Brainscape's Knowledge GenomeTM

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


See full index

Thera IX > 06c Hormonal Agents Camarero > Flashcards

06c Hormonal Agents Camarero Flashcards

1
Q

What is the rationale behind Hormonal Agents?

A

Some of the tumors of endocrine origin (breast, prostate, endometrium) may (or may not) have hormone receptors. This determines whether they may respond to endocrine stimuli/inhibition

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

What are the sub-classes of hormonal agents used?

A

Estrogen & Androgen Inhibitors. Gonadotropin-Releasing Hormone Agonists. Aromatase Inhibitors

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

What are the Estrogen & Androgen Inhibitors used?

A

Tamoxifen

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

What are the Gonadotropin-Releasing Hormone Agonists used?

A

Leuprolide

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

What are the Aromatase Inhibitors used?

A

Aminogluthethimide

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

What are Antiestrogens?

A

Selective estrogen receptor modulator (SERM), possess both estrogenic and antiestrogenic effects on various tissues. Binds to estrogen receptors (ER) and induces conformational changes in the receptor. Has antiestrogenic effects on breast tissue. The ability to produce both estrogenic and antiestrogenic affects is most likely d/t the interaction with other coactivators or corepressors in the tissue and the binding with different estrogen receptors, ER-a and ER-B. The expression of estrogen dependent genes is blocked or altered. Resulting in decreased estrogen response

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

What is Tamoxifen?

A

Antiestrogen. Most of Tamoxifen’s effects occur in the G1 phase of the cell cycle

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

How is Tamoxifen administered?

A

Orally and is rapidly absorbed from the GI tract. Drug distributes widely through the body. Extensively metabolized in the liver

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

What are the therapeutic uses of Tamoxifen?

A

Can be used as primary therapy for metastatic breast cancer in both men and postmenopausal women. Reduces breast cancer incidence when used prophylactically

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

What is the toxicity associated with Tamoxifen?

A

Hot flashes, fluid retention and nausea

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is Megestrol?

A

Antiestrogen. Synthetic oral progestin (induces endometrial secretory changes, increases basal body temperature, inhibits pituitary function)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is Megestrol used for?

A

To stimulate appetite in AIDS patients and as antieoplasic (breast, renal cell and endometrial carcinoma)

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

What is the MOA of Megestrol?

A

Suppression of luteinizing hormone release may have negative effect on cancerous tissues (breast and endometrial lining). Enhances estrogen metabolism, which may suppress estrogen-dependent tumors by lowering plasma estrogen concentrations

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

What is the PK/PD of Megestrol?

A

Rapidly absorbed across the GI tract. BA > 90%. Strongly bound to plasma proteins. Tendency to concentrate on adipose tissue. Completely metabolized by the liver. Major route of drug/metabolites elimination is urine

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

What is the toxicity related to Megestrol?

A

Adrenal insufficiency

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

What is the MOA of Antiandrogens?

A

Compete with ligand for AR binding (sequesters AR in cytoplasm). Prevents dimerization and/or DNA binding, prevents formation of active transcription complex

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

What is Flutamide?

A

Oral nonsteroidal Antiandrogen used in the treatment of metastatic prostatic carcinoma. Most effective when used in combination with LHRH antagonists (e.g. Leuprolide). Not effective in treating other hormonally dependent diseases (breast cancer or benign prostatic hypertrophy). Antiandrogenic effects mediated by inhibition uptake and/or nuclear binding of testosterone and dihydrotestosterone by prostatic tissue

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

How is Flutamide administered?

A

Orally and rapidly absorbed by the GI tract (BA > 90%)

19
Q

What is the PK/PD of Flutamide?

A

Highly bound to plasma proteins. Quickly metabolized in the liver to its primary active form, Hydroxyflutamide. Excreted by the kidneys, and not removed by hemodialysis

20
Q

What are the side-effects associated with Flutamide?

A

Gynecomastia (abnormal enlargement of mammary glands in males), mild liver injury, and GI problems

21
Q

What has Flutamide been largely replaced by?

A

Bicalutamide, due to a better side-effect profile

22
Q

What is the MOA of Bicalutamide?

A

Binds to the androgen receptor (AR) and prevents the activation of the AR and subsequent up-regulation of androgen responsive genes by androgenic hormones. Accelerates the degradation of the androgen receptor

23
Q

What is the MOA of Aromatase Inhibitors?

A

Inhibit or inactivate Aromatase (Aromatase is the rate-limiting step in estrogen production). Suppression of estrogen biosynthesis and estrogen plasma levels

24
Q

What are the Type 1 Aromatase Inhibitors?

A

Steroidal Inhibitors: Formestane, Exemestane

25
Q

What are the Type 2 Aromatase Inhibitors?

A

Non-Steroidal Inhibitors: Aminoglutethimide, Anastrozole, Letrozole

26
Q

What is Aminoglutethimide?

A

Oral adrenal steroid inhibitor used for suppression of adrenal function in Cushing’s syndrome, and as drug of abuse for body builders. Used in the treatment of metastatic breast cancer

27
Q

How does Aminoglutethimide work?

A

Inhibits the conversion of both cholesterol to pregnolone and androstenedione to estrone/estradiol. Reduces biosynthesis of glucocorticoids, mineralcorticoids, estrogens and androgens

28
Q

What are the therapeutic uses of Aminoglutethimide?

A

Estrogen receptor (ER)- and progesterone receptor (PR-) positive metastatic breast cancer

29
Q

What are the toxicity and side-effects associated with Aminoglutethimide?

A

Dizziness. Lethargy. Visual blurring. Rash. It may cause hepatotoxicity and hypothyroidism

30
Q

What is Exemestane?

A

Oral, irreversible, steroidal aromatase inhibitor (reduces plasma estrone and estradiol levels by ~90%). Does not exhibit cross-resistance with other non-steroidal aromatase inhibitors. Structurally related to Androstenedione. Functions as suicidal substrate for aromatase

31
Q

How is Exemestane metabolized?

A

Extremely metabolized via oxidation of methylene group at position 6 and reduction of keto group at position 17

32
Q

What is Anastrozole?

A

A novel selective non-steroidal inhibitor used to treat advanced ER- and PR- positive breast cancer that is no longer responsive to Tamoxifen. Unlike Aminoglutethimide, an early Aromatase Inhibitor, Anastrozole does not inhibit adrenal steroid synthesis. Patients do not require gluco- and minieral-corticoid replacement therapy

33
Q

What is the PK of Anastrozole?

A

Well absorbed and distributed through systemic circulation (BA ~85%). Mostly metabolized in the liver (85%), metabolites are not active

34
Q

What is Gonadotropin-Releasing Hormone (GnRH)?

A

A decapeptide. Released from the hypothalamus with paradoxical effects on the pituitary gland. Initially stimulates release of follicle-stimulating hormone (FHS) and luteinizing hormone (LSH), followed by inhibition of the release of these hormones (negative feedback inhibitor). Resulting in reduced testicular androgen production (chemical castration)

35
Q

What are the GnRH Agonists used?

A

Leuprolide. Goserelin

36
Q

What is the therapeutic use of GnRH Agonists?

A

Metastatic carcinoma of prostate. Hormone receptor-positive breast cancer

37
Q

What are the toxicity and side-effects of GnRH Agonists?

A

Gynecomastia (enlargement of mammary glands in males). Loss of libido, impotence. Edema. Thromboembolism

38
Q

What is Leuprolide (Lupron) and Goserelin (Zoladex)?

A

Synthetic analog (super-agonists) of GnRH. Good BA. Renal excretion. Poorly protein bound

39
Q

How are Leuprolide (Lupron) and Goserelin (Zoladex) administered?

A

Intramuscular (IM, daily) or subcutaneous (SC, patch 1 or 3 months)

40
Q

In summary, what is the function and cancer treatment of Antiestrogens?

A

Estrogen receptor antagonist; prevents tumor growth stimulation - breast cancer

41
Q

In summary, what is the function and cancer treatment of Antiandrogens?

A

Androgen (testosterone) antagonist and uptake inhibitor - prostate cancer

42
Q

In summary, what is the function and cancer treatment of Aromatase inhibitors?

A

Reduce levels of circulating estradiol/estrone - advanced breast cancer

43
Q

In summary, what is the function and cancer treatment of GnRH Agonists?

A

Decrease androgen production - prostate cancer

Thera IX (29 decks)

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