Please enable JavaScript.
Coggle requires JavaScript to display documents.
Gonadal Hormones, Aromatase Inhibitors, SERD (Selective Estrogen Receptor…
Gonadal Hormones
Progesterone
Pharmacological Actions
- secretory changes in endometrium
- ↑Basal body temperature
- ↑Aldosterone secretion – salt & water retention – edema
- Depressant & hypnotic effects on brain
Uses - endometriosis
- contraception
- postponement of menstruation
- delayed menstruation
- Dysfunctional Uterine Bleeding
- dysmenorrhoea
- 1st trimester of pregnancy
19-nor testosterone derivatives - Norethindrone, Levonorgestrel, Gestodene, Norgestimate, Desogestrel, Drospirenone
Drospirenone - aldosterone antagonist
Norgestimate, Desogestrel - no androgenic effects
Progesterone derivatives - Medroxy progesterone acetate, Hydroxyprogesterone caproate
-
Danazol
Has weak progestational, androgenic & glucocorticoid activity
Uses - rarely - endometriosis
- Fibrocystic breast disease
- hematologic or allergic disorders- hemophilia, Christmas disease, ITP, angioneurotic edema
ADRs – weight gain, edema, acne & oily skin, hirsutism, deepening voice, hot flushes
MIFEPRISTONE
Progesterone receptor antagonist, Antagonist at glucocorticoid receptor also
- Uses - medical termination of pregnancy - Mifepristone 600mg single dose, Followed by Misoprostol 400μg single dose – 48 hours later
(90% success rate when given before 42 days)
- Post-coital contraception
- Once-a-month contraceptive
- Cervical ripening, induction of labor
- Endometriosis, uterine fibroid
- Cushing’s syndrome – palliation
ADRs - 1st trimester Medical Abortion
– prolonged, heavy bleeding, abdominal cramps, anorexia, nausea, vomiting, diarrhea
-
ADRs - headache, acne, fluid retention, breast tenderness, weight gain, depression, changes in libido
irregular periods
- Secreted by corpus luteum
- After 8 weeks, the placental syncytiotrophoblasts secrete P (if there is a delay, it leads to early pregnancy loss)
Estrogen
Natural Estrogens
Estradiol - most potent
Estrone - primary estrogen after menopause
Estriol - least potent, secreted by placenta
Synthetic (steroidal)
Ethinyl estradiol, Mestranol, Tibolone, Estradiol valerate/ cypionate
-
Pharmacokinetics-
- Routes - Oral, vaginal, parenteral, transdermal, topical
- Enterohepatic circulation – contributes to hepatic effects (↑clotting factors), which are more frequent in oral E, rather than other routes
Pharmacological Actions
- breast development, female body contours
- ovulation, proliferation of endometrium, vaginal lubrication
- prevents atherosclerosis
- maintenance of bone density, muscle mass
- Normal structure & function of skin & blood vessels
- ↑Hepatic clotting factors – II, VII, IX, X & ↓AT-III → ↑blood coagulability
- CNS - libido, memory, mental health
- Contraception
- Dysmenorrheoa
- Dysfunctional uterine bleeding
- Infertility/ PCOS
- acne, hirsutism
- senile vaginitis (topical E)
-
SERMs (Selective Estrogen Receptor Modulators)
Tamoxifen, Toremifene, Raloxifene, Bazidoxifene, Ospemifene, Clomiphene
Uses - Tamoxifen, Toremifene - hormone therapy to prevent breast cancer in contralateral breast
- Raloxifene - post menopausal osteoporosis, breast cancer
- Bazedoxifene - Osteoporosis, menopausal symptoms
- Ospemifene - Menopausal dyspareunia
CLOMIPHENE - MOA - partial agonist - inhibits negative feedback of E & P at anterior pituitary → increased secretion of FSH & LH
Use - ovulation induction
To ↑sperm count
ADRs - multiple pregnancy (10%), ovarian hyperstimulation
depression, visual disturbances
ADRs - hot flushes, loss of libido, peripheral vein thrombosis
Tamoxifen - endometrial hyper proliferation & endometrial cancer
Clomiphene - ovarian hyper stimulation, multiple pregnancy
- Uses of E - Hormone replacement therapy - for control of vasomotor symptoms, premature ovarian failure
Advantages - strengthens bones, maintains favorable lipid profile
Disadvantages - ↑risk of breast & endometrial cncer, thromboembolism, ↑Cardiovascular risk when given as E + P
ADRs - peripheral edema, breast tenderness, nausea
migraine, cholestasis, gall stones
hypertension
thromboembolism, myocardial infarction
-
MOA
- hormone binds to cytoplasmic receptor → receptor-hormone complex dimerizes → enters nucleus → interacts with specific DNA regulatory sequences → controls gene transcription
- Action is site & hormone specific
-
Steroidal hormones synthesized from cholesterol - also cortisol, aldosterone
Aromatase Inhibitors
-
-
Steroidal – Exemestane
Non-steroidal - Anastrozole, Letrozole, Fadrozole
-