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233 2nd midterm > Reproductive System > Flashcards

Reproductive System Flashcards

1
Q

describe the normal menstrual cycle

A
  • Kisspeptin and neurokinin B act on hypothalamus at beginning of menstrual cycle leading to pulsatile GnRH once an hr
    – Gonadotrophin-releasing hormone
    (GnRH) stimulates secretion of follicl stimulating hormone (FSH) and luteinizing hormone (LH) from the
    anterior pituitary
    – FSH & LH stimulate ovarian follicle development
    ▪ FSH stimulates estrogen release and feedback to stop secreting FSH and regenerate endometrium
    ▪ LH stimulates ovulation and controls progesterone secretion from the corpus luteum
    – Estrogen controls proliferation of the endometrium
    – Progesterone controls the later secretory phase
  • prog and es tells ant pit to stop secreting LH
  • corp lut degneerates if no pregnancy
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2
Q

what are the types of estrogen?

what is the diff b/w endogenous and synthetic?
receptors?

A

– Endogenous estrogens: estradiol (most potent), estrone, and estriol
– Synthetic forms: ethinylestradiol & mestranol
– endog. are heptatically metaboilized, most contra uses synth

via nuclear estrogen receptors (ER) a and b
may also act via GPCR (vascular actions)

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3
Q

estrogen receptors and actions?

A

– nuclear estrogen receptors (ER) α and β, regulate transc factors, gene expression

–Vascular actions mediated via a GPCR also known as GPR30 or GPER

  • Activation of endothelial nitric oxide (NO) synthase (eNOS) increases NO causing vasodilation
  • influence lipid metabolism
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4
Q

Hormonal Contraceptives

what are the 2 main types of hormonal contraceptives?

define progestogen

A

– Combined pill (has both estrogen & a progestogen)
– The progestogen-only pill

Progestogen: Progesterone (naturual) or progestin (synthetic)

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5
Q

Hormonal Contraceptives

what makes up the combine pill?

A

– Estrogen is usually ethinylestradiol (synth)
– Progestogens can be
▪ Noresthisterone (Norethindrone), levonorgestrel, or ethynodiol
(2nd generation)
▪ Desogestrel, gestodene (3rd generation)
– Taken for 21 consecutive days followed by 7 pill-free days (can differ)

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6
Q

Hormonal Contraceptives

combined pill MOA?

A

– Estrogen inhibits secretion of FSH via negative feedback on anterior pituitary, which suppresses ovarian follicular development
– Progestogen inhibits secretion of LH and prevents ovulation
– Discourage implantation

– In combo, not suitable for implantation, impede tubomotility

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7
Q

Hormonal Contraceptives

combined pill
AE? (1)

A

– Mild nausea, Breast tenderness, Flushing
– Breakthrough bleeding (amenorrhea no mens for no hromone free intervals)
– Dizziness
– Depression or irritability

– Skin changes (e.g. acne)

  • estrogen reduces acne as they increase sex hormone binding globulin, less free androgens
  • prog component causes acne
  • 3rd gen prog less likely to cause acne, higher thromboembolism risk

– Weight gain: Fluid retention - mineralocorticoid activities

– *Thromboembolism: obstruction in blood vessel due to clot
- Smoking, HTN increases risk for thromboemolism, should not use

  • Blood pressure increased in small percent of women, increase angiotensinogen, reversible increase in bp
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8
Q

Hormonal Contraceptives

combined pill
beneficial effects

A

– Reduction in risk of ovarian and endometrial cancer
- earlier detection in breast cancer
– Decreased menstrual symptoms (e.g. irregular periods)
– Reduced iron deficiency anemia (risk)

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9
Q

Hormonal Contraceptives

Progestogen-Only Pill

composition? when is this given instead of combined pill?

A

– Progestogen includes norethindrone or ethynodiol
– Taken daily without interruption
– A suitable alternative for people who experience blood pressure increases resulting from estrogen or other contraindications of estrogen

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10
Q

Hormonal Contraceptives

Progestogen-Only Pill

MOA?

A

– Acts primarily on the cervical mucus making it inhospitable to sperm
– Also inhibits implantation through its actions on the endometrium and by altering motility and secretions of the fallopian tubes

not as effective as combined one, missing a day can lead to pregnancy
CYP450

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11
Q

Hormonal Contraceptives

name 2 other hormonal contraceptives

when are they used?

A

Postcoital (Emergency) Contraception
– Oral administration of levonorgestrel (2nd gen)
▪ Can be taken alone or combined with an estrogen
– Effective up to 72 hrs post-unprotected intercourse with a repeat dose 12 hrs later (now usually just give 1 dose of 1.5mg)
– Nausea and vomiting are common (can be taken with
diphenhydramine (Gravol))

Long-Acting Progestogen-Only Contraception
– Depot medroxyprogestogen given intramuscularly
– Menstrual irregularities are common
– Infertility may persist for months upon stopping treatment
– Non-biodegradable capsules - release over 5 year period

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12
Q

Drugs that Act on the Uterus

name 3 agents that enhance uterine motility

A

– Oxytocin
– Ergometrine
– Mifepristone/Misoprostol
- Cervical resistance must diminish for uterine contractions to be effective at driving uterine contents through the cervix

  • During preg, estrogen actions potentiated by progesterone makes the uterine not contract and hyperpolarize the cells
  • Near term, oxytocin - post pit should release
  • When baby pushes it oxytocin release and starts contraction
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13
Q

Drugs that Act on the Uterus

oxytocin
what is it? use?

A

– A nonapeptide that regulates myometrial activity to promote uterine contraction (given by intravenous or intramuscular injection)
– Release is facilitated by cervical dilatation and expression of its receptor is induced by estrogen

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14
Q

Drugs that Act on the Uterus

oxytocin
MOA?

A

– Oxytocin receptor is a GPCR that promotes increases in intracellular calcium
– Activation of calmodulin (CaM) stimulates myosin
light chain kinase (MLCK) to induce uterine contraction

more details
– Gq coupled to phospholipase C acts on membrane phospholipids, release IP3 which activates calcium channels in sarc ret to release Ca2+
- binds to calmodulin and activate it, MLCK phsophorylates myosin light chain -> contractile response

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15
Q

Drugs that Act on the Uterus

dosage form?
AE?

A

As a peptide cannot be taken orally and has an extremely short half-life (3 min) -> IV

– *Hypotension (when administered rapidly) - must be strarted at low dose and increased every 30 mins until max dose
– *Higher doses can cause sustained contractions reducing blood flow & O2 delivery to the placenta that lead to fetal distress & potentially death
– Uterine rupture (contraindicated in people with previous rupture)
– Antidiuretic effect, vasopressin from pituitary

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16
Q

Drugs that Act on the Uterus

Ergometrine

where does it come from?

A

Isolated from the fungus Ergot (Claviceps purpurea)
– Contracts the human uterus (minimal effect on a contracted uterus, but will elicit strong contraction from an inappropriately relaxed uterus)

17
Q

Drugs that Act on the Uterus

Ergometrine

MOA?

A

– Action on uterine smooth muscle is not completely understood
– May act partly on α-adrenoceptors and partly on 5-HT (serotonin) receptors (similar to ergotamine)

Beta adrenoceptors inhibit uterine contraction

18
Q

Drugs that Act on the Uterus

Mifepristone/Misoprostol

purpose? other altenratives?

A

– Mifepristone followed by a prostaglandin analog (e.g. misoprostol) is used to induce medical *abortion
– Gemeprost is another alternative given intravaginally following mifepristone
– Dinoprostone (prostaglandin E2 analog) and carboprost (prostaglandin F2⍺ analog)

19
Q

Drugs that Act on the Uterus

Mifepristone/Misoprostol

MOA?

A

Mifepristone is an antiprogestogen that acts as a competitive progesterone receptor antagonist in the presence of progesterone
– Misoprostol/gemeprost are prostaglandin E1 analogs that induces myometrial contraction leading to expulsion of tissue (e.g. fetus)
- mife partial agonist, sensitizes uterine muscle so lower doses of prostaglandins needed

20
Q

Drugs that Act on the Uterus

Ergometrine

AE?

A

– *Vomiting (D2 receptors in the chemoreceptor trigger zone)
– Vasoconstriction and increased blood pressure
▪ Nausea
▪ Blurred Vision
▪ Headache
▪ Angina: vasospasms of coronary arteries

21
Q

Drugs that Act on the Uterus

Agents that inhibit uterine motility
Name 2

A

– Atosiban: oxytocin receptor ant

– Salbutamol: b receptor agonist

22
Q

Drugs that Act on the Uterus

Agents that inhibit uterine motility

MOA of atosiban and salbutamol?

A

delay for 48 hr window
– Atosiban is a competitive antagonist of the oxytocin receptor and thus can be used to delay labour
▪ Prevents intracellular increase in inositol triphosphate (IP3) and intracellular calcium
▪ Also suppresses oxytocin-induced release of prostaglandins (PGE and PGF)

– Salbutamol is a β2-adenoceptor agonist that can inhibit spontaneous oxytocin-induced contractions of the pregnant uterus

23
Q

Drugs that Treat Infertility

name 4 main?

A

– Clomiphene (often leads to twins)
– Gonadorelin (synthetic GnRH)
– Follitropin (recombinant FSH)
– Lutropin (recombinant LH)

– Other GnRH analogues include
▪ Buserelin
▪ Leuprorelin
▪ Goserelin
▪ Nafarelin
24
Q

Drugs that Treat Infertility

MOA (clomiphene)

A

– Clomiphene is an estrogen antagonist that promotes gonadotrophin release by inhibiting the negative feedback effects of estrogen on the hypothalamus and anterior pituitary
– Promotes FSH secretion

Increase Release of GnRH and LH to promote ovulation - fertility purpose

25
Q

Drugs that Treat Infertility

AE?

A

– Flushing
– Vaginal dryness
– Bone loss
– Reversible ovarian enlargement (clomiphene), more FSH

26
Q

Drugs that Treat Infertility

when is GnRH/Gonadorelin given?
how should it be administered?

A

– GnRH/Gonadorelin given for infertility following failure of treatment with clomiphene
– GnRH/Gonadorelin can also be used to induce ovulation for collecting eggs for in vitro fertilization
– GnRH/Gonadorelin given in a pulsatile fashion, if given continuously will inhibit FSH release

27
Q

Drugs for Erectile Dysfunction

Phosphodiesterase Type V (PDE V) Inhibitors
name 3

A

Sildenafil (Viagra)
– Tadalafil (longer acting)
– Vardenafil (more selective for PDE V)

28
Q

Drugs for Erectile Dysfunction

MOA?

A

– During sexual stimulation nitrergic nerves release nitric oxide (NO) into smooth muscle cells
– NO activates guanylyl cyclase to generate cyclic GMP (cGMP)
– Inhibition of PDE V prevents breakdown of cyclic GMP
– cGMP is an allosteric activator of protein kinase G (causes vasodilation)

29
Q

Drugs for Erectile Dysfunction

AE? (2)

A

– *Hypotension: contraindicated in anyone taking vasodilators
– Flushing
– Headache
– *Visual disturbances (inhibition of PDE VI): not for ppl with hereditary degenerative retinoic diseases
varden is more for V but still not recommended

233 2nd midterm (13 decks)

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