Chemotherapeutic Mechanisms and Drugs

Question 1

What are primary chemotherapeutics?

Answer 1

Chemotherapeutics that are being used as the primary means of addressing cancer.

Either their is no alternative and chemotherapy is slowing the growth of an inevitably lethal tumor.

-or-

Chemotherapy alone is curative for the type of cancer.

Question 2

What are neoadjuvant chemotherapeutics?

Answer 2

Chemotherapeutics used to augment alternative primary means of treatment that will not be sufficient on their own.

ie. shrinking a tumor with chemo to make it more easily removable during surgery

Question 3

What are adjuvant chemotherapeutics?

Answer 3

Chemotherapeutics given after surgery to reduce risk of recurrence.

Question 4

What types of tissues/tumors are chemotherapeutics most effective on?

Answer 4

Tissues and tumors with high growth fractions (fast growth).

Chemotherapuetics work by killing replicating cells, therefore cells that are replicating more will be killed more efficiently.

reduce tumor size via surgery or radiation -> tumors increase growth fraction -> chemotherapy is more effective.

Question 5

What are the adverse effects common to almost all chemotherapeutics?

Answer 5

Almost universal:

• nausea/vomiting
• fatigue
• stomatitis (ulceration of mucous membranes of the mouth)
• alopecia (hair loss)
• myelosupression (decreased bone marrow activity -> cytopenias + risk of infections)
• low sperm count

*almost all of these are caused by collateral damage to healthy, rapidly dividing tissues that are also affected by chemotherapeutics

Question 6

What medications are frequently given with chemotherapeutics to minimize common adverse effects?

Answer 6

• hematopoietic agents: increase bone marrow activity
• serotonin receptor antagonist (ondesetron): antiemetic
• bisphosphates: minimize bone damage

Question 7

What is the mechanism of alkylating agents?

Are they cell cycle specific or non-specific?

Answer 7

• form covalent linkages between guanine nucleotides in DNA
• cell cycle non-specific

Question 8

What is cyclophosphamide?

Answer 8

Alkylating agent -> chemotherapeutic

Question 9

What is a common adverse effect of cyclophosphamide administration and what medication is given in addition to it to prevent this?

Answer 9

hemorrhagic cystitis due to acrolein, a metabolite of cyclophosphamide

mensa is given to inactivate acrolein

Question 10

What is ifosfamide?

Answer 10

Alkylating agent -> chemotherapeutic

Question 11

What is busulfan?

Answer 11

Alkylating agent -> chemotheraputic

Question 12

What is a common adverse effect of busulfan administration?

Answer 12

-pulmonary fibrosis

Question 13

What is cisplatin?

Answer 13

Platinum compound with alkylating agent-like behavior -> chemotherapeutic

Question 14

What is a common adverse effect of cisplatin administration?

Answer 14

• renal tubular damage
• otoxicity

Question 15

What is the mechanism of antimetabolites?

Are they cell cycle specific or non-specific?

Answer 15

• analogs to substances needd for cell growth; block those required pathways
• folic acid analogs
• pyrimidine analogs
• purine analogs
• cell cycle specific (S-phase)

Question 16

What is methotrexate?

What alternative uses does it have?

Answer 16

folic acid analog (antimetabolite) -> chemotherapeutic

-inihibits dihydrofolate reductase preventing nucleoside synthesis

can also be used as an immunosupressant as immune cells are highly sensitive to chemotheraputics

Question 17

What medication can be given with methotrexate to reduce damage to healthy cells?

Answer 17

leucovorin

-can enter THF synthesis pathway down stream of dihydrofolate reductase, the target of methotrexate, allowing some nucleotide synthesis to occur

Question 18

What is flurouracil?

Answer 18

pyrimidine analog (antimetabolite) -> chemotherapeutic

-inhibits thymidylate synthetase preventing thymidine synthesis

Question 19

What is mercaptopurine (6-MP)?

Answer 19

purine analog (antimetabolite) -> chemotherapeutic

inhibits purine synthesis

Question 20

What medication can be given with mercaptopurine (6-MP) to increase toxicity and decrease adverse effects?

Answer 20

Allopurinol

inhibits xanthine oxidase which metabolizes 6-MP to an inactive form; also prevents hyperurcemia

Question 21

What is the mechanism of vinca alkaloids?

Are they cell cycle specific or non-specific?

Answer 21

bind β-tubulin, inhibit microtubule assembly

-cell cycle specific (M-phase)

Question 22

What is vinblastine?

Answer 22

microtubule assembly inhibitor (vinca alkaloid) -> chemotherapeutic

Question 23

What is vincristine?

What specific adverse effects is associated with it?

Answer 23

-peripheral neuropathy (neurotoxicities)

Question 24

What is the mechanism of topoisomerase inhibitors?

Are they cell cycle specific or non-specific?

Answer 24

inhibition of topoisomerase I and II resulting in inability to release super coiling -> chemotherapeutic

cell cycle specific (S phase)

Question 25

What is etoposide?

Answer 25

topoisomerase II inhibitor -> chemotherapeutic

Question 26

What is topotecan?

Answer 26

topoisomerase I inhibitor -> chemotherapeutic

topotecan (topo 1)

Question 27

What is doxorubicin?

What specific adverse effects is associated with it?

Answer 27

antibiotic (inhibits topoisomerase II)

-creates free radicals leading to caridotoxicity

Question 28

What is bleomycin?

What specific adverse effects is associated with it?

Answer 28

antitumor antibiotic (creates DNA strand breaks)

pulmonary fibrosis

Question 29

What is asparaginase?

What specific adverse effects is associated with it?

Answer 29

hydrolyzes L-asparagine (acute lymphoblastic leukemia cells lack the ability to make L-asparagine and instead take if from the extracellular environment; asparaginase removes exogenous L-asparagine) -> chemotherapeutic

Question 30

What is the mechanism of differentiating agents?

Answer 30

stimulate differentiation of cancers of immature cell types (mostly acute leukemias) which are unable to survive as mature cells -> chemotherapeutic

Question 31

What is the mechanism of tyrosine kinase inhibitors?

Answer 31

tyrosine kinases act as signal transducers for growth factors and can be oncogenes, when this happens, inhibiting their function stops uncontrolled proliferation -> chemotherapeutic

Question 32

What is tretinoin?

Answer 32

differntiating agent

ATRA -> used in actue promyleocytic leukemia which has a mutation in the RARα gene

Question 33

What is imatinib?

Answer 33

Tyrosine kinase inhibitor (intracellular) -> chemotherapeutic

Question 34

What is ziv-aflibercept?

Answer 34

soluble VEGF receptor -> binds free VEGF preventing activation of tyrosine kinases

Question 35

What is rituximab?

Answer 35

monoclonal antibody (specific for CD-20 on B cells but not plasma cells) leading to destruction of the cell -> chemotheraputic for B cell lymphomas

Question 36

What is paclitaxel?

Answer 36

Taxane -> stabilizes microtubules inhibiting mitosis

Question 37

What are camptothecins?

Answer 37

topoisomerase I inhibitors

(ie. topotecan)

Question 38

What are epipodophyllotoxins?

Answer 38

topoisomerase II inhibitors

(ie. etoposide)

Question 39

What are anthracyclines?

Answer 39

Topoisomerase II targeting antibiotics

(ie. doxorubicin)