reproductive pharmacology Flashcards
Describe the pathway from hypothalamus to its effects on the reproductive tract
mention
- GnRH
- anterior pituitary
- FSH and LH
- oestrogen and progesterone
mention
-
a surge of what hormone occurs immediately after ovulation?
LH - ruptures the follicle
How does estrogen influence fertility control?
influences ovum maturation/development of the ovum/follicular unit
- it controls the timing of the follicular phase
How does estrogen effect the uterus?
prepares the uterus for implantation
–proliferation/vascularisation of endometrial cells
–induction of progesterone receptors to allow progesterone response during luteal phase
How does estrogen levels effect FSH and the anterior pituitary?
Inhibit FSH release, negative feedback on AP
what is the metabolic action of estrogen? effect on lipids? bones? skin?
what is the classical mechanism of action of estrogen?
acts on ERalpha and ER beta (estrogen response element) which are in different locations around the body - they induce/repress gene transcription intracellularly
•Metabolic action
–Mineralocorticoid-like - retention of Na+ and water
•Lipids
–Increase [HDL] in plasma
–Decrease [LDL], [cholesterol]
•Increase coagulability of blood
–Increases a number of clotting factors
•Maintains bone density and elasticity of skin & blood vessels
what is the non-classical MOA of estrogen?
recently discovered are membrane receptors - that are responsible for the rapid estrogen effects and mediate non-genomic mechanism of signaling
why do we use synthetic versions of estrogens?
mestranol, stilbestrol and ethinylestradiol
synthetic versions are used more often b/c they are degraded less rapidly by the liver -
estrogen is almost alwys administerd with what?
with a progestogen
given always unless to woemn with historectomy
b/c unopposed estrogen can have an effect on endometrial cancers
Under what circumstances do we give estrogen?
contraception
estrogen replacement therapy (ovarian failure, or menopause)
what are some side effects of estrogen?
- nausea/vomiting
- retention of salt and water
- risk of thromboembolism
- risk for uterine cancer
- in males - feminisation
what are some contraindications of estrogen therapy?
- estrogen dependent tumours
- undiagnosed genital bleeding
- liver disease - liver metabolises estrogen - so woman will be exposed to a much higher dose of estrogen
- history of thromboembolic disorder
- best avoided by heavy smokers - increased risk factors particularly in over 40 years of age
what are anti - estrogens?
they compete with endogenous estrogen to bind to recpetors in the body and thereby block estrogen effects
what are some examples of anti-estrogens?
Tamoxifen - estrogen antagonist (SERM- selective estrogen receptor modulator) - treat estrogen receptor positive breast cancer and has mild estrogen agonist effects in other tissues like bone, endometrium, and plasma lipids
clomifene - is an SERM as well and induces ovulation (infertility treatment) - by binding in anterior pituitary blocking the normal negative feedback loop - this may be enough to induce FSH and LH to stimulate ovaries in infertility
what is the effect of progestogens?
hormonal effects = maturation of endometrium and supports gestation and embryogenesis
other effects = increase basal insulin and insulin response to glucose - increases body temp (has a depressant effect)
traditional progesterone pills are derivatives of what?
they are testosterone derivatives so they can be taken orally without risk of first pass metabolism
the only downside to this is that they have slight androgenic activity which is not ideal for women (ex. Norgestrel)
the newer ones
“desogestral” used for contraception has less adverse effects but a higher risk of thromboembolism
what are some clinical uses of progestogens?
contraception, HRT, endometriosis, and endometrial cancer
What is Mifepristone?
works in the presence of progesterone as a competitive receptor antagonist - so you block the effect of progesterone causing termination of a pregnancy up to 7 weeks
used alone or in combination with prostaglandin E1 analogue - which induces uterine contractions and causes expulsion of the fetus - this is the most effective means.
what is the approx. life of egg after ovulation?
12-24 hours
what is the life of sperm after ejaculation in the reproductive tract?
up to 3-5 days
what is the mechanism of action of the combined estrogen/progestogen oral contraceptive pill?
Describe the MOA of a progestogen only pill
MOA = makes cervical mucus inhospitable to sperm, hinders implanation, inhibit LH release and prevents ovulation -
99% reliable if compliant - must be taken within 3 hours of same time everyday
side effects= ovarian cysts potential, irregular menstruation or amenorrhoea
used mostly when estrogen pills are contraindicated
ie.) raised blood pressure with estrogen, history of venous thromboembolism, smokers over 35, and can be used by nursing mothers
does prevention of ovulation delay menopause?
- no, you cannot ‘save’ up eggs- there is no evidence that there is protective effect from menopause this way -
what are some potential drug interactions with oral contraceptives?
any diarrhea, or vomitting between 2-3 hours after taking the pill will prevent the effectivenes of the drug -
the cytochrome P450 in the liver metabolises both estrogen and progeston- so anything hindering that enzyme will effect the effectiveness of the pill
ex) rifampicin and rifabutin antibiotics, St John’s Wort
Describe the progestogen only injectable contraceptive
progestogen-only injectables given intramuscularly every 3 months
slowly released into the systemic circulation following intramuscular injection
- some women report menstrual irregularities on it
- increased risk in osteoporosis and therefore should not be used longterm (no longer than 2 years of continuous use)
- works by suppressing ovulation and cervical mucous thickening
describe the progestogen only subdermal implant
implanted subcutaneously - non-biodegradable capsules
releases over 3 years, removed no later than end of 3rd year, irregular bleeding/headaches
suppress ovulation and cervical mucus is thickened, prevent sperm penetration
Describe the emergency contraception pill
not 100% effective - they work by delaying or inhibiting ovulation and modifying cervical mucous - they have slightly different effects dependent on what time in the cycle you might use
if ovulation has already taken place - it delays the movement of the egg in the fallopian tube and produces mucuous to try to prevent egg/sperm introduction
*note if the pregnancy is already established it will not disrupt it- generally it has no effect on the fertilized egg*
describe the progestin-only emergency contraceptive pill
- must be taken within 72 hours (efficacy decreases with time)
- nausea and vomiting is common
- weight will effect the efficacy (not as efective in women who are obese)
*ex) levonelle or NorLevo, or Plan B
Describe the ellaOne emergency contraceptive pill
- used to prevent pregnancy up to 5 days without a deterioration of efficacy or contraindication of weight
- it is a progesterone receptor modulator
*she says to study MOA more than anything*
