IC15 Pharmacology of Medications for Reproductive Disorders

Question 1

What is the MOA and indication of ethinyl estradiol?

Answer 1

MOA:
* A synthetic estrogen (birth control pill; oral contraceptive)
* An estrogen receptor agonist
* Inhibit follicle-stimulating hormone (FSH) release from anterior pituitary and suppresses the development of ovarian follicle. This makes the endometrium unsuitable for implantation of the ovum (Follicular phase affected)

Tx:
(a) menopausal symptoms
(b) gynecological disorders and
(c) certain hormone-sensitive cancers

Question 2

What is the distribution of EE?

Answer 2

Very high plasma protein bound (Albumin)

Question 3

How is EE eliminated?

Answer 3

Metabolized by liver:

Phase I – EE undergoes hydroxylation CYP3A4
Phase II – Conjugation with glucuronide and sulfation into hormonally inert ethinyl estradiol glucuronides and ethinyl estradiol sulfate

Due to the formation of EE sulfate, enterohepatic recirculation* is involved

Excreted in feces and urine

Question 4

What are the ADR of EE?

Answer 4

• Breast tenderness
• Headache
• Fluid retention (bloating)
• Nausea
• Dizziness
• Weight gain
• Venous Thromboembolism (VTE)
• Myocardial infarction/stroke
• Liver damage

Question 5

What are the contraindications of EE?

Answer 5

• History or susceptibility to arterial or venous thrombosis
• Advanced diabetes with vascular disease
• Hypertension ≥160/100
• Avoid in breastfeeding (<21 days postpartum) and breast cancer women

Question 6

What is the MOA and Tx of Norethindrone?

Answer 6

MOA:
* A synthetic progestogen (birth control pill; oral contraceptive)
* Inhibits Luteinizing hormone (LH) release and prevents ovulation (Luteal phase affected). This makes the endometrium unsuitable for implantation of the ovum
* Act as a progesterone receptor agonist

Tx:
(a) endometriosis
(b) abnormal periods or bleeding and to bring on a normal menstrual cycle

Question 7

How is norethindrone distributed and eliminated?

Answer 7

Plasma protein binding is high

Metabolized in liver by reduction follow by glucuronidation and sulfation

Some evidence suggest some % norethindrone can be metabolized in liver to EE* (ethinyl estradiol)

Excreted in the urine and feces

Question 8

What are some ADRs of norethindrone?

Answer 8

• Headache
• Dizziness
• Bloating
• Weight gain
• Episodes of unpredictable spotting and bleeding (initial)
• Amenorrhea

Question 9

Why is norethindrone undesirable for women planning pregnancy soon after cessation of therapy?

Answer 9

May not be desirable for women planning a pregnancy soon after cessation of therapy because ovulation suppression can sometimes persist for as long as 1.5yrs

Question 10

Why is there a concern over norethindrone’s potential metabolism to EE?

Answer 10

The partial conversion of norethindrone to EE requires special attention due to the potential cardiovascular related complications (eg. VTE) of EE.