CPT8 - Sex-Steroid Pharmacology

Question 1

3 features of pharmacokinetics of oestrogen and progesterone

Absorption
Metabolism
Excretion

Answer 1

1. ) Oestrogen
   - absorption: GI tract and skin/mucous membranes
   - metabolism: liver
   - excretion: urine as glucuronides and sulfates
2. ) Progesterone
   - absorption: when injected, it is bound to albumin while some is stored in adipose tissue
   - metabolism: liver
   - excretion: urine conjugated to glucuronic acid

Question 2

4 features of pharmacokinetics of oral contraceptives (COCP and POP)

Metabolism
Enzyme Inducing Drugs x3
Soya Proteins
Adverse Effects of COCP

Answer 2

1. ) Metabolism - liver by CYP450 enzymes
   - therefore efficacy is reduced by enzyme inducing drugs because they ↑production of hepatic CYP450s
2. ) Enzyme Inducing Drugs
   - anti-epileptics: carbamazepine or phenytoin
   - antibiotics: rifampicin and rifabutin
   - natural products: St John’s Wort
3. ) Soya Proteins - ↑oestrogen absorption
   - also ↓storage in adipose and muscle
   - causes half-life to reduce from 15 to 7 hours
4. ) Adverse Effects of COCP - thromboembolism
   - smoking increases risk substantially as well as:
   - long term use in women over 35

Question 3

4 features of hormone replacement therapy (HRT)

Usage
Administration Routes x5
Risks x3
Other Benefits x5

Answer 3

1. ) Usage - prescribed for symptoms of menopause
   - e.g. hot flushes, dyspareunia, osteoporosis
   - it is NOT prescribed for heart disease
2. ) Routes of Administration
   - oral, transdermal, implant, transvaginal, nasal
3. ) Risks of HRT
   - endometrial/ovarian (ERT) and breast (HRT) cancer
   - venous thromboembolism
   - oral oestrogen associated w/ ↑ risk of stroke
4. ) Other Benefits of HRT - ↓risk of CVD
   - ↑HDL, ↓LDL, ↓triglycerides, ↓lipoproteins

Question 4

5 other drugs acting on the reproductive sytstem

Mifepristone (RU486)
SERMs
Clomiphene
Tamoxifen
Ulipristal Acetate

Answer 4

1. ) Mifepristone (RU486) - progesterone antagonist
   - sensitises myometrium to prostaglandin-induced contractions
   - used for termination of pregnancy
2. ) SERMs - mixed ER agonists and antagonists
   - have varying effects in differing tissues
   - raloxifene used for post-menopausal osteroporosis
3. ) Clomiphene - SERM used to treat anovulation
   - ER antagonist in the hypothalamus, preventing negative FB of oestrogen so ↑GnRH
   - induces ovulation by ↑production of FSH and LH
4. ) Tamoxifen - SERM used to treat breast cancer
   - pro-drug: activated by metabolism in the liver
   - ER antagonist in the breast
   - ER agonist in endometrium (↑ endometrial cancer)
5. ) Ulipristal Acetate - emergency contraception
   - selective progesterone receptor modulator (SPRM)
   - delays/inhibits ovulation
   - also used to treat uterine fibroids