Week 4: Reproductive Pharmacology: Antiandrogens Flashcards
Flutamide MOA
Competitive antagonist of androgen receptors
Flutamide clinical use
- Prostate carcinoma
- Off-label treatment of androgen excess
Flutamide side effects
- Hot flash
- decreased libido
- diarrhea
- vomiting
Flutamide contraindications
- 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
Finasteride MOA
5α-reductase inhibitor (which catalyzes the conversion of testosterone to DHT)
Finasteride clinical uses
- 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
Finasteride side effects
- Orthostatic hypotension
- dizziness
- decreased libido
- fatigue
- jaundice
Finasteride contraindications
- 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
Ketoconazole MOA
- Inhibitor of androgen synthesis as a result of inhibiting CYP17A1 (also called 17α-hydroxylase/17; 20-lyase; C 17-20 desmolase)
Ketoconazole clinical uses
- Steroid-responsive metatstatic prostate cancer
Ketoconazole side effects
- Orthostatic hypotension
- Dizziness
- fatigue
- jaundice
- nausea
- vomiting
Ketoconazole contraindications
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
Ketoconazole notes
- An antifungal agent
- Also inhibits cortisol synthesis due to CYP11B1 inhibition
Ketoconazole notes
- Antifungal agent
- Also inhibits cortisol synthesis due to CYP11B1 inhibition
Leuprolide MOA
Gonadotropin releasing hormone (GnRH) agonist
Leuprolide clinical uses
- advanced prostate cancer
- endometriosis
- uterine leiomyomata (fibroids)
- central precocious puberty
- off-label use in breast cancer
- androgen excess
Leuprolide side effects
- Edema
- headache
- depression
- hot flashes
- allergic skin reaction
- pain at injection site
Leuprolide contraindications
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
Leuprolide notes
- Decreased bone density has been reported when used for more than 6 months
- Use caution in patients with addition risk factors for bone loss
Spironolactone MOA
Androgen receptor antagonist
Spironolactone clinical uses
off-lable use for treatment of acne and hirsutism in females
Spironolactone side effects
- 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
Spironolactone contraindications
Spironolactone has the potential to induce hyperkalemia
Spironolactone notes
Primarily used as a potassium-sparing diuretic
