male pharm

Question 1

Testosterone Serum levels and biosynthesis

Answer 1

Spikes in puberty and starts to go down at 20

Needs cholesterol, pregnenolone, 10 OH preg, DHEA, Androstenedione, testosterone

Precursors androstenedione and dehydroepiandrosterone (DHEA) are weak androgens converted in peripheral tissues to testosterone

Question 2

Control of testosteron synthesis and secretion

Answer 2

GnRH (pulsatile) stimulates LH ( also pulsatile)
Continous GnRH disrupts LH secretion

Negative feedback, adult male testosterone concentration 20x females

5areductase–> DHT
aromatase–> estradiol

Question 3

Testosterone metabolites and effects

Answer 3

DHT- External genitalia, differentiation during gestation, maturation during puberty, adulthood prostatic disease. Hair follicles- increased growth during puberty

Testosterone- Internal genitalia (wolfian development during gestation), Skeletal muscle (increase mass and strength during puberty), erythropoiesis bone

Estradiol- Bone (epiphyseal closure increased density) libido

Question 4

Testosterone receptor activation

Answer 4

SHBG- T releases T
T or DHT binds to receptor which then dissaciates Hsp 90, Dimerizes, then enters the nucleus and binds to its HRE and induces the transcription of DNA

Question 5

T preps

Answer 5

need to bypass the liver- rapid liver metabolism of oral testosterone

T creams, gels and patches

T esters as injections- cypionate and enanthate IM, slow hydrolyzed

17 Alk compound oral but hepatotoxicity, methyltestosterone, danazol

Question 6

Why transdermal preparations

Answer 6

Avoid first pass effect, consistent serum concentration but caution regarding skin exposure, 80% stays on skin

Question 7

therapeutic uses of androgens

Answer 7

adult male hypogonadism or sensescence- (t, Te, MethylT)

Delayed puberty in young men (Te, MethylT)

Wasting due to AIDs (T or Te)

Endometriosus (Danazol)

Hereditary angioedema (Danazol)

Gynocomastia and heart disease, mood booster, muscele tofat ratio is high

Question 8

SE of androgen therapy

Answer 8

Suppress gonadotropin release, feminzing side effects, female virilization, others

shutting down FSH and LH

Eryhtrhrocytosis and epiphsyeal clocure

Cont- pregnancy or carcinoma of breast or prostate

Question 9

Steroid abuse

Answer 9

various androgens, 17 Alkylated forms (Stanozolol) testosterone esters, precursors (DHEA)

1-50 high school students, physical and psychological addiction, mood swings, depression, fatigue, suicide

Question 10

Consequences of anabolic steroid

Answer 10

Infertility, low sperm coun, breast development, shrining of the testicles, male pattern baldness, Short, tendon rupture
Women- enlargement of the clitoris excessive growth of body hair, male pattern baldness

CV- decreases in HDL, high bp, heart attacks, enlargement of the hearts left ventricle

Liver- cancer, tumor

Question 11

Anti androgens and androgen antagonists

Answer 11

Inhibitors of synthesis GnRH analog (Leuprolide)
Steroidogenesis inhibitors (Spironolactone, ketoconazole)
5A reductase inhibitor- Finasteride
Androgen receptor antagonist- Flutamide and spironolactone

Question 12

Leuprolide

Answer 12

GnRH analog (Agonist if pulsatile, antagonist if continuous)

Initial surge of testosterone, after a few weeks, testosterone levels decline

Indications- metastatic prostate cancer with flutamide, central precocious puberty

SE- hot flushes impotencee

Question 13

Danazol

Answer 13

Testosetone (17 alk) orally active

MOA- Suppresses LH release, testicular, ovarian functions

Indications- treat endometriosis and hereditary angioedema

SEs- hepatotoxix acne

Question 14

Steroidogenic enzyme inhibitors

Answer 14

Spironolactone- MOA- weak antagonist of androgen receptor and weak inhibitor of 17 hydroxylase, aldosterone antagonist, indications-used to treat hirsutism, SE- gynecomastia

Ketoconazole- Antifungal, inhibits 17 20 lyase blocks DHEA, andrestenedione, testoseterone, syntheisis

Advanved prostate cancer, black box warning, hepatotoxiticity, QT prolongation

Question 15

finasteride

Answer 15

5alpha reductase inhibitor
MOA- blocks the conversion of testosterone to DHT

Indications- treats BPH (proscar), Treats male pattern baldness (propecia)

SE- impotence

Question 16

flutamide

Answer 16

Non steroidal, competitive antagonist of the androgen receptor

indication- used with leuprolide to treat metastatic prostate cancer (due to increase LH), hirsutism (off label)

Side effects- hepatotoxic, hot flashes, impotence, gynecomastia

Spironolactone- weak receptor antagonist

Question 17

Treatment of male infertility

Answer 17

Often not a drug treatment- hypogonadotropic hypogonadism may respond

Therapeutic approaches, hCG alone, or in combination with menotropins (FSH and LH)

not androgens because of negative feedback

Question 18

Erectile dysfunction

Answer 18

vasodilate corpus cavernosum
Prostaglandin analogs- Alprostadil (PGE1), intracavernous injection, pellet placed in the urethra
Phosphodiesterase type 5 (PDE5) inhibitors
sildenafil- 1 hr peak, 4 hr duration
Vardenafil- 1 hr peak, 4 hr duration
Tadalafil- 2 hr peak, 36 hr duration

Question 19

PDE5 inhibitors mechanism

Answer 19

Nitric oxide pathway

Ca–> Larg releases No and citrulline–> Guanylyl cyclase–> cGMP–> decreased Ca2–> PDE5 inhibition

SE- hypotension, headache, heart burn, drug interactions- dontt take with nitrates –> hypotension

Question 20

BPH

Answer 20

70% of men age 60+

Treatment
terazosin, tamsulosin - alpha 1 blocker, relax smooth muscle in bladder neck and prostatic urethra, rapid onset
Terazosi- orthostatic Hypotension
Tamsulosin- less hypotension but decreased ejaculate volume
flomax
Drug interactions with phosphodiesterase inhibitors potentiate hypotensive effects

Finasteride- 5 a reductase inhibor- may reduce prostate size, ED