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70 Cards in this Set
- Front
- Back
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Name alkylating anticancer drugs
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Cyclophosphamide
Ifosfamide melphalan chlorambucil Dacarbazine and Temozolamide Nitrosoureas: lomustine, carmustine, streptozocin |
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MOA of Alkylating anticancer drugs
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metabolized in liver to cytotoxic Phosphoramide mustard
-reacts with DNA |
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Cyclophosphamide in high doses is
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cell cycle nonspecific
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Uses of cyclophosphamide
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tx: lymphoreticular neoplasms
tx: carcinomas and sarcomas w/ Doxorubicin combo |
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cyclophosphamide pharmacokinetics:
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good orally (preferred)
can go IV -liver metabolizes it to -->Phosporamide (DNA alkylation) and ----->acrolein (responsible for cystitis) -wide dist: CNS, cross placenta, milk -excretion: mostly kidney, some bile |
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Cyclophosphamide side effects
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bone marrow suppression
GI upset hemorrhagic cystitis-due to acrolein --rare in cats, common in dogs -hi water intake dilutes effectiveness -give in morning to reduce night accumulation of metabolites |
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clinical uses of cyclophosphamide
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lymphoma, carcinoma, mast cell tumor, hemangiosarcoma
-immunosuppressant: rheumatoid conditions, idiopathic thrombocytopenic purpura, immune mediated hemolytic anemia |
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Ifosfamide
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-similar to cyclophosphamide
-causes hemorrhagic cystitis so give w/MESNA which scavenges the irritant metobolites |
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High doses of Ifosfamide produces what
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neurotoxic metabolite -->chloroacetaldehyde
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Melphalan
(Phenylalanine mustard) MOA |
interferes w/ RNA transcription and DNA replication
-cell cycle nonspecific |
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Melphalan Pharmacokinetics
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absorbed orally
good distrib. EXCEPT CNS hydrolysis in plasma |
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Uses of Melphalan
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plasma cell tumors, myeloma, extramedullary plasmacytoma
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melphalan side-effects
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bone marrow suppression
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What is the slowest acting and least toxic alkylating anticancer agent used in vet med?
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Chlorambucil
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Chlorambucil uses
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tx chronic lymphocytic leukemia
small cell lymphoma Waldenstrom's Macroglobulinemia Thymoma inflammatory bowl ds |
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Chlorambucil can be used as a replacement for cyclophosphamide to:
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use chlorambucil instead of cyclophosphamide to avoid hemorrhagic cystitis
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Chlorambucil side-effects
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Causes reversible bone marrow suppression
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Decarbazine
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used for melanoma and skin cancer
active metabolites: -->methyltriazenoimidazole carboxamide (MTIC) Does not cross BBB give IV |
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Temozolamide MOA
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inhibits thr repair enzyme O6-guanine-DNA-alkyltransferase
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Temozolamide pharmacokinetics
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absorbed orally
crosses BBB active metabolite is MTIC |
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uses of Temozolamide
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used for resistant glioma and anaplastic astrocytomas
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side effects of Temozolamide and Dacarbazine
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both cause nausea and vomiting
bone marrow suppression |
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Lomustine (CCNU) and Carmustine (BCNU) are both classified as
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Nitrosoureas, both alkylating agents
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T/F, CCNU and BCNU both cross the BBB
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TRUE
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Lomustine is absorbed orally
is this true or false |
TRUE
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Carmustine is absorbed orally
true or false |
FALSE: carmustine (BCNU) is given IV and it is painful
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Uses of Loumestine (CCNU)
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-used for CNS tumors
- mast cell tumors -lymphoma |
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side effects of CCNU
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-delayed bone marrow suppression
-->neutropenia 1wk into tx |
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Select the true statement about Streptozocin:
A. it is a Nitrosourea B. it is an antibiotic C. it is cytotoxic to pancreatic beta cells D. it is used to tx insulinomas E. it can cause renal toxicity F. all of the above are true |
F. all of the above are true
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Name the microtubule inhibitor anticancer drugs
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Vincristine
Vinblastine --> semisynthetic: Vinorelbine Paclitaxel |
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MOA of Vincristine and Vinblastine
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bind tubulin, inhibiting formation of microtubules --> which inhibits mitosis (M phase)
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Vincristine is phase specific, true or false?
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True
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Is Vinblastine phase specific?
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No, it also blocks glutamate, thus inhibiting purine synthesis, which inhibits other cell phases
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Venblastine and Vincristine pharmacokinetics
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-give IV
-not distrib. to CNS -metabolized in liver -excreted in bile |
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Vincristine uses
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use in combo w/ other drugs to tx lymphoma and lymphoid leukemia
also tx transmissible venereal tumor (TVT) |
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side effects of Vincristine
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-perivascular damage if catheter not used
-peripheral neural damage in cats |
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Vinblastine uses
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use in combo w/other drugs to tx lymphoma and lymphoid leukemia
substitute for vincristine in cats if neuropathy occurs |
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Vinblastine side effects
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-perivascular damage if catheter not used
-bone marrow suppression - GI toxicity |
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If Paclitaxel is effective in tx of carcinoma in humans why is it not widely used in vet med?
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It causes severe hypersensitivity in dogs and cats
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Doxorubicin Pharmacokinetics
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-goes IV
-binds plasma protein and tissue -good distrib. Except CNS -excreted in bile -low renal excretion (red urine) RED THUNDER |
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uses of Doxorubicin
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in combo w/ cyclophosphamide to tx lymphosarcoma
-lymphoma and leukemia in dogs and cats |
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Doxorubicin MOA
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-binds irreversibly w/ DNA ( interferes w/topoisomerase II)
- prevents DNA and RNA synthesis - produces free radicals which damage cellular DNA (happens in tissues wich are low in superoxide dismutase) ex: tumor cells and cardiac cells |
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side effects of Doxorubicin
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- cardiotoxicity in dogs due to free radicals
-dose dependent arrhythmias -anorexia in cats -Nephrotoxicity in cats -congestive heart failure -bone marrow suppression -tissue necrosis from extravasation |
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What is used to tx Doxorubicin cardiotoxicity in dogs?
A. Penicillin B. Ultralente C. Dexrazoxane D. Lactated Ringers soln |
C. Dexrazoxane, also for tx of skin lesions caused by doxorubicin.
Dexrazoxan is a EDTA derivative which chelates the free radicals |
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Palmer-Plantar-Erythrodysesthesia Syndrome (PPES) is:
A. something I just made up B. caused by 2nd yr finals C. a difficult to tx RBC neoplasm arising from the bone marrow D. one more side effect of Doxorubicin |
D. side effect from Doxorubicin, the syndrome involves irritation, alopecia, ulceration in the axilla, inguinal region and footpad
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Palmer-Plantar-Erythrodysesthesia Syndrome caused by Doxorubicin can be treated with:
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vitamin B6
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MOA of dactinomycin
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-binds DNA and causes breaks
-Inhibits RNA and protein synth |
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Uses of Dactinomycin
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tx lymphoma in dogs
used as substitute for doxorubicin to avoid cardiotoxicity it has low bone marrow depression |
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Bleomycin MOA and administration
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-binds DNA causes fragmentation
administer IV, IM, SC, intralesional |
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Bleomycin uses and side effects
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tx squamous cell carcinoma in dogs and cats
side effects: pulmonary toxicity, rales, cough, fatal fibrosis after prolonged use |
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Very expensive anticancer drug, MOA similar to Doxorubicin, used to tx drug resistant lymphoma, it causes severe extravasation necrosis, causes low bone marrow depression, and causes sclera and urine to take on a blue-green color.
Hint: Blue thunder |
Answer: what is Mitoxantrone
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An antimetabolite anticancer drug that inhibits dihydrofolic acid reductase leading to the inhibition of neucleotide synthesis (DNA, RNA, protein synthesis inhibited) causing cell death.
This drug is highly active against the cell at the S phase, and it is used in combo w/ other drugs to tx lymphoma. |
Methotrexate
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side effects of Methotrexate
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causes mylosupression, oral ulceration (tx this w/ folonic acid/ Leucovorin)
concurrent use w/ NSAIDs and sulfatrimethoprim INCREASES TOXICITY |
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Another S phase inhibitor that incorporates in DNA and causes retardation of DNA elongation.
It also crosses BBB and is used to tx lymphoma w/ CNS involvement and acute leukemias. |
Cytosine Arabinoside (Cytarabine)
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A new antimetabolite drug used in resistant tumors such as hepatobiliary pancreatic, mammary, transitional cell, and bronchoalveolar carcinoma.
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Gemcitabine
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A pyrimidine analouge that inhibits DNA synthesis and to a lesser extent RNA sysnthesis. It is used to tx slow growing solid tumors of colorectal, gastric, pancreatic, mammary, and ovarian carcinoma.
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5-Fluorouracil
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5-Flurorouracil is very neurotoxic, true or false
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True, it can't be used in cats even topically b/c of the neurotoxicity. Toxic signs in dogs includes barking and running in circles.
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Anticancer drug used for eosinophilic leukemia/hypereosinophilic syndrome in cats
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Hydroxyurea
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Anticancer drug used in basophilic leukemia in dogs, and polycythemia vera in dogs and cats.
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Hydroxyurea
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What drug causes dogs to lose toenails after chronic use?
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Hydroxyurea
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Platinum anticancer drugs such as Cisplatin are used :
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-after amputation in K9 osteosarcoma
-metastatic seminomas -pleural effusion due to mesothelioma carcinoma |
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Platinum anticancer drugs such as Cisplatine are very effective in cats? True or false
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False: causes dyspnea, pulmonary edema and death in 48-96 hrs
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side effects of Cisplatin
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-Nephrotoxic to dogs ( must pre-hydrate) will see electrolyte deficiencies after repeated doses
-nausea and vomiting |
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Carboplatin is similar to cisplatin but has less renal toxicity and is safe for cats, how is it administered and what does it tx?
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Intralesional injection to tx squamous cell carcinoma of the nasal planum in cats
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Carboplatin use is contraindicated with
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Aminoglycosides
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L-Asparaginase MOA
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cleaves extracellular L-asparagine, which is essential for tumor cell proliferation
-Effective at G1 phase |
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Piroxicam is a NSAID that is used to tx:
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transitional cell carcinoma of the urinary tract ( relieves hematuria in 4-11 mo)
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Piroxicam side effects
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causes GIT ulceration and bleeding may cause perforation
--> prevent this by giving misoprostol at the same time |
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Why are corticosteroids used in cancer treatments?
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-they are directly lymphocytotoxic
- they improve quality of life due to euphoria effect -anti-inflammatory effect may control pain |
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What are the down side to using corticosteroids in cancer tx?
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-high doses cause pu/pd and polyphagia
-resistance can develop in tumor cells and other anticancer drugs won't work either |
