Lecture 12 2/21/25 Flashcards
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
What are the unique side effects of vincristine?
-peripheral neuropathy
-functional ileus
-increase in platelet counts
What is the pathophysiology of peripheral neuropathy?
damage to microtubules leads to abnormal conduction down the axon
What are the clinical signs of peripheral neuropathy?
-paresthesia and numbness
-collapse
-pelvic limb weakness
-decrease in spinal reflexes
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
What is the process behind vincristine increasing platelet counts?
-vincristine causes megakaryocyte fragmentation
-fragmentation leads to platelet and precursor release
-platelet count goes up
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
What is the mechanism of alkylating agents?
cross links DNA so it cannot be separated for division
Which chemo drugs are alkylating agents?
-chlorambucil
-cyclophosphamide
-CCNU/lomustine
-melphalan
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
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
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
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
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
What are the characteristics of CCNU/lomustine?
-used for mast cell tumors, lymphoma, and histiocytic sarcoma
-oral administration
-crosses the BBB
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
