HORMONES Flashcards
Tamoxifen is FDA approved for
Premenopausal breast cancer
DCIS
Class of tamoxifen
Serm, non steroidal anti estrogen
Dose of tamoxifen
20 mg oral once daily
Duration of tamoxifen
Dcis 5 years
Invasive ca breast 10 yrs increased OS
Positive effects of tamoxifen
Decrease in total cholesterol
Preservation of bone density in post menopausal
Negative effects of tamoxifen
Negative effects on bone marrow in pre menopausal
Hot flashes
Endometrial ca in post menopausal
Thromboembolism when used along with chemo
Vaginal dryness
Treatment of hot flashes
Antidepressants like venlafaxine, desvenlafaxine, citalopram,
Anticonvulsant like gabapentin and pregabalin
Moa of tamoxifen
Competes with estrogen in binding to ER causes ER dimerisation which is transported to nucleus
Blocking estrogen stimulation of breast cancer cells - translocation and nuclear binding of ER.
Metabolites of tamoxifen
4 hydroxy tamoxifen 7 percent
N desmethyl tamoxifen further converted to Endoxifen major
Metabolism of tamoxifen
Liver - cyp2D6 - endoxifen most abundant
Distribution of tamoxifen
Plasma
Liver, lungs, brain, pancreas, skin and bones
Polymorphism in cyp2D6 causes , and how to treat it
Recurrence due to reduced endoxifen levels
Alternate hormonal therapy or high dose of tamoxifen 40 mg per day dose
Is tamoxifen cell cycle specific
Mid G1 phase
Absorption, excretion of tamoxifen
In GI tract
Excreted in feces 75 percent
Drug interactions of tamoxifen
Inhibitors of Cyp2D6 like SSRI SNRI cimetidine quinine terfanadine inhibits tamoxifen metabolism, lowers the level of active tamoxifen metabolites
Can u breast feed with tamoxifen
No cat D
What is tumor flare
In tamoxifen first two weeks ,
Increased bone pain, urinary retention, back pain
Does tamoxifen cause myelosuppression
No
Classify aromatise inhibitors
Steroidal : 2nd gen - formestane
3 rd gen x exemestane
Non steroidal
1st gen aminogletheamine
2 nd gen fadrozole
3 rd gen letrozole anastrozole and vorzole
Action of AI
Steroidal : compete with endogenous steroids; irreversibly inhibits by suicide capture , covalent binding
Non steroidal : reversible binding to endogenous substrate ; ionic bonds
Class of anastrozole
Non steroidal AI
Moa of anastrozole
Inhibits Aromatase
No inhibition of adrenal glands
No of days after which estrogen falls in anastrozole therapy
Suppressed by 90% within 14 days of treatment
Completely suppressed in 6 weeks
Absorption of anastrozole
85% oral within 2 hrs
Distribution of anastrozole
40% plasma protein binding
Metabolism and excretion of anastrozole
Liver
Excretion in feces / renal 10%
Indications and dose of anastrozole
1 mg PO once daily for 5 years
In hormone positive post menopausal women and premenopausal women after ovarian ablation
Adverse effects of anastrozole
Decrease in BMD - supplement with calcium 1200 to 1500 and vit D
If bmd decrease can also start on zoledronic acid
Dose of letrozole
2.5 mg PO once daily for five years in post menopausal women
Should you reduce anastrozole letrozole doses
Anastrozole dose need not be reduced
Letrozole reduce by 50% in cirrhoses and hepatic dysfunction- 2.5 mg PO every alternate day
What happens even we give letrozole in pre menopausal group
No efficacy
Increased benign ovarian tumours and cystic ovarian disease
Moa of exemestane
Steroidal ai
Irreversibly inhibits Aromatase
Causes of resistance in exemestane
Cross between steroidal and non steroidal Ai
PHARMA OF EXEMESTANE
Absorption : oral 85%
Distribution: 90% plasma protein
Metabolism : cyp3A4 liver
Excretion: feces , renal only 10%
Indications of exemestane
25 mg PO once Daily
Interaction of exemestane
Drugs that inhibit cyp3A4 decrease the metabolism of exemestane
What are bisphosphonates
Pyrophosphate analogues that bind to calcium phosphate with high affinity
Affect bone resorption by osteoclasts inhibition
Additional Moa of Za
Inhibits the tumor cell adhesion to ECM
Dose of ZA
4mg intravenous over 15 mins every4 weeks
Complications of ZA
Orn of jaw
Renal insufficiency
Check RFT
