Pharmacology of Androgens and Anabolic Steroids Flashcards
Testosterone acts as a prohormone for
- 5alpha-dihydrotestosterone production ctalyzed by 5alpha-reductase enzyme
- Estrogen production catalyzed by aromatase enzyme
5alpha-DHT acts as the mediator of
the actions of testosterone in certain target tissues in which the 5alpha-reductase is expressed
What does the removal of methyl group in the 19 position of the androgen molecule do?
enhances its anabolic effects
Degradation and excretion of androgens
Androgens are metabolized in the liver to inactive 17-ketosteroids; 17-ketosteroids are excreted as conjugates of glucuronic and sulfuric acids
Effective systemic concentrations of exogenously administered native testosterone cannot be maintained for a considerable length of time because;
it is inactivated readily in the liver when given orally; also it is absorbed quickly and degraded quickly in liver when administered parenterally
Type A androgen preparation
esterified androgens
Type B androgen preparation
17alpha-alkylated androgens
Type C androgen preparation
androgens with changes in the ring structure
Some androgenic steroids
- Testosterone cypionate
- Testosterone propionate
- Testosterone enanthate
- Methyltestosterone
Some anabolic steroids
- Nandrolone decanoate
- Oxandrolone
- Oxymetholone
- Fluoxymesterone
- Stanozolol
Clinical uses of androgenic and anabolic steroids
- Androgen replacement therapy in men
- As protein anabolic agents
- Growth stimulators
- Endometriosis
- Osteoporosis
- Stimulation of erythropoiesis
Women respond to androgens with
hirsutism, acne, amenorrhea, clitoral enlargement, deppening of voice
Contraindications and cautions for the use of androgens
- Androgenic steroids should not be used in pregnant women or women who may become pregnant
- Male patients with carcinoma or prostate or breast
- Avoid the use of androgens in infants
Antiandrogens are useful in the management of
- hyperplasia and carcinoma of the prostate
- acne
- baldness
- virilizing syndromes in females
- precocious puberty in boys
- inhibition of sex drive in men who are sex offenders
Antiandrogens that inhibit androgen synthesis
- Gonadotropin Releasing Hormone
- Spironolactone
- Ketoconazole
Antiandrogens that block androgen action
- Cyproterone acetate
- Flutamide
- Finazteride (inhibits 5alpha-reductase)
MOA of GnRh as an antiandrogen
uncoupling of GnRH receptors from their effectors; internalization of GnRH receptors; depletion of LH stores in pituitary gonadotrophs
Therapeutic uses of GnRH as an antiandrogen
to manage prostate metastatic carcinoma and precocious puberty
Abiraterone as an antiandrogen
inhibits activity of 17alpha-hydroxylase; used to treat prostate cancer
Spironolactone as an antiandrogen
aldosterone antagonist; inhibits the activity of CP-450 enzymes involved in androgen synthesis
Ketoconazole as an antiandrogen
blocks adrenal and testicular androgen synthesis
Two types of antiandrogens that block androgen action
- drugs that compete for binding of testosterine and DHT to the androgen receptor
- inhibitors of 5alpha-reductase
Cyproterone Acetate
Progestin; potent androgen antagonist; used to treat acne, baldness, hirsutism, virilizing of syndromes, precocious puberty, prostatic hypertrophy and carcinoma, inhibition of libido in men
Flutamide
competes with androgens for the androgen receptor; used for the treatment of prostatic cancer usually in conjunction with GnRH analogs
Bicalutamide
competes with androgens for the androgen receptor; treatment of early stages of prostate carcinoma and hirsutism
Nilutamide
treatment of advanced stage prostate cancer; competes with androgens
Cimetidine
used primarily in the treatment of peptic ulcer disease; H2 antagonist; competes
Drugs that inhibit 5alpha-reductase
Finasteride and Dutasteride
used to treat BPH
