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7361 Hem/Onc Block 3 > Hormonal > Flashcards

Hormonal Flashcards

1
Q

___ are c18 steroids with an aromatic A ring formed by CYP19 enzyme known as aromatase

a. progestins
b. estrogens
c. androgens

A

b. estrogens

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2
Q

The most potent endogenous estrogen is __, but __ is the major circulating estrogen.

a. estrone (E1), estradiol (E2)
b. estradiol (E1), estrone (E2)
c. estradiol (E2), estrone (E1)

A

c. estradiol (E2), estrone (E1)

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3
Q

Activation of ___ receptors leads to the increase or decrease of there transcription of multiple target genes

A

estrogen

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4
Q

Dysregulation of __ signaling fuels the growth of certain types of tumors

A

estrogen

termed HR+ breast cancer

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5
Q

Aromatase inhibitors are used to block estrogen production by the ovaries

a. true
b. false

A

b. false

can be used to block synthesis of estrogens in the periphery, but are not effective in blocking estrogen production by the ovaries

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6
Q

Tamoxifen drug class?

A

selective estrogen receptor (SERM)

directly blocks binding of estrogens to estrogen receptors, and is an option for premenopausal pts

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7
Q

Tamoxifen is an option for postmenopausal pts

a. true
b. false

A

b. false

PREmenopausal pts

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8
Q

Tamoxifen is highly ___

a. hydrophilic
b. lipophilic

A

b. lipophilic

contributes to its high protein binding (> 98%) and long terminal half life (5-7 days)

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9
Q

Poor CYP___ metabolizers may benefit less from tamoxifen therapy

A

2D6

pts taking concomitant meds that are strong CYP2D6 inhibitors may benefit less from tamoxifen therapy

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10
Q

Tamoxifen is generally well tolerated, the most frequent side effect is ___

A

hot flashes

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11
Q

Tamoxifen stimulates the proliferation of ___ cells

A

endometrial

causes thickening of the endometrium, and increases the risk for developing endometrial cancer

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12
Q

What is the most frequent side effect of the SERM tamoxifen?

A

hot flashes

generally well tolerated

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13
Q

___ aromatase inhibitors are steroidal and bind irreversibly at the androgen binding site

a. type I
b. type II

A

a. type I

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14
Q

Which type of aromatase inhibitor binds irreversibly?

A

type I

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15
Q

which type of aromatase inhibitor binds reversibly?

A

type II

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16
Q

___ aromatase inhibitors are non-steroidal and bind reversibly to the heme of the enzyme.

a. type I
b. type II

A

b. type II

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17
Q

Type I aromatase inhibitor:

___ is a synthetic derivative of androstenedione where changes in the A/B ring system make the A ring electrophilic and able to form a covalent bond with the enzyme.

A

exemestane

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18
Q

What is the most common AE of exemestane?

A

hot flashes

generally well tolerated

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19
Q

Exemestane places pts at a greater risk for what condition?

A

osteoporosis

causes loss in bone density

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20
Q

___ are type II aromatase inhibitors

a. exemestane
b. anastrozole
c. letrozole

select all that apply

A

b, c

Type II aromatase inhibitors are non-steroidal and bind reversibly to the heme of the enzyme

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21
Q

Two most common AEs of the type II aromatase inhibitors anastrozole and letrozole?

A

hot flashes

night sweats

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22
Q

The type II aromatase inhibitors anastrozole and letrozole can cause what condition?

A

osteoporosis

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23
Q

Selective estrogen receptor degraders (SERD) are always ___

a. agonistic
b. antagonistic

A

b. antagonistic

devoid of estrogenic activity in all tissues

In addition to blocking estrogen receptor activation, a SERD makes the estrogen receptor a target for proteolytic degradation, thereby reducing the total number of receptors present

24
Q

What drug class if fulvestrant?

A

SERD

25
Q

___ is an estradiol analog with a lipophilic side chain at the 7-position

A

fulvestrant

26
Q

What enables the long duration of action of fulvestrant?

A

it is lipophilic and very insoluble

once monthly dosing

27
Q

Activation of __ receptors increases or decreases the transcription of multiple target genes

a. estrogen
b. androgen

A

b. androgen

28
Q

Dysregulation of androgen signaling fuels the growth of __ cancer

A

prostate

29
Q

Inhibition of what CYP blocks testosterone biosynthesis?

A

CYP17

30
Q

4 approaches to limit the ability of androgens to cause prostate cancer?

A
  • GnRH agonists down regulate GnRH receptors
  • GnRH antagonists block GnRH receptors
  • CYP17 inhibitors block testosterone biosynthesis
  • androgen receptor antagonists block androgen receptors
31
Q

GnRH agonists are modified analogs of GnRH with changes to the AA residues at positions __ and __ that lead to increased receptor affinity and resistance to enzymatic degradation

A

6, 10

GnRH agonists:

  • leuprolide
  • histrelin
  • triptorelin
  • goserelin
32
Q

Which GnRH agonist is a biodegradable implant?

A

goserelin

other implants must be removed

33
Q

GnRH agonists:

After one week the continuous GnRH receptor activation causes negative feedback and down regulation, decreasing LH and FSH with testosterone reaching castation levels (<50ng/dL) after ___ weeks

A

3-4

34
Q

GnRH agonists:

During the ___, the increased testosterone levels may stimulate prostate cancer growth and lead to a flare in symptoms

A

transient surge

35
Q

Degarelix is a GnRH ___

a. agonist
b. antagonist

A

b. antagonist

36
Q

__ is a 10 AA peptide that contains 3 proteinogenic AA residues and 7 residues that are synthetic AA derivatives

A

degarelix

37
Q

What is the MOA of the GnRH antagonist degarelix?

A

competes directly wit GnRH for binding site on anterior pituitary gland where its binding inhibits release of LH and FSH causing drop in serum testosterone

38
Q

How is the GnRH antagonist degarelix administered?

a. IM
b. SC
c. IV

A

b. SC

forms a depot for continuous delivery, making it suitable for once monthly dosing

39
Q

With the GnRH antagonist degarelix pts reach castration level of testosterone about ___ days after the initial dose and avoid the flare phenomenon seen with GnRH agonists

A

3

40
Q

GnRH antagonists:

___ is a small molecule (non-peptide) competitive antagonist of GnRH receptors that is available as a once daily oral tablet

a. degarelix
b. relugolix

A

b. Relugolix

41
Q

The GnRH antagonist relugolix is a substrate of what transporter?

A

P-gp

strong inhibitors/inducers of P-gp should be avoided if possible

42
Q

Which CYP catalyzes two important reactions in the biosynthesis of testosterone and DHT?

A

CYP17

43
Q

CYP17 inhibition can prevent synthesis of testosterone in ___

a. peripheral tissues
b. tumors
c. none of the above
d. a and b

A

d. a and b

44
Q

CYP17 inhibitors should be administered with low dose ___

A

glucocorticoids

ex. prednisone

45
Q

A double bond at what position is critical for irreversible inhibition of CYP17?

A

C16-C17

46
Q

An acetate ester instead of a hydroxyl at the C3 position is hydrolyzed in vivo to what active metabolite?

A

abiraterone

47
Q

The CYP17 inhibitor abiraterone is a strong inhibitor of what CYP?

A

CYP2D6

can increase the exposure of drugs metabolized by CYP2D6

48
Q

What drug class competes directly with DHT for the binding site on androgen receptors and inhibits the activation of gene transcription targets?

A

non-steroidal anti-androgens (NSAA)

49
Q

What drug class is bicalutamide?

A

non-steroidal anti-androgen (NSAA)

50
Q

non-steroidal anti-androgen:

Which bicalutamide enantiomer is directly glucuronidated and rapidly cleared?

a. S-enantiomer
b. R-enantiomer

A

a. S-enantiomer

51
Q

non-steroidal anti-androgen:

Which bicalutamide enantiomer is first oxidized by CYP3A4 prior to conjugation and has an elimination half life of one week?

a. S-enantiomer
b. R-enantiomer

A

b. R-enantiomer

52
Q

non-steroidal anti-androgen:

Which bicalutamide enantiomer has higher plasma concentrations at steady state?

a. S-enantiomer
b. R-enantiomer

A

b. R-enantiomer

100x higher

53
Q

Enzalutamide drug class?

A

non-steroidal anti-androgen (NSAA)

54
Q

non-steroidal anti-androgen:

Which is an active metabolite too enzalutamide that has equal AR potency and terminal half life to enzalutamide?

a. M1
b. M2

A

b. M2

t1/2 = 7.8 to 8.6 days

55
Q

The non-steroidal anti-androgen enzalutamide is a strong inducer of CYP___ and moderate inducer of CYP ___ and CYP___

A

3A4, 2C9, 2C19

avoid use with drugs that are metabolized by these enzymes and have narrow therapeutic indices

7361 Hem/Onc Block 3 (9 decks)

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