Repro - Pharm - 1-6 Androgens

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PPt of this lecture is good. has tons of words and he basically read off the slides

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adsf

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Most common secreted and circ androgen

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testosterone.

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Testis produce...

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testosterone (leydig cells), dihydrotestosterone, andostenedione, dehydroepiandrosterone, dehydroepiandrosterone-sulfate.

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How much circ androgen is free?

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2%

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5-alpha reductase

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conv testosterone to dihydrotestosterone

inhib by finasteride (proscar)

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p450 aromatase

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converts testosterone to estrogen

inhib by anastrazole

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Issue of intervening pharm of androgens

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messes with many many pathways (which are all reversible and sensitive)

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Phases of testosterone secretion

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trimester 1 in utero
neonatal life
after puberty

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Sex hormone binding globulin

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most androgens are bound up by this.

most of the rest by serum albumin

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Androgen levels with age

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decline with age.
(more steroid hormone binding globulin to bind it up)

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androgen deficiency in aging men

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just know that this happens and testosterone level decline is a strong predictor of mortality in men

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Mech of action of androgens

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Diffuses in, binds androgen receptor (which binds to palindromic DNA sequences as a homodimer).

Results in activation.

Without androgen bound, AR actively represses target genes. Also associates with heat shock proteins.

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Androgen target cell

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androgens can get into all cells, so it is those cells that express androgen receptor

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Antagonists to androgen receptor

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Flutamide or bicalutamide

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Histone-deacetylase

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Inhibition of txpn

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Histone acetyltransferase

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Txpn of genes

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selective androgen receptor modulators

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can be androgenic or anti-androgenic.

depends on whether co-activators outnumber co-repressors or vice-versa

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Effect of aromatase inhibitors

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Example is anastrozole

Block estrogen production and enhance androgen levels.

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Testosterone esters

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More activ than testosterone. Given parenterally.

T-proprionate
T-enanthanate
T-cypionate.

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Alkylated testosterones

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Orally active but liver toxicity is possible.

Methyltestosterone and fluoxymesterone

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Transdermal systems

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Testoderm (patch)
Androderm (patch)
Androgel (topical gel)

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Androgenic to anabolic ratio

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Lower number (more anabolic) has more potential for anabolic abuse)

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Main risk to balance with androgen enhancement

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Prostate CA is mroe likely.

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Ways to cause anti-androgenic therapy

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GnRH agonists/antag
Steroid synth inhibitors
5-alpha reductase inhibitors
Androgen rec modulators

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GnRH analogs

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Goserelin, nafarelin, buserelin, leuprolide.

Overrides pulsatile secretion of GnRH by hypothal to cease prod of LH and FSH.

There is an initial increase in testosterone though. Then after that there is androgen suppression.

***pulsatile GnRH secretion is a RELIC of the pasdt.

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Cyproterone and Cyproterone acetate

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ANDROGEN RECEPTOR MODULATOR

Inhib actions of androgens at target organ.

Good in females with hirsutism.

***Sip up that androgen receptor

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Finasteride

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5-alpha reductase inhibitor.

Good for BPH.

Takes adv of DHT being the primary androgen in the prostate

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Flutamide

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ANDROGEN RECEPTOR MODULATOR

Anti-androgen to tx prostate carcinoma

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bICALUTAMIDE AND NILUTAMIDE

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ANDROGEN RECEPTOR MODULATOR

Tx of metastatic prostate CA

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Spironolactone

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ANDROGEN RECEPTOR MODULATOR

Competes with DHT for AReceptor binding.

Tx of hirsutism.

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AR antagonists - which are rev, non-rev

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Bicalutamide - Competitive antagonist

Nilutamide - Irrev AR antag

Flutamide - Blocks reuptake of tesos and nuclear binding of T and DHT to androgen rec.

***Flu? Not In B C

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There are self eval ques at the end

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asdlkf

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"There are a couple of androgens on our "to know drug" list that are mentioned in the lecture, specifically on slides 20, 21 like methandrostenolone, oxymetholone, ethylestrenol, etc. That were mentioned very briefly in class and there's not much info about them in the power point. Should we memorize the ratio of androgenic to anabolic and route of administration/dose for these drugs since that is all that's mentioned about them in the powerpoint or what should we know about these androgens?"

I am posting the reply via blackboard so that the information is available to all members of the class.

The drugs mentioned were included on the drug list because they were mentioned in the lecture and appear in the slides. These were the instructions I (and I assume others) recieved from the course directors. Having said that the specific answer to the question above is NO. You will not be held responsible for the androgenic to anabolic ratios for those drugs. That information was included simply to illustrate that there are distinct pharmacologic profiles among the synthetic androgens.

Contact me if you have additional questions on this topic.

Best
Jim

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