Chemo Agents Flashcards
What are the general mechanisms of action of chemo agents?
Targeting the cell cycle and biology of tumor growth
In order for chemo to work, cancer cells must be more/less sensitive to the drugs than normal tissue?
More; rely on normal tissue to be able to respond appropriately and recover
Which are the phase-specific chemo agents?
Vincristine, Vinblastine (M), Cytosine arabinoside (Cytosar), Methotrexate (S)
Which are the phase non-specific agents?
- Alkylating agents
- Nitrosoureas
- Antitumor antibiotics
- Procarbazine
- Platinum derivatives
What is the most commonly use and largest group of chemo agents?
Alkylating agents
Carboplatin
Classification: Alkylating agent
Non-phase specific
MOI: crosslinks DNA, inhibits protein synthesis
Toxicity: myelosuppression, monitor platelets
SAFE FOR CATS, fewer GI SE
Antimetabolites
- Cell cycle phase specific- S phase
- MOI: Cuts out folate in cell cycle; inserted into DNA and non-functional
- Agents: Methotrexate, cytosine arabinoside (Cytosar)
- Cross BBB
Methotrexate
Classification: Antimetabolite
Cell cycle phase specific- S phase
MOI: Cuts out folate in cell cycle; inserted into DNA and non-functional
Uses: lymphoma, CNS tumors, osteosarcoma
Toxicity: GI and myelosuppression
Cytosine Arabinoside (Cytosar)
Classification: Antimetabolite
Cell cycle phase specific- S phase
MOI: Cuts out folate in cell cycle; inserted into DNA and non-functional
Uses: renal lymphoma, lymphoma rescue, CNS tumors
Toxicity: none mentioned, efficiently removed from circulation by the kidney
Antibiotic Chemo Agents
Cell cycle phase nonspecific
MOA: free radical damage, inhibition of topoisomerase II
Agents: Doxorubicin, Actinomycin D, Mitoxantrone
Doxorubicin
Classification: Antibiotic
Cell cycle phase nonspecific
MOA: free radical damage, inhibition of topoisomerase II
Uses: lymphoma, osteosarcoma, hemangiosarcoma
Toxicity: anaphylaxis, vesicant, cardiotoxicity
Mitoxantrone
Classification: Antibiotic
Cell cycle phase nonspecific
MOA: free radical damage, inhibition of topoisomerase II
Uses: LSA rescue, TCC, thymomas
Toxicity: myelosuppression, GI
Actinomycin D
Classificiation: Antibiotic
Cell cycle phase nonspecific
MOA: free radical damage, inhibition of topoisomerase II
Uses: lymphoma rescue, non-cardiotoxic substitute for Doxorubicin
Toxicity: myelosuppression and GI
Plant Alkaloids
Cell cycle phase specific - M phase
MOI: Bind microtubules, prevent assembly/disassembly
Agents: Vincristine, Vinblastine, Vinorelbine, Taxanes
Vincristine
Classification: Plant Alkaloid
Cell cycle phase specific - M phase
MOI: Bind microtubules, prevent assembly/disassembly
Uses: lymphoma (combo protocols), transmissible venereal tumor, thrombocytopenia
Toxicity: vesicant, myelosuppression, peripheral neuropathy
Vinblastine
Classification: Plant alkaloid
Cell cycle phase specific - M phase
MOI: Bind microtubules, prevent assembly/disassembly
Uses: Mast cell tumor, sub for vincristine if neuropathy suspected
Toxicity: vesicant, myelosuppression (> vincristine)
Hormones
- Agents: Prednisone
- MOA: bind to cytoplasmic receptors & inhibit DNA synthesis
- Uses: lymphoma, mast cell tumor, insulinoma, intracranial neoplasia
- Toxicity: PU/PD, polyphagia, panting, GI ulcers
DO NOT USE CONCURRENTLY WITH NSAIDS
Enzymes
Cell cycle phase nonspecific - max G1 phase activity Agents: L-asparaginase
L-asparaginase
Classification: Misc. Enzyme
Cell cycle phase nonspecific - max G1 phase activity
MOI: Breaks down asparagine w/o which cancer cells cannot make DNA
Uses: lymphoma
Toxicity: anaphylaxis!, potentiate vincristine-induced myelosuppression, pancreatitis; Alone NOT myelosuppressive
Receptor-Tyrosine Kinase Inhibitors
Targeted therapy - only in vet med!
Toceranib and Masitinib
MOA: targets RT-kinases
Uses: Mast cell tumors
Toxicity (KIT): bone marrow, GI, skin, renal Also Masitinib (Kinavet) - not found in US
Tanovea
Classification: Targeted Therapy
MOA: prodrug - active phosphorylated form = potent inhibitor of replicative DNA polymerases
Uses: canine lymphoma (1st FDA approved tx)
Toxicity: Decr WBC count, diarrhea, vomiting, decreased/loss of appetite, weight loss, skin problems, pulmonary fibrosis in dogs (NOT USED IN WESTIES)
Describe alkylating agents
- Largest group of chemo agents
- Cell cycle non-specific
- MOI: cross-link DNA, inhibit protein synthesis
- Class cross-resistance
- All derivatives of nitrogen mustard (mustard gas)
What do we associate with cytotoxicity of alkylating agents?
Inter-strand crosslinking
Cyclophosphamide
- Classification: Alkylating agent
- Non-phase specific
- MOI: crosslinks DNA, inhibits protein synthesis
- Uses: lymphoma, hemangiosarcs, STS
- Toxicity: myelosuppresion, sterile hemorrhagic cystitis***, GI
What is the active ingredient that causes cystitis?
Acrolein
Chlorambucil
- Classification: Alkylating agent
- Non-phase specific
- MOI: crosslinks DNA, inhibits protein synthesis
- Uses: multiple myeloma (most common), substitute for Cytoxan, chronic lymphocytic leukemia, feline GI (small cell) lymphoma
- Toxicity: mild myelosuppression, GI
- KEEP COLD!
Lomustine
Classification: Alkylating agent
MOI: cross links DNA
Non-phase specific
Uses: LOPP rescue protocol
Toxicity: myelosuppressive and hepatotoxic (alpha-lipoic acid and Denamarin are protectants), Neutropenia nadir variable (immunosuppressive)
Procarbazine
Classification: Alkylating agent
Non-phase specific
MOI: crosslinks DNA, inhibits protein synthesis
Uses: LOPP/MOPP rescue protocol
Toxicity: none?
Cisplatin
Classification: Alkylating agent
Non-phase specific
MOI: crosslinks DNA, inhibits protein synthesis
Uses: osteosarcoma, squamous cell carcinoma, equine sarcoids
Toxicity: nephrotoxic (diurese), nausea, fatal pulmonary edema in cats
Melphalan
Classification: Alkylating agent
Non-phase specific
MOI: crosslinks DNA, inhibits protein synthesis
Uses: multiple myeloma, lymphoma rescue
Toxicity: myelosuppression (thrombocytopenia), GI
