Pharm Ii Exam Ii- Gonadal Hormones 3

Front 1

1. Androgens are synthesized in:

Back 1

a. Testicular Leydig cells
b. Ovarian theca cells
c. Adrenal glands

Front 2

1. Androgens are Converted to dihydrotestosterone (DHT) by 5-alpha-reductase in target tissues including

Back 2

a. Prostate
b. Hair follicles
c. Non-genital skin

Front 3

1. Primary source of estrogens in men and postmenopausal women.

Back 3

a. Testosterone is converted to estradiol in various extra-glandular tissues

Front 4

1. Reduction of testosterone to DHT results in

Back 4

a. Increased receptor affinity
b. More stable receptor-ligand complex

Front 5

1. Esterification of androgens at C-17 results in:

Back 5

a. Increased lipid solubility
b. Decreased release into general circulation
c. Longer effect

Front 6

1. Alkylation of androgens at C-17 results in:

Back 6

a. Decreased hepatic metabolism
b. Longer half-life

Front 7

1. Androgens play a role in:

Back 7

a. Development
b. Puberty
c. Fertility
d. Formation of EPO
e. Retention of electrolytes
f. And some anabolic effects

Front 8

1. What role do androgens play in development

Back 8

a. Development of the male phenotype

Front 9

1. What role do androgens play in Puberty

Back 9

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

Front 10

1. What role do androgens play in Fertility

Back 10

a. Spermatogenesis,
b. maturation of sperm &
c. Controls the growth and function of the seminal vesicle and prostate.

Front 11

1. Anabolic Effects of androgens

Back 11

a. Muscle development
b. Pronounced in women, prepubertal boys or hypogonadal men than normal men

Front 12

1. MOA of androgens

Back 12

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.

Front 13

1. Natural Androgens include

Back 13

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.

Front 14

1. Testosterone derivatives include

Back 14

a. Fluoxymesterone (HALOTESTIN)
b. Methyltestosterone (VIRILON)
c. Oxandrolone (OXANDRIN)
• Methyl substitutions at C17

Front 15

1. Methyl substitutions at C17 results in:

Back 15

a. decreased hepatic metabolism
b. longer half-life
c. oral administration

Front 16

1. Synthetic Androgens

Back 16

a. Danazol (DANACRINE)
• Decreased hepatic metabolism
• Weak androgen
• Oral administration

Front 17

1. DHEA and derivatives

Back 17

a. Dehydroepiandrosterone
b. Fluasterone

Front 18

1. How much of the androgens are protein bound

Back 18

a. Extensively plasma protein bound (98%)
• Only 50% of testosterone in the general circulation is available

Front 19

1. Metabolites of androgens

Back 19

a. Primarily inactive metabolites
• Androsterone and androstenedione.
• Except small amounts of estradiol

Front 20

1. Urinary excretion of androgens allows for

Back 20

a. drug testing of athletes.

Front 21

1. Therapudic uses of androgens

Back 21

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

Front 22

1. How are androgens used for hypogonadism

Back 22

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

Front 23

1. How are androgens used for Refractory Anemia

Back 23

a. Testosterone stimulates the production of renal erythropoietin

Front 24

1. How are androgens used for Hereditary Angioneurotic Edema

Back 24

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

Front 25

1. How are androgens used for Systemic lupus erythematosus (SLE), and Diabetes mellitus type II

Back 25

a. DHEA and fluasterone currently in clinical trials

Front 26

1. How are androgens used for Nitrogen Balance/Muscle Development

Back 26

a. Promote weight gain after
• chronic infection
• severe trauma
• AIDS-associated wasting syndrome
b. Drug of choice: Oxandrolone
• Dihydrotestosterone - clinical trials
• Use is controversial.

Front 27

1. How are androgens used for BREAST CANCER

Back 27

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.

Front 28

1. How are androgens used for ENDOMETRIOSIS

Back 28

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.

Front 29

1. How are androgens used for ATHLETIC PERFORMANCE

Back 29

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

Front 30

What is the time frame for an SDR when material is shipped to gov't activities?

Back 30

15 days from receipt

Hint 30

1

Front 31

1. Adverse effects of androgens in males

Back 31

• Prostate hyperplasia
• Decrease testicular function, decreasing spermatogenesis
• Impotence, gynecomastia

Front 32

1. Adverse effects of androgens in both females and males

Back 32

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)

Front 33

1. Contraindications to androgens

Back 33

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

Front 34

1. Inhibitors of androgen synthesis

Back 34

a. GnRH Analogs
b. Antifungal agents
c. 5-alpha Reductase Inhibitors
d. Finasteride

Front 35

1. How do GnRH Analogs affect androgens

Back 35

• 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

Front 36

1. how do Antifungal agents affect androgens

Back 36

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

Front 37

1. How do 5-alpha Reductase Inhibitors affect androgens

Back 37

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)

Front 38

1. How does Finasteride affect androgens

Back 38

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%

Front 39

1. ADVERSE EFFECTS of Finasteride

Back 39

a. Impotence, decreased libido
b. Gynecomastia

Front 40

1. Contraindications to Finasteride

Back 40

a. women and children
b. hepatic function impairment
c. obstructive uropathy

Front 41

1. Androgen Receptor Antagonists

Back 41

a. Nonsteroidal competitive receptor antagonists
• Flutamide
• Bicalutamide
b. Nonsteroidal irreversible receptor antagonist
• Nilutamide

Front 42

1. Mechanism of Action of Androgen Receptor Antagonists

Back 42

• Potent antagonists of DHT

Front 43

1. Therapeutic Uses of Androgen Receptor Antagonists

Back 43

• Flutamide and Bicalutamide
1. Metastatic prostatic carcinoma in combination with GnRH agonists
• Nilutamide
1. Metastatic prostatic carcinoma in combination with orchiectomy

Front 44

1. Adverse Effects of Androgen Receptor Antagonists

Back 44

a. Hepatitis, anemia, leukopenia
• Except bicalutamide
b. GI effects, anemia

Front 45

1. Drug interaction of Androgen Receptor Antagonists

Back 45

a. Warfarin

Front 46

1. Contraindications of Androgen Receptor Antagonists

Back 46

a. Liver disease
b. Pregnancy