Endocrine cancer Flashcards
Tamoxifen is a
selective estrogen receptor modulator (SERM)
MOA of tamoxifen:
competitively blocks endogenous estrogen binding to estrogen receptor in target tissue -> complex alters estrogen-responsive gene expression
prevent cell activation & proliferation
describe the effects of tamoxifen’s stereoisomers
Cis-isomer: estrogenic effect
Trans-isomer: anti-estrogenic effect
Tamoxifen’s absorption in the body
rapidly & extensively absorbed (F ~100%)
peak time ~5 (3-7)h
Css reached ~3-4weeks (possible up to 16 weeks)
Tamoxifen’s distribution in the body
High plasma protein binding (>98%), high Vd (50-70L/kg) -> highly concentrated in breast/uterus/ liver/ kidney/ lung/pancreas/ ovary tissue
uterus: 2-3x higher than circulation levels
breast: 10x higher than circulation levels
Tamoxifen’s metabolism in the body
CL = 1.4ml/min/kg
T1/2: 5-7d
major pathway: N-methylation (catalysed by CYP3A4)
*major metabolites: N-desmethyltamoxifen (t1/2: 14d)
*DFI (grapefruit)
(others: phase 1 hydroxylation, N-oxidation, dealkylation; phase 2: glucuronidation, sulphation)
other metabolites by CYP2D6
Tamoxifen’s elimination in the body
mainly eliminated by faeces (negligible <!% urinary excretion)
Tamoxifen’s indications
- breast cancer (early & metastatic)
*useful for pre- & post-menopausal women - may be useful in chemoprevention of breast cancer for high risk
- reduces severity of osteoporosis (but not indicated due to availability of other agents that have superior side effect profile)
Tamoxifen’s side effects
hot flashes
increases risk of ENDOMETRIAL CANCER
Venous thromboembolic events (DVT)
menstrual irregularities
vaginal bleeding & discharge
nausea & vomiting
Tamoxifen’s toxicity
acute neurotoxicity from HIGH dose(tremor, hyperreflexia, unsteady gait, dizziness)
*if overdose: supportive treatment
