Drugs that Interrupt Mitosis/Cytotoxic Drugs Flashcards Preview

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

Flashcards in Drugs that Interrupt Mitosis/Cytotoxic Drugs Deck (30)
1

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

1. Vinca alkaloids
2. Epilones
3. Taxanes

2

Drugs that interrupt mitosis - CCS or CCNS?

CCS - M phase
-Act as mitotic spindle proteins

3

What drugs are vinca alkaloids?

Vinblastine, Vincristine, Vinorelbine

4

What are the epilones?

Ixabepilone

5

What are the taxanes?

Cabazitaxel, Docetaxel, Paclitaxel

6

What is the difference in toxicity between Vincristine and Vinblastine?

Vincristine = CNS
Vinblastine = Bone Marrow suppression

7

What are the classes of plant alkaloids?

-Camptothecans
-Epipodophylotoxin
-Taxanes
-Vinca alkaloids

8

What drug is an epipodophylotoxin?

Etoposide

9

What drugs are a Camptothecins?

Irinotecan, Topotecan

10

What is the MOA for Vinca Alkaloids?

-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

11

What resistance has developed against Vinca alkaloids?

-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

12

What is the therapeutic use of vinca alkaloids?

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

13

What regimens is Vincristine involved in?

(Oncovin)
-MOPP for Hodgkin's disease
-CHOP for non-Hodgkin's lymphoma

14

What regimens is Vinblastine involved in?

-ABVD for Hodgkin's disease
-PVB for testicular cancer

15

What toxicities are caused by vinca alkaloids as a class?

-Bone marrow suppression
-Neurotoxicity

16

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

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

17

What are other toxicities of vinca alkaloids?

-BMS (greater for Vinblastine)
-Nausea and vomiting (greater for Vinblastine)
-Alopecia

18

What is important about the neurotoxicity seen in vinca alkaloids?

-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

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

-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

What is the mechanism of action for taxanes?

-Bind in tubulin and ENHANCE AND STABILIZE spindle assembly

21

What resistance has developed against taxanes?

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

22

What is the pharmacokinetics for taxanes?

Excessive CYP450 metabolism

23

When you think paclitaxel. what should you think?

Drug interactions

24

What are the toxicities for taxanes?

-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

What is the MOA of IXABEPILONE (Epilone)?

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

26

What is Ixabepilone used with?

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

27

Where is Ixabepilone metabolized?

in the liver

28

What side effects can Ixabepilone cause?

-Bone marrow suppression, peripheral neuropathy and cardiac arrhythmias
-Hypersensitivity

29

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

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

30

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

Ixabepilone
-It does not produce MDR