Antihormones Flashcards
SERDs
competes with Estrogen for E receptor and destroys Estrogen receptor
Fulvestrant
SERD
Fulvestrant [ADE]
menopausal symptoms
SERMs
behaves like SERD & turn OFF signals in some tissues and turns ON receptor in other tissues
turns OFF in breast tissue, but turns ON in most others
Tamoxifen
SERM–> used as adjuvant therapy in early breast cancer, therapy in advanced breast cancer, prophylaxis
Tamoxifen [PK]
Prodrug– requires activation by CYP2D6
CPIC guidelines exist
Tamoxifen [ADE]
Menopause symptoms
Tumor flare –ER activation if tumors are ER/PR+ and do not have appropriate coregulators in gene expression
Stroke/PE – ER activation in liver –> enhanced clotting factor synthesis
Retinal Deposits/cataracts
Pleotropic Effects of Tamoxifen
Enhanced bone health
Lower total cholesterol and LDL
Tamoxifen [Mechanisms of Resistance]
CYP2D6 polymorphism
ER and HER2/neu pathway crosstalk or redundancy –> another pathway may “pick up the slack”
Tamoxifen [Contraindications]
Warfarin
History of PE
Aromatase Inhibitors [MOA]
CYP19A1
Inhibit conversion of androgens to estrogens
Aromatase Inhibitors [drugs]
Exemestane – IRREVERSIBLE
Anastrozole and Letrozole – REVERSIBLE
Aromatase Inhibitors NOT used in premenopausal women – WHY?
primary source of estrogen in premenopausal women is OVARIES –> turned off signal in ovaries will STILL signal to make more due to feedback loop– this won’t work & ovaries will still call for more synthesis
Anti-Androgens [MOA]
bind AR and competitively inhibit the binding of testosterone and dihydrotestosterone
does NOT increase LH, therefore testosterone levels are normal or even increased
Anti-Androgens [Benefit]
maintain libido and sexual function
