Pharm: Androgens

Question 1

Natural androgens (4)

Which is the most potent?

Answer 1

Testosterone

Dihydrotestosterone (DHT) –> most potent

Androstenedione

Dehyroepiandrosterone (DHEA)

Question 2

What is the benefit of synthetic androgens?

Answer 2

Longer half live (like all synthetic hormones)

Question 3

What are 2 metabolic conversions of teststerone?

Answer 3

T + 5aReductase –> DHT

T + aromatase –> Estrogen

Question 4

What is the basic mechanism of action of androgens (3 steps)

Answer 4

1. Testosterone diffuses into the cell and binds to an intracellular androgen receptor
2. 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
3. This promotes or inhibits transcription of specific genes, resulting in physiologic effect

Question 5

What are the REPRODUCTIVE actions of androgens? (5)

Answer 5

1. growth, development and maintenance of primary (genitalia and genital tract) and secondary sex characteristics in men
2. early stages of breast and pubertal development in girls (adrenarche)
3. promote spermatogenesisi (with help of FSH)
4. neuroendocrine regulation of gonadotropin secretion (negative feedback)
5. stimulate libido

Question 6

What are the ANABOLIC action of androgens? (4)

Answer 6

Increase protein synthesis

increase lean body mass

increase growth

reduce fat mass

similar to GH

Question 7

What is the effect of androgens on growth (2)

Answer 7

Skeletal growth and CLOSURE of epiphyses of long bones during puberty and adolescence

Growth of larynx and voice deepening at puberty

Question 8

Metabolic / hematologic actions of androgens?

Answer 8

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

Question 9

Consequences of androgen deficiency in men (6)

Answer 9

1. Decreased libido; erectile dysfunction
2. Decreased lean muscle mass; increased adipose tissue mass
3. Decreased axillary and pubic hair
4. Anemia
5. Osteoporosis
6. Decreased energy, sense of well being

Question 10

What are the therapeutic uses of androgens (3)

Answer 10

1. HRT in primary or secondary hypogonadism
   (gonads must be responsive)
2. Induction of puberty in delayed maturation
3. Rx of osteoporosis in males

Question 11

What androgens could be used as HRT? (2)

Answer 11

T. enanthate

T. cypionate

Question 12

What is the clinical indicator of T. enathate and T. cypionate?

Answer 12

Hypogonadism

Question 13

What is the MOA of T. enanthate and T. cypionate?

What are the effects of these androgens? (7)

Answer 13

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

Question 14

SE of T. enanthate and T. cypionate? (6)

Contraindications (3):

Answer 14

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

Question 15

Delivery routes and formulations of T. enanthate and T. cypionate (4)

Which is prefered and why?

Answer 15

Intramuscular, transdermal, topical
gel and oral.

The transdermal is preferred to prevent first-pass hepatic metabolism.

Question 16

Drug class of flutamide?

Answer 16

Androgen receptor antagonist

Question 17

Flutamide:

Clinical Indicaiton

MOA

Answer 17

Flutamide:

Clinical Indication- metastatic prostate CA, BPH

MOA- competitive inhibitor of DHT and T binding to R

Question 18

Flutamide SE (6)

Contraindications (1)

Answer 18

Flutamide SE:

Hepatotoxicity

Hematopoietic disorders

Diarrhea

Nausea

Rash

Hot Flashes

Contraindications (1):

Severe hepatic impairment

Question 19

Effectiveness of flutamide:

Comparative effectivity of androgen antagonist in treatment of prostate CA:

Answer 19

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

Question 20

Spironolactone drug class

Answer 20

Androgen receptor antagonist and aldosterone receptor antagonist

Question 21

Spiranolactone:

Drug indications (8)

MOA:

Answer 21

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

Question 22

SE of spiranolactone:

Contraindications: (3)

Answer 22

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

Question 23

Finasteride drug class

Answer 23

inhibitor of peripheral testosterone converstion to DHT

Question 24

Finesteride drug indications (2)

MOA

Answer 24

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)

Question 25

Finasteride SE:

Contraindicaitons:

Answer 25

Side Effects:

Neoplasm of male breast

Breast tenderness

DEC libido

Erectile dynsfunction

Ejacultory disorder

Contraindications:

Known or suspected pregnancy, women and children

Question 26

Effects of finasteride (2 major)

Answer 26

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