5. Reproductive And Post Reproductive Pharmacology

Question 1

What are the actions of oestrogen?

Answer 1

Mild anabolic
Sodium and water retention
Raises HDL, lowers LDL
Decrease bone resorption 
Impair glucose tolerance 
Increase blood coagulability

Question 2

What are the side effects of oestrogen?

Answer 2

Breast tenderness
Nausea, vomiting
Water retention
Increased blood coagulability
Thromboembolism
Impaired glucose tolerance 
Endometrial hyperplasia and cancer
Ovarian metaplasia and cancer
Breast hyperplasia and cancer

Question 3

What are the actions of progesterone?

Answer 3

Secretory endometrium
Anabolic
Increases bone mineral density
Fluid retention
Mood changes
Maintains pregnancy

Question 4

What are the side effects of progesterone?

Answer 4

Weight gain
Fluid retention
Anabolic
Acne
Nausea/vomiting
Irritability, depression, PMS
Lack of concentration

Question 5

What are the actions/side effects of testosterone?

Answer 5

Male secondary sex characteristics
Anabolic
Acne
Voice changes
Increases aggression
Metabolic

Question 6

Give some oestrogen pharmacokinetics points

Answer 6

Natural and synthetic oestrogens well absorbed in GI tract
Also really absorbed from in and mucous membranes
Metabolised in liver
Excretion - in urine as glucuronides and sulfates

Question 7

Give some progesterone pharmacokinetics points

Answer 7

Injected progesterone is bound to albumin with some stored in adipose tissue
Metabolised in liver
Metabolites excreted in urine conjugated to glucuronic acid

Question 8

What are the adverse effects of the combined pill?

Answer 8

Risk of thromboembolism
Smoking increases this risk significantly
Also increases for long-term use in women over 35

Question 9

Which enzyme metabolises COCP and POP in the liver?

Answer 9

CYP 450 enzymes

Question 10

Which drugs can reduce efficacy of oral contraceptives?

Answer 10

Enzyme inducing drugs:

• anti-epileptic (carbamazepine or phenytoin)
• some antibiotics (rifampicin or rifabutin)
• some natural products (st johns wort)

Question 11

Why can some drugs reduce efficacy of oral contraceptives?

Answer 11

They increase the production of hepatic CYP450

Question 12

Why is HRT prescribed?

Answer 12

Symptoms - hot flushes, sweats, dyspareunia

Protect against risk of osteoporosis

Question 13

What are the risks of HRT?

Answer 13

ERT - increases risk of developing endometrial and ovarian cancers
HRT - increases risk of developing breast cancer
Increase risk of venous thromboembolism
Cardiovascular disease
Increased risk of stroke

Question 14

What are the treatments for osteoporosis?

Answer 14

Bisphosphonates

• class of frugs that reduce bone turnover
• act by controlling osteoclast activity

Question 15

What are the pharmacokinetic considerations for osteoporosis treatments?

Answer 15

Long biological half life
Poor gut absorption
Absorption affected by food so must be taken on empty stomach

Question 16

What are the adverse drug reactions to osteoporosis treatments?

Answer 16

Upper GI effects - oesophagitis

Hypocalcaemia - check calcium and vit D levels prior to initiating treatment

Question 17

What is the action of mifepristone (RU486)?

Answer 17

Progesterone receptor antagonist
Acts as an anti-progesterone
Sensitising the myometrium to prostaglandin-induced contractions
Used for termination of pregnancy

Question 18

What are selective estrogen receptor modulator (SERM)?

Answer 18

Pure agonists and pure antagonists in different tissues

Question 19

What are drugs in the SERM class?

Answer 19

Tamoxifen

Raloxifene (treatment for osteoporosis)

Question 20

What is the function of clomiphene?

Answer 20

Used in treatment of an ovulation
Competes with oestrogen for ER binding
Leads to ovulation induction through increased production of anterior pituitary hormones

Question 21

What is tamoxifen?

Answer 21

A pro-drug - little affinity for the ER
Metabolised in liver to active derivatives
Active metabolites compete with oestrogen for binding to the ER

Question 22

How does tamoxifen act in endometrium?

Answer 22

Acts as ER agonist

Question 23

How does tamoxifen act in breast tissue?

Answer 23

Acts as ER antagonist

Binding of the ER following tamoxifen treatment causes cells to arrest the cell cycle

Question 24

What is ulipristal acetate?

Answer 24

Selective progesterone receptor modulator
When used for emergency contraception the primary mode of action is thought most likely to be delay or inhibition of ovulation
Also effective treatment for uterine fibroids