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
Transderm preparations of combo E/P contraceptives are beneficial for what reason?
- Bypass first pass effect of liver metabolism
Cytochrome P450 inducing agents that may increase liver catabolism of estrogen or progestin include? x2
phenytoin/ rifampin
A 25 year old sexually active healthy woman presents to your clinic asking for a morning after pill because of having unprotected sex the night before. You prescribe her a drug that isn’t indicated for post coital emergency contraceptive, but effectively terminates >95% of pregnancis when dministered during the 1st 7 weeks of conception.
- What is the MOA?
- What is the major ADR?
- usually used in combo with what?
- norsteroid that acts as a progesterone Receptor antagonist and induces luteolysis
- major ADR is prolonged bleeding, requires intervention in 5% of cases.
- synthetic prostaglandin E1 (misoprostol)
mifepristone
What is Mifepristone labeled for use as in the United states?
Pregnancy termination agent
Mornin after agents (postcoital emergency contraceptives) include? x2
- Levonorgestrel (plan B one step, next choice)
- Ulipristal acetate (ella)
A 24 year old woman goes and picks up a morning after agent at the pharmacy w/o a presciption. She has read that this agent is more effective than estrogen-progesterone combinations and less likely to cause Nausea and vomiting, prompting her choice of this agent.
- What is its MOA?
- Can it stope a pregnancy that has already occured?
- Progesterone receptor agonist
- Does not stop pregnancies that have occured
99% of postcoital contraceptives are effectivee when administered within what time frame?
within 72 hours of coitus
Absolute contraindications of estrogen therapy include? x5
- active or Hx of TE disease
- Undiagnosed abnormal genital bleeding
- Known or suspect Hx of estrogen dependent neoplasia
- impaired liver function
- known or suspected pregnancy
What may worsen with estrogen and/ or progestin therapies? x6
- gallbladder disease
- hypertiglyceridemia
- asthma
- migraines
- epilepsy
- SLE
SERM agents include? x3
Tamoxifen, toremifene, Raloxifene
MOA of SERM Tamoxifen
competitive partial agonist inhibitors of estradiol at Estrogen Reeptors (antagonist on breast, agonist on other tissues)
Tamoxifen is used to treat what?
Estrogen responsive (ER+) breast cancer and chemoprevention of breast cancer in high risk individuals
Raloxifene MOA
agonist effects on lipids and bone; antagonist on endometrium and breast
Aromatase inhibitors include? x3
- MOA
- used to treat?
- anastrazole, letrozole, exemenstane
- inhibit function of aromatase (enzyme required for biosynth of estrogens from androgens)
- treat beast cancer in postmenopausal women
Advantage of Aromatase inhibitors over SERMs
significantly less incidence of vaginal bleeding, discharge, hot flashes, endometrial cncer, DVT when compared to SERMs
