Pharm: Androgens Flashcards
Natural androgens (4)
Which is the most potent?
Testosterone
Dihydrotestosterone (DHT) –> most potent
Androstenedione
Dehyroepiandrosterone (DHEA)
What is the benefit of synthetic androgens?
Longer half live (like all synthetic hormones)
What are 2 metabolic conversions of teststerone?
T + 5aReductase –> DHT
T + aromatase –> Estrogen
What is the basic mechanism of action of androgens (3 steps)
- Testosterone diffuses into the cell and binds to an intracellular androgen receptor
- Hormone-receptor complex dimerizes in the cell nucleus and binds to specific hormone-response elements on DNA, along with a complex of co-activator or co-repressor proteins
- This promotes or inhibits transcription of specific genes, resulting in physiologic effect
What are the REPRODUCTIVE actions of androgens? (5)
- growth, development and maintenance of primary (genitalia and genital tract) and secondary sex characteristics in men
- early stages of breast and pubertal development in girls (adrenarche)
- promote spermatogenesisi (with help of FSH)
- neuroendocrine regulation of gonadotropin secretion (negative feedback)
- stimulate libido
What are the ANABOLIC action of androgens? (4)
Increase protein synthesis
increase lean body mass
increase growth
reduce fat mass
similar to GH
What is the effect of androgens on growth (2)
Skeletal growth and CLOSURE of epiphyses of long bones during puberty and adolescence
Growth of larynx and voice deepening at puberty
Metabolic / hematologic actions of androgens?
Erythropoiesis
DEC synthesis of several clotting factors (opposite estrogen)
INC sebum production in skin
DEC synthesis of HDL cholesterol, INC LDL-chol (opp estrogen)
Androgenic alopecia (male pattern baldness)
INC bone density
Consequences of androgen deficiency in men (6)
- Decreased libido; erectile dysfunction
- Decreased lean muscle mass; increased adipose tissue mass
- Decreased axillary and pubic hair
- Anemia
- Osteoporosis
- Decreased energy, sense of well being
What are the therapeutic uses of androgens (3)
- HRT in primary or secondary hypogonadism
(gonads must be responsive) - Induction of puberty in delayed maturation
- Rx of osteoporosis in males
What androgens could be used as HRT? (2)
T. enanthate
T. cypionate
What is the clinical indicator of T. enathate and T. cypionate?
Hypogonadism
What is the MOA of T. enanthate and T. cypionate?
What are the effects of these androgens? (7)
MOA: replacement of testosterone
Produces ANDROGENIC effects such as:
- Growth and maturation of prostate (like estrogen and endometrium/breast)
- Seminal vesicles
- Penis & Scrotum
- Development of male hair distribution
- Laryngeal enlargement
- Vocal cord thickening
- Alterations in body musculature, fat distribution
SE of T. enanthate and T. cypionate? (6)
Contraindications (3):
Side Effects:
Cholestatic jaundice sundrome (protein synthesis in liver)
Liver carcinoma
Benign prostatic hyperplasia
Prostate cancer
Gynecomastia
Acne
Headache
Contraindications:
Breast CA in men
Prostate CA
Pregnancy
Delivery routes and formulations of T. enanthate and T. cypionate (4)
Which is prefered and why?
Intramuscular, transdermal, topical
gel and oral.
The transdermal is preferred to prevent first-pass hepatic metabolism.
Drug class of flutamide?
Androgen receptor antagonist
Flutamide:
Clinical Indicaiton
MOA
Flutamide:
Clinical Indication- metastatic prostate CA, BPH
MOA- competitive inhibitor of DHT and T binding to R
Flutamide SE (6)
Contraindications (1)
Flutamide SE:
Hepatotoxicity
Hematopoietic disorders
Diarrhea
Nausea
Rash
Hot Flashes
Contraindications (1):
Severe hepatic impairment
Effectiveness of flutamide:
Comparative effectivity of androgen antagonist in treatment of prostate CA:
Effectiveness: EXCELLENT when combined with medical or surgical castration
Comparative effectivity for prostate CA treatment”
Flutamide > DES and leuprolide which shut down LA and FSH to block androgen synthesis
Spironolactone drug class
Androgen receptor antagonist and aldosterone receptor antagonist
Spiranolactone:
Drug indications (8)
MOA:
Spiranolactone Drug Indications:
Hirsutism
Hypertension
Acne vulgaris
Edema associated with heart failure
Cirrhosis or nephrotic syndrome
Hypokalemia
Primary aldosteronism
MOA:
Competitive inhibition of DHT and T binding to receptor
SE of spiranolactone:
Contraindications: (3)
SE of spiranolactone:
Gastrointestinal hemorrhage
Hyperkalemic metabolic acidosis
Agranulocytosis systemic lupus erythematosus
Gynecomastia
Dyspepsia
Lethargy
Abnormal menstruation
Impotence
Rash
Breast cancer - not yet established
Contraindications: (3)
Anuria
Hyperkalemia
Acute renal insufficiency
Finasteride drug class
inhibitor of peripheral testosterone converstion to DHT
Finesteride drug indications (2)
MOA
Drug indications:
benign prostatic hyperplasia, androgenic alopecia
MOA: Selective inhibition of type II 5 a-reductase (enzyme responsible for conversion of testosterone to DHT in prostate, liver and skin)
Finasteride SE:
Contraindicaitons:
Side Effects:
Neoplasm of male breast
Breast tenderness
DEC libido
Erectile dynsfunction
Ejacultory disorder
Contraindications:
Known or suspected pregnancy, women and children
Effects of finasteride (2 major)
Improves urine flow (alternative to transurethral resection of prostate- TRUP)
Up to 25% reduction in prostate size when consistently used for one year
Most effective in patients with large prostates
