Term
Androgens What is it? What does it do? |
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Definition
• the principal androgen synthesized is testosterone • androgen receptor is a nuclear hormone receptor that recruits co-activators or co-repressors, binds androgen response elements in genes to increase or decrease gene expression • conversion of testosterone to: – estrogen, via the aromatase pathway • this pathway is responsible for most estradiol in men • estrogen increases bone density in men, causes gynecomastia
– dihydrotestosterone, via 5-alpha reductase • dihydrotestosterone is a more potent and efficacious androgen receptor agonist than is testosterone |
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Term
| Effects of Androgen during puberty |
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Definition
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Term
| Effects of Androgen in Adults |
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Definition
*Then the levels of testosterone peak around the ages of 25 -30 then decline throughout the rest of life
Adults: – male pattern baldness – growth of prostate gland • development of BPH (compression of urethra as it passes through prostate) – prostate cancer • Initially androgen-dependent, then becomes androgen-independent |
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Term
Therapeutic uses of androgens |
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Definition
Replacement therapy post-menopausal females also receiving estrogens male hypogonadism (testosterone deficiency) male senescence (reduced androgens with age) restores libido, fertility, muscle mass, strength, bone density
• AIDS-related muscle wasting -increases muscle mass and strength |
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Term
Testorsterone as Hormone Replacement Therapy (there are 6) |
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Definition
*High First pass Metabolism so cant give it orally - IM Depo Testosterone
- Trandsdermal: Androderm patch
- Topical gel: ANdrogel and Testim
Gels give a more contant levels than patch. If females come in close contact to gel then it will ab absorded and will lead to female virilization (hirsutism, acne, deepening of voice) - Methyltestosterone
- Flyoxymmesterone
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Term
Anabolic Steriods (there are 4) |
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Definition
– oxandrolone – oxymetholone – stanozolol (Winstrol) – nandrolone (Deca Durabolin) |
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Term
Anabolic Steriods uses? MOA? ADR? |
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Definition
*AKA: 17-alpha-alkylated compounds *designed for greater anabolic effects than testosterone *lower first-pass metabolism, less conversion to estrogen indicated for treating anemia, bone pain in osteoporosis and increasing weight misused for performance enhancing effects
Adverse effects hepatotoxicity (peliosis hepatis: the hepatoctyes and some spleen cells are replaced with blood filled sacs) hepatocyte tumors (benign and malignant) increased LDL, reduced HDL gynecomastia feedback inhibition: testicular atrophy, decreased sperm production and fertility
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Term
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Definition
Weak synthetic androgen Reduces FSH, LH and therefore testosterone and estrogen production via feedback inhibition Treats endometriosis in females
• Adverse effects – Thromboembolic events – Intracranial hypertension – Peliosis hepatis – Increased LDL, reduced HDL – Contraindicated in pregnancy • Androgenic effect on female fetus |
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Term
Androgen Deprivation Therapy |
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Definition
• Four pharmacological approaches: – GnRH receptor antagonists – GnRH receptor agonists – 5-alpha reductase inhibitors – Androgen receptor antagonists |
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Term
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Definition
*Antagonism of GnRH receptors reduces LH release and thus testosterone synthesis |
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Term
GnRH Receptor Agonists What are they? WHat do the they? Uses? |
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Definition
*The idea behind this drug is that over time the agonist will actually desensitized the GnRH receptor. That is why GnRH is only released in a pulsatile manner, if released in a continous fashion, it will result in desensitization. • Agonists cause an initial transient increase in gonadotropins and thus testosterone production • Over the next few weeks, agonists down-regulate the GnRH receptor and effector system – Long-term suppression of gonadotropin secretion – Long-term suppression of testosterone and estrogen production – Indicated for treatment of: • prostate cancer • advanced breast cancer • precocious puberty (premature sexual maturation) • endometriosis |
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Term
GnRH Receptor Angonist Drugs ADR |
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Definition
Peptides: leuprolide (Lupron), nafarelin, goserelin, buserelin, histrelin, triptorelin *Symptoms worsen during the first month due to receptor stimulation • Depot injections or implants for long-term effects, also intranasal administration • Adverse effects: – menopause like effects in men and women • Hot flashes, night sweating, reduced libido – reduced bone density – may add back low doses of progestins/estrogens to minimize these – memory loss (reversible) – Category X: fetal abnormalities |
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Term
5-alpha reductase inhibitors What is it? Uses? AdR? |
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Definition
*Also classified as Androgen Deprivation Therapy *will inhibit the conversion of testosterone to potent Dihydrotestosterone *So the levels of Tesoterone will not change but the effects will bc we are blcoking the potent metabolite There are two types of 5-ARi -Type 1: located on skin -Type2: located in prostate and Hair Follicles -Rx for BH -Rx for baldness (propecia) Reduces size of prostate gland and reduces PSA levels – 6 to 12 months for effects – used along with an alpha-1 receptor antagonist (FLOMAX) - it only relaxes the smooth muscles of prostate to reduce Sx of urethra and does not reduce prostate size ADR: -cannot donate blood -reduced libido -reduce fertility -if female absorbs it, it will adversely affect male fetus |
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Term
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Definition
*5-Alpha Reductase inhibitor |
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Term
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Definition
Duasteride (5-Alpha-reductase) inhibits type I and II Rx for BPH
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Term
Androgen receptor antagonists |
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Definition
"Androgen Deprovation therapy" • block androgen receptors in prostate to reduce prostate growth and treat prostate cancer • unlike GnRH receptor inhibitors, these also block the effects of circulating androgen produced by adrenal gland • blocking negative feedback in hypothalamus and pituitary gland can increase LH and testosterone production – often combine a GnRH receptor inhibitor • Can cause gynecomastia bc testosterone is converted to estrogen |
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Term
Androgen Receptor Antagonist Drugs |
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Definition
• flutamide (Eulexin): hepatotoxicity • bicalutamide (Casodex): less hepatotoxic • nilutamide (Nilandron): visual disturbances, alcohol intolerance |
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