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Pharmacology II > Androgens > Flashcards

Androgens Flashcards

1
Q

Hypothalamic “releasing hormones” target the…

A

Anterior pituitary

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2
Q

Pituitary “stimulating hormones” target…

A

Various systemic organs and glands

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3
Q

Hormones released by the

  1. Anterior pituitary
  2. Posterior pituitary
A
  1. GH, TSH, ACTH, LH, FSH, PRL

2. ADH, oxytocin

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4
Q

Negative feedback

A

Elevated levels of hormones inhibit further release from hypothalamus and anterior pituitary
Regulates release of hormones to prevent over stimulation of target tissues

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5
Q

3 classes of gonadal hormones

A

Androgens (ex: testosterone)
Estrogens (ex: estradiol)
Progestins (ex: progesterone)

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6
Q

3 hormones that regulate gonadal hormones

A 
Gonadotropin-releasing hormone (GnRH - from hypothalamus)
Luteinizing hormone (LH - from pituitary)
Follicle-stimulating hormone (FSH - from pituitary)
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7
Q

Pulsate vs Constant release of GnRH

A

Pulsate: stimulates release of LH and FSH from pituitary (normal activity)
Constant: inhibits secretion of LH and FSH (down regulation and desensitization of GnRH receptors)

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8
Q

LH

function and location

A

Stimulates testosterone production in the Leydig cells in the testes

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9
Q

FSH

function and location

A

Stimulates spermatogenesis in Sertoli cells of the testes

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10
Q

Inhibins

A

Produced by Sertoli cells

Inhibits FSH production

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11
Q

Testosterone

from blood to cell

A

Circulates in blood bound to sex hormone binding globulin (can only pass through membrane when it is unbound)
Enters target cells and binds to intracellular androgen receptors (normally bound to heat shock proteins, will dissociate when test binds)
AR forms a dimer and translocates to the nucleus
Initiates gene transcription

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12
Q

Sex hormone binding globulin

A

The way testosterone is transported in the blood

But testosterone can only pass into cells when it is unbound

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13
Q

Testosterone can be converted to ____ by ____

what other male sex hormone

A

5alpha-dihydrotestosterone (DHT)
In target tissues
By 5alpha-reductase

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14
Q

DHT

A

5alpha-dihydrotestosterone

More potent agonist of the androgen receptor

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15
Q

Testosterone can be converted to what other hormone? By what enzyme?

A

Small amounts can be converted to estrogen

Done by aromatase, whose levels are higher in adipose tissue

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16
Q

What tissues are affected by:

  1. Dihydrotestosterone (4)
  2. Testosterone (4)
  3. Estradiol (2)
A
  1. External genitalia, skin, hair, prostate
  2. Muscle, bone marrow, bone, brain
  3. Bone, brain
17
Q

Cortisol

A

Causes negative regulation of sex hormones
Produced in the adrenal gland
Decrease testosterone levels in men (from inhibition of GnRH secretion)
Inhibit ovulation in women (from suppression of LH, estrogen and progestin secretion)

18
Q

Hypogonadism

A

Diminished functional activity of the gonads
Can be congenital or acquired
Symptoms: low sex drive, erectile dysfunction, mood disturbances, fatigue and sleep disruptions, delayed sexual development

19
Q

Testosterone

  1. Lipid or water soluble
  2. High or low oral bioavailability
A
  1. Lipid

2. Low (metabolized by the liver before entering systemic circulation)

20
Q

Testosterone enanthate

A

Ester derivative of testosterone
Used for androgen replacement therapy
Administered as an intramuscular injection
Highly lipophilic and diffuses slowly from injection site
Ester group is cleaved by cellular enzyme, then free testosterone enters systemic circulation

21
Q

2 brand names used for androgen replacement therapy (and how they are absorbed)

A
  1. Androderm (transdermal patch)
  2. Striant (buccal system)
    Both have direct absorption of testosterone into systemic circulation to avoid first pass
22
Q

Anabolic steroids

A

Synthetic derivatives of testosterone
More anabolic (muscle building) than androgenic
Used by athletes to increase body mass, strength, and performance
Many designer drugs to escape detection in urine
Typically illegal due to many adverse effects

23
Q

Benign prostate hyperplasia

A

Non-malignant
Symptoms may include urinary retention
Need androgen suppression therapy

24
Q

Prostate cancer

A

Malignant, uncontrolled growth
High prevalence of metastasis
Need androgen suppression therapy

25
Q

GnRH Analogs

A

Can act as agonists or antagonists
Pulsatile application can be used to increase FSH and LH to promote ovulation
Long term use overrides hypothalamic GnRH pulses (to decrease FSH and LH secretion, and test and estrogen secretion)

26
Q

Leuprolin

A

GnRH analog
Non-pulsatile application used for precocious puberty and prostate cancer
Subcutaneous implantation of pellet
Undesirable initial “flare” of increased testosterone (antagonist given until levels drop)

27
Q

GnRH Antagonist

A

Binds to and blocks GnRH receptor

Decreases LH and FSH and results in decreased testosterone levels

28
Q

Degarelix

A

GnRH antagonist
Synthetic peptide that binds to GnRH receptor
Used to teat advanced prostate cancer
Does not cause initial flare like leuprorelin

29
Q

3 points in time where the effects of androgens can be suppressed

A
  1. Testosterone biosynthesis
  2. Testosterone –> DHT conversion
  3. Androgen receptor
30
Q

Ketoconazole

A

Antifungal

Can technically be used to suppress androgen levels (but not typically)

31
Q

Spironolactone

A

Diuretic used for cardiac failure
Can technically be used to suppress androgen levels (but not typically)
Can block biosynthesis of testosterone from cholesterol

32
Q

Finasteride

A

Similar structure to testosterone
Competes for binding to 5alpha reductase
Decreases the levels of DHT
Used to treat BPH (reduces prostate size and resolves urinary retention) and male pattern baldness

33
Q

Flutamide

A

Synthetic, non-steroidal anti-androgen
Androgen receptor antagonist (competitive)
Used in combination with GnRH antagonists (leuprorelin) in prostate cancer

34
Q

Cyproterone

A

Used to treat excess sex drive

Androgen receptor antagonist (competitive)

Pharmacology II (24 decks)

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