Endo Exam 1: Sharma ED + Testosterone

Normal penile erection is regulated by 3 components: __________ & neural → __________, vascular → __________, hormonal → __________

Psychogenic, DA/ACh, NO, testosterone

Visual, tactile, olfactory, and imaginative inputs reach the __________ area of the hypothalamus. The primary erectogenic neurotransmitter in the hypothalamus is __________, which activates efferent __________ nerves from S2-S4 that release __________

Preoptic, dopamine, parasympathetic, ACh

Olfactory and imaginative inputs can produce inhibitory effects through __________ receptors → efferent __________ nerves from T1-L2 → release __________

alpha-2, sympathetic, NE

Penile tissue contains __________ corpora cavernosa and __________ corpus spongiosum. Neuronal stimulation releases __________, which causes release of __________ and relaxation of sinusoid smooth muscle

2, 1, ACh, NO

ACh activates __________ receptors on endothelial cells → releases __________ → stimulates __________ cyclase → converts GTP to __________ → causes dephosphorylation of __________ filaments → smooth muscle relaxation and vasodilation

Muscarinic, NO, guanylate, cGMP, myosin

In the flaccid penis, arterial inflow and venous __________ are balanced. During erection, arterial inflow increases and rigidity drastically __________ venous outflow

Outflow, decreases

The enzyme __________ breaks down cGMP into inactive __________

Phosphodiesterase, GMP

Normal testosterone levels are needed for normal development and growth of __________ tissue and maintenance of __________

Penile, libido

Erectile dysfunction is the consistent or recurrent inability to __________ and/or __________ an erection sufficient for sexual performance

Attain, maintain

Major causes of ED include __________ causes, organic causes, and __________-induced causes. Organic causes include vascular, neurologic, and __________ problems

Psychogenic, drug, hormonal

Vascular causes of ED include __________, __________, and arteriosclerosis. Neurologic causes include spinal cord injury, stroke, and __________

Hormonal ED can result from primary or secondary __________, leading to low __________ levels

HTN, PAD, diabetes, Hypogonadism, testosterone

Drugs that may affect the neural/psychogenic component include __________, __________ inhibitors, antipsychotics that block __________, TCAs, and diphenhydramine

Drugs that may affect the vascular component include __________ and __________. Drugs affecting the hormonal component include __________ and __________.

SNRIs, MAO, D2, Diuretics, BBs, spironolactone, ketoconazole

The PDE5 inhibitors used for ED are __________, __________, __________, and __________

Sildenafil, vardenafil, tadalafil, avanafil

PDE5 is an enzyme expressed in penile tissue that metabolizes __________ to inactive __________. PDE5 inhibitors block this metabolism, prolonging __________ action and promoting vasodilation and erection

PDE5 inhibitor → ↓ __________ breakdown → ↑ __________ → prolonged smooth muscle relaxation → penile __________.

cGMP, GMP, cGMP, cGMP, cGMP, erection

__________ has the longest half-life among the PDE5 inhibitors, with a t½ of approximately __________ hours, so its effect can last for days and it is sometimes called the __________ pill

Tadalafil, 17.5, weekend

PDE5 inhibition in peripheral vascular tissue can cause __________, facial flushing, nasal congestion, and __________

PDE6 inhibition in rods and cones can cause __________ vision, while PDE11 inhibition in striated muscle can cause __________

Headache, hypotension, Blue-tinged, myalgia/muscle pain

The PDE5 inhibitor with the highest PDE11 inhibitory activity is __________.

Tadalafil

A rare but serious adverse effect associated with PDE5 inhibitors is nonarteritic anterior ischemic __________ neuropathy (NAION), which can cause __________ loss.

Optic, vision

PDE5 inhibitors must NOT be coadministered with organic __________ because this can cause life-threatening __________

Nitrates, hypotension

Nitrates are __________ donors, while PDE5 inhibitors prevent breakdown of __________, causing excessive cGMP and excessive vasodilation

NO, cGMP

Alprostadil activates __________ receptors → activates __________ cyclase → increases __________ → penile vasodilation and erection

Alprostadil is __________ E1 and is available as an __________ injection or __________ administration. Its onset is approximately – minutes and systemic absorption is minimal

Alprostadil is metabolized locally by __________-hydroxy dehydrogenase.

Prostaglandin, adenylate, cAMP, Prostaglandin, intracavernosal, intraurethral, 5, 15, 15

The main Alprostadil MOA slide describes ↑ __________ through prostaglandin receptor activation, while a later summary line states ↑ __________.

cAMP, cGMP

The hypothalamus releases __________ in pulses → acts on anterior pituitary gonadotrophs → releases __________ and __________.

GnRH, FSH, LH

FSH stimulates __________ cells to synthesize/release __________-binding protein and help sperm maturation. LH stimulates __________ cells to synthesize/release testosterone

Sertoli, androgen, Leydig

Circulating testosterone exerts negative feedback on the hypothalamus to decrease __________ and on pituitary gonadotrophs to decrease __________

GnRH, LH

High amounts of therapeutic testosterone suppress __________ and __________. Low LH then impairs __________ by decreasing testosterone levels in the testes

GnRH, LH, spermatogenesis

Binding of testosterone to ABP maintains a high local concentration for __________. Testosterone concentration in the testes is approximately __________ times higher than circulating plasma concentrations

Spermatogenesis, 100

Increased testosterone at puberty increases testicle size, axillary/facial/pubic hair, __________ growth, deepening of the __________, and __________ synthesis

During adulthood, testosterone helps maintain __________, libido, and RBC synthesis and is associated with male pattern __________ and prostate __________

Musculoskeletal, voice, RBC, Spermatogenesis, baldness, hyperplasia

During senescence, a major decrease in testosterone can cause decreased __________, muscle mass, __________, and bone density

Energy, libido

Approximately __________% of testosterone in plasma is protein-bound. About __________% is bound to beta-globulin and __________% to albumin

98, 65, 33

Testosterone is metabolized to the more potent __________ by __________-alpha-reductase, to __________ by aromatase (CYP19), and to inactive metabolites __________ and __________ in the liver

DHT, 5, estradiol, androsterone, etiocholanolone

The active testosterone metabolites are __________ and __________. The inactive metabolites are __________ and __________

DHT, estradiol, androsterone, etiocholanolone

Testosterone → __________-alpha-reductase → __________ → acts in external genitalia, hair follicles, and contributes to __________

Testosterone binds the __________ receptor and affects internal genitalia, skeletal __________, and __________

Testosterone → aromatase/CYP19 → __________ → estrogen receptor → effects on __________ and libido.

5, DHT, acne, Androgen, muscle, marrow, Estradiol, bone

Androgen receptors belong to the __________ receptor superfamily.

Nuclear

Androgen receptors are located in the __________ of testosterone-responsive cells and are initially bound to a repressor __________ shock protein (HSP).

Cytosol, heat

Testosterone binds the androgen receptor → HSP __________ → receptors form __________ → dimers translocate to the __________ → bind DNA → alter __________ expression

Dissociates, dimers, nucleus, gene

__________ has approximately __________ times greater affinity for the androgen receptor than testosterone, making it a more potent androgen at physiologic concentrations

DHT, 5

__________ hypogonadism results from a defect in the testes, while __________ hypogonadism results from problems involving the hypothalamus or pituitary

Primary, secondary

Causes of primary hypogonadism include Klinefelter syndrome (__________ trisomy), undescended testes/__________, mumps orchitis, testicular injury, chemotherapy/radiation, and drugs such as __________, __________, and marijuana.

XXY, cryptorchidism, ketoconazole, spironolactone

Causes of secondary hypogonadism include Kallmann syndrome, __________ disorders, inflammatory disease, hemochromatosis, pituitary lesions, HIV/AIDS, __________, and late-onset hypogonadism from normal aging.

Pituitary, obesity

Late-onset hypogonadism due to normal aging is also called __________.

Andropause

Before puberty, hypogonadism can cause decreased muscle mass, lack of deepening of the __________, impaired body __________, impaired growth of the penis and __________, excessive arm/leg growth relative to the trunk, __________, and eunuchoid appearance

Adult hypogonadism can cause erectile dysfunction, __________, decreased muscle mass, , osteoporosis, and decreased hemoglobin/.

Voice, hair, testicles, gynecomastia, Infertility, gynecomastia, hematocrit

The two chemical classes of testosterone derivatives are __________-methyl derivatives and __________ derivatives.

17-alpha, ester

17α-methyl testosterone derivatives contain an alpha-methyl group at the __________ carbon, making them less susceptible to __________ metabolism and increasing __________ bioavailability.

The major limitation of 17α-methyl testosterone derivatives is __________.

Testosterone ester derivatives are created by esterification of the __________ group at carbon 17. The esters are highly __________ and formulated in oil for __________ depot injections

Examples of testosterone esters include testosterone __________, __________, and __________

17, hepatic, oral, Hepatotoxicity, Hydroxyl, lipophilic, IM, Undecanoate, cypionate, enanthate

Major testosterone formulations/routes include __________, __________, __________, __________, and __________

Oral, nasal, topical, subdermal, IM

The oral testosterone formulation listed in the lecture is testosterone __________. Its advantages are __________ administration and good __________

Undecanoate, noninvasive, compliance

The nasal formulation is a gel __________ pump such as __________. Advantages include quick onset, quick reversal, noninvasive administration, and lack of __________.

Spray, Natesto, transference

Topical testosterone formulations include pump __________, tubes, and __________. Advantages are quick onset/reversal and noninvasive administration. The major limitation is risk of __________

The risk of testosterone __________ with topical products is significant enough to carry a __________ warning

Gels, solution, transference, Transference, Box

Subdermal testosterone is administered as __________. Advantages include good compliance and lack of __________. Limitations are that it is __________ and there is no easy withdrawal if needed

Pellets, transference, invasive

IM testosterone formulations include testosterone __________, __________, and __________. Advantages include good compliance, lack of transference, less frequent dosing, and less __________

The major limitations of IM testosterone are that it is __________ and there is no easy __________ if needed.

Undecanoate, cypionate, enanthate, cost, Invasive, withdrawal

Testosterone cypionate should be considered carefully in a patient with a __________ seed oil allergy

Cotton

Nasal = quick onset/reversal + noninvasive + no __________, topical = noninvasive but risk of __________, subdermal = good compliance but __________ and difficult to withdraw, IM = good compliance + less frequent dosing + less __________ but invasive, oral = noninvasive + good compliance.

Transference, transference, invasive, cost

Low testosterone can contribute to ED because testosterone is required for penile tissue __________/growth and maintenance of __________

Development, libido

PDE5 inhibitors increase/prolong __________ signaling by preventing its breakdown, while alprostadil activates prostaglandin receptors to increase __________.

PDE5 inhibitors inhibit the enzyme __________ that breaks down cGMP. Alprostadil directly activates __________ receptors

cGMP, cAMP, PDE5, prostaglandin

The major life-threatening drug interaction with PDE5 inhibitors is concomitant use of organic __________ because both pathways increase __________-mediated vasodilation

Nitrates, NO/cGMP

Psychogenic/neural input → hypothalamic __________ → parasympathetic __________ release → endothelial __________ release → guanylate cyclase → ↑__________ → smooth muscle relaxation → increased penile blood __________ → erection.

DA, ACh, NO, cGMP, flow

Hypothalamus → __________ → anterior pituitary → / → Sertoli/Leydig cells → testosterone → negative feedback on __________ and __________.

GnRH, FSH, LH, GnRH, LH

17α-methyl derivatives = increased __________ bioavailability but __________. Ester derivatives = highly __________, formulated in oil for long-duration __________ injections.

Oral, hepatotoxic, lipophilic, IM

Testosterone → 5α-reductase → __________, Testosterone → aromatase/CYP19 → __________, Testosterone → liver → inactive __________ and __________

DHT, estradiol, androsterone, etiocholanolone

Testosterone binds androgen receptor → HSP __________ → receptor __________ → moves into the __________ → binds DNA → changes gene __________.

Dissociates, dimerizes, nucleus, expression

Primary hypogonadism = defect in the __________. Secondary hypogonadism = defect involving the __________ or __________. Late-onset hypogonadism from normal aging = __________

Testes, hypothalamus, pituitary, andropause

Topical testosterone's major limitation is __________, subdermal/IM's major limitation is __________, and 17α-methyl derivatives' major limitation is __________.

Transference, invasiveness/no easy withdrawal, hepatotoxicity

PDE5 normally converts __________ → inactive GMP. PDE5 inhibitors prevent this breakdown → prolonged __________ → vasodilation and erection

cGMP, cGMP

PDE5 inhibitors can cause headache, flushing, nasal congestion, hypotension, __________ vision with PDE6 inhibition, __________ with PDE11 inhibition, and must not be combined with __________

Blue-tinged, myalgia, nitrates