Drugs Affecting Reproduction Function Flashcards
Where is estrogen produced ?
Synthesised by the ovary and the placenta and in small amounts in the adrenal cortex and testis.
Identify the main endogenous estrogen of the body. How many types of estrogens are there ?
There are 3 main endogenous oestrogens in humans.
Oestradiol is the most potent and principal oestrogen
Which types of receptors does estrogen usually interact with ?
- Main mechanism of action involves interaction with nuclear receptors (ERα and ERβ) to regulate gene transcription.
- Some estrogen effects (rapid vascular actions) are initiated by interaction with membrane receptors (e.g. GPER)
What is the primary factors influencing the kind of effects of estrogen.
Effects of estrogen depend on the state of sexual maturity
Identify the main therapeutic uses of estrogen.
- Replacement therapy in primary ovarian failure (Turner syndrome) to promote sexual maturation.
- Replacement therapy for menopausal symptoms such as flushing, vaginal dryness and osteoporosis.
- In contraception, they are used singly or in combination with progestogens.
- Prostate and breast cancer.
- When administered to males they cause feminisation.
Identify the main natural, and synthetic estrogen preparations which exist.
Natural: estradiol, estriol
Synthetic: mestranol
Identify the main unwanted effects of estrogen.
Unwanted effects of estrogens include: breast tenderness, nausea, vomiting, anorexia, retention of salt and water with resultant oedema and increased risk of thromboembolism
Identify the main kinds of drugs which affect reproductive function.
- Estrogens
- Selective Estrogen Receptor Modulators (SERMs)
- Progestogens
- Contraceptive Pills (including CCP, Progestin Only Contraceptive Pill, Post-coital (emergency) contraception, Long-acting progestogen only contraception)
- Post menopausal hormone replacement therapy
- Androgens (and antiandrogens)
- Anabolic Steroids
- Gonadotrophin-releasing hormone analogues
What is the mode of action of Selective Estrogen Receptor Modulators (SERMs) ?
Competitive antagonists or partial agonists of oestrogens are called selective oestrogen receptor modulators (SERMs).
(this includes some drugs that are selective oestrogen agonists in some tissues but antagonists in others)
Identify the main SERMs.
- Tamoxifen
- Raloxifene
- Clomiphene
State the main therapeutic uses of Tamoxifen. Is this an estrogen agonist or antagonist ?
Oestrogen-dependent breast cancer (anti-oestrogenic action on mammary tissue)
So selective oestrogen agonists in some tissues but antagonists in others.
State the main therapeutic uses of Raloxifene. Is this an estrogen agonist or antagonist ?
Used to treat and prevent post- menopausal osteoporosis (antiestrogenic effects on breast and uterus but oestrogenic action on bone)
So selective oestrogen agonists in some tissues but antagonists in others.
What is the mode of action of Clomiphene ? Is this an estrogen agonist or antagonist ?
Pure estrogen antagonist at the hypothalamus and pituitary - acts to block negative feedback which leads to increased gonadotropin secretion, increased E2 and ovulation.
Where and when is progesterone secreted ?
Progesterone is secreted by the corpus luteum late in the menstrual cycle and by the placenta during pregnancy.
Which receptors does progesterone act on ? What is its exact mode of action ?
Acts on the progesterone receptor (PR) to regulate gene transcription in target tissues.
Progesterone inhibits the synthesis of oestrogen receptors (after estrogen stimulates synthesis of PR)
To what extent is progesterone used therapeutically ?
• Progesterone is not used therapeutically due rapid clearance. Instead synthetic deriviatives are used – called progestins.
Identify progestogens used therapeutically.
PROGESTINS:
Medroxyprogesterone (derivative of natural progesterone)
Norethisterone (testosterone derivatives)
Distinguish between progestin and progestogen and progesterone.
Progestins are synthetic progestogens and are used in medicine
Progesterone is also an endogenous progestogen
Identify therapeutic uses of progestogens.
1) Main therapeutic uses are in the oral contraceptive pill alone or in combination with oestrogen
2) Used as progesterone only injectable or implantable contraception or part of an intrauterine contraceptive.
3) Combined with oestrogen for oestrogen replacement therapy in women, with an intact uterus, to prevent:
– endometrial hyperplasia
– carcinoma
– endometriosis
Identify any unwanted side effects of progestogens.
Adverse effects of progestogens include: acne, fluid retention, weight gain, depression, change in libido, breast discomfort, menstrual cycle irregularity and increased thromboembolism.
Identify an anti-progestogen, and a therapeutic use of this anti-progestogen.
The anti-progestogen, mifepristone, in combination with prostaglandin analogues is an effective medical alternative to surgical termination of early pregnancy (up to 9 wks).
What are the main components of the combined contraceptive pill ?
-Oestrogen in most combined pills is ethinyloestradiol or
mestranol.
-The progestogen can be norethisterone, levonorgestrel, ethynodiol or in 3rd generation pills desogestrel or gestodene (more potent and have less androgenic actions).
What is the normal dose of combined contraceptive pill ? How often is this taken ?
Advice is to use the lowest dose that is well tolerated and gives good cycle control.
Most combined pills are taken for 21 consecutive days followed by 7 days pill free to allow a withdrawal bleed.
What is the consequence of discontinuation of the combined contraceptive pill ?
Menstrual cycles return quickly after discontinuation.
