Testosterone Pharmacology (Dr. Sharma)

Binding of testosterone to ABP maintains local high concentration of testosterone for what

spermatogenesis

testis contains how many higher concentration of testosterone compared to the circulating concentration in plasma

100 times high concentration

circulating levels of what exert negative feedback effect on hypothalamus to decrease GnRH and on pituitary gonadotrophs to decrease LH

testosterone

when high amounts of therapeutic testosterone are administered, it suppresses GnRH and LH.

Low LH levels in turn impair spermatogenesis by decreasing testosterone levels in testis

true about testosterone negative feedback

when does testosterone start at

at puberty to 30s

• LH is release in the pulses of 2h interval

• Peak LH pulse is in the morning

• peak testosterone levels at 8AM lowest at 8PM

testosterone variation

physiological effects of testosterone is what

• at puberty

• during adulthood

• during aging

at puberty, the increased level of testosterone causes what

• increase in testicle size

• growth of male genitali

during adulthood what are the physiological effects of testosterone

• maintenance of spermatogenesis

• libido

• erythropoiesis

• male pattern baldness

• prostate hyperplasia

• low testosterone causes decreased energy, muscle mass, libido, bond density in what

during aging (senescence)

95% testosterone in plasma in bound to proteins

true

65% is bound to b-globulin called what

GBG (gonadal steroid binding globulin)

1)To a more potent derivative dihydrotestosterone (DHT) by enzyme 5α-reductase in skin, prostrate gland, hair follicles and some other tissues

2)To estradiol in bone and adipose tissue by enzyme aromatase (CYP19)

3)To inactive metabolites androsterone and etiocholanolone in liver

testosterone is metabolized

active metabolite of testosterone

dihydrotestosterone

estradiol

Inactive metabolite of testosterone

androsterone and etiocholanolone

receptors for testosterone are called what

androgen receptors

what are present in cytosol of testosterone repsonseive cells and are bound to a repressor heart shock protein

androgen receptor

what has approximately 5 times greater affinity for the androgen receptors than testosterone which makes DHT more potent androgenic steroid at physiologic concentrations

dihydrotestosterone

Klinefelter syndrome (XXY trisomy)

Undescended testicles (Cryptochidism)

Mumps orchitis

Injury to the testicles

Chemotherapy or radiation therapy

Drugs (Ketoconazole, Spironolactone, Marijuana)

are etiology of what

małe hypogonadism primary (defect in testeS)

Kallmann syndrome (Abnormal development of the hypothalamus)

Pituitary disorders

Inflammatory disease (sarcoidosis, histiocytosis and tuberculosis)

Hemochromatosis (Excessive iron) and pituitary lesions

HIV/AIDS

Obesity

Late onset hypogonadism due to normal aging (Andropause)

are etoiology of what

małe secondary hypogonadism

Erectile dysfunction

Infertility

Decrease in muscle mass

Gynecomastia

Osteoporosis

Decreased hemoglobin and hematocrit

symptoms what ?

hypogonadism in adulthood

Decreased development of muscle mass

Lack of deepening of the voice

Impaired growth of body hair

Impaired growth of the penis and testicles

Excessive growth of the arms and legs in relation to the trunk of the body

Gynecomastia

symptoms of what

before puberty for hypogonadism

what is rapidly absorbed orally but undergoes extensive first pass metabolism. Thus, very low levels reach the systemic circulation.

testosterone

therapeutic use of testosterone required either what

• development of testosterone derivatives that undergo less hepatic metabolism

• use routes of administration that bypass first pass metabolism

what is testosterone derivatives for oral administration

17a methyl derivatives

what is the testosterone derivates for parental intramuscular administration

ester derivatives

testosterone derivaties have an alpha methyl group at what carbon

17 carbon position

17a methyl tsetosterone derivates are what

hepatotoxicity

what are the 2 testosterone derivates

1. 17a methyl derivatives

2. ester derivates

esterification of the hydroxyl group present at what carbon to generate ester derivates

carbon 17

testosterone esters are highly lipophilic and are formulated in oils for intramuscular depot injections for long duration of action

true

which formulation are oily injection containing testosterone ester

intramuscular

the formulation for the following routes contain testosterone except what

• Oral: Testosterone undecanoate

• Nasal: Spray pump

• Subdermal: Pellets

• Topical: Gel, Solution

• Intramuscular

oral and IM

for testosterone what is at carbon 3

ketone

for testosterone what is on carbon 17

hydroxyl

Self-emulsifying lipoprotein particle formulation

• by-passes hepatic metabolism

Jatenzo (oral testosterone undecanoate)

black box warning for what kind of formation in testosterone

topical