Cancer Pharm: Natural Products Flashcards

1
Q

What is the MOA of the vinca alkaloids, vinblastine, vincristine, and vinorelbine; specific to which phase?

A
  • Inhibit tubulin polymerization by DISRUPTING assembly of microtubules; especially those involved in mitotic spindle
  • M-phase specific: results in mitotic arrest in metaphase
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2
Q

AE’s of vinblastine?

A
  • N/V, bone marrow suppression (vin-blast-tine), and alopecia
  • Potent vesicant (blistering)
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3
Q

Vinblastine is used for what cancers?

A

Hodgkin’s and NHL’s, breast, and germ cell cancer

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4
Q

Vincristine is similar to vinblastine but has a higher affinity for what?

A

Axonal microtubules

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5
Q

What is the dose-limiting AE’s of Vincristine?

A
  • Neurotoxicity –> Peripheral sensory neuropathy manifesting as:
  • ANS dysfunction w/ orthostatic hypotension; urinary retention; paralytic ileus or constipation; CN palsies; ataxia; seizures; coma
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6
Q

Which 2 vinca alkaloids are associated with SIADH as potential AE’s?

A
  • Vincristine
  • Vinorelbine
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7
Q

List 4 AE’s associated with Vinorelbine?

A
  • N/V
  • Transient elevations in LFT’s
  • Neurotoxicity
  • SIADH
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8
Q

Which vinca alkaloid can be used for pediatric tumors, rhabdomyosarcoma, neuroblastoma, Ewing’s sarcoma, and Wilms tumor?

A

Vincristine

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9
Q

Which 3 natural products work by binding to microtubules and enhancing tubulin polymerization causing cell death; which phase do they work in?

A
  • Paclitaxel, Docetaxel, and Cabazitaxel (Taxanes)
  • Work in the M phase
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10
Q

Which 2 natural products are associated with hypersensitivity reactions as AE’s?

A
  • Paclitaxel
  • Docetaxel
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11
Q

What are acute vs. delayed dose limiting toxicities associated with Paclitaxel?

A
  • Acute = N/V, hypotension, arrhythmias, hypersensitivity
  • Delayed = myelosuppression, peripheral sensory neuropathy
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12
Q

Which form of paclitaxel is NOT associated w/ hypersensitivity rxns, has reduced myelosuppressive effects, and neurotoxicity more easily reversed?

A

Albumin-bound paclitaxel

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13
Q

What are the acute vs. delayed toxicities assoc. w/ Docetaxel?

A
  • Acute = hypersensitivity
  • Delayed = neurotoxicity, fluid retention, myelosuppression w/ neutropenia
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14
Q

Why is Cabazitaxel more useful in treating multi-drug resistant tumors than other taxanes?

A

Is poor substrate for P-glycoprotein

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15
Q

How does Ixabepilone differ in its MOA from the taxanes?

A

Microtubule inhibitor that binds directly to β-tubulin subunits on microtubules —> dynamic inhibition of microtubule

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16
Q

One of the benefits of Ixabepilone is due to its activity in tumors with what features?

A

Resistant tumors w/ tubulin mutations and overexpression of P-glycoproteins

17
Q

What are 2 unique AE’s of Ixabepilone?

A
  • Hypersensitivity rxns
  • Neurotoxicity in the form of peripheral sensory neuropathy
18
Q

Ixabepilon has been approved for tx of what cancer?

A
  • Metastatic breast cancer as monotherapy
  • Or in combo w/ capecitabine
19
Q

What is the MOA of Eribulin?

A

Inhibits microtubule function leading to a block in the G2-M phase

20
Q

Eribulin is used in which cancers; has activity in tumors with what features?

A
  • Metastatic breast cancer
  • Has activity in tumors that overexpress P-glycoprotein
21
Q

What is the MOA of the epipodophyllotoxin, Etoposide?

A

Forms complex w/ and inhibits activity of topoisomerase II and DNA

22
Q

What is the MOA of the camptothecins, Topotecan and Irinotecan?

A

Inhibit activity of topoisomerase I, the key enzyme for cutting and religating single DNA strands –> DNA damage

23
Q

What are 2 forms of diarrhea which may arise as AE of camptothecins, Topotecan and Irinotecan?

A
  • Early form = occurs within 24-hrs of tx; cholinergic event; tx w/ atropine
  • Late form = occurs 2-10 days after tx; can be severe and leads to electrolyte imbalances and dehydration
24
Q

Which camptothecin, topotecan or irinotecan, is more potent and why?

A

Irinotecan (prodrug) converted to SN-38 in liver, which is 1000-fold more potent topoisomerase I inhibitor