Lecture 12 2/21/25 Flashcards by Danika Boltz

What are the characteristics of vincristine?

-used for lymphoma, TVT, and immune-mediated thrombocytopenia
-exclusively eliminated by liver
-must reduce dose in patients with Tbili > 2

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What are the unique side effects of vincristine?

-peripheral neuropathy
-functional ileus
-increase in platelet counts

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What is the pathophysiology of peripheral neuropathy?

damage to microtubules leads to abnormal conduction down the axon

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What are the clinical signs of peripheral neuropathy?

-paresthesia and numbness
-collapse
-pelvic limb weakness
-decrease in spinal reflexes

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What are the characteristics of functional ileus?

-GI tract is paralyzed
-causes prolonged vomiting, anorexia, and abdominal pain
-assessed via abdominal radiographs +/- ultrasound
-treated with fluids and prokinetics

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What is the process behind vincristine increasing platelet counts?

-vincristine causes megakaryocyte fragmentation
-fragmentation leads to platelet and precursor release
-platelet count goes up

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What are the characteristics of vinblastine?

blasts masts
-used for mast cell tumors and transitional cell carcinoma
-decreased affinity for microtubules
-less GI signs, but more neutropenia than vincristine

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What is the mechanism of alkylating agents?

cross links DNA so it cannot be separated for division

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Which chemo drugs are alkylating agents?

-chlorambucil
-cyclophosphamide
-CCNU/lomustine
-melphalan

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What are the characteristics of chlorambucil?

-used in small cell GI lymphoma in cats
-used in chronic lymphatic leukemia in dogs
-oral administration
-main side effect is long term thrombocytopenia
-used in metronomic chemo protcols

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What are the characteristics of cyclophosphamide?

-used for leukemia and lymphoma
-given via IV bolus or PO
-causes sterile hemorrhagic cystitis
-used in metronomic chemo protocols

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How does cyclophosphamide cause sterile hemorrhagic cystitis?

-drug is metabolized into acrolein by the liver
-acrolein can irritate the bladder mucosa if left in the bladder too long

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What are the diagnostics for sterile hemorrhagic cystitis?

-UA on free catch urine to look for blood
-UA culture on cysto urine to rule out bacteria
-blood on cysto urine is not always beneficial since it could be collection artifact

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What are the steps to sterile hemorrhagic cystitis prevention/treatment?

prevention:
-give with furosemide to increase drinking/urination to clear drug faster
-split total dose over 3 days to reduce amount of drug in bladder at once
-substitute for chlorambucil
treatment:
-stop drug
-NSAIDs OR steroids
-no known effective treatment

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What are the characteristics of CCNU/lomustine?

-used for mast cell tumors, lymphoma, and histiocytic sarcoma
-oral administration
-crosses the BBB

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What are the unique side effects of CCNU/lomustine?

-hepatotoxic (dogs)
-delayed and variable nadir
-cumulative myelosuppression
-significant neutropenia

What steps should be taken to prevent hepatotoxicity when using CCNU/lomustine?

-always give with denamarin
-check ALT before every dose
-delay or discontinue based on blood work/clinical signs

What step should be taken to prevent bone marrow toxicity when using CCNU/lomustine?

check CBC 7 and 14 (and 21 in cats) days after first dose to identify nadir

What are the characteristics of melphalan?

-used for multiple myeloma
-oral admin.
-main side effect is bone marrow suppression with chronic use
-not toxic but not well-tolerated in cats

What are anthracyclines?

derivatives of Streptomyces spp.

How do anthracyclines work?

-DNA intercalation
-inhibition of RNA and DNA polymerases and topoisomerase-II
-formation of reactive oxygen species

What are the characteristics of doxorubicin?

-#1 drug for lymphoma and sarcoma
-#2 drug for carcinomas
-causes mild to moderate GI upset in dogs; counteract with cerenia
-causes histamine release; counteract with pre-med diphenhydramine and drug dilution
-MDR-1 substrate

What are the characteristics of doxorubicin cardiotoxicity?

-cumulative cardiotoxicity
-has lead to a lifetime limit on the amount of drug that can be used in each dog
-screening should be done via chest rads and ECG +/- echo
-should push for echo in breeds prone to DCM and ARVC
-VPCs and decreased fractional shortening are indication for stopping drug
-can substitute for mitoxantrone

What are the characteristics of doxorubicin extravasation?

-severe vesicant that causes tissue necrosis and could lead to need for amputation
-must have a first stick IV cath when using this drug
-dilute drug
-hand push; no IV pumps
-zinecard/dexrazoxane is antidote

What are the characteristics of doxorubicin-induced nephrotoxicity?

-only seen in cats -monitor renal function -discontinue if BUN and/or creatinine increase

What are the characteristics of mitoxantrone?

-substitute for doxorubicin -second line for TCC/UC -no cardiotoxicity -decreased GI effects compared to doxorubicin -causes profound neutropenia

How do platinum agents work?

cause inter- and intrastrand cross-links leading to DNA damage and cell death

What are the characteristics of cisplatin?

-used intra-tumor for carcinomas in large animal; not used clinically in small animal -highly nephrotoxic; active drug excreted -requires at least 4 hours of diuresis -causes fatal pulmonary edema in cats -risk for emesis

What are the characteristics of carboplatin?

-used for osteosarcoma and carcinomas -full excretion via kidney -should check renal panel and USG prior to admin. -okay to use in cats -cumulative myelosuppression, especially platelets -variable nadir; should check CBC at 7 and 14 days

What are the characteristics of antimetabolites?

-mimic normal nucleotide bases needed for RNA and DNA synthesis -most active in S phase

What are the characteristics of 5-FU?

-prevents DNA and RNA synthesis -used in combo with other drugs for carcinomas in dogs -used for sarcoids and SCC in horses -given IV in dogs; intratumorally or topically in horses -neurotoxic in cats

What are the characteristics of tanovea?

-animal drug fully licensed for canine lymphoma -B-cell lymphoma rescue agent -causes dermatopathy and pulmonary fibrosis -contraindicated in west highland white terriers -rare reports of extravasation

What are the characteristics of small molecule inhibitors?

-targeted drugs used for specific cancers -can still cause BAG side effects -usually oral admin.

What are the characteristics of palladia?

-used for unresectable or metastatic mast cell tumors -used for neuroendocrine tumors -given on alternating days at home -DO NOT use label dose; too high

What are the side effects of palladia?

-GI upset (most common) -neutropenia -proteinuria -systemic hypertension -lameness

What are the characteristics of L-asparaginase?

-bacterial enzyme -only affects neoplastic lymphocytes that lack I-asparagine synthase -only used in lymphoma and leukemia -risk of anaphylaxis that increases with each dose; pre-med with benadryl

What are the characteristics of NSAIDs?

-carcinomas tend to overexpress COX2 -COX2 inhibitors increase survival in urothelial, prostatic, and mammary carcinomas -can use piroxicam and COX2 inhibitors; not galliprant -part of metronomic chemo for hemangiosarcoma; decreases angiogenesis

What are the characteristics of prednisone?

-glucocorticoids are cytotoxic to many round cell tumors -effective against lymphoma, leukemia, plasma cell tumor, multiple myeloma, and mast cell tumor -can be used alone or in combo with chemo -may treat paraneoplastic syndromes -NEVER combine with NSAIDs

What are the characteristics of zoledronate?

-bisphosphonate/osteoclast inhibitor -used in hypercalcemia of malignancy and to treat pain from bone tumors -given IV about once a month -check renal function