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46 Cards in this Set
- Front
- Back
- 3rd side (hint)
1. Androgens are synthesized in:
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a. Testicular Leydig cells
b. Ovarian theca cells c. Adrenal glands |
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1. Androgens are Converted to dihydrotestosterone (DHT) by 5-alpha-reductase in target tissues including
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a. Prostate
b. Hair follicles c. Non-genital skin |
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1. Primary source of estrogens in men and postmenopausal women.
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a. Testosterone is converted to estradiol in various extra-glandular tissues
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1. Reduction of testosterone to DHT results in
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a. Increased receptor affinity
b. More stable receptor-ligand complex |
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1. Esterification of androgens at C-17 results in:
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a. Increased lipid solubility
b. Decreased release into general circulation c. Longer effect |
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1. Alkylation of androgens at C-17 results in:
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a. Decreased hepatic metabolism
b. Longer half-life |
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1. Androgens play a role in:
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a. Development
b. Puberty c. Fertility d. Formation of EPO e. Retention of electrolytes f. And some anabolic effects |
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1. What role do androgens play in development
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a. Development of the male phenotype
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1. What role do androgens play in Puberty
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a. Growth of penis and scrotum
b. Skeletal/musculature growth c. Development of secondary sexual characteristics d. Stimulation of sebaceous glands e. Male pattern baldness |
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1. What role do androgens play in Fertility
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a. Spermatogenesis,
b. maturation of sperm & c. Controls the growth and function of the seminal vesicle and prostate. |
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1. Anabolic Effects of androgens
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a. Muscle development
b. Pronounced in women, prepubertal boys or hypogonadal men than normal men |
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1. MOA of androgens
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a. Testosterone and dihydrotestosterone (DHT) bind to a nuclear receptor
b. Receptor interacts with response elements in target gene • Increased protein synthesis c. Androgen receptor is encoded by a gene on the X chromosome. |
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1. Natural Androgens include
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a. Testosterone
• IM injection (TESTOJECT-50) b. Esters of testosterone: • Testosterone cypionate (DEPO-TESTOSTERONE) • IM injection, depot preparation c. Dihydrotestosterone • ANDRACTIM - topical gel, investigational d. Transdermal testosterone: • TESTODERM - patches applied to scrotum • ANDRODERM - patches applied to nonscrotal skin 1. *****Daily application of 2 patches at 10 PM a. **********plasma levels which mimic normal circadian rhythm. |
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1. Testosterone derivatives include
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a. Fluoxymesterone (HALOTESTIN)
b. Methyltestosterone (VIRILON) c. Oxandrolone (OXANDRIN) • Methyl substitutions at C17 |
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1. Methyl substitutions at C17 results in:
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a. decreased hepatic metabolism
b. longer half-life c. oral administration |
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1. Synthetic Androgens
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a. Danazol (DANACRINE)
• Decreased hepatic metabolism • Weak androgen • Oral administration |
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1. DHEA and derivatives
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a. Dehydroepiandrosterone
b. Fluasterone |
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1. How much of the androgens are protein bound
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a. Extensively plasma protein bound (98%)
• Only 50% of testosterone in the general circulation is available |
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1. Metabolites of androgens
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a. Primarily inactive metabolites
• Androsterone and androstenedione. • Except small amounts of estradiol |
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1. Urinary excretion of androgens allows for
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a. drug testing of athletes.
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1. Therapudic uses of androgens
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a. HYPOGONADISM - Primary use
b. Refractory Anemia c. Hereditary Angioneurotic Edema d. Systemic lupus erythematosus (SLE), e. Diabetes mellitus type II f. Nitrogen Balance/Muscle Development g. BREAST CANCER h. ENDOMETRIOSIS i. ATHLETIC PERFORMANCE |
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1. How are androgens used for hypogonadism
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a. Delayed puberty
• Primary testicular failure • Hypopituitarism or decreased GnRH • IM injections or patch most effective b. Complete testicular failure or hypopituitarism • Prolonged therapy required (years) • Give concurrently with growth hormone for maximum effect. • Monitor plasma testosterone concentrations • If therapy is delayed until long after normal onset of puberty, results may be variable. c. Alkylated testosterone derivatives should NOT be used for replacement therapy • Risk of liver damage |
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1. How are androgens used for Refractory Anemia
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a. Testosterone stimulates the production of renal erythropoietin
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1. How are androgens used for Hereditary Angioneurotic Edema
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a. Nonfunctional or decrease levels of inhibitor of 1st complement component
• Increase permeability of blood vessels and episodes of angioedema. b. 17-alkylated testosterones increase • Concentration of clotting factors • Complement component inhibitors • Action not through the androgen receptor c. Weak androgens (danazol) are commonly used |
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1. How are androgens used for Systemic lupus erythematosus (SLE), and Diabetes mellitus type II
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a. DHEA and fluasterone currently in clinical trials
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1. How are androgens used for Nitrogen Balance/Muscle Development
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a. Promote weight gain after
• chronic infection • severe trauma • AIDS-associated wasting syndrome b. Drug of choice: Oxandrolone • Dihydrotestosterone - clinical trials • Use is controversial. |
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1. How are androgens used for BREAST CANCER
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a. Testosterone has a palliative effect.
b. May act as an antiestrogen. c. Conventional chemotherapy is more effective, therefore this is not a common use. |
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1. How are androgens used for ENDOMETRIOSIS
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a. Drug of choice: Danazol (DANACRINE)
b. Normal and ectopic endometrial tissue becomes inactive and atrophic c. Danazol also used to symptomatically treat fibrocystic breast disease. |
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1. How are androgens used for ATHLETIC PERFORMANCE
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a. NOT AN APPROVED USE!!
b. Promote muscle growth in boys and women, little effect in normal men c. MASSIVE pharmacological doses required, many adverse effects: • hepatic abnormalities • increased aggression • psychotic episodes |
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What is the time frame for an SDR when material is shipped to gov't activities?
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15 days from receipt
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1
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1. Adverse effects of androgens in males
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• Prostate hyperplasia
• Decrease testicular function, decreasing spermatogenesis • Impotence, gynecomastia |
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1. Adverse effects of androgens in both females and males
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a. Nausea, vomiting, diarrhea
b. Altered libido, acne c. Edema, decreased HDL/LDL ratio d. Jaundice, cholestatic hepatitis, may lead to hepatic adenocarcinoma (alkyl substituted androgens) |
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1. Contraindications to androgens
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a. Pregnancy
b. Prostate or breast cancer c. Hepatic or renal disease d. Cardiac disease e. Children - may cause premature closure of epiphysis, serious disturbances of growth and osseous development |
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1. Inhibitors of androgen synthesis
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a. GnRH Analogs
b. Antifungal agents c. 5-alpha Reductase Inhibitors d. Finasteride |
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1. How do GnRH Analogs affect androgens
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• Suppress LH production and synthesis of testosterone
• Therapeutic Uses: Advanced prostatic cancer • Agents: Leuprolide (LUPRON) • Adverse effects: decrease testicular size, bone pain • Contraindicated in pregnancy, lactation |
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1. how do Antifungal agents affect androgens
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a. Agent: Ketoconazole (high doses), oral
b. Block cytochrome P450 enzymes c. Therapeutic Uses - Advanced prostatic cancer d. Adverse Effects: GI effects, impotence, hepatotoxicity e. Drug interactions: Antacids, warfarin benzodiazepines |
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1. How do 5-alpha Reductase Inhibitors affect androgens
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a. Competitively inhibits synthesis of DHT
b. Blocks androgen action in prostate, hair follicles and non-genital skin c. Therapeutic Use: Benign prostatic hyperplasia, male pattern baldness d. Agent: Finasteride (PROSCAR, PROPECIA) |
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1. How does Finasteride affect androgens
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a. Oral administration
b. Clinical effects: 3-6 months c. 90% plasma protein bound d. Half-life 5-6 hours e. Accumulates, increased plasma levels by 50% |
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1. ADVERSE EFFECTS of Finasteride
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a. Impotence, decreased libido
b. Gynecomastia |
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1. Contraindications to Finasteride
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a. women and children
b. hepatic function impairment c. obstructive uropathy |
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1. Androgen Receptor Antagonists
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a. Nonsteroidal competitive receptor antagonists
• Flutamide • Bicalutamide b. Nonsteroidal irreversible receptor antagonist • Nilutamide |
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1. Mechanism of Action of Androgen Receptor Antagonists
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• Potent antagonists of DHT
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1. Therapeutic Uses of Androgen Receptor Antagonists
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• Flutamide and Bicalutamide
1. Metastatic prostatic carcinoma in combination with GnRH agonists • Nilutamide 1. Metastatic prostatic carcinoma in combination with orchiectomy |
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1. Adverse Effects of Androgen Receptor Antagonists
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a. Hepatitis, anemia, leukopenia
• Except bicalutamide b. GI effects, anemia |
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1. Drug interaction of Androgen Receptor Antagonists
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a. Warfarin
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1. Contraindications of Androgen Receptor Antagonists
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a. Liver disease
b. Pregnancy |
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