FERTILITY AND REPRODUCTION MEDS
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- -Present in males and females-diff. amounts
- -Androgens (Testosterone)
- -Progestins (Progesterone)
- -Development stimulated by LH
- -Produced by:
- -Ovaries in females in small quantities
- -Testes in males in larger quantities
ESTROGEN AND PROGESTERONE-
- Estrogens- produced ovary and placenta, testes, and adrenal cortex.
- Progesterone- produced in the adrenal glands, the gonads (specifically after ovulation in the CORPUS LUTEUM), the brain, and during pregnancy the PLACENTA.
- -Begins with menstruation (3-6 days)
- -Releases gonadotropin-releasing hormone (GnRH) to act on the anterior pituitary which stimulates FSH.
- -Follicular phase-
- -FSH is released (ant. pit)
- -Estrogen secretion dominates and increases.
- -Causes endometrium to proliferate
- -Stimulates ovulation at midcycle
- Luteal phase-
- -Surge of LH started the luteal phase (ant. pit). LH SURGE TRIGGERS OVULATION!!!!!!
- -Triggers ovulation
- -LH surge causes Graffian follicle to swelland rupture resulting in ovulation
- -Graffian follicle turns into the corpus luteum
- -Preparation of uterus for pregnancy
- -Secretes estrogen and progesterone
- -If no pregnancy, corpus luteum decreases estrogen and progesterone and you menstrate.
- -If pregnancy, placenta secretes human chorionic gonadotropin.
- -FSH AND LH ARE HORMONES FROM THE ANTERIOR PITUITARY!!!!!
PHYSIOLOGIC EFFECTS OF ESTROGEN-
- -Sensitize myometrium (in uterus) to oxytocin at parturition labor
- -Stimulates secondary sex characteristics
- -Affect mood andemotions
- -Affect body feminine body fat distribution
- -Enhances blood coagulation
- -Inhibits bone resorption (STRENGTHENS THE BONES)
- -Mild mineralocorticoid properties (SALT AND WATER RETENTION)
- -Increase HDL (CHOLESTEROL LEVELS DECREASE)
PHYSIOLOGIC EFFECTS OF PROGESTERONE-
- -Increase basal body Temperature at ovulation and luteal phase
- -Affects emotional state
- -Mild mineralcorticoid properties
PHYSIOLOGIC EFFECTS OF TESTOTERONE-
- -Development of 2ndary sex characteristics in males
- -Growth of larynx, thickening of vocal cords
- -Stimulates growth of penis, scrotum, seminal vesicle and prostate gland
- -Stimulates and maintains sexual function
- -Increases in lean body mass
- -Stimulates skeletal growth
- -Accelerate epiphyseal closure
- -Incrases sebaceous gland activity and sebum production which produces acne
- -Incrases erythropoietin in the kidneys
- -Decreases HDL cholesterol
- -Mild mineralcorticoid properties
ESTROGENS- 2 TYPES-
- 1. Natural-
- -Conjugated estrogens (OBTAINED FROM THE URINE OF A PREGNANT MARE (HORSE)
- 2. Synthetic
- -Ethinyl estradiol
PHARMACOKINETICS OF ESTROGEN-
- -Well absorbed from GI tract
- -Natural estrogens rapidly metabolized in the liver
- -Synthetic estrogens are degraded (metabolized) less rapidly
- -Most estrogens are readily absorbed from skin and MM, and vaginally
- -Enterohepatic cycling- (ESTROGEN GOES TO LIVER AND IS BROKEN DOWN THEN GOES TO GI AND BACTERIA REACTIVATES ESTROGEN MOLECULES AND THEY ARE REASBSORBED BACK INTO THE SYSTEM)accounts for drug interactions, broad-spectrum antibiotic use alters bowel flora and rend OC ineffective.
- -Depends on the sexual maturity of the recipient
- -Before puberty- Stimulate development of 2ndary sex characteristics
- -Adult female- given cycliacally induce artificial menstrual cycle
- -Used for contraception
- -MUST BE GIVEN WITH PROGESTERONE DUE TO ENDOMETRIAL HYPERPLASIA
- -At or after menopause- prevent s/s of menopause, MUST BE GIVEN WITH PROGESTERONE DUE TO ENDOMETRIAL HYPERPLASIA if patient has an intact uterus.
- -Protects against Osteoporosis- but shouldn't be prescribed for this alone use Fosamax.
- -THE ONLY TIME ESTROGEN CAN BE GIVEN ALONE IS IF PATIENT HAS NO UTERUS!!!
PHARMACOLOGICAL PREPARATIONS- what it is used for:
- 1. Hormone replacement therapy- Estrogen/Progesertone preapartions
- 2. Oral contraception/acne/dysmenorrhea-
- Estrogen/Progesterone prepartions
- Progesterone preparations
- 3. Estrogen receptor antagonist
- -hormonal therapy for breast cancer
- 4. Testosterone and adrogens
- -replacement therapy- in men with decreased levels of testosterone.
- -breast tenderness
- -edema (NA AND H20 RETENTION)
- -changes in libido
- -HTN (NA AND H20 RETENTION)
- -thromboembolic disorders
- -gallbladder disease
- -MONITOR PTS BP FREQUENTLY.
CLINICAL USE OF ESTROGENS-
- -Replacement therapy for -
- Primary ovarian failure (Turner's syndrome)- Estrogen will stimulate sexual characteristics.
- Secondary ovarian failure (menopause) for flushing, vaginal dryness and to preserve bone loss
- Male Cancer- decreases the aggressiveness of the cancer.
- CONTRAINDICATED IN PREGNANCY, UTERINE FIBROIDS, HEPATIC DISEASE, ENDOMETRIOSIS, THROMBOEMBOLIC DISEASE, AND HYPERCALCEMIA.
- -Suppress ovarian function
- -Uterine bleeding
- -Mifepristone-termination of pregnancy
- -Cancers- breast, endometrial, and renal.
- -Hydroxyprogesterone caproate
- -Medoxyprogesterone acetate
- BIRTH CONTROL PILL NAMES TO RECOGNIZE-
- -19 norprogestines-
- -Estranes- Norethindrone and Norethynodrel
- -Gonanes- Levonorgesterol, Desogestrel, and norgestimate.
HORMONE REPLACEMENT THERAPY-
- -must be combinationwith progesterone
- -giving estrogen alone to women who have not had a hysterectomy increases risk of endometrial cancer
- -relieves vasomotor symptoms of meopause such as dizziness, h/a, tachycardia, palpitations, night sweats, atrophic vaginitis
- -benefits in Osteoporsis and CV disease
- -decreases levels of LDL and lipoproeinemia, increases levels of HDL - PROGESTERONE IS THE OPPOSITE!
TREATMENT FOR HRT-
- 1. Oral preparations-
- -First pass metabolism
- -Thromboembolic d/o
- -gall bladder disease
- -induction of drug-metabolizing enzymes-metabolize other drugs faster..which we don't want...ex. seizure med.
- -uterine bleeding
- -increased r/f breast cancer-mild
- 2. Transdermal estradiol preparation-
- -physiologic levels of estradiol
- -consistent blood levels
- -Long duration of action
- -Apply 1-2 x per week
- -Mild skin reactions
- 3. Vaginal administration- cream used primarily for vaginal s/s of menopause
- 4. Vaginal ring- releases estrogen for 3 months- helps atrophic vaginitis and releives menopause s/s
WHY DOES ESTROGEN WORK FOR CONTRACEPTION?
- It stops the pituitary gland from producing LH and FSH which causes a decreased level of estrogen. It also supports the uterine ling to prevent BREAK THROUGH bleeding mid-cycle
TREATMENT FOR HRT-
- -cyclic or continuous replacement
- -estrogen is for 25 days then progesterone starts on day 10 per cycle
- -may or maynot have rx for 5-6 for menses
- -progesterone suppresses risk of endometrial hyperplasia and r/f endometrial cancer.
- -contain femail hormones
- -prevent ovulation
- -estrogen and progestin or progestin only
- -progestin- long acting subdermal implants and Depot IM injections.
- -same amt of progestin and estrogen throughout cycle
- -biphasic and triphasic- mimic menstrual cycle- incrased amount after first 1/3 cycle
USE OF CONTRACEPTIVES-
- -prevent midcycle FSH/LH surge (big peak)
- -stimulates ovualtion
- -Indications- 21 cycle day pilss, start day 5 of menstural cycle or "Sunday start", acne, dysmenorrhea (is a result of increase in uterine prostaglandins which cause ischemia from small arteries in uterus at time of menstration.
- -NSAIDS- prohibit prostaglandin synthesis
ADVERSE EFFECTS OF ORAL CONTRACEPTIVES-
- -risk of stroke
- -MI, DVT
- -thromoembolic complicaitons
- -smokeer over age 35- do not give!
- -caution- in GB disease, thromboembolic disease, and h/o MI or CAD
- -contraindicated in active liver disease (where they are metabolized), breast cancer, or CA of reproductive tract
- -increased r/f ovarian and endometrial ca
- -increased r/f breast ca
S/E OF ORAL CONTRACEPTIVES-
- -acne better or worse
- -increased libido
- -oily skin
- -Mastalgia- painful breasts
- -migraines better or worse
- -no menses- amenorrhea
- -weight gain
POSTCOITAL CONTACEPTION RX-
- -"The morning after pill- plan B"
- -estrogen and progesterone
- -not taking other contraceptives!
- -taken 72 hours within intercourse
- -followed by two doses 12 hours later
- -inhibit transport of ova in fallopian tubes and later endometrium to prevent implantation of fertilized ovum
- -adverse effects- N/V, h/a, dizziness, leg cramps, abdominal cramps
- -comes with a pre-packaged uterine pregnancy test.
ORAL CONTRACEPTIVE DANGEROUS S/E'S-
- A- abdominal pain (GB disease)
- C- chest pain (MI)
- H- headache
- E- eye problems
- S- severe leg pain (DVT)
- STOP TAKING IF ANY OCCUR!!!!
- -drugs which increase heaptic metabolism of OC
- -increases possiblitly of contraceptive failure- metabolized out of the system
- -Phenytoin, barbituates, carbamazepine, antibiotics alter intestinal flora, warfarin, cyclosporine, anti-depressants, glucosteroids, increased hepatotoxic effects with dantrolene.
PROGESTIN- ONLY CONTRACEPTIVES
- -work against egg implantation in the uterus
- -blunts LH surge that produces ovulation
- -thickens and decreases cervical mucous
- -create thin, atrophic endometrium hostile to implantation of blastocyt
- -IUD- localized effects on the endometrium
- -higher failure rates with progestin-only contraceptives
- -frequent spotting
- -increased r/f ectopic pregnancy
- -Norethindrone (minipills", Medroxyprogesterone acetate- depo shot, progesterone IUD's- release a small amount locally.
ALL CONTRACEPTIVES SHOULD BE TAKEN?
AT THE SAME TIME EACH DAY TO DECREASE THE R/F BREAK THROUGH BLEEDING.
- -Have tissue specific action- work against the estrogen in the body- meds treat infertility.
- -med has to bind to estrogen receptors to be effective if blocked can't connect
- -FOOL the body into thinking not enough estrogen so FSH and LH are increased to stimulate ovaries for ovulation
- -exert tissues-specific antagonist or partial agonist effects
- 1. Clomiphene
- 2. Raloxifene
- 3. Tamoxifen
- -taken day 5 of cycle- when ovulation occurs
- -estrogen agonist and moderate estrogen antagonist
- -indications- anovulatory infertility
- -antagonizes estrogen receptors in hypothalamic-pituitary-ovarian axis- all of these need to be secreting normally for med to work- can't increase them if they are not functioning normally
- -blocks estrogen negative feedback and incrases FSH and LH secretion helps ovarin follicle development and ovulation.
- -anovulatory d/o; infertility
- -inhibits GnRH by inhibiting neg feedbck effects of endogenous estrogen
- -less successful in women with decreased estrogen levels
- -unlikely to benefit women with FSH levals at or above 40.
- -taken days 5-10 mesntrual cycle
- -ovulation expected 5-10 days after last dose of clomiphene
- -adverse effects- MULTIPLE BIRTHS
- -breast tissue-estrogen receptor antagonist
- -TREATS BREAST CANCER
- -adverse effects- N/V, hot flashes, vaginal bleeding, menstrual irregularities
- -possibly stimulates proliferation of endometrial cells-endometrial CA
- -possibly stimulates proliferation of endometrial cells- endometrial CA
- -selective estrogen receptor modulator (SERM)
- -TREATS OSTEOPOROSIS IN MENOPAUSAL WOMEN.
- -but allows estrogen-like effects on bone and lipid metabolims- good for bones
- -antagonizes effects of estrogen on breast tissue
- -estrogen antagonist in uterine tissue
- 1. Mifepristone-
- -an antagonist of progesterone receptors
- -sentisizes uterus to action of prostaglandins
- -inhibits ovulation
- -alternative to surgical termination of pregnancy before 9 WEEKS of pregnancy
ANDROGENS- TESTOSTERONE THERAPY-
- 1. Hypogonadism- primary testicular failure
- 2. Hypopituitarism- given with growth hormone to obtain maximal effect on skeletal growth. Occassionally used in given in GYN d/o of endometrial bleeding and osteoporosis.
TESTOSTERONE-(MAIN NATURALLY OCURRING ANDROGEN)-
- -first-pass metabolism extensive- if taken orally and some is reabsorbed so give IM or TD.
- -given parenterally or transdermally
- -ONLY ORAL ONE IS METHYLTESTERONE- IF NO OTHER CHOICE- RESISTANT TO HEPATIC METABOLISM BUT CAN CAUSE HEPATIC DAMAGE AND LIVER FAILURE WITH PROLONGED TX.
ANDROGENS- TESTOSTERONE UNWANTED EFFECTS-
- -if given for a long period the normal testosterone in your body will lose its effect
- -salt and water retention with edema
- -CA of liver
- -impairs growth in children
- -masulinization in girls
- ANABOLIC STEROIDS-
- 1. Fluoxymesterone
- 2. Oxandrolone
- -3 x more potent than testosterone
- -promote wt gain and muslce development
- -what athletes use- ABUSE
- -counteract protein metabolism
- -treat breast CA
- -controlled substances
- -increase body mass, strength, physical performance
- -adverse eff-hepatic dysfunction, jaundice, aggressiveness, psychotic symptoms, acne, decreased testicular size and function, impotence
- -women- masculinization, hirsuitism, deep vouce, menstral irregularities
- -athlete abuse
DANAZOL - look up what is- anabolic steroid?
- -testosterone derivative
- -weak androgenic and progestational activity
- -half life 5 hours: excreted in urine
- -acts on pituitary gland to reduce secretion of GnRH, FSH, and LH, which leads to decreased estrogen production.
- -RX- endometriosis, fibrocystic breast disease, gynecomastia, hereditary angioedema
- -adverse eff.- mild hirsuitism, oily skin and acne, menstural irregulatities, hypercholsterolemia, hepatotoxicity, thromboembolic event, TERATOGENIC
- -decreases growth rate of abnormal breast tissue
- -compete with estrogens and progesterones- inhibit gonadotropin secretion and/or compete with androgens in target organs
- 1. Cyproterone-
- -androgen receptor antagonist
- -adjunct in rx of PROSTATIC CA
- -RX of precociuous puberty in males
- -RX of masculinization and acne in women
- 2. Gonadotropin-releasing hormone analogues-
- -decrease LH secretion which decreases testosterone synthesis by the testes
- -Leuprolide- prostate cancer
- -prolongs progression-free period and length of survival of men with advanced prostate cancer
- 3. Flutamide-
- -androgen receptor antagonists
- -competes with testosterone for androgen receptor
- -RX of prostate CA
- -adverse eff- mild gynecomastia, mild reversible hepatic toxicity
- 4. Finasteride-
- -has affinity for androgen receptors in prostate gland
- RX- BPH, and baldness
ANDROGEN SYNTHESIS INHIBITORS-
- -inhibit synthesis of testosterone
- -antifungal drug
- -inhibits CP450 enzymes inchluding those involved in steroidgenesis
- -inhibits fungal infections and testosterone sythesis
- -causes gynecomastia
- -RX of prostate CA and Cushings syndrome- reduces steroid synthesis in the body.
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