Reproductive Pharmacology 2 Flashcards
anti-progestin - example
*mifepristone
mifepristone - MOA
*anti-progestin
*MOA: competitively binds to the progesterone receptor, blocking the effects of progesterone:
1. breakdown of endometrium
2. embryo detachment
3. contraction-inducting activity in myometrium
4. cervical dilation & expulsion of embryo
mifepristone (anti-progestin) - ADEs
*vaginal bleeding
*cramping
*N/V/D
*chills
*headache
*dizziness
mifepristone (anti-progestin) - place in therapy
*used in termination of intrauterine pregnancy (first trimester)
*labor induction
*hyperglycemia in pts with Cushing syndrome
termination of pregnancy - overview
*mifepristone → 24-48 hours → misoprostol
*misoprostol (e.g. Cytotec; prostaglandin analogue) causes cervix to soften/dilate → expulsion
*very high efficacy early on in pregnancy
*buccal misoprostol > vaginal
*no evidence to suggest adverse outcomes with subsequent pregnancies
misoprostol - overview
*aka Cytotec
*a prostaglandin E1 analog
*effects: softens / dilates (ripens) the cervix to allow for easier expulsion
*place in therapy:
-following mifepristone during medical abortion
-component of labor induction to soften cervix
roles of endogenous testosterone
*anabolic effects (muscle mass/strength)
*maturation of sex organs and development of secondary sex characteristics
*recall: testosterone is converted to estradiol via aromatase enzyme
synthetic androgen - example
*danazol
danazol - MOA
*synthetic androgen
*MOA: suppresses FSH and LH at the pituitary → atrophy of endometrial tissue (antiestrogen)
*also inhibits gonadal synthesis of hormones
danazol (synthetic androgen) - ADEs
*voice deepening
*hirsutism
*weight gain
*acne
*hot flashes
*decreased breast size
*hepatic dysfunction and dyslipidemia
*anovulation
*amenorrhea
*teratogenic
danazol (synthetic androgen) - place in therapy
*endometriosis (last line)
*fibrocystic breast disease
exogenous androgens: testosterone & methyltestosterone - MOA
*stimulates androgen receptors in organs and tissues to promote growth and development of male sex organs and maintains secondary sex characteristics in androgen-deficient males
androgens: testosterone & methyltestosterone - ADEs
*sodium retention (HTN/HF)
*acne
*facial hair growth
*deepened voice
*increased muscle development
*decreased spermatogenesis
*gynecomastia
*liver abnormalities
*aggressive behavior
*BPH
*erythrocytosis
androgens: testosterone & methyltestosterone - place in therapy
*delayed puberty (males)
*hypogonadism
*hormone therapy in transgender males (female to male)
considerations for male hypogonadism treatment
*exogenous androgen is NOT recommended for men with NORMAL testosterone levels (goal to achieve normal levels)
*benefits of exogenous androgen: development of secondary sex characteristics and increase libido, muscle strength, bone density, and mood (3-24 months)
*PO testosterone products has rapid hepatic clearance, so alternative routes are typically preferred (topical gels)
*monitoring: screen for prostate cancer, monitor hematocrit, and consider CV risk factors
anti-androgens (androgen antagonists) - examples
*flutamide
*bicalutamide
*nilutamide
*enzalutamide
anti-androgens (androgen antagonists) - MOA
*inhibits androgen uptake and/or inhibits binding of androgen in target tissues → blocking bindings of dihydrotestosterone
examples: flutamide, bicalutamide, nilutamide, enzalutamide
anti-androgens (androgen antagonists) - ADEs
*gynecomastia
*hot flashes
*GI disturbances
*elevated LFTs
*breast tenderness
*sexual dysfunction
examples: flutamide, bicalutamide, nilutamide, enzalutamide
anti-androgens (androgen antagonists) - place in therapy
*metastatic prostate cancer
examples: flutamide, bicalutamide, nilutamide, enzalutamide
anti-androgens (androgen antagonists): SPIRONOLACTONE
*MOA: competes with aldosterone for receptor sites in the distal renal tubules → increasing sodium chloride and water excretion
*may block the effect of aldosterone on arteriolar smooth muscle as well
*ADEs: hyperkalemia, gynecomastia
*place in therapy: hirsutism (females), acne (females), primary aldosteronism, diuretic, heart failure
anti-androgen-SYNTHESIS inhibitor (ketoconazole) - MOA
*inhibits gonadal and adrenal steroid synthesis and potential cytotoxic effect of prostate cells
*note - normally used an as ANTIFUNGAL
anti-androgen-SYNTHESIS inhibitor (ketoconazole) - ADEs
*QTc prolongation
*drug interactions
*GI disturbances
*hepatotoxicity
anti-androgen: 5alpha reductase inhibitors - examples
*finasteride
*dutasteride
finasteride & dutasteride - MOA
*anti-androgens: 5alpha reductase inhibitors
*MOA: inhibits 5-alpha reductase → resulting in inhibition of the conversion of testosterone to dihydrotestosterone → reduction in size of prostate gland
finasteride & dutasteride - ADEs
*decreased libido
*gynecomastia
*sexual dysfunction
*prostate cancer
finasteride & dutasteride - place in therapy
*benign prostatic hyperplasia
*male pattern baldness (finasteride)
*hirsutism in females (finasteride - off label)
considerations for benign prostatic hyperplasia
-
alpha-1-adrenergic antagonists:
-tamsulosin, terazosin, doxazosin, alfuzosin
-MOA: relaxation of smooth muscle in bladder neck and prostate → improved urine flow and decreased sx of BPH -
5-alpha reductase inhibitors:
-finasteride, dutasteride
-used for those unable to tolerate hypotension/ADEs of alpha1 antagonists - anticholinergic agents
- phosphodiesterase-5 inhibitors
considerations for androgenic alopecia (male pattern baldness)
- first line = oral finasteride (5-alpha reductase inhibitor)
- topical minoxidil (vasodilation → increased cutaneous blood flow → stimulates resting hair follicles)
GnRH agonists - examples
*leuprolide
*goserelin
*triptorelin
GnRH agonists - MOA
*MOA: agonist of GnRH → initial increase in LH → increase in testosterone / dihydrotestosterone (males) and estrone / estradiol (females) → long term use results in suppression of ovarian and testicular steroidogenesis due to decreased LH/FSH → decreased testosterone (males) and estrogen (females)
*examples: leuprolide, goserelin, triptorelin
GnRH agonists - ADEs
*initial worsening of symptoms (waiting for feedback system to kick in)
*can cause pretty much any gonadal hormone-related sx (erectile dysfunction, hot flashes, etc)
GnRH agonists - place in therapy
*advanced prostate cancer
*endometriosis
*advanced breast cancer (goserelin)
*central precocious puberty (leuprolide)
considerations for endometriosis-associated pain
-
combined or progestin-only hormonal contraceptive:
-MOA (combined): induce anovulatory state and hypoestrogenic state → decreased menstrual flow and regression of endometrial implants
-first line therapy -
GnRH agonist (eg. leuprolide):
-MOA: functional oophorectomy via FSH/LH → diminish endometrial implants - danazol (not favored)
phosphodiesterase-5 inhibitors - examples
*sildenafil (Viagra)
*vardenafil
*tadalafil
*avanafil
phosphodiesterase-5 inhibitors - MOA
*inhibition of phosphodiesterase-5 → prevent degradation of cGMP and enhances effects of nitric oxide → smooth muscle relaxation and increase in blood flow to corpus cavernosum
*VASODILATORS
*examples: sildenafil (Viagra), vardenafil, tadalafil, avanafil
phosphodiesterase-5 inhibitors - ADEs
*headache
*hypotension
*flushing
*dyspepsia
*nasal congestion
*examples: sildenafil (Viagra), vardenafil, tadalafil, avanafil
phosphodiesterase-5 inhibitors - place in therapy
*erectile dysfunction
*pulmonary hypertension (Sildenafil, Vardenafil)
*examples: sildenafil (Viagra), vardenafil, tadalafil, avanafil
sildenafil - class, MOA
*phosphodiesterase-5 inhibitor (PDE5 inhibitor)
*MOA: inhibition of phosphodiesterase-5 → prevent degradation of cGMP and enhances effects of nitric oxide → smooth muscle relaxation and increase in blood flow to corpus cavernosum
*VASODILATOR
considerations for erectile dysfunction
- PDE-5 inhibitors - first line
-vasodilators
-note: contraindicated with nitrates; use cautiously with alpha-1 antagonists - second line: intraurethral suppository, injectable meds
considerations for tocolysis
*tocolysis = inhibit labor (stop/delay labor)
*considered when overall benefits of delaying delivery outweigh the risks in preterm labor (postpone delivery long enough to allow max effect of antenatal steroid administration, allow transportation of mother to facility equipped to handle the risk)
*lower limit = 22-24 weeks
*upper limit = 34 weeks
tocolytics - inhibitors of labor: examples
- NSAIDs (indomethacin) - inhibit prostaglandins to prevent/delay labor; usually used in early-gestation (24-32 weeks GA)
- calcium channel blockers (nifedipine) - decrease in intracellular free calcium → myometrial relaxation; usually used in later gestation (32-34 weeks GA)
OTHER:
3. beta2 agonists (terbutaline, ritodrine)
4. magnesium sulfate (neuroprotective)
inducers of labor: oxytocin - MOA
*stimulates uterine contraction by activating GPCR → increased intracellular calcium levels in uterus
*also increases local prostaglandin production → stimulating uterine contraction
inducers of labor: oxytocin - ADEs
*arrhythmias
*TACHYSYSTOLE (intense, high frequency contractions)
*hypotension
*uterine hypotonia
*postpartum hemorrhage
*hyponatremia
*nausea and vomiting
inducers of labor: oxytocin - place in therapy
*induction of labor (after cervical ripening with misoprostol / dinoprostone - prostaglandin analogues)
*postpartum uterine bleeding
*adjunctive treatment of abortion
which tocolytic should be used for early gestational age preterm labor (24-32 weeks)?
*NSAIDs: indomethacin
which tocolytic should be used for later gestational age preterm labor (32-24 weeks)?
*CCB: nifedipine
