Hormone contraception pharmacology CIS (Linger) - MT Flashcards
Endogenously, GnRH is released in a pulsatile manner. During exogenous GnRH therapy, what are the respective actions of GnRH agonists and antagonists?
- Agonists will have brief flare phase of 7 days where LH and FSH are increased, but after that period, negative feedback inhibition is maintained and levels of LH and FSH are lowered
- Antagonists immediately block the pathway of LH and FSH production
The treatment of hormone responsive breast cancer and infertility usually involves which group of pharmaceuticals?
- Anti estrogens
Prevention of breast cancer and osteoporosis usually involves which group of pharmaceuticals?
Selective estrogen receptor modulators (SERMs)
Medical abortions usually involve which group of pharmaceuticals?
anti progestins
Hormone contraception, Tx of hyperandrogenism and hypogonadism, postmenopausal HRT can involve which group of pharmaceuticals?
Estrogen progestin combinations
Endogenous estrogen effects on female maturation causes what two occurences?
- required for nmml sexual maturation and growth of female
- responsible for accelerated growth phase and closing of epiphyses of long bones occuring at puberty
Estrogen effects on endometrium?
- on metabolic and CV effects?
- on blood coagulation?
- with progesterone causes regular periodic bleeding and shedding of endometrial lining
- decreases rate of bone resorption
increases HDL and TGs slightly reduces LDL, reduces Total cholesterol
- enhances coagulability of blood
What are the two types of synthetic estrogen?
which one i more commonly used?
- Ethinyl estradiol, Mestranol
- Ethinyl estradiol
Adverse effects of therapeutic Estrogen include endometrial cancer risk. What other drug is taken with estrogen to protect against this risk?
- Progestin concmitant use
(in women with functional uteruses)
Estrogen is contraindicated in patients with what conditions? x7
- estrogen dependent neoplasms
. 2. undiagnosed genital bleeding
- liver disease
- hx of thromboembolic disorder
- heavy smoker over 35
- CV disease
- migraine w/ aura
Which has the higher risk for venous thromboembolisms?
- Pregnancy or Contraceptive estrogen
Pregnancy
Endogenous progestins have what effects on:
- hypothalamus pituitary axis during luteal phase?
- endometrium?
- Menstruation?
- maintenance of _________ and _________ development?
- production in luteal phase decreases frequency of GnRH pulses
- decreases estrogen driven endometrial prolif
- abrupt decline at end of cycle is main determinant of onset of mestruation
- key in maintaining pregnancy and mammary gland development (with estrogen)
Progestins are primarily used for what in concurrence with Estrogen? x2
- HRT
- Hormonal contraception (also alone)
benefits to using progestins include? x2
- multiple routes of administration, include long acting reversible contrceptives LARCs
- useful when estrogen is poorly tolerated or contraindicated
Adverse effects of progestins? x3
- breakthrough bleeding is common in progestin only contraceptives
- HRT w/ estrogen and progestin may increase breast cancer risk when compared to risk in women taking estrogen alone
- Progestins with androgenic effects: weight gain, acne, hirsutism, reduced plasma HDL
Progestin may be recommended over estrogen for contraceptive source in what situations? x6
- migraine HA
- age over 35 and smoker or obese
- Hx of thromboembolic disease
- Hx of CV disease
- Hypertriglyceridemia
- SLE with vascular disease, nephritis, or antiphospholipid Abs
What are the progestatinoal agents focused on which have varying degrees of estrogeni and androgenic potencies? x4
- Medroxyprogesterone acetate
- Desogestrel (etonogestrel active metabolite)
- norethindrone
- L Norgestrel
Progestational agents with more androgenic activity like acne hirsutism, weight gain include which two agents?
- L norgestrel
- norethindrone
potential progestational agents used to treat acne are?
- why?
- Norgestimate, Drospirenone
- lower or anti androgenic potency
Molecular mechanism of ER and PR induced activation of gene transcription:
- hormone enters cell membrane (lipid soluble)
2.
3.
4.
5.
6.
7.
- Nuclear receptor and Heat shock protein complex forms intracellularly
- NR and hormone complex dissociates from HSP
- NR/hormone complex forms dimer with another NR/homone complex
- dimer enters nuclus through nuclear pore
- NR dimer binds coactivator and RNA polymerase and sims production of mRNA
- mRNA goes into cytoplasm and is translated into proteins that change cell function
Combination oral contraceptives work by?
- what is suppressed? x3
preventing ovulation via feedback inhibition of HPA
- LH and FSH levels suppressed, Mid cycle surge of LH is absent, endogenous steroid levels diminished
Progestin only contraceptives are highly efficacious but block ovulation in only about 60% of cycles. Their affectiveness is thought to stemm from what? x3
- thickening of cervical mucus (decreases sperm penetration.
- and endometrial alterations that impair implantation
- decreases GnRH pulse frequency
Tow types of preparatinos used for oral contraceptives include combinations of estrogens and progestins, and Continuous progestin therapy w/o estrogen.
What are the two forms of combo E/P contraceptives?
- Monophasic form = constant dose of both components
- Biphasic/Triphasic forms = dosage of one or both components that is changed once (bi) or twice (tri) during cycle
continuous progestin therapy may be beneficial to patients in which estrogen use carries more risk.
What is the concern with using continuous progestin oral contraceptives? (higher incidence of what ADR?)
Abnormal bleeding risk increases
