male pharm Flashcards
Testosterone Serum levels and biosynthesis
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
Control of testosteron synthesis and secretion
GnRH (pulsatile) stimulates LH ( also pulsatile)
Continous GnRH disrupts LH secretion
Negative feedback, adult male testosterone concentration 20x females
5areductase–> DHT
aromatase–> estradiol
Testosterone metabolites and effects
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
Testosterone receptor activation
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
T preps
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
Why transdermal preparations
Avoid first pass effect, consistent serum concentration but caution regarding skin exposure, 80% stays on skin
therapeutic uses of androgens
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
SE of androgen therapy
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
Steroid abuse
various androgens, 17 Alkylated forms (Stanozolol) testosterone esters, precursors (DHEA)
1-50 high school students, physical and psychological addiction, mood swings, depression, fatigue, suicide
Consequences of anabolic steroid
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
Anti androgens and androgen antagonists
Inhibitors of synthesis GnRH analog (Leuprolide)
Steroidogenesis inhibitors (Spironolactone, ketoconazole)
5A reductase inhibitor- Finasteride
Androgen receptor antagonist- Flutamide and spironolactone
Leuprolide
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
Danazol
Testosetone (17 alk) orally active
MOA- Suppresses LH release, testicular, ovarian functions
Indications- treat endometriosis and hereditary angioedema
SEs- hepatotoxix acne
Steroidogenic enzyme inhibitors
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
finasteride
5alpha reductase inhibitor
MOA- blocks the conversion of testosterone to DHT
Indications- treats BPH (proscar), Treats male pattern baldness (propecia)
SE- impotence
flutamide
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
Treatment of male infertility
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
Erectile dysfunction
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
PDE5 inhibitors mechanism
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
BPH
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
