Week 4: Reproductive Pharmacology: Antiandrogens

Question 1

Flutamide MOA

Answer 1

Competitive antagonist of androgen receptors

Question 2

Flutamide clinical use

Answer 2

• Prostate carcinoma
• Off-label treatment of androgen excess

Question 3

Flutamide side effects

Answer 3

• Hot flash
• decreased libido
• diarrhea
• vomiting

Question 4

Flutamide contraindications

Answer 4

• There have been reports of hospitalization and rarely death due to liver failure in patients taking Flutamide
• Serum transaminase levels should be measured monthly for the first 4 months of therapy and periodically thereafter
• Liver function tests also should be obtained at the first signs and symptoms suggestive of liver dysfunction

Question 5

Finasteride MOA

Answer 5

5α-reductase inhibitor (which catalyzes the conversion of testosterone to DHT)

Question 6

Finasteride clinical uses

Answer 6

• Benign prostatic hyperplasia
• treatment of male pattern hair loss in men only
• off-label use for female hirsutism (idiopathic and related to polycystic ovary syndrome

Question 7

Finasteride side effects

Answer 7

• Orthostatic hypotension
• dizziness
• decreased libido
• fatigue
• jaundice

Question 8

Finasteride contraindications

Answer 8

• Use with caution in patients with hepatic impairment
• Should be avoided by women who are pregnant, who may become pregnant, unless effective forms of contraception are being used due to Pregnancy Risk factor classification X

Question 9

Ketoconazole MOA

Answer 9

• Inhibitor of androgen synthesis as a result of inhibiting CYP17A1 (also called 17α-hydroxylase/17; 20-lyase; C 17-20 desmolase)

Question 10

Ketoconazole clinical uses

Answer 10

• Steroid-responsive metatstatic prostate cancer

Question 11

Ketoconazole side effects

Answer 11

• Orthostatic hypotension
• Dizziness
• fatigue
• jaundice
• nausea
• vomiting

Question 12

Ketoconazole contraindications

Answer 12

Rare:

• causes reversible (although can be fatal) hepatotoxicity
• can cause elevated plamsa concentrations of certain drugs and may prolong QT interval, sometimes resulting in life-threatening ventricular dysrhythmias
• Multiple drug-interactions due to inhibition of CYP3A4, CYP1A2
• CYP2C9

Question 13

Ketoconazole notes

Answer 13

• An antifungal agent
• Also inhibits cortisol synthesis due to CYP11B1 inhibition

Question 14

Ketoconazole notes

Answer 14

• Antifungal agent
• Also inhibits cortisol synthesis due to CYP11B1 inhibition

Question 15

Leuprolide MOA

Answer 15

Gonadotropin releasing hormone (GnRH) agonist

Question 16

Leuprolide clinical uses

Answer 16

• advanced prostate cancer
• endometriosis
• uterine leiomyomata (fibroids)
• central precocious puberty
• off-label use in breast cancer
• androgen excess

Question 17

Leuprolide side effects

Answer 17

• Edema
• headache
• depression
• hot flashes
• allergic skin reaction
• pain at injection site

Question 18

Leuprolide contraindications

Answer 18

For prostate cancer treatment

• an initial rise in serum testosterone concentrations may cause “tumor flare” or worsening of symptoms during the first 2 weeks

In women:

• similarly an initial increase in estradiol levels with a temporary worsening of symptoms may occur in women treated with leuprolide

Question 19

Leuprolide notes

Answer 19

• Decreased bone density has been reported when used for more than 6 months
• Use caution in patients with addition risk factors for bone loss

Question 20

Spironolactone MOA

Answer 20

Androgen receptor antagonist

Question 21

Spironolactone clinical uses

Answer 21

off-lable use for treatment of acne and hirsutism in females

Question 22

Spironolactone side effects

Answer 22

• Side-effects at doses recommended for hirsutism and acne are minimal
• Occasionally, polyuria, headaches, fatigue and gastritis may occur
• some normal ovulatory women may experience menstrual irregularity

Question 23

Spironolactone contraindications

Answer 23

Spironolactone has the potential to induce hyperkalemia

Question 24

Spironolactone notes

Answer 24

Primarily used as a potassium-sparing diuretic