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Reproductive > PHARM: Prostate Cancer > Flashcards

PHARM: Prostate Cancer Flashcards

1
Q

True or false: prostate cancer is the most hormone sensitive of all cancers.

A

TRUE

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2
Q

Which has a longer ligand binding time to androgen receptors, testosterone or DHT?

A

DHT

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3
Q

What is commonly used with GnRH agonists to prevent the disease flare?

A

androgen receptor antagonists

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4
Q

How does prostate cancer evolve into an androgen-insensitive growth pattern?

A

Changes in AR amplification by point mutation

Changes in expression of AR co-regulatory proteins

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5
Q

What is a super androgen receptor?

A

AR receptor that can respond to lower concentrations of androgens or has the ability to function in a ligand-independent manner.

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6
Q

What is the consequence of a gain of stability mutation in 3β-hydroxysteroid dehydrogenase?

A

can lead to DHT mediated tumor activation (because it governs the conversion of DHEAS to DHT)

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7
Q

What were the problems in using estrogens for the treatment of prostate cancer?

A

when used in oral (high dose) regimens the produced significant adverse effects– primarily those impacting the CV system (DVT, thromboembolism, salt/water retention)

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8
Q

How are researchers planning to renew the use of estrogens for the treatment of prostate cancer?

A

using transdermal estrogens

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9
Q

Why are 5-alpha reductase inhibitors not used for prostate cancer?

A

recent data shows that there is not a benefit from using them

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10
Q

What are ER-alpha receptors?

A

receptors in the prostate that mediate aberrant proliferaiton, inflammation and malignancy when stimulated by estrogen

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11
Q

What are ER-beta receptors?

A

receptors int he glandular epithelium of the prostate that may have a tumor supressive effect (initiate apoptosis via TNF-alpha)

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12
Q

What receptor is consistently expressed in androgen-insensitive tumors?

A

progesterone receptor (but no drug for it)

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13
Q

What is first line treatment for prostate cancer?

A

combined androgen blockage (medical or surgical castration) + pure anti-androgen

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14
Q

What is brachytherapy?

A

non-drug treatment for prostate cancer that includes implanted I125 Titanium coated “seeds”

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15
Q

List the androgen receptor blockers?

A

Bicalutamide
Enzalutamide
Flutamide
Nilutamide

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16
Q

Which androgen receptor blocker is a CYP inhibitor?

A

Bicalutamide

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17
Q

Which androgen receptor blocker is specific for prostate AR?

A

Flutamide

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18
Q

Which androgen receptor blocks both central and prostate AR but is better at blocking prostate?

A

Bicalutamide

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19
Q

Which androgen receptor blocker has both antagonist and agonist activity?

A

Bicalutamide

20
Q

Which androgen receptor blocker is NOT a teratogen?

A

nilutamide

21
Q

Which androgen receptor blocker can cause male-mediated teratogeniticy?

A

enzalutamide

22
Q

Which androgen receptor blocker has a BBW for hepatotoxicity and liver failure?

A

Flutamide

23
Q

Whch androgen receptor blocker has CNS effects like dizziness, insomnia and seizures as well as UTRIs?

A

Enzalutamide

24
Q

Which androgen receptor blocker’s main side effect is blood dyscrasias?

A

Flutamide

25
Q

Which androgen receptor blocker has a BBW for respiratory insufficiency (interstitial pneumonitis)?

A

Nilutamide

26
Q

What is a strange adverse effect of Nilutamide?

A

increased time to transition from light to dark

27
Q

MOA: Alkylating agent + estradiol structure (target EBP on prostate cancer to deliver alkalyating agent (microtubule inhibitor → disassembly, G2/M arrest, and DNA strand breaks). Inhibits testosterone by negative feedback on GnRH

A

Entramustine

28
Q

List the GnRH agonists that work by providing continual drug stimulation of the GnRH receptors in the pituitary–> the receptors down regulate secretion of FSH and LH is attenuated

A

Goserelin
Histerelin
Leuprolide
Triptorelin

29
Q

List the reversible GnRH antagonist.

A

Degarelix (SC)

30
Q

Which works faster, GnRH agonists or angatonists?

A

GnRH antagonists

31
Q

MOA: Inhibitor of 17-alpha hydroxylase (CYP17) which prevents conversion of pregnenolone or progesterone to androgens (VERY SPECIFIC)

A

Abiraterone

32
Q

MOA: Culture patient APCs (leukapheresis) and culture with recombinant PAP-GM-CSF (APCs Take up antigen, process it, and express fragments on surface), renifuse product to stimulate CD8 T-cell immunity against prostatic acid phosphatase (PAP)

A

Sipuleucel-T

33
Q

What drug is commonly taken with abiraterone?

A

steroid

34
Q

TOXICITY: Prolonged treatment produces elevated levels of estradiol (gynecomastia, mastalgia, impotence, increased CV risk factors—edema, TE, MI, PE and stroke); GI Upset; elevated hepatic enzymes and hyperbilirubinemia

A

Entramustine

35
Q

TOXICITY: Decrease in bone mineral density (low estrogen), Increased CV risk (elevated serum lipids, weight gain and DN), Sexual dysfunction, loss of libido, gynecomastia; CNS problems (seizures/suicide with HIS only); TERATOGEN (Cat X)

A

Goserelin
Histerelin
Leuprolide
Triptorelin

36
Q

TOXICITY: QT prolongation, hepatic enzyme changes; hot sweats, injection site RXN, weight gain, HTN, arthralgia, chills, fatigue, impotence

A

Degarelix

37
Q

TOXICITY: Tends to produce hypermineralocorticoid state→ HTN, hypoK and edema watch out for CV history (provides more substrates for that pathway); Teratogen; elevated hepatic enzymes

A

Abiraterone

38
Q

Why must you withdrawal abiraterone slowly?

A

adrenocortical insufficiency if withdrawn quickly

39
Q

TOXICITY: Mild infusion RXN; fever/chills/ dyspnea, GI effects (N/V); Paresthesias, cirtrate toxicity and fatigue

A

Sipuleucel-T

40
Q

What conventional chemo drugs are used in prostate cancer?

A

Docetaxel
Carbazitaxel
MItoxantrone

41
Q

What is the indication for carbazitaxel? Why?

A

Poor substrate for the multidrug resistance P-glycoprotein efflux pump (good for treating multidrug-resistant tumors)

42
Q

What is the indication for mitoxantrone?

A

Palliation of severe pain from advanced hormone refractory disease

43
Q

What do you take with mitoxantrone?

A

prednisone

44
Q

What conventional chemotherapy drug for prostate cancer can cross the BBB?

A

carbazitaxel

45
Q

What is the MOA of Mitoxantrone?

A

type II topoisomerase inhibitor; disrupts DNA synthesis/ repair in both healthy cells and cancer cells, by intercalation.

46
Q

What do you take with Carbazitaxel? Why?

A

Premedicate with corticosteroids +/- antihistamine blockers to pevent edema and injection reactions produced with these surfactant-containing drugs

Reproductive (21 decks)

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