Repro drugs Flashcards
19-Norsteroids
Progestin a. Good bioavailability b. Original – some androgenic activity c. Newer – less androgenic activity Adverse effects – weight gain, acne, hirsutism with progestins having androgenic activity, BTB when used as progestin-only contraceptive
C-21 compounds
spectrum of effects close to that of progesterone
a. Drospirenone – newest C-21 based on spironolactone
b. Weak agonist at androgen and mineralocorticoid receptors
4. Adverse effects – weight gain, acne, hirsutism with progestins having androgenic activity, BTB when used as progestin-only contraceptive
Mifepristone (RU486)
Progesterone Receptor Modulators (antagonists)
a. Competitive progesterone receptor antagonist and glucocorticoid receptor antagonist
b. Considered selective progesterone receptor modulator (SPRM)
c. Orally active, good bioavailability
d. Used for medical termination of pregnancy
Ulipristal
Progesterone Receptor modulator (antagonist)
a. Partial agonist at progesterone receptor
b. Blocks ovulation (multiple mechanisms), blocks ovarian rupture at or just after LH surge
c. Used for emergency contraception!
Estradiol
a. Steroid highly absorbed by epithelial surfaces
b. Micronized for sufficient surface area for rapid absorption
c. High first-pass hepatic metabolism
3. ADRs – may cause breast tenderness, nausea or venous thromboembolism when used in combined oral contraceptive preparations
Ethinyl estradiol
a. Estrogenic component of most combined oral contraceptives
b. More resistant for hepatic degradation than estradiol (higher bioavailability)
c. Not nearly as highly bound to SHBG as estradiol
d. Increases production of SHBG
3. ADRs – may cause breast tenderness, nausea or venous thromboembolism when used in combined oral contraceptive preparations
Clomiphene
a. MOA – estrogen receptor antagonist or selective estrogen receptor modulator (SERM) with context-dependent actions. Competes with circulating estrogens for binding to estrogen receptors and prevents activation of estrogen receptors.
b. Effects – prevents activation of estrogen receptors
i. Blocks HPO axis
ii. Inhibits estradiol negative feedback on gonadotropin secretion leading to ↑↑↑LH and FSH
iii. Stimulates development of ovarian follicles and eventually induces ovulation
iv. used for polycystic ovarian disease (induce ovulation so so woman can conceive)
Combined Oral Contraceptives (COC)
a. Contain both estrogen and progestin (P suppresses ovulation, E enhances P responsiveness and regulates endometrium to prevent irregular bleeding and spotting)
b. Many different formulations and schedules utilizing some combination
c. Oral pills, transdermal patch, vaginal ring
d. MOA – acts on both hypothalamus and pituitary to decrease GnRH.
i. PROGESTERONE prevents ovulation by suppressing LH
ii. ESTROGEN prevents emergence of dominant follicle by suppressing FSH
iii. Progestin component suppresses hypothalamic pulsatility and ovulation
e. Endometrium, cervical mucus and fallopian tube effects reflect progesterone actions
i. Thick cervical mucus – prevents sperm travel
ii. Decidualized endometrium not receptive to implantation
iii. Possibly decreased fallopian tube motility – may also play role in preventing fertilization
f. Estrogen
i. Increases responsiveness to progesterone – induction of expression of progesterone receptors
ii. Stabilizes endometrium – reduces irregular spotting and bleeding
iii. Supports bone health – but may decrease bone density
g. Adverse effects
i. Thrombotic effects – increased production of clotting factors
ii. Nausea, breast tenderness
h. Contraindications
i. Absolute – smokers or over 35 years of age
ii. History of thromboembolism
iii. Diabetes with vascular disease
Emergency Contraception
Levonorgestrel– twice 12 hours apart or all at once. best in first 24 hours after unprotected sex
Ulipristal– selective progestin receptor modulator, most effective and best tolerated, prevents ovulation, works up to 5 days after intercourse, can work at or just after LH surge.
Testosterone
poor bioavailability (can’t be used therapeutically when given orally)
ROA: patch, gel, buccal tabled
gel preferred for males with hypogonadism
adults only
Testosterone enanthate (ester)
increased lipid solubility
ROA- depot IM injections (bypass enterohepatic circulation)
(T released slowly over 3 weeks– cleaved in vivo to suply bioactive T)
preferred for T replacement in male children with hypogonadism
17alpha-alkylated androgens
hepatotoxic
flutamide
not steroid compound
ROA-oral
MOA:
- androgen receptor antagonist (blocks acitviation of androgen R by testosterone–or any other androgen
- blocks T feedback inhibition on hypothalamus and pituitary. Leads to increased LH which leads to increased testicular T production
not effective along– use in combo with GnRH
Increases Testosterone, Increases LH & FSH
+GnRH
Finasteride
5alpha reductase inhibitor
MOA: blocks conversion of T to DHT (primarily in genitalia
effective in male pattern baldness and benign prostatic hyperplasia
5alphaReductase binds to free testosterone and DHT attacks hair follicles
Leuprolide
GnRH agonist (@ pituitary GnRH receptors) pulsatile admin can mimic normal secretion and activate gonadotropic axis. Continuous exposure leads to down-regulation of GnRH receptors and shutting down axis = chemical castration
eventually results in suppression of testituclar testosterone production without affecting adrenal androgen synthesis
(used to treat advanced prostate cancer)
in females: Leurprolide used to induce menopause
used for endometriosis
Sildenafil; Tadalafil
phosphodiesterase-5-inhibitor.. inhibits degradation of cGMP by inhibiting PDE-5 which increases NO which causes penile erection
AEs- blue vision in men, vasodilator properties (flushing, HA, nasal congestion)
contraindication in patients taking Nitrates (severe hypotension –> tachyarrhythmia)
Alprostadil
intrapenile admin, intraurethal… you know the drill on this one.
Treatment of androgen-dependent cancers (i.e. Prostate)
give Leurpolide (GnRH agonist…chem castration) and Flutamide (androgen receptor antagonist)
Spironolactone
Aldosterone receptor antagonist
DHT receptor antagonist
can be used to treat Hirsutism in females
Hypogonadism (male)
if primary hypogonadism (drugs won’t work, infertile)
LH and FSH needed to establish fertility
begin low dose Testosterone at puberty (stimulate skeletal growth and secondary sex characteristics)– gradually increase dose
(pre-pubertal therapy is the IM testosterone ester), adults = topical gel
hypogonadism (female)
Estrogen days 1-21
progestin 12-21
orally or via patch
when fertility is desired – pulsatile GnRH or FSH + hCG to induce ovulation at appropriate time
in adult women:
if uterus present (estrogen AND progesterone to prevent endometrial hyperplasia)
bromocriptine
Hyperprolactinema (Dopamine D2 agonist)
polycstic ovarian disease
clomiphene (disinhibit HPO axis)
hypogonadotropic anovulation
gonadotropins or pulsatile GnRH agonist
