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Part 2

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waveurflag's version from 2018-03-29 01:20

Section

Question Answer
Estrogen receptors are important foro Breast development during puberty o Lactation – upregulation of estrogen receptor during lactation. Goes back to normal after lactation is stopped
Pre-menopausal – ER+must stop contraceptive and not recommended to have any pregnancies within 5 years
ERE estrogen response element, specific part of DNA that ER dimers attach to and activate the gene
Coactivator must be present to be able to bind the ER dimer to DNA
Cyclin D1D1 is completely dependent on estrogen stimulation  right next to ERE promotor region oLocation is optimal to have estrogen receptor come and attach to ERE. Plays a HUGE role in cell divison
G1/S Regulation • D1 activates CDK4/5 (cyclin dependent kinase) • Kinase phosphorylates retinoplastomaprotein (pRb) • pRB releases E2F to promote DNA synthesis
Tamoxifen MOAinteracts with co-repressors, that prevents the transcription of proliferative genes. • Competitively binds to estrogen receptor • Removes co-activators and attracts co-repressors • Blocks cyclin d1 and prevents G1 to S phase transition
Helix 12 • Tamoxifen changes conformation of this hidden arm and moves it out farther away from the estrogen receptor o Now unable to attract good coactivators to help it activate o It has now become more attractive to corepressors instead of coactivators
Main Tamoxifen MOAChromatin Remodeling
TamoxifenInhibits estrogen-dependent proliferation of breast cancer cells • 3-Pharmacologic class: Estrogen receptor antagonist (competitive:partial agonist) • Currently, antiestrogens are the most effective and commonly prescribed treatments for patients with ERa-positive breast cancer
Tamoxifen is hydroxylated byCYP2D6
Endoxifenactive form of tamoxifen via demethylation by CYP3A4 & CYP3A5
partial agonists drugs that bind to and activate a given receptor, but only have partial efficacy at the receptor relative to a full agonist.
Falsodex MOAused in postmenopausal women whose breast cancer has progressed after treatment with other anti-estrogen medication. Completely degrades estrogen receptors
Aromatase Inibitors Who Are they FOR??????• Post-menopausal women with breast cancer
• Testosterone active metabolite 5-αDHT,
AndroGelthe risks involved in use of the drug in pregnant women clearly outweight potential benefits. • Avoid in patients with prostate cancers
Androgen regulates genes critical for the development and maintenance of the male sexual phenotype. • Bound to heatshockprotein 90 • ARE (androgen response element) • Same process as in estrogen
Flutamideoral, non-steroidal antiandrogen drug primarily used to treat prostate cancer. • It competes with testosterone and its powerful metabolite, dihydrotestosterone (DHT) for binding to androgen receptors in the prostate gland.
Bicalutamide• Replaces Flutamide due to less adverse effects
Abiraterone Acetate• Used for prostate cancer not responding to androgen deprivation or treatment with antiandrogens.
Finasteride• Is a synthetic drug for the treatment of benign prostatic hyperplasia (BPH) and male pattern baldness (MPB). It is a type II 5α-reductase inhibitor. 5α-reductase is an enzyme that converts testosterone to dihydrotestosterone (DHT)
Dutasterideis a l 5-α reductase inhibitor that inhibits conversion of testosterone to dihydrotestosterone (DHT). Used for benign prostatic hyperplasia; however, it increases the risk of erectile dysfunction and decreased sexual desire.
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