56 - SAM

What is the major determinant of specificity for traditional cytotoxic chemotherapy?

Differential growth fraction

What are the three normal tissues most susceptible to predictable chemotherapy toxicity (BAG)?

Bone marrow causes cytopenias

What is the difference between cell cycle-specific and non-cycle-specific chemotherapy drugs?

Cell cycle-specific drugs act during particular phases and are time-dependent with a plateau effect

What is the MDR-1 (MRP-1/ABCB1) protein and what happens when it is dysfunctional?

A transmembrane drug transporter that pumps drugs and toxins out of cells

Which dog breeds are predisposed to the MDR-1 mutation?

Collies approximately 70%

What is the inheritance and effect of the MDR-1 mutation?

A recessive 4-base-pair deletion

What are the typical timing and unacceptable severity of chemotherapy-induced bone marrow suppression?

Neutrophil nadir varies by drug but commonly occurs around 5-10 days

What are the common delayed GI side effects of chemotherapy and when do they occur?

Nausea vomiting and diarrhea

How do alkylating agents work and what are common examples?

Form covalent bonds with cellular targets especially DNA, causing cross-linking and DNA damage

What is the major unique toxicity of cyclophosphamide and what causes it?

Sterile hemorrhagic cystitis caused by the toxic metabolite acrolein irritating the bladder epithelium

What are the major uses and unique toxicity of lomustine (CCNU)?

Used for lymphoma mast cell tumors histiocytic sarcoma and brain tumors

How do anti-microtubule agents such as vincristine and vinblastine work?

Bind microtubules and prevent polymerization, blocking mitosis during the M phase

What are the major uses and unique toxicities of vincristine and vinblastine?

Used for lymphoma TVT and mast cell tumors

What is a vesicant and why is chemotherapy extravasation dangerous?

A drug that causes severe tissue damage and blistering when it escapes the blood vessel

What are the major unique toxicities of doxorubicin?

Cumulative irreversible cardiotoxicity from free radical damage, nephrotoxicity in cats, anaphylaxis and vesicant injury

How do platinum compounds work and what is the major difference between cisplatin and carboplatin?

They bind and cross-link DNA similar to alkylating agents

How do antimetabolites work and what are important examples?

Mimic normal cellular metabolites and interfere with DNA RNA or protein synthesis

How does L-asparaginase work and what is its major administration precaution?

Depletes circulating asparagine, inhibiting protein synthesis in lymphoid cells

What is Palladia (toceranib) and how does it work?

An oral tyrosine kinase inhibitor that inhibits c-kit PDGFR and VEGFR

What are the major mechanisms of chemotherapy resistance?

Impaired cellular uptake