Chemotherapeutic Mechanisms and Drugs Flashcards
What are primary chemotherapeutics?
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.
What are neoadjuvant chemotherapeutics?
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
What are adjuvant chemotherapeutics?
Chemotherapeutics given after surgery to reduce risk of recurrence.
What types of tissues/tumors are chemotherapeutics most effective on?
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.
What are the adverse effects common to almost all chemotherapeutics?
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
What medications are frequently given with chemotherapeutics to minimize common adverse effects?
- hematopoietic agents: increase bone marrow activity
- serotonin receptor antagonist (ondesetron): antiemetic
- bisphosphates: minimize bone damage
What is the mechanism of alkylating agents?
Are they cell cycle specific or non-specific?
- form covalent linkages between guanine nucleotides in DNA
- cell cycle non-specific
What is cyclophosphamide?
Alkylating agent -> chemotherapeutic
What is a common adverse effect of cyclophosphamide administration and what medication is given in addition to it to prevent this?
hemorrhagic cystitis due to acrolein, a metabolite of cyclophosphamide
mensa is given to inactivate acrolein
What is ifosfamide?
Alkylating agent -> chemotherapeutic
What is busulfan?
Alkylating agent -> chemotheraputic
What is a common adverse effect of busulfan administration?
-pulmonary fibrosis
What is cisplatin?
Platinum compound with alkylating agent-like behavior -> chemotherapeutic
What is a common adverse effect of cisplatin administration?
- renal tubular damage
- otoxicity
What is the mechanism of antimetabolites?
Are they cell cycle specific or non-specific?
- analogs to substances needd for cell growth; block those required pathways
- folic acid analogs
- pyrimidine analogs
- purine analogs
- cell cycle specific (S-phase)
What is methotrexate?
What alternative uses does it have?
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
What medication can be given with methotrexate to reduce damage to healthy cells?
leucovorin
-can enter THF synthesis pathway down stream of dihydrofolate reductase, the target of methotrexate, allowing some nucleotide synthesis to occur
What is flurouracil?
pyrimidine analog (antimetabolite) -> chemotherapeutic
-inhibits thymidylate synthetase preventing thymidine synthesis
What is mercaptopurine (6-MP)?
purine analog (antimetabolite) -> chemotherapeutic
inhibits purine synthesis
What medication can be given with mercaptopurine (6-MP) to increase toxicity and decrease adverse effects?
Allopurinol
inhibits xanthine oxidase which metabolizes 6-MP to an inactive form; also prevents hyperurcemia
What is the mechanism of vinca alkaloids?
Are they cell cycle specific or non-specific?
bind β-tubulin, inhibit microtubule assembly
-cell cycle specific (M-phase)
What is vinblastine?
microtubule assembly inhibitor (vinca alkaloid) -> chemotherapeutic
What is vincristine?
What specific adverse effects is associated with it?
-peripheral neuropathy (neurotoxicities)
What is the mechanism of topoisomerase inhibitors?
Are they cell cycle specific or non-specific?
inhibition of topoisomerase I and II resulting in inability to release super coiling -> chemotherapeutic
cell cycle specific (S phase)
What is etoposide?
topoisomerase II inhibitor -> chemotherapeutic
What is topotecan?
topoisomerase I inhibitor -> chemotherapeutic
topotecan (topo 1)
What is doxorubicin?
What specific adverse effects is associated with it?
antibiotic (inhibits topoisomerase II)
-creates free radicals leading to caridotoxicity
What is bleomycin?
What specific adverse effects is associated with it?
antitumor antibiotic (creates DNA strand breaks)
pulmonary fibrosis
What is asparaginase?
What specific adverse effects is associated with it?
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
What is the mechanism of differentiating agents?
stimulate differentiation of cancers of immature cell types (mostly acute leukemias) which are unable to survive as mature cells -> chemotherapeutic
What is the mechanism of tyrosine kinase inhibitors?
tyrosine kinases act as signal transducers for growth factors and can be oncogenes, when this happens, inhibiting their function stops uncontrolled proliferation -> chemotherapeutic
What is tretinoin?
differntiating agent
ATRA -> used in actue promyleocytic leukemia which has a mutation in the RARα gene
What is imatinib?
Tyrosine kinase inhibitor (intracellular) -> chemotherapeutic
What is ziv-aflibercept?
soluble VEGF receptor -> binds free VEGF preventing activation of tyrosine kinases
What is rituximab?
monoclonal antibody (specific for CD-20 on B cells but not plasma cells) leading to destruction of the cell -> chemotheraputic for B cell lymphomas
What is paclitaxel?
Taxane -> stabilizes microtubules inhibiting mitosis
What are camptothecins?
topoisomerase I inhibitors
(ie. topotecan)
What are epipodophyllotoxins?
topoisomerase II inhibitors
(ie. etoposide)
What are anthracyclines?
Topoisomerase II targeting antibiotics
(ie. doxorubicin)
