are more likely to develop this cancer. Symptoms include nocturia, dysuria, blood in the urine or semen, painful ejaculation, and pain in the pelvis or lower back Can be treated through surgery, radiation, and hormones Prostate cancer serious condition, more treatable with newer neoplastic agents 33

12 Drug Treatment for Prostate Cancer These agents decrease hormone production which in turn slows the cell growth. Treatment: Determined by stage of the cancer Hormone therapy Antiandrogens or luteinizing hormone-releasing hormone (LHRH) agonists Usually started in Stage II 34 Sexually Transmitted Diseases STD affects both males and females Transmitted by sexual intercourse and nonsexually Can stay hidden for long periods Caused by bacterial, viral, fungal, and protozoal organisms If untreated can cause irreversible sterility, blindness, and death Education is key to the prevention of STDs. Any disease that can be transmitted by sexual intercourse is considered to be an STD. This does not mean, however, that these diseases cannot be transmitted in other ways. For example, HIV can be spread by either intercourse or the sharing of needles. Herpes virus can be spread from a mother to a child through childbirth, and pubic lice and scabies can be transmitted from the sharing of towels or bedding and by close contact. Several of these diseases, including chlamydia, gonorrhea, hepatitis, acquired immunodeficiency syndrome (AIDS), and syphilis, are on the list of Notifiable Infectious Diseases. The general public may mistakenly believe that taking oral birth control or using a contraceptive gel can protect against STDs; however, this belief is not true. Some vaccines, such as Gardasil, can provide protection against certain human papillomavirus (HPV) infections but will not provide protection against all STDs. 35