Sex Hormone Pharmacology Flashcards
(29 cards)
Estrogens :
- Estradiol or E2
- primary systemic ___
-Avail in many formulations (4) ? - estrone or E1
- how active?
-Available as a component of ? (2) - Ethinyl estradiol
-synthetically modified to have?
- how potent?
-available in ? - Estriol or E3
- not a __
-Less potent than ?
- estrogen
tablet, cream, patch, ring - 1/3 as active as estradiol
- conjugated estrogens like premarin , esterified estrogens (Menest) - slower hepatic metab
- 15-20x more potent than e2
- combo products - drug
E2
MOA OF ESTROGEN
1. Slow effects are transcription mediated. describe 3 steps
- rapid effects are transcription INDEPENDENT (three steps)
- estrogen binds receptor in cytoplasm or nucleus. E-R complex dimerizes and initiates transcription . protein synthesis mediates cell growth, function and differentiation
- E binds R in cytoplasm or cell membrane
E-R complex activates kinases and other proteins
2nd messengers mediate rapid cellular effects
Developmental effects of ESTROGEN :
F, G, S
Excess = incr risk of?
female genitalia
growth like puberty growth spurt and epiphyseal closure of long bones
secondary sex traits like body contours, hair growths, skin pigmentation, breast devel
excess = incr risk of breast cancer
Estrogen Nervous System Effects : B, M, S
behavior
mood –> menopause causes mood swings and depression
sympathetic tone -> menopause causes vasomotor sx’s like hot flashes
Cardio Effects of Estrogen
- Coagulation . helps incr factors (5) and decrease ? (3)
If excess leads to increased?
-Cholesterol
incr __ decr _(3)__, menopause causes __
Smooth musc relaxation and vasodilation
incr __ and __, decr __ and __
-menopause causes hot flashes
-excess causes ? (3)
2, 7, 9,10, 12
protein s and C, antithrombin
thrombosis risk like : stroke, MI, DVT, PE
HDL, LDL LPA and total cholesterol , dyslipidemia
nitric oxide, prostacyclin
angiotensin, endothelin
paradoxical HTN, edema, bloating
Metabolic and Hepatic Effects :
-Increases T_____
-Incr B____
-Incr Synthesis of ___
-___ resistance
Oral admin increases __ and decr __
triglycerides, bile concentration leading to gallstones, clotting factors , insulin
Toxicity, bioavailability
Repro Effects
-Increases __ growth
proliferative phase. Menopause causes __
Progesterone required for ?
Secretory phase
an imbalance results in ?
Enhances progesterone’s suppression of ___
-combined with progestins in OC’s
endometrial growth
abnormal uterine bleeding
endometrial maturation
endometriosis, endometr cancer
GnRH
Skeletal effects of Estrogen :
Increases ___ by inhibiting __ stimulating __ incr ___ survival
Menopause causes : ___
Epiphyseal closure ! (men and women)
bone mineral density
osteoclasts (major effect)
osteoblasts
osteocyte
osteoporosis
Avoid contraindications for giving HRT!
What are 6 CI’s?
Select the right drug !
Uterus intact –>
Uterus absent –>
Moderate CVD Risk –>
breast cancer, liver disease, stroke, DVT, CVD, High CVD Risk
estrogen + progestin
estrogen only
Avoid oral route
Progestins
MOA?
Many progestins act on receptors for other hormones such as (3)?
nuclear/cytoplasmic receptors similar to estrogen
estrogen, androgen, mineralocorticoid
Nervous System effects of Progestins
1. D__
2. INCR ___
3. INCR ___ (weight gain possible ae)
drowsiness, take oral contra’s at night
body temp, used for fertility monitoring
appetite
Repro effects : Contraceptive effect by 3 mechs
- Decreases transit of ___
-thickens ___ and impairs ___ through __ - Suppresses ___
- decr ___ by neg feedback
-effect enhanced by combining with estrogen - Matures ____
-secretory phase
-continuous admin impairs ___
-Abrupt withdrawal triggers ___
-Deficiency : may trigger ___
- sperm
cervical mucus, motility, fallopian tubes - ovulation , GnRH
- endometrial lining
- implantation
menstruation
breakthrough bleeding LATE CYCLE
Estrogen Deficiency :
Causes? (3)
Progestin deficiency?
Causes (2)?
Progestin Excess causes ? (2)
What can cause hypertension?
Early cycle breakthru bleeding
HYPOmenorrhea, or amenorrhea
LATE CYCLE breakthru bleeding
HYPERmenorrhea
HYPOmenorrhea or AMENORRHEA
estrogen excess
Estrogen + Progestin
-Contraindicated in women with risk factors for ___ like ?
Progestin only
-PO more difficult to take and can be less reliable
-less ___
Half life of ?
-Requires?
-Same ____
-What forms avoid these issues?
thrombosis (CVD, DVT/PE, Afib, Stroke, smokers >35 yo)
pituitary suppression
8 hrs
perfect adherence
time daily plus or minus three hrs
parenteral
Dosage forms for Estrogen + progestin (3)
for progestin only? (4)
What’s the most effect dosage form?
- oral, td patch, intravag ring
- oral, im injection, subdermal implant, intrauterine device
- Implant or IUD
Classification of Progestins : Progesterone derivs
- Progesterone has short ___ but low __
- Medroxyprogest is more __ and longer __
acetate used as ? - Megestrol
-Unique effects at multiple receptors like ____
-Used for ___ and __
half life, bioavail
potent, half life, long acting injection
mineralcorticoid, glucocorticoid
promotion of weight gain, breast cancer palliation
Testosterone Derivs
1. first gen is ? It is moderately __ and the ONLY ___
2. second gen? it is the MOST ___
- third gen? ___ androgenic
- fourth gen is a ___ derivative called ?
-It is ____ androgenic
- norethindrone
androgenic
progestin only OCP - norgestrel, levonorgestrel , androgenic
- norgestimate. LESS
- spironolactone , drospirenone , ANTI
Androgens :
- Primary systemic androgen?
-available in ___ forms?
-NOT ___ - DHT
-more potent than?
-Produced ___ in certain tissues
-NOT a __
- testosterone
parenteral (patch, gel, injection, implant)
orally bioavail
Testosterone
locally (Skin and prostate)
drug
Androgen Devel Effects
-___ genitalia , growth , secondary sex traits like?
-___ devel .
if pregnant woman exposed to androgen, can be __. pregnant woman dont touch drug products of androgens
male , deepening of voice
fetal
teratogenic , preg categ X
Androgen Nervous System Effects
-Behavior, energy and mood
an excess causes? Deficiency?
Cardio effects
-Coag : Increases ? Excess causes?
-Cholest : DECR __, excess?
-Sodium/H2O retention : ____ stimulation?
Excess? (3)
-Red blood cell production : Stimulation of __
Deficiency?
Aggression (think body builders)
depression
clotting factor synthesis. incr risk of stroke, heart attack and DVT
HDL, dyslipidemia
mineralocorticoid receptor . edema, HTN, electrolyte imbalance
erythropoietin , anemia
Metab and Hepatic Effects
-Metab of lipids, proteins, and carbs so an imbalance of the androgens causes ? (2)
-High first pass ___. (use parenteral routes)
-___ . incr risk of cholestasis and liver cancer especially with oral admin
insulin resistance, dyslipidemia
metabolism
hepatotoxicity
Repro Effects : Incr ___ growth which can cause? (2)
-Sexual Function : Deficiency causes ?
-Spermatogenesis : Imbalance causes?
Also has endometrial effects in females so its combined with ___ for female __
prostate, BPH, Prostate cancer
decr libido
infertility
estrogen, hrt
SKM effects
-Incr muscle __ and __. deficiency = ___. this is why its abused in performance enhancing drugs
-Incr ___ so a deficiency causes osteoporosis
Dermatological effects
“Male Pattern “ ____
Increases __ and ___ production so an excess causes ___
hair growth on face and body so an excess in females is known as ___
growth, strength. muscle weakness
bone mineral density
baldness
sweat , sebum, acne
hirsutism
Modified Androgens have decreased ___ which allows for increased bioavail and ___ dosing
-increased half life allows for ____
- Methyltestosterone is used for?
- Oxandrolone used for ?
- Danazol used for?
hepatic metabolism
PO
once daily dosing
hypogonadism
weight gain
endometriosis
