NCM 106: DRUGS AFFECTING THE REPRODUCTIVE SYSTEM (Doc Salinas)

Hormones (Sex Hormones)

- Estrogen - Progestin

MENOPAUSE IS ASSOCIATED WITH LOSS OF MANY OF THE EFFECTS OF THESE TWO HORMONES ON THE BODY (3) RLM

1. Retention of calcium in the bones Which leads to osteoporosis 2. Lowered serum lipid levels 3. Maintenance of secondary sex characteristics

MENSTRUAL CYCLE: menstruation, repeats approximately every ___to ___ days.

28 to 32

MALE REPRODUCTIVE NA

ATOO

THERAPEUTIC ACTIONS AND INDICATIONS

Alprostadil acts locally when injected directly into the cavernosum to relax the vascular smooth muscle and allow filling of the corpus cavernosum, causing penile erection. PDE5 inhibitors are selective inhibitors of cyclic guanosine monophosphate (cGMP). These are taken orally and act to increase nitrous oxide levels in the corpus cavernosum.

____________________is contraindicated in patients who are at risk for hyperkalemia due to renal disorders, liver disease, adrenal dysfunction.

Drospirenone

Period of stimulation with mild increases of sensitivity and simulation of your Sympathetic Nervous System

EXCITEMENT

Sites of erogenous stimulation Entryway for sperm to reach the uterus to allow conception and the exit path for the developed fetus at birth.

EXTERNAL GENITALIA (CLITORIS, LABIA & VAGINA)

___________________ which is responsible during reproductive years.

Estradiol

___________ which increases during pregnancy

Estriol

ADVERSE EFFECTS (OXYTOCICS)

Excessive effects: uterine hypertonicity and spasm, uterine rupture, postpartum hemorrhage, decreased fetal heart rate. Gl upset, nausea, headache, and dizziness also are common. Methylergonovine can produce ergotism, manifested by nausea, blood pressure changes, weak pulse, dyspnea, chest pain, numbness and coldness in extremities, confusion, excitement, delirium, convulsions, and even coma.

muscular tube with a ciliated lining that is constantly moving.

FALLOPIAN TUBE

ADVERSE EFFECTS (Estrogen Receptor Modulators)

Gl upset, nausea, and vomiting. headache, dizziness, visual changes, and mental changes. Hot flashes, skin rash, edema, and vaginal bleeding may occur secondary to specific estrogen receptor stimulation Venous thromboembolism.

reduce the risk of preterm birth in women with a single-fetus pregnancy and a history of singleton spontaneous preterm birth.

HYDROXYPROGESTERONE CAPROATE (MAKENA)

POSTPUBERTAL MALES

Inhibition testicular function Gynecomastia Testicular atrophy Priapism Baldness Change in libido

MENSTRUAL CYCLE: ________________________ also cause the inner lining of the uterus to slough off because it is no longer stimulated by the hormones.

Lowered hormone levels

____________________ is administered orally and takes 5 to 7 days to produce the desired effect.

Mifepristone

Produces enzymes to stimulate sperm maturation, as well as Lubricating fluid

PROSTATE GLAND

MENSTRUAL CYCLE: __________________ in the uterus stimulate uterine contraction to clamp off vessels as the lining sheds away.

Prostaglandins

ESTROGEN RECEPTOR MODULATORS (2)

RALOXIFENE (EVISTA) TOREMIFENE (FARESTON)

Resolution when the effects of the parasympathetic stimulation are restored.

RECOVERY

THERAPEUTIC ACTIONS AND INDICATIONS (Androgens)

Responsible for the growth and development of male sex organs and the maintenance of secondary male sex characteristics. Act to increase the retention of nitrogen, sodium, potassium and phosphorus and to decrease the urinary excretion of calcium. Testosterones increases protein anabolism and decrease protein catabolism. Also increases red blood cell production When used on women, it is able to inhibit the hypothalamic- pituitary-adrenal axis and gonadotropin-releasing hormone which leads to a decrease in FSH and LH.

glands respond to follicle- stimulating hormone (FSH) and luteinizing hormone (LH), which are released from the _____________ in response to stimulation from gonadotropin-releasing hormone (GnRH) released from the hypothalamus

anterior pituitary

FEMALE

cells remain in the abdomen. develop into the ovaries, the female sexual glands.

MENSTRUAL CYCLE: If pregnancy does not occur, after about 14 days, the _____________ involutes, and the levels of estrogen and progesterone drop off.

corpus luteum

Testosterone is long acting and is available in several forms:

depot injections, buccal systems topical gels topical sprays urethral pellets, and dermal patch

MENSTRUAL CYCLE: After ovulation, the lining of the uterus begins to produce __________ and other nutrients that would nurture a growing embryo; this is called a _____________________________.

glucose; secretory endometrium

The ______________ and ___________ produce increased levels of GnRH, FSH, and LH for a while in an attempt to stimulate the ovaries to produce estrogen and progesterone. If that does not happen, the levels of these hormones fall back within a normal range in response to their own negative feedback systems.

hypothalamus and pituitary

the onset of the first menstrual cycle

menarche

PREGNANCY: Local _______________ stimulate uterine contraction and the onset of labor. Once the fetus and the placenta have been expelled from the uterus, the hormone levels plummet toward the ________________. It often takes ___ to ____ weeks to reverse the effects of these hormones.

prostaglandins; nonpregnant state; 6 to 8 weeks

The male hormones are produced in the _________ and affect the entire male reproductive system

testes

MENSTRUAL CYCLE: The ________ becomes thicker and more vascular as the cycle progresses and develops a __________________________.

uterus; proliferative endometrium

THE REPRODUCTIVE SYSTEMS IN MALES AND FEMALES ARE COMPOSED OF:

- the STRUCTURES that support conception and development of a fetus. - the ENDOCRINE GLANDS that produce the hormones that facilitate reproduction and are necessary for the regulation and maintenance of these structures. - The same fetal cells in males and females give rise to the glands that produce SEXUAL HORMONES.

used to evacuate uterine contents via intense uterine contractions.

ABORTIFACIENT

ADVERSE EFFECTS ALPROSTADIL (4) Pain at injection site Priapism Fibrosis Rash

ALPROSTADIL

Analogues of testosterone that have been developed to produce the tissue-binding effects of testosterone with less androgenic effects

ANABOLIC STEROIDS

used for replacement therapy in cases of hypogonadism and to treat certain breast cancers

ANDROGENS

DRUGS AFFECTING MALE REPRODUCTIVE SYSTEM (3) AAD

ANDROGENS (Male Steroid Hormones) ANABOLIC STEROIDS DRUGS THAT ACT TO IMPROVE PENILE DYSFUNCTION

Period of lessened sexual activity and loss of testosterone effects The hypothalamus and anterior pituitary put out larger amounts of GnRH, FSH, and LH in an attempt to stimulate the gland If no increase in testosterone or inhibin occurs, the levels of GnRH, FSH, and LH eventually return to normal levels.

ANDROPAUSE

ADVERSE EFFECTS (Abortifacient)

Abdominal cramping, heavy uterine bleeding, perforated uterus, and uterine rupture Headache, nausea and vomiting, diarrhea, diaphoresis (sweating), backache, and rash

ANDROGENIC EFFECTS

Acne Edema Hirsutism The most common Deepening of the voice Oily skin and hair Weight gain Decrease in breast size Testicular atrophy

PHARMACOKINETICS (Estrogen Receptor Modulators)

Administered orally Rafloxifene is well absorbed from the Gl tract Metabolized in the liver Excretion occurs through the feces. Cross the placenta and to enter into breast milk

CONTRAINDICATIONS AND ACTIONS (Abortifacient)

After 20 weeks from the last menstrual period Active PID or acute CV, hepatic, renal, or pulmonary disease Active PID or acute CV, hepatic, renal, or pulmonary disease

ABORTIFACIENT (3) CDM

CARBOPROST (HEMABATE) DINOPROSTONE (CERVIDIL, PREPIDIL GEL, PROSTIN E2) MIFEPRISTONE (RU-486, MIFEPREX)

Massive stimulation of the body

CLIMAX

________________________ is available as an IM injection with an onset of 15 minutes and a duration of 2 hours.

Carboprost

CONTRAINDICATIONS AND ACTIONS (Oxytocics)

Cephalopelvic disproportion Unfavorable fetal position Complete uterine atony Early pregnancy Caution should be used in patients with coronary disease and hypertension

CONTRAINDICATIONS AND ACTIONS

Contraindicated in the presence of any anatomical obstruction or condition that might predispose the patient to priapism. Cannot be used with penile implants Not indicated for use to improve sexual performance in women Caution should be used in patients with bleeding disorders.

CONTRAINDICATIONS AND ACTIONS (Estrogen)

Contraindicated in the presence of any known allergies to estrogens to avoid hypersensitivity reactions. Diopathic vaginal bleeding, breast cancer, or any estrogen-dependent cancer. History of thromboembolic disorders Pregnancy Breastfeeding Hepatic impairment

CONTRAINDICATIONS AND ACTIONS (Fertility Drugs)

Contraindicated in the presence of primary ovarian failure Thyroid or adrenal dysfunction Ovarian cysts Pregnancy Idiopathic uterine bleeding Caution should be used in women who are breastfeeding

CONTRAINDICATIONS AND ACTIONS (Anabolic Steroids)

Contraindicated with any known allergy to prevent hypersensitivity reactions, during pregnancy and lactation because of the potential masculinization in the neonate. Presence of prostate or breast cancer in men Presence of any liver dysfunction and coronary diseases

CONTRAINDICATIONS AND ACTIONS (Androgens)

Contraindicated with any known allergy to the drug ingredients in the drug to prevent hypersensitivity reactions during pregnancy and lactation because of the potential adverse effects on the neonate. Presence of prostate or breast cancer in men Presence of any liver dysfunction or Cardiovascular diseases. Topical forms of testosterone come with a black box warning alerting the user to the risk of virilization in children who come in contact with the drug. Danazol has a black box warning regarding the risk for thromboembolic events, fetal abnormalities, hepatitis, intracranial hypertension.

ANDROGENS (4) DTFM

DANAZOL (GENERIC) TESTOSTERONE (Androderm, Depo-testosterone, Straint, Androgel, Fortesta, Natesto, Aveed) FLUOXYMESTERONE(GENERIC) METHYLTESTOSTERONE(GENERIC)

____________________ is given by intravaginal suppository with an onset of effects in 10 minutes and a duration of effects of 2 hours.

Dinoprostone

THERAPEUTIC ACTIONS AND INDICATIONS (Oxytocics)

Directly affect neuroreceptor sites to stimulate contraction of the uterus. Effective in the gravid uterus. Oxytocin, a synthetic form of the hypothalamic hormone, also stimulates the lacteal glands in the breast to contract, promoting milk ejection in lactating women. Oxytocics are indicated for the prevention and treatment of uterine atony after delivery.

Produced by the ovaries include estradiol, estrone, and estriol. Enter cells and bind to receptors within the cytoplasm to promote messenger ribonucleic acid (mRNA) activity, which results in specific proteins for cell activity or structure.

ESTROGEN

estradiol (Estrace, Clmara, and others) conjugated estrogens (Premarin) esterified estrogen (Menest) estropipate (Ogen)

ESTROGEN

HUMAN SEXUAL RESPONSE (4) EPCR

EXCITEMENT PLATEAU CLIMAX RECOVERY

__________________ after menopause

Estrone

______________, in addition to being available as a vaginal ring, NuvaRing, is available as a subdermal implant that may be left in place for up to 3 years and then must be removed

Etonogestrel

storage site of each ovum. Act as endocrine glands producing the hormones estrogen and progesterone.

FOLLICLE

MENSTRUAL CYCLE: Each cycle starts with release of _____ and _______ and stimulation of the ovarian follicles.

FSH and LH

MENSTRUAL CYCLE: _____ and _____ again, along with the start of another menstrual cycle.

FSH and LH

THERAPEUTIC ACTIONS AND INDICATIONS (Fertility Drugs)

Fertility drugs work either directly to stimulate follicles and ovulation or stimulate the hypothalamus to increase FSH and LH levels. Used to treat infertility in women with functioning ovaries whose partners are fertile. Used to stimulate multiple follicle development for the harvesting of ova for in vitro fertilization.

ANTIESTROGEN EFFECTS (5) FSVNE

Flushing Sweating Vaginitis Nervousness Emotional lability (can be anticipated if these drugs are used by women)

ADVERSE EFFECTS (Estrogen)

GU effects: breakthrough bleeding, menstrual irregularities, dysmenorrhea, amenorrhea, and changes in libido. Systemic effects: fluid retention, electrolyte disturbances, headache, dizziness, mental changes, weight changes, and edema. Gl effects: nausea, vomiting, abdominal cramps and bloating, and colitis.

OTHER COMMON EFFECTS:

Headache Dizziness Sleep disorders and fatigue Rash Altered serum electrolyte

THERAPEUTIC ACTIONS AND INDICATIONS (ESTROGENS)

In small doses, they are used for hormone replacement therapy (HRT) when ovarian activity is blocked or absent. Used as palliation for the discomforts of menopause in the first few years of menopause. Important for the development of the female reproductive system and secondary sex characteristics. Responsible for the proliferation of the endometrial lining. Known to compete with androgens for receptor sites. Produce a wide variety of systemic effects, including protecting the heart from atherosclerosis, retaining calcium in the bones, and maintaining the secondary female sex characteristics

ADVERSE EFFECTS (Fertility Drugs)

Increased risk of multiple births and birth defects Ovarian overstimulation (abdominal pain, distention, ascites, pleural effusion) Headache, fluid retention, nausea, bloating, uterine bleeding, ovarian enlargement, gynecomastia, and febrile reactions

MENSTRUAL CYCLE: By about day 14, the estrogen levels have caused the____________, and ___________ occurs.

LH surge; ovulation

__________________ was once available as an implant system (Norplant System) but now is available only in combination-form oral contraceptives or as a uterine insert. It is also used as a "morning-after" pill be removed.

Levonorgestrel

The cessation of menses

MENOPAUSE

____________________ stimulate spermatogenesis in men with low sperm counts and otherwise normally functioning testes.

MENOTROPINS

OXYTOCICS (2)

METHYLERGONOVINE (METHERGINE) OXYTOCIN (PITOCIN)

THERAPEUTIC ACTIONS AND INDICATIONS (Estrogen Receptor Modulators)

Not hormones but affect specific estrogen receptor sites, stimulating some and blocking others. Developed to produce some of the positive effects of estrogen replacement while limiting the adverse effects

Almond-shaped organs located on each side of the pelvic cavity Store the ova, or eggs.

OVARIES

o Promotion of weight gain in debilitated patients, treatment of certain cancers, relief of bone pain, and promotion of catabolism with prolonged corticosteroid use.

OXANDROLONE (GENERIC)

o Treatment of anemias in adults

OXYMETHOLONE (Anadrol-50)

stimulate contraction of the uterus, much like the action of the hypothalamic hormone oxytocin, which is stored in the posterior pituitary.

OXYTOCICS

PHARMACOKINETICS (Estrogen) Oral estrogens are well absorbed

Oral estrogens are well absorbed through the gastrointestinal (GI) tract. Undergo extensive hepatic metabolism. They are excreted in the urine. Estrogens cross the placenta and enter breast milk

PHARMACOKINETICS (Anabolic Steroids)

Oxandrolone and oxymetholone are available orally. Well absorbed and distributed in the body. Metabolized in the liver Excreted in the urine. Another method of feeding the baby should be used if these drugs are needed during lactation.

are selective inhibitors of cyclic guanosine monophosphate (cGMP). These are taken orally and act to increase nitrous oxide levels in the corpus cavernosum.

PDE5 inhibitors

Includes two corpora cavernosa and a corpus spongiosum, which are structures that allow massively increased blood flow and erection.

PENIS

When stimulation levels off

PLATEAU

released into circulation after ovulationn many effects that support the early development of the fetus effects on body temperature are monitored in the rhythm method of birth control to indicate that ovulation has just occurred.

PROGESTERONE

ADVERSE EFFECTS (ALPROSTADIL) PPFR

Pain at injection site Priapism Fibrosis Rash

is a condition in which the corpus cavernosum does not fill with blood to allow for penile erection.

Penile Erectile Dysfunction PROSTAGLANDIN ALPROSTADIL PHOSPHODIESTERASE TYPE 5 (PDE5) RECEPTOR INHIBITORS (Avanafil, Sildenafil, and Vardenafil)

CONTRAINDICATIONS AND ACTIONS (Progestin)

Presence of pelvic inflammatory disease (PID), sexually transmitted diseases, endometriosis, or pelvic surgery. Epilepsy, migraine headaches, asthma, or cardiac or renal dysfunction.

PHARMACOKINETICS (Progestin)

Progestins are well absorbed Undergo hepatic metabolism Excreted in the urine. Known to cross the placenta and to enter breast milk.

THERAPEUTIC ACTIONS AND INDICATIONS (Anabolic Steroids)

Promote tissue-binding processes, reverse catabolic or tissue. destroying processes, and increase hemoglobin and red blood cell mass. Used to treat anemias, certain cancers and angioedema. Known to be used illegally for enhancement of athletic performance by promoting increased muscle mass, increased hematocrit, and theoretically an increase in strength and endurance.

CONTRAINDICATIONS AND ACTIONS (Estrogen Receptor Modulators)

Raloxifene is contraindicated in the presence of any known allergy to raloxifene to avoid hypersensitivity reactions. Pregnancy and lactation Caution should be used in patients with a history of venous thrombosis or smoking

FERTILITY DRUGS

Stimulate the female reproductive system. CETRORELIX(CETROTIDE) CHORIONIC GONADOTROPIN (PREGNYL) CHORIONIC GONADOTROPIN ALPHA (OVIDREL) CLOMIPHENE (CLOMID AND OTHERS) FOLLITROPIN ALFA (GONAL-F) FOLLITROPIN BETA (FOLLISTIM AQ) GANIRELIX (GENERIC) MENOTROPINS (PERGONAL) UROFOLLITROPIN(BRAVELLE)

THERAPEUTIC ACTIONS AND INDICATIONS (Abortifacient)

Stimulate uterine activity, dislodging any implanted trophoblasts and preventing implantation of any fertilized egg. Used to terminate pregnancy at 12 to 20 weeks from the date of the last menstrual period.

ADVERSE EFFECTS (Progestin)

Systemic effects: Dermal patch contraceptives. Local skin irritation Intrauterine systems are associated with abdominal pain, intensifying endometriosis symptoms, abortion, PID, and expulsion of the intrauterine device.

a beta2 - selective adrenergic agonist, was widely used off-label as a tocolytic agent to relax the gravid uterus to prolong pregnancy.

TERBUTALINE-

Major reproductive structure in males Produces the sperm and the hormone testosterone

TESTES

MALE REPRODUCTIVE SYSTEM (5) TVPPU

TESTES VAS DEFERENS PROSTATE GLAND PENIS URETHRA

Responsible for many sexual and metabolic effects in the male. Like estrogen, testosterone enters the cell and reacts with a cytoplasmic site to influence mRNA activity, resulting the production of proteins for cell structure or function.

TESTOSTERONE

are drugs used to slow uterine activity

TOCOLYTICS

PHARMACOKINETICS (Androgens)

Testosterone is long acting and is available in several forms: depot injections, buccal systems, topical gels, topical sprays urethral pellets, and dermal patch. Danazol, a synthetic androgen, is only available in oral form but is also long acting Methyltestosterone and fluoxymesterone have long half-lives and are available in oral form. Well absorbed and distributed in the body. Metabolized in the liver Excreted in the urine.

PHARMACOKINETICS (Abortifacient)

These drugs are well absorbed when administered. Metabolized in the liver Excreted in the urine. Because of their effects on the uterus, they are used during pregnancy only to end the pregnancy.

Through which urine and the sperm and seminal fluid are delivered.

URETHRA

stimulate uterine contractions to assist labor (oxytocins) or induce abortion (abortifacients).

UTERINE MOTILITY DRUGS

Muscular organ that can develop a blood- filled inner lining, the endometrium. Allows for implantation of the fertilized egg and supports the development of the placenta, which provides nourishment for the developing fetus. Acts as an endocrine gland producing the hormones needed to maintain the active metabolic state of the pregnancy.

UTERUS

THERAPEUTIC ACTIONS AND INDICATIONS (PROGESTINS)

Used as contraceptives, most effectively in combination with estrogens. Used to treat primary and secondary amenorrhea and functional uterine bleeding and as part of fertility programs. Transform the proliferative endometrium into a secretory endometrium, inhibit the secretion of FSH and LH, prevent follicle maturation and ovulation, inhibit uterine contractions, and may have some anabolic and estrogenic effects.

female reproductive system comprises: (3) UOF and the accessory organs (3) VLC

Uterus, Ovary and Fallopian tube Vagina, Labia, and Clitoris

Stores produced sperm Carries sperm from the testes to be ejaculated from the body

VAS DEFERENS

_______________ use is associated with headache, nervousness, constipation, breast enlargement, and perineal pain.

Vaginal gel

ADVERSE EFFECTS (Anabolic Steroids) PREPUBERTAL MALES

Virilization phallic enlargement hirsutism increased skin pigmentation

Hirsutism Hoarseness Deepening of voice Clitoral enlargement Baldness Menstrual irregularities

WOMEN (6) H2DCBM

PHARMACOKINETICS (Fertility Drugs)

Well absorbed and are treated like endogenous hormones within the body. Undergoing hepatic metabolism and renal excretion. Drugs that are available in injectable form include cetrorelix, chorionic gonadotropin, chorionic gonadotropin alpha, follitropin alfa, follitropin beta, menotropins, ganirelix, and urofollitropin. Clomiphene is available as an oral agent

Drospirenone, used in combination contraceptives, has ___________________ activity and can block aldosterone, leading to increased potassium levels

antimineralocorticoid

MALE

cells migrate out of the abdomen to form the testes (the male sexual glands), which are suspended from the body in the scrotum.

PROGESTIN

drospirenone (Yasmin, Yaz) etonogestrel (Implanon) levonorgestrel (Mirena), medroxyprogesterone (Provera) norethindrone (Aygestin) norgestrel (generic) progesterone (Prometrium, and others) desogestrel (found in many contraceptive combinations) ulipristal (Ella)

PREGNANCY: When the ovum is fertilized by a sperm, a new cell is produced that rapidly divides to produce the __________.

embryo

The female sex hormones can be used to replace hormones that are missing or to act on the control mechanisms of the _________________ to decrease the release of endogenous hormones.

endocrine system; endogenous hormones.

Produced by the ovaries include:

estradiol, estrone, and estriol

Drugs that act like __________, particularly at specific estrogen receptors, are also used to stimulate the effects of ________ in the body with fewer of the adverse effects.

estrogen

MENSTRUAL CYCLE: About the next 14 days, the developing follicles release ___________ into the body. Woman may notice the many effects of estrogen.

estrogen

Two Important Hormones produced by Follicles

estrogen and progesterone

PREGNANCY: The embryo implants in the wall of the uterus, and the interface between the fetal cells and the uterus produces the ___________, a large, vascular organ that serves as a massive endocrine gland and a transfer point for nutrients from the mother to the fetus.

placenta

MENSTRUAL CYCLE: High levels of ______________ in the uterus prevent clotting of the lining as the vessels shear off.

plasminogen

Hormones in Male (2)

testosterone and andropause

PREGNANCY: Eventually, the tendency to block uterine activity (an effect of progesterone) is overcome by the stimulation to increase _______________ caused by oxytocin.

uterine activity