Breast and Endometrial Cancer Flashcards
MOA of anastrozole
aromatase inhibitor. non-steroidal (reversible)
prevents conversion of testosterone to E2
ADE of anastrozole
hot flashes, nausea, hair thinning.
joint stiffness
NO effects on adrenal steoids, thyroids or other homones.
MOA of exemestane
aromatase inhibitor. steroidal (irreversible)
prevents conversion of testosterone to E2
Exemestane exterminates permanently
ADE of exemestane
hot flashes, nausea, hair thinning.
joint stiffness
NO effects on adrenal steoids, thyroids or other homones.
MOA of letrozole
aromatase inhibitor. non-steroidal (reversible)
prevents conversion of testosterone to E2
ADE of letrozole
hot flashes, nausea, hair thinning.
joint stiffness
NO effects on adrenal steoids, thyroids or other homones.
MOA of raloxifene
SERM. ER agonist/antagonist depending on location.
Estrogen effect on bone
Anti-estrogen effect on mammary tissue.
Monthly IM.
Decreases bone resoprtion and lowers serum cholesterol.
ADE of raloxifene
retinal degeneration at high doses
BBW for DVT, PE, and stroke
teratogen
NO AGONISM IN ENDOMETRIUM.
MOA of tamoxifen
SERM. ER agonist/antagonist depending on location. Estrogen effect on bone Anti-estrogen effect on mammary tissue. Daily per oral. CYP 2D6
Decreases bone resoprtion and lowers serum cholesterol.
ADE of tamoxifen
retinal degeneration at high doeses
teratogen
Black BOX warning for endometrial hypertrophy, vaginal bleeding, ednometiral cancer and DVT or PE and stoke
MOA of toremifene
SERM. derivative of tamoxifen with antiestrogenic properties. CYP 3A4
ADE of toremifene
Similar to SERMs but also has BLACK BOX warning for prolonged QT interval.
(retinal degeneration at high doeses
teratogen
Black BOX warning for endometrial hypertrophy, vaginal bleeding, ednometiral cancer and DVT or PE.)
CYP 3A4 metabolism
Contraindicated in endometrial cancer and thromboembolism.
MOA of fulvestrant
SERD. Pure antagonist with NO estrogenic actions.
Impairs receptor dimerization and decreases ER levels.
ADE of fulvestrant
PM symptoms (nausea, asthenia, pain, vasodilation hot flashes and headache)
MOA of goserelin
GnRH agonist. Initially increases FSH/LH leading to disease flare, but then negatively inhibits them, decreasing estradiol to PM levels within 2-4 weeks.
ADE of goserelin
initial transiet disease flare of bone pain from mets, hypercalcemia, breast enlargment and tenderness.
well tolerated long term therapy
PM side effects: hot flashes, down libido, vaginal dryness, emotional, depression, gynecomastia, decreased bone density.
MOA of pertuzumab
Her-2 antibody for dimerization domain. Given IV with long half-life
ADE of pertuzumab
BBW for pregnancy!
hypersensitivity reactions, GI upset, asthenia, blood dyscrasias, fatigue.
Alopecia, loss of appetite
decreased LVEF
neutropenia and leukopenia.
MOA of trastuzumab
Her-2 antibody for extracellular domain
ADE of trastuzumab
peripheral edema, rash, weight gain, URTIs BBW for: Cardiomyopathy, HF RENAL FAILURE HEPATOTOXICITY pneumonia and respiratory failure. CID with pregancy.
MOA of lapatinib
TKI. Prevents downstream signalling of HER1 and HER2. extensive hepatic metabolism and CYP3A4.
ADE of lapatinib
BBW for liver disease. elevates LFTs.
GI issues, anemia, thrombocytopenia, HAND-foot Syndrome, rash
Interstitial lung disease
QT prolongation
MOA of everolimus
mTOR inhibitor. mTOR regulates cell proliferation and angiogneneis. Drug binds to FKBP-12 and forms a 3-2ay complex with mTOR to inhibit it.
ADE of everolimus
BBW for risk of opportunistic infections and neoplasia.
Blood dyscrasia, hyperglycemia and hyperlipidemia, high TGs and elevated creatinine and liver enzymes
NV, diarrhea, pain, constipation.
How can resistance to tamoxifen develop?
variable expression of ERa or ERb. interference with binding alternative splicing of ER mRNA variants modulation of ER expression and function by EGFR1 and EGFR2 growth factors. CYP2D6 genotype.
Which drug should a pre-menopausal women be given?
tamoxifen.
If post-menopausal switch to other drugs.
