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Renal and Endocrine Biology > REB 18. Reproductive Pharmacology > Flashcards

REB 18. Reproductive Pharmacology Flashcards

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1
Q

What are some of the actions of estrogen on the body?

A

[1] ovum maturation/timing of follicular phase
[2] preparation of uterus for implantation
[3] inhibits FSH release - negative feedback on Anterior Pituitary
[4] mineralocorticoid-like retention of Na+ and water
[5] increases coagulability of blood (increase in clots)
[6] maintains bone desnity and elasticity of skin + blood vessels
[7] induces progesterone receptors to allow progesterone response in luteal phase

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2
Q

What are the 2 main estrogen receptors?

A

[1] ER(alpha)

[2] ER(beta)

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3
Q

What type of hormone is estrogen? What does this mean in regards to placement of receptors?

A
  • steroid hormone (hydrophobic)
  • passes through cell membrane easily, but cannot travel in blood
  • intracellular receptors!
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4
Q

Why is synthetic estrogen more therapeutically effective than natural estrogens? Give examples of both types of estrogen.

A

Natural vs. Synthetic

Natural = estradiol/estriol
Synthetic = Mestranol/Stilbestrol/Ethinylestradiol

Natural estrogens are degraded more rapidly than synthetic ones. Synthetic estrogens are degraded less rapidly and so, they have a greater therapeutic effect.

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5
Q

Normally, estrogen is administered with another hormone….which hormone and why?

A

Progesterone

  • if not administered with progesterone, the estrogen would be “unopposed”
  • estrogen has a proliferative effect on the endometrium and so, if given without progesterone, it would increase in proliferation, increasing the chances of endometrial cancer
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6
Q

What is the most common synthetic estrogen?

A

Ethinylestradiol

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7
Q

What are the clinical uses of estrogen?

A

[1] contraception
[2] replacement therapy
- primary ovarian failure (e.g. Turner’s Syndrome)
- secondary ovarian failure (e.g. menopause)

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8
Q

What is an example of primary ovarian failure? What is the treatment?

A

example: Turner’s Syndrome
- female born with only 1 X chromosome
- treatment: estrogen + progesterone

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9
Q

What is an example of secondary ovarian failure? What is the treatment?

A

example: menopause

- treatment: hormone replacement therapy

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10
Q

What are some of the side effects after taking the hormone, estrogen?

A
  • nausea + vomiting
  • retention of salt + water (leads to oedema then increased blood pressue)
  • increased risk of thromboembolism (due to increased coagulability)
  • increased risk of uterine, ovarian + breast cancer (endometrial - due to increased cell proliferation in uterus)
  • in males – leads to feminisation
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11
Q

What are some things that may arise when using the hormone, estrogen, as a drug? (some possible side effects and what may happen when using estrogen with another drug)

A

[1] estrogen-dependent tumours
- e.g. carcinoma of the endometrium or high risk of breast cancer

[2] undiagnosed genital bleeding
- may be associated with endometrial cancer

[3] liver disease
- if estrogen is not metabolized, there would be an increase in estrogen in the body

[4] history of thromboembolic disorder

[5] best avoided by heavy smokers

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12
Q

What is the general function of anti-estrogens?

A

they compete with estrogens for receptors in the target organs
- competitive binding with the natural estrogen

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13
Q

What are the 2 examples of estrogens?

A

[1] Tamoxifen

[2] Clomifene

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14
Q

What is Clomifene used to treat and what is its function?

A
  • estrogen antagonist (SERM)
  • induces ovulation (infertility treatment!)
  • inhibits estrogen binding in anterior pituitary preventing normal negative feedback
  • causes increase in FSH and LH
  • stimulates the ovaries
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15
Q

What is Tamoxifen used to treat and what is its function?

A
  • estrogen antagonist (SERM)
  • to treat estrogen +ve breast cancer
  • mild estrogen-like side effects (partial agonist on plasma lipids, endometrium + bone)
  • reduction in osteoporotic fractures
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16
Q

What are the hormonal effects and other effects of Progestogens?

A

Hormonal Effects:

  • maturation of endometrium
  • supports gestation and embryogenesis (fetus growing in womb)

Other Effects:

  • increases basal insulin + insulin response to glucose
  • increases body temp
  • depressant
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17
Q

What are some ways that progestogen may be prepared?

DO THIS

A

[1] Naturally Occuring Hormone

[2] Derivatives

[3] Testosterone Derivatives

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18
Q

What are the clinical uses of Progestogens?

A

[1] Contraception
[2] Hormone Replacement Therapy
[3] Endometriosis (growth of tissue-like endometrium, beyond or outside the uterus)
[4] endometrial cancer

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19
Q

What are some side effects of progestogens?

A
  • weak androgenic action (e.g. acne)
  • fluid retention
  • weight changes
  • libido changes
  • depression
  • premenstrual symptoms, irregular menstrual cycles
  • increased risk of thromboembolism
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20
Q

What is the name of an anti-progestogen? How does the anti-progestogen work?

A

Mifepristone (RU486)

- in the presence of progesterone, it acts as a competitive receptor antagonist at the progesterone receptor

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21
Q

In the absence of progesterone, how does Mifepristone work?

A

it acts as a partial agonist at the progesterone receptors

22
Q

What are the uses of Mifepristone?

A
  • medical termination of intrauterine pregnancies
  • used alone or in combination with prostaglandin E1 analogue [gemeprost or misoprostol] (it induces uterine contractions)
23
Q

How long can the egg survive after ovulation to be fertilized?

A

12 to 24 hours

24
Q

How long can sperm live in the female reproductive tract?

A

around 3 to 5 days (up to 5 days!)

25
Q

What are some different types of hormonal contraceptives?

A

[1] Oral Contraceptives

(a) combined pill (estrogen + progesterone)
(b) progestogen-only pill

[2] Long-Acting Progestogen - Only

[3] Emergency (Post-Coital) Contraception

26
Q

What is an example of the composition of the combined pill?

A

> 20ug Ethinylestradiol + >100ug Norethisterone (or Levonorgestrel)

27
Q

What are the time periods that the combined pill is taken for?

A
  • taken for 21 consecutive days

- 7 hormone free days

28
Q

What is the method of action of the combined pill?

A

ESTROGEN:

  • inhibits FSH release
  • inhibits development of ovarian follicle

PROGESTOGEN:

  • inhibits LH release
  • prevents ovulation
  • makes cervical mucus inhospitable to sperm
29
Q

What is the success rate of the combined pill?

A

99.5%

30
Q

What does it mean if the combined pill is mono-, bi- or tri- phasic?

A
  • it refers to the concentration of estrogen and progestegon in the pill
  • the concentration differs to mimic hormone concentration in the body
31
Q

What are some of the side effects of using the combined pill?

A
  • weight gain
  • nausea
  • mood changes
  • skin pigmentation
  • hypertension
  • breast cancer
  • thromboembolism

*side note: side effects are most limited to the first few cycles

32
Q

What is an example of the composition of the progestogen-only pill (mini pill)?

A
  • 350ug Norethisterone (Noriday)

- 75 ug Desogestrel (Cerazette) less common

33
Q

What are the time periods that the progestogen-only pill (mini pill) taken for?

A

taken daily, NO interruption

34
Q

What is the method of action of the progestogen-only pill (mini pill)?

A
  • makes cervical mucus inhospitable to sperm
  • it hinders implantations
  • inhibits LH release
  • prevents ovulation
35
Q

What is the success rate of the progestogen-only pill?

A

99.0%

36
Q

What are the side effects of the progestogen-only pill (mini pill)?

A
  • irregular menstruation/amenorrhoea (no bleed at all)

- ovarian cysts a risk

37
Q

When is the progestogen-only pill (mini pill)?

A

used where estrogen is containdicated…
- increased blood pressure with estrogen (increasd salt + water leading to oedema)
- history of venous thromboembolism (VTE)
- smokers over 35 years
- CAN BE USED BY NURSING MOTHERS!
(you cannot use estrogen-containing pills!)

38
Q

What are the 2 types of long-acting progestogen only contraception?

A

[1] Progestogen-Only Injectables

[2] Progestogen-Only Subdermal Implant

39
Q

What may Progestogen-Only Injectables be made of?

A

Medroxyprogesterone Acetate 150mg (DepoProvera)

40
Q

How is Progestogen-Only Injectables released into circulation? How long may it be effective for?

A
  • slowly released into the systemic circulation following intramuscular injection
  • every 3 months effective
    (but menstrual irregularities common!)
41
Q

What is a side effect of the Progestogen-Only Injectables?

A
  • reduction in bone mineral density and rarely, osteoporosis
  • not suitable for long term use (>2 years)
42
Q

What is the mechanism of action of Progestogen-Only Injectables?

A
  • suppresses ovulation

- cervical mucus is thickened (preventing sperm penetration)

43
Q

What may Progestogen-Only Subdermal Implant be made of?

A

Etonogestrel 68mg implanted subcutaneously non-biodegradable capsules (Implanon NXT/Nexplanon)

44
Q

How is Progestogen-Only Injectables released into circulation? How long may it be effective for?

A
  • released over 3 years

- removed no later than end of 3rd year

45
Q

What is a side effect of the Progestogen-Only Subdermal Implant?

A
  • irregular bleeding

- headaches

46
Q

What is the mechanism of action of Progestogen-Only Subdermal Implant?

A
  • suppresses ovulation

- cervical mucus is thickened (prevent sperm penetration)

47
Q

What are the mechanisms of action of post-coital contraception? How does this work in the first half of cycle and the second half of cycle?

A

Mechanism of Action:

  • delay/inhibit ovulation
  • modifies cervical mucus

First Half of Cycle:
- prevents ovulation (egg not released)

Second Half of Cycle:
- if ovulation has occurred - delays movement of egg in fallopian tube and thickens cervical mucus

48
Q

What are 2 examples of emergency (post-coital) contraception?

A

[1] Progestin-Only: Levonorgestrel (1.5 mg tablet)

[2] Ulipristal Acetate (ellaOne)

49
Q

When should Levonorgestrel be used? What are some side effects? Other effects?

A
  • must be taken within 72 hours
  • efficacy decreases with time

side effect: nausea + vomiting

  • weight will affect efficacy
50
Q

When should Ulipristal Acetate (ellaOne) be used? What are some side effects? Other effects?

A
  • used to prevent pregnancy up to 120 hours (5 days!)

- a progesterone receptor modulator

Renal and Endocrine Biology (25 decks)

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