HORMONES

Question 1

Tamoxifen is FDA approved for

Answer 1

Premenopausal breast cancer
DCIS

Question 2

Class of tamoxifen

Answer 2

Serm, non steroidal anti estrogen

Question 3

Dose of tamoxifen

Answer 3

20 mg oral once daily

Question 4

Duration of tamoxifen

Answer 4

Dcis 5 years
Invasive ca breast 10 yrs increased OS

Question 5

Positive effects of tamoxifen

Answer 5

Decrease in total cholesterol
Preservation of bone density in post menopausal

Question 6

Negative effects of tamoxifen

Answer 6

Negative effects on bone marrow in pre menopausal
Hot flashes
Endometrial ca in post menopausal
Thromboembolism when used along with chemo
Vaginal dryness

Question 7

Treatment of hot flashes

Answer 7

Antidepressants like venlafaxine, desvenlafaxine, citalopram,
Anticonvulsant like gabapentin and pregabalin

Question 8

Moa of tamoxifen

Answer 8

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.

Question 9

Metabolites of tamoxifen

Answer 9

4 hydroxy tamoxifen 7 percent
N desmethyl tamoxifen further converted to Endoxifen major

Question 10

Metabolism of tamoxifen

Answer 10

Liver - cyp2D6 - endoxifen most abundant

Question 11

Distribution of tamoxifen

Answer 11

Plasma
Liver, lungs, brain, pancreas, skin and bones

Question 12

Polymorphism in cyp2D6 causes , and how to treat it

Answer 12

Recurrence due to reduced endoxifen levels
Alternate hormonal therapy or high dose of tamoxifen 40 mg per day dose

Question 13

Is tamoxifen cell cycle specific

Answer 13

Mid G1 phase

Question 14

Absorption, excretion of tamoxifen

Answer 14

In GI tract
Excreted in feces 75 percent

Question 15

Drug interactions of tamoxifen

Answer 15

Inhibitors of Cyp2D6 like SSRI SNRI cimetidine quinine terfanadine inhibits tamoxifen metabolism, lowers the level of active tamoxifen metabolites

Question 16

Can u breast feed with tamoxifen

Answer 16

No cat D

Question 17

What is tumor flare

Answer 17

In tamoxifen first two weeks ,
Increased bone pain, urinary retention, back pain

Question 18

Does tamoxifen cause myelosuppression

Answer 18

No

Question 19

Classify aromatise inhibitors

Answer 19

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

Question 20

Action of AI

Answer 20

Steroidal : compete with endogenous steroids; irreversibly inhibits by suicide capture , covalent binding

Non steroidal : reversible binding to endogenous substrate ; ionic bonds

Question 21

Class of anastrozole

Answer 21

Non steroidal AI

Question 22

Moa of anastrozole

Answer 22

Inhibits Aromatase
No inhibition of adrenal glands

Question 23

No of days after which estrogen falls in anastrozole therapy

Answer 23

Suppressed by 90% within 14 days of treatment
Completely suppressed in 6 weeks

Question 24

Absorption of anastrozole

Answer 24

85% oral within 2 hrs

Question 25

Distribution of anastrozole

Answer 25

40% plasma protein binding

Question 26

Metabolism and excretion of anastrozole

Answer 26

Liver Excretion in feces / renal 10%

Question 27

Indications and dose of anastrozole

Answer 27

1 mg PO once daily for 5 years In hormone positive post menopausal women and premenopausal women after ovarian ablation

Question 28

Adverse effects of anastrozole

Answer 28

Decrease in BMD - supplement with calcium 1200 to 1500 and vit D If bmd decrease can also start on zoledronic acid

Question 29

Dose of letrozole

Answer 29

2.5 mg PO once daily for five years in post menopausal women

Question 30

Should you reduce anastrozole letrozole doses

Answer 30

Anastrozole dose need not be reduced Letrozole reduce by 50% in cirrhoses and hepatic dysfunction- 2.5 mg PO every alternate day

Question 31

What happens even we give letrozole in pre menopausal group

Answer 31

No efficacy Increased benign ovarian tumours and cystic ovarian disease

Question 32

Moa of exemestane

Answer 32

Steroidal ai Irreversibly inhibits Aromatase

Question 33

Causes of resistance in exemestane

Answer 33

Cross between steroidal and non steroidal Ai

Question 34

PHARMA OF EXEMESTANE

Answer 34

Absorption : oral 85% Distribution: 90% plasma protein Metabolism : cyp3A4 liver Excretion: feces , renal only 10%

Question 35

Indications of exemestane

Answer 35

25 mg PO once Daily

Question 36

Interaction of exemestane

Answer 36

Drugs that inhibit cyp3A4 decrease the metabolism of exemestane

Question 37

What are bisphosphonates

Answer 37

Pyrophosphate analogues that bind to calcium phosphate with high affinity Affect bone resorption by osteoclasts inhibition

Question 38

Additional Moa of Za

Answer 38

Inhibits the tumor cell adhesion to ECM

Question 39

Dose of ZA

Answer 39

4mg intravenous over 15 mins every4 weeks

Question 40

Complications of ZA

Answer 40

Orn of jaw Renal insufficiency Check RFT