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IHO Week 4 > Drugs that Interrupt Mitosis/Cytotoxic Drugs > Flashcards

Drugs that Interrupt Mitosis/Cytotoxic Drugs Flashcards

1
Q

What are the two main groups of drugs that interrupt mitosis?

A
  1. Vinca alkaloids
  2. Epilones
  3. Taxanes
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2
Q

Drugs that interrupt mitosis - CCS or CCNS?

A

CCS - M phase

-Act as mitotic spindle proteins

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3
Q

What drugs are vinca alkaloids?

A

Vinblastine, Vincristine, Vinorelbine

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4
Q

What are the epilones?

A

Ixabepilone

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5
Q

What are the taxanes?

A

Cabazitaxel, Docetaxel, Paclitaxel

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6
Q

What is the difference in toxicity between Vincristine and Vinblastine?

A 
Vincristine = CNS
Vinblastine = Bone Marrow suppression
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7
Q

What are the classes of plant alkaloids?

A
  • Camptothecans
  • Epipodophylotoxin
  • Taxanes
  • Vinca alkaloids
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8
Q

What drug is an epipodophylotoxin?

A

Etoposide

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9
Q

What drugs are a Camptothecins?

A

Irinotecan, Topotecan

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10
Q

What is the MOA for Vinca Alkaloids?

A
  • Vinblastine, vinorelbine, vincristine
  • Bind to tubulin at the forming end of microtubules and TERMINATE spindle assembly
  • Minor changes in structure can result in significant changes in toxicity and anti-tumor activity
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11
Q

What resistance has developed against Vinca alkaloids?

A
  • Dec. accumulation of drug via INCREASED P-GLYCOPROTEIN expression –> MDR
  • Changes in target proteins
  • –Mutations to tubular that prevent binding
  • Cross reactivity among vinca alkaloids is not absolute
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12
Q

What is the therapeutic use of vinca alkaloids?

A

-Routinely used in combination therapy because of distinct mechanisms of action and toxicities

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13
Q

What regimens is Vincristine involved in?

A

(Oncovin)

  • MOPP for Hodgkin’s disease
  • CHOP for non-Hodgkin’s lymphoma
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14
Q

What regimens is Vinblastine involved in?

A
  • ABVD for Hodgkin’s disease

- PVB for testicular cancer

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15
Q

What toxicities are caused by vinca alkaloids as a class?

A
  • Bone marrow suppression

- Neurotoxicity

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16
Q

What are the different degrees to which Vinblastine and Vincristine cause toxicity?

A 
Vincristine = more CNS toxicity (more lipid soluble) --> fatal if given intrathecally
Vinblastine = more Bone marrow suppression
17
Q

What are other toxicities of vinca alkaloids?

A
  • BMS (greater for Vinblastine)
  • Nausea and vomiting (greater for Vinblastine)
  • Alopecia
18
Q

What is important about the neurotoxicity seen in vinca alkaloids?

A
  • Prominent because of the requirement for microtubules
  • Common symptoms:
  • –Motor: loss of reflexes
  • –Autonomic: constipation, paralytic ileus, orthostatic hypotension
  • –Sensory: paresthesias (“pins and needles”)
19
Q

What would cause you to decrease the dose of a vinca alkaloid?

A
  • Depression of deep tendon reflexes occurs within 2-3 weeks in 100% of patients – this is used as an indication of sufficient dose
  • This can be followed by severe paresthesias and mild to moderate sensory loss - this is used as an indication to decrease the dose
20
Q

What is the mechanism of action for taxanes?

A

-Bind in tubulin and ENHANCE AND STABILIZE spindle assembly

21
Q

What resistance has developed against taxanes?

A

-Decreased accumulation via increased P-glycoprotein expression –> MDR

22
Q

What is the pharmacokinetics for taxanes?

A

Excessive CYP450 metabolism

23
Q

When you think paclitaxel. what should you think?

A

Drug interactions

24
Q

What are the toxicities for taxanes?

A
  • Bone marrow suppression
  • Hypersensitivity/Allegic reactions
  • –An albumin-bound formulation of PACLITAXEL has been developed that has significantly reduced toxicity
  • Peripheral neuropathy
  • Nausea and vomiting
  • Hypotension, arrhythmias
25
Q

What is the MOA of IXABEPILONE (Epilone)?

A

-Binds to tubulin and ENHANCES AND STABILIZES spindle assembly (similar to PACLITAXEL)

26
Q

What is Ixabepilone used with?

A

Capecitabine - for treatment of breast cancer (3rd line treatment)

27
Q

Where is Ixabepilone metabolized?

A

in the liver

28
Q

What side effects can Ixabepilone cause?

A
  • Bone marrow suppression, peripheral neuropathy and cardiac arrhythmias
  • Hypersensitivity
29
Q

Like other natural product drugs, Vinca alkaloids and taxanes lead to the development of. . .

A

. . .multidrug resistance due to increased expression of P-glycoprotein

30
Q

What drug is used for breast cancer patients who have failed anthracycline antibiotic and taxane treatments? Why?

A

Ixabepilone

-It does not produce MDR

IHO Week 4 (25 decks)

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