Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Therapeutics > Exam 1 Lecture 2 > Flashcards

Exam 1 Lecture 2 Flashcards

1
Q

most commonly mutated gene in cancer

A

P53

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

can you get to estrogens without going through androgens? What is the order?

A

No, you must go through androgens to get to estrogens

Progestin–>androgen–>estrogen

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What enzyme forms pregninolone

A

P 450 SCC

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What happens to pregninolone? What is it hydroxylated by? What does it turn to?

A

17-alkyl hydroxylase hydroxylates pregninolone to 17-a- hydroxy pregninolone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What happens to 17- a- hydroxy pregninolone? in body

A

17, 20 lyase converts 17-a- hydroxy pregninolone to dehydroepiandosterone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What happens to dehydroepiandosterone in body

A

Dehydroapiandosterone is converted to androstenediol , which is converted into testosterone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What happens to testosterone in body

A

Testosterone is converted to dihydrotestpsterone (DHT) by 5-a reductase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What happens to androstenedione and testosterone in body?

A

androstenedione is converted to estrone and testosterone is converted to estradiol

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is the most active estrogen in body

A

Estradiol

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Collective steps from Pregninolone to estradiol/estrone

A
  1. P 450 SCC forms pregninolone
  2. 17-alkyl hydroxylase hydroxylates pregninolone to 17-a hydroxy pregninolone
  3. 17, 20 Lyase converts 17-a- hydroxy pregninolone to dehydroepiandosterone
  4. dehydroepiandosterone is converted to androstenediol, which is converted into testosterone
  5. Testosterone is converted to DHT by 5-1 reductase
  6. ANdrostenedione and testosterone are converted by aromatase to either estrone or estradiol
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Understand the use of corticosteroids in lymphoid cancers

A
  • pediatric acute lymphoblastic leukemia
  • multiple myeloma
    -lymphomas
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

When are glucocorticoids used in chemo

A

Used as palliative care to reduce inflammation, edema e.t.c

Can be used to reduce hypersensitivity, nausea and vomiting and immune related adverse effects

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What are the most common glucocorticoids

A

Methylprednisolone, Prednisolone, Dexamethasone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

When are hormonal therapies used in cancer

A

Disease specific… only for hormone dependent cancers

Breast cancer, Prostate cancer, Endometrial cancer

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What do hormone therapies target

A

Estradiol (breast and endometrial)

Dihydrotestosterone(DHT) (prostate)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

molecular activity of steroidal hormones?

A

Only unbound hormones can diffuse into target cell (if bound to plasma protein, carrier wont cross)

Steroid hormone receptors are in cytoplasm or nucleus.

receptor-hormone complex forms and binds to DNA. This either activates or represses one or more genes.

activated genes create new mRNA that moves to cytoplasm and translation produces new protein.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What are the two major strategies to inhibition of steroid signaling?

A
  1. stop steroid receptor function
  2. Decrease production of steroids
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Which tumors are likely to be well differentiated and which ones are more likely to be poorly differentiated

A

ER (+) are well differentiated and ER (-) are poorly differentiated. ER= estrogen receptors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Which tumors have a higher growth factor? Well differentiated tumors or poorly differentiated tumors

A

Poorly differentiated tumors have higher growth fractions. (thus are more reactive to cytotoxic agents as opposed to hormonal agents)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Which tumors have a better prognosis(ER+ or ER-)

WHat about when PR (progesterone receptor is involved)

A

ER+

Even better prognosis with ER+/PR+ tumors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

what type of breast cancer is hormone therapy used in?

A

ER+/PR+

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Where do estrogen receptors bind Estrogen in cell

A

In cytoplasm

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Where is LH (leutenizing hormone ) produced? Andosterone is converted to estrone by?

A

Pituitary gland

Andristenedione is converted to estrone by CYP 19 (aromatase)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

ER+ tumors will be treated with

A

Endocrine therapy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

The range of ER positivity to be treated with endocrine therapy?

A

about 10%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

What are the 4 different types of breast cancer?

A
  1. Luminal A, Luminal B
  2. HER-2
  3. Basal like
  4. claudin low
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Describe Luminal A and B breast tumor subtypes

A

Luminal A and B are more differentiated and are the most estrogen and progesterone receptor positive. They are also the most responsive to endocrine therapy.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

What is HER 2

A

Type of cancer cell that is a receptor tyrosine kinase (oncogene)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

What breast tumor subtype is BRCA 1

A

basal like

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Describe basal like and claudin low cancers

A

They are triple negative breast cancers (no estrogen, progesterone receptor or HER-2), will all be treated by cytotoxics.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

What is the most used drug in (ER+) breast cancer

A

tamoxifen

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

Is tamoxifen a prodrug? If yes what is it hydrolyzed into?

A

yes it is a prodrug. It is metabolized into 4- hydroxy tamoxifen

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

What is a SERM? Name a SERM drug?

A

SERM is a selective estrogen receptor modulator. Tamoxifen is a SERM. It has both agonist and antagonist effects depending on what tissue it is in.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

What does tamoxifen bind? Where is it an agonist? Where is it an antagonist?

A

Tamoxifen binds estrogen receptors. It has antagonist effects in brain and breast. Agonist in bone.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

What enzyme metabolizes tamoxifen to 4-hydroxy tamoxifen?

A

CYP2D6.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

Estrogen antagonist effects of tamoxifen

A

Blocks estrogen dependent breast cancer cell proliferation
Hot flashes due to anti estrogen effects

37
Q

Is tamoxifen effective for both pre and post menopausal women?

A

Yes

38
Q

What type of cell warants tamoxifen usage

A

ER/PR + breast cancer

39
Q

What is the 1st drug approved for breast cancer prevention

A

Tamoxifen

40
Q

Tamoxifen is much less effective in which type of cell

A

CYP2D6

41
Q

Adverse effects of tamoxifen in different parts of the body

A

Brain- ER antagonist (hot flashes, thermoregulation)
blood- ER agonist (increased coagulability, clot and VTE risk)
Uterus- ER agonist (endometrial hyperplasia)

42
Q

Beneficial effects of tamoxifen in different body parts

A

Breast- antagonist (antiproliferative)
bone- partial agonist (blocks bone resorption)

43
Q

Raloxifene adverse effects

A

Only differs from raloxifene in that there is no endometrial hyperplasia in uterus

44
Q

Raloxifene beneficial effects

A

Same as tamoxifene only differs in uterus as raloxifene has no endometrial hyperplasia. It also increases bone mass is osteoporosis.

45
Q

What is a SERD? What are some SERD drugs?

A

SERD= selective estrogen receptor down- modulator.

Fluvestrant and elacestrant are SERD drugs.

SERD is a pure ER antagonist that has no agonist effects (elacestrant acts as a partial agonist at low doses and full SERD at high doses)

46
Q

What reactions does aromatase control

A

Androstenedione—> estrone

Testosterone—-> estradiol

47
Q

Do inhibitors of aromatase block the synthesis of estrogens? androgens? progesterone?

A

Only blocks synthesis of estrogens, but not androgens or progesterone.

48
Q

What is another source of estrogen in post menopausal women?

A

adipocytes

49
Q

primary target of aromatase inhibitors? (is it ovary or adipose tissue)

A

Peripheral tissue (adispose tissue)

50
Q

what is the primary application of aromatase inhibitors

A

Estradiol suppression in post menopausal women

51
Q

What are some imidazole based non-steroidal aromatase inhibitors? How do they work? Primary indication?

A

Anastrazole and letrozole.

Are competitive inhibitors of aromatase activity.

Tx of breast cancer in post menopausal women

52
Q

Name the steroidal aromatase inhibitor

A

Exemestane

53
Q

How does exemestane work?

A

Is a suicide inhibitor. Aromatase thinks that exemestane is androstenedione due to structural similarity. Intermediate binds irreversibly to aromatase at active site and inactivates enzyme.

54
Q

Primary indication of exemestane

A

Primary indication is tx of estrogen responsive breast cancer in POST MENOPAUSAL women

55
Q

Is exemestane in pre or post menopause? Both?

A

Post menopause

56
Q

How does fluvestrant work?

A

Fluvestrant inhibits the activity of the estrogen receptor throughout the body

57
Q

The HPA axis is regulated by

A

feedback inhibition

58
Q

What are the roles of FSH and LH in steroid hormone biosynthesis

A

LH activates chol-scc enzyme (side chain cleaving enzyme)

FSH increases expression of aromatase

59
Q

What are LH and FSH regulated by

A

Feedback mechanism

60
Q

What is the effect of chronic administration of GnRH analogues

A

Chronic administration of GnRH analogues downregulate pituitary GnRH receptors. And leads to pituitary desensitization.

leads to severe loss of estrogen within 3-4 weeks

inhibition of estrogen dependent breast cancer in women.

61
Q

What is the effect of acute administration of GnRH analogues

A

Acute administration induces surge of LH and FSH

Acute increase in all steroidal hormone levels.

Corresponding transient increase in tumor growth

62
Q

What are some GnRH analogues

A

Leuprolide
Goserelin
Triptorelin

63
Q

Long term side effects of GnRH analogues

A

Hot flashes and sexual dysfunction

64
Q

primary indication of GnRH analogues

A

PREMENOPAUSAL breast cancer

65
Q

Summary of hormonal therapy in breast cancer

A

For postmenopausal women with ER+
-Tamoxifen
-Nonsteroidal aromatase inhibitors (anastrazole, letrozole)
-Steroidal aromatase inhibitor (exemestane)
- Pure anti-estrogens (fluvestrant)

For premenopausal women
- GnRH agonist (goserelin and leuprolide)
-surgical oophorectomy
-tamoxifen

66
Q

What is the prostate cancer staging? What is it called? What are the grades? Which ones are differentiated? Undifferentiated?

A

Called the gleason score

  1. Small uniform glands
  2. more space between glands
  3. infiltration of cells from glands at margin
  4. irregular masses of cells with few glands
  5. lack of glands

Well differentiated is 1

poorly differentiated is 5. There is a gradient

67
Q

What happens to testosterone in prostate

A

Testosterone is rapidly and irreversibly converted by type II 5-a reductse to DHT (dihydrotestosterone) in prostate cells.

68
Q

What happens to dihydrotestosterone in prostate

A

DHT binds to androgen receptor (AR) in prostate cells

DHT-AR complex is activated and translocated to nucleus

DNA binding stimulates transcription of AR responsive genes.

69
Q

describe AR signaling

A

AR is a cytoplasmic receptor

AR can be amplified in prostate cancer

Binding of AR to DHT leads to translocation to nucleus and action of genes that drive cell proliferation

70
Q

describe the role of PSA is diagnosis of prostate cancer. What can it also be raised by

A

High level of PSA can be a sign of prostate cancer.

It can also be a sign of UTI, vigorous exercise, Medication, recent ejaculation or anal sex

71
Q

Effect of GnRH analogues in men

A

Just as in women, prolonged tx with these analogues lead to decrease in LH production.

Transient increase in testosterone, but results in “chemical castration” in men within 3-4 weeks

72
Q

GnRH analogues

A

Leuprolide acetate
Goserelin
Triptorelin

73
Q

primary indication of GnRH

A

Palliative tx of advanced prostate cancer.

74
Q

What is the transient worsening of symptoms related to in GnRH

A

initial agonist effects “flare”

75
Q

Long term side effects of GnRH

A

Long term side effects related to testosterone- deficient feminization

Gynecomastia
sexual dysfunction

76
Q

GnRH antagonists in men drugs

A

Degarelix, relugolix

77
Q

primary indication of GnRH antagonist

A

advanced prostate cancer with need for androgen deprivation therapy

78
Q

difference between GnRH analogues and antagonist

A

GnRH antagonist does not lead to flare of testosterone production

79
Q

What are the long term side effects of GnRH antagonist

A

Same as GnRH analogues (gynecomastia and sexual dysfunction.

80
Q

What is another way we prevent DHT production

A

Abiraterone (zytiga)

81
Q

How does abiraterone (zytiga) prevent DHT production

A

Inhibits function of 17-a-hydroxylase and C 17,20 lyase

it is a steroidal analogue

82
Q

What is a common side effect of abiraterone

A

Increase in cholesterol

83
Q

What is another way to block AR signaling

A

Androgen receptor (AR) antagonists

84
Q

Name AR antagonists

A

Enzalutamide
Apalutamide
Darolutamide

85
Q

How do AR antagonists block AR signaling

A

All inhibit AR binding to DNA

Prevent AR translocation to nucleus

86
Q

What are AR antagonists approved in?

A

Metastatic and non metastatic prostate cancer

87
Q

MOA of resistance to endocrine therapy in prostate cancer

A

Mutations in AR can arise that result in androgen independent activation and prevent binding of AR antagonists.

This is referred to as castration resistant prostate cancer (CRPC)

88
Q

What is CRPC

A

castration resistant prostate cancer (CRPC)

mutations in AR that result in androgen independent activation and prevent binding of AR antagonists

Therapeutics (15 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions