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68 Cards in this Set

  • Front
  • Back
Principal androgen in men?

What secretes 95% of it?

What secretes 5% of it?
Testosterone

Leydig cells

Adrenal Cortex
What are the plasma levels of Testosterone in males after puberty?

When do they start to decline?
0.6 mg/dL

after age 50
What is the level of Testosterone in females?

What 2 sites secrete Testosterone in females?
.03 mg/dL (vs. 0.6 in males)

Adrenal Cortex & Corpus Luteum
What are 2 weak androgens secreted along with Testosterone in men?

What is their precursor?
Androstenedione & De-hydro-epi-androsterone (DHEA)
In target tissues, Testosterone is converted into active and inactive metabolites...what are the 2 ACTIVE metabolites?

Which is the major active androgen in most tissues?
1. Dihydro-testosterone
2. Estradiol


Dihydrotestosterone
In the Liver, Testosterone is metabolized into what 2 INACTIVE METABOLITES?
1. Andro-sterone

2. Etio-cholan-olone
List the changes that both Testosterone and Dihydrotestosterone cause at PUBERTY
1. general GROWTH-promoting properties
2. Penile & Scrotal growth
3. Thicker and oilier skin with more SEBACEOUS glands
4. appearance of pubic, axillary, and beard hair
5. Laryngeal growth, thicker vocal cords = lower-pitched voice
6. Accelerated Skeletal growth & Epiphysial closure
7. Growth of Prostate and Seminal Vesicles
8. Stimulating and maintaining Male Sexual fxn
List the 2 changes produced by Testosterone & Dihydrotestosterone in EARLY ADULTHOOD & MIDLIFE
1. gradual development of MALE PATTERN BALDNESS = begins with recession of hair at temples & vertex

2. development of BENIGN PROSTATIC HYPERPLASIA or PROSTATIC CANCER
Serum Testosterone declines gradually as men age so that by age 80 free testosterone concentration is about ____% of that at age 20
40%

**may be related to decreases in energy, libido, muscle mass/strength, and bone mineral density
Why is Oral Testosterone ineffective?
b/c it is catabolized in the liver
What type of preparations of Testosterone are able to bypass hepatic catabolism and are injected IM every 2-4 wks in Hypogonadal males
synthetic preps as LIPOPHILIC ESTERS dissolved in OIL
List 3 esters that are used to prolong and have greater activity release of free testosterone at injection sites
Propionate

Enan-thate

Cypio-nate

**are not Androgens themselves but help in the slow release of Testosterone
What are the 2 uses of Synthetic Androgens?
1. Anabolic effects (but increase in muscle strength is ALWAYS accompanied by adverse effects)

2. treating Testosterone deficiency
What do large doses of Synthetic Androgens cause in Adult Males?
suppress Gonadotropin secretion ➡ testicular atrophy
What can happen if Synthetic Androgens are given to women?
develop Secondary Male characteristics
What product is reduced in the urine due to taking Synthetic Androgens? What is the cause?
Urinary Nitrogen

Increased protein synthesis or decreased protein breakdown
When would Synthetic Androgens be used in boys?
as a growth stimulator in boys with delayed puberty
List 5 uses of Synthetic Androgens in treating women
1. Postpartum breast engorgement
2. Endometriosis
3. Endometrial bleeding (& to enhance libido) after menopause
4. Postmenopausal Osteoporosis (alone or combined with estrogens)
5. Chemotherapy of Premenopausal breast tumors
Give 3 situations in which Synthetic Androgens would be used as a protein anabolic agent to reverse protein loss
1. after trauma

2. after surgery

3. prolonged immobilization
What are the possible adverse effects of Anabolic Steroid abuse?
1. suppress endogenous Testosterone
2. suppress Sperm production
3. may cause Gynecomastia
4. may cause Virilization
What are 2 possible adverse effects if Synthetic Androgens are given to elderly males to replace low androgen levels
1. may worsen Benign Prostatic Hyperplasia

2. increase risk of Prostate CA
What are the adverse effects of Synthetic Androgens in Women?
1. Acne
2. Hirsutism
3. Amenorrhea
4. Clitoral enlargement
5. deep voice
6. ALTER SERUM LIPIDS TO INCREASE ATHEROSCLEROTIC SUSCEPTIBILITY
What are the adverse effects of Synthetic Androgens in Men? (6)
1. Acne (nathan)
2. Sleep apnea
3. Erythrocytosis
4. Gynecomastia
5. Azoospermia
6. decreased testicular size = due to decreased Gonadotropin secretion (FSH/LH)
List 2 Gonadotropin-releasing hormone (GnRH) analogs used for gonadal suppression in treatment of Prostatic Cancer
Gose-relin

Leu-prolide
Antifungal imidazole used to inhibit adrenal and gonadal steroid synthesis to treat Cushing's disease (adrenal) and Prostate Cancer (gonadal)

What is it's mechanism of action?
Ketoconazole

inhibits Desmolase
5-alpha-reductase inhibitor that reduces conversion of Testosterone to Dihydrotestosterone
Fin-asteride
What is Finasteride used to treat?
Benign Prostatic Hyperplasia

**5-alpha-reductase inhibitor
3 non-steroidal competitive inhibitors of androgens (anti-androgens) used to treat PROSTATIC CARCINOMA
F-lutamide

Bica-lutamide

Ni-lutamide
Aldosterone antagonist used clinically as a potassium-sparing diuretic, also lowers 5-alpha-reductase activity to lower plasma levels of Testosterone & Androstenedione
Spironolactone
Cottonseed derivative used as a male contraceptive in China
Gossypol
2 major constituents of Bone
Calcium & Phosphate

**bones contains 98% of total body Ca++; 85% of total body Phosphate
Which has higher intestinal absorption, phosphate or calcium?
Phosphate
Larger amounts of ______ are present in bone and reabsorbed by the Kidneys
Calcium

**more calcium is present in bone; more calcium is reabsorbed in the kidney as compared to Phosphate
Calcium enters the body only through the __1__ resulting in daily absorption of about __2__. An obligatory loss of 150 mg/day occurs in __3__ & __4__ secretions, and in sloughed __5__ cells
1. intestine
2. 300 mg
3. mucus
4. biliary
5. intestinal
What accounts for a fecal loss of 650 mg/day of Calcium?
1. mucosal + biliary secretions & sloughed intestinal cells = 150 mg

2. redisual 500 mg remaining from the unabsorbed intake (800 mg intake; 300 is absorbed)
What is urinary excretion of Ca++ determined by?
Tubular reabsorption
-highly efficient = more than 98% of the 9 g filered daily is reabsorbed
What are the prinipal regulators of Calcium bone homeostasis?
1. PTH

2. Vitamin D
What is the primary function of PTH?
to keep Ca++ concentration in the extracellular fluid constant
What is the plasma half-life of PTH?

How is it removed from the body?
2-5 min

hepatic and renal clearance
What influences the secretion of PTH from the parathyroid gland?
low Ca++ = secretion of PTH

high Ca++ = inhibition of PTH secretion
In what 2 ways does PTH increase the plasma concentration of Ca++
1. increase Bone resorption = increase Ca++ mobilization

2. increase reabsorption of Ca++ in Kidneys
List the 6 preparations of Vitamine D
Calci-fed-iol

Calci-triol

Chole-calci-ferol

**Dihydro-tachy-sterol**

Doxy-calci-ferol

Ergo-calci-ferol
What are the sources of Vitamin D?
1. formed in skin by UV radiation

2. Plants
Intrinsic and dietary forms of Vitamin D are inactive precursors that have to be converted to active metabolites of which _______ is the most active
Calci-triol
In what 3 ways does Vitamin D regulate Ca++ homeostasis?
1. increase bone resorption

2. kidneys to increase tubular reabsorption

3. small intestines to increase Ca++ absorption
What does deficiency of Vitamin D in children cause?

In adults?
Children = Rckets

Adults = Osteomalacia
The only regulator affecting intestinal Ca++ absorption
Vitamin D
Hormone secreted by Parafollicular cells (C cells) in the Thyroid when serum Ca++ is high
Calcitonin
What is the action of Calcitonin? How does it achieve it?
Lowers serum Ca++

inhibits Osteoclastic bone resorption; reduces tubular reabsorption of Ca++ & phosphate
What 3 diseases is Calcitonin used to treat?
1. Paget's disease = excessive breakdown & formation of bone tissue

2. Hypercalcemia

3. Osteoporosis
How do Glucocorticoids affect Ca++ homeostasis? (2)
1. antagonize Vitamin D-stimulated intestinal Ca++ absorption

2. stimulate renal Ca++ excretion

**ultimately cause decreased body Calcium
What do Glucocorticoids block the synthesis of in bone?
Collagen synthesis
What 3 conditions are Glucocorticoids used to treat in regards to Mineral Homeostasis?
1. to reverse Hypercalemia in Lymphomas

2. Sarcoidosis (has hypercalcemia due to elevated conversion of vitamin D to its active form in Epithelioid macrophages)

3. Vitamin D intoxication
How do Estrogens prevent accelerated bone loss?
act by decreasing PTH-induced bone resorption
Are Estrogens more effective in preventing or restoring bone loss?
PREVENTING
Used for treatment or prevention of Postmenopausal Osteoporosis
Estrogens
What is the ending for all Pyrophosphate analogs of Bisphosphonates?
-DRONATE
What is the mechanism of action of the -DRONATE's?
Bisphosphonate pyrophosphate analogs

Act by retarding formation & dissolution of hydroxyapatite crystals in the skeleton = decrease bone resorption
What is the adverse effect of the -Dronate's?
Gastric irritation

**< 10% of oral doses is absorbed
What are the -Dronate's used clinically to treat?
1. Hypercalcemia associated with malignancy (bone metastases)

2. Osteoporosis

3. Syndromes of ectopic calcification

4. Paget's disease = enlarged & deformed bones
Diuretic used to treat HypercalciURIA
Thiazides
Explain why Thiazides are used to treat HypercalciURIA
1. block sodium reabsorption in distal tubule
2. increase Calcium-sodium exchange in basolateral membrane
3. Increase Ca++ reabsorption = reduced renal excretion
Cytotoxic antibiotic used for treatment of Paget's disease and Hypercalcemia
Plica-mycin (Mithramycin)
Define Osteoporosis

Who is it most common in?
abnormal bone loss predisposing to fractures

Postmenopausal women (but also occurs in older men)
Aside from Menopause and aging, what other 5 things can Osteoporosis result from?
1. Chronic treatment with Glucocorticoids
2. Endocrine disorders such as Thyrotoxicosis or Hyperparathyroidism
3. Malabsorption syndrome
4. Alcohol abuse
5. Idiopathic
What is Postmenopausal Osteoporosis due to?
Estrogen deficiency
Partial Estrogen Agonist used to prevent Postmenopausal Osteoporosis BUT does NOT affect Endometrium or Breast
Ralox-ifene
What is idiopathic Osteoporosis in Elderly men usually treated with?
Vitamin D & dietary Calcium