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Oncology II

Specific Cell Cycle Cytotoxic Drugs: Folate Antimetabolites

what is the MOA of folate antimetabolites? - block the di-hydrofolate reductase --> block purine/ pyrimidine synthesis --> block the folic acid cycle - S PHASE
which phase dose the folate antimetabolites act on? the S-phase
What are some recommendation to minimize the risk of folate antimetabolites toxicities? - give folic acid & vitB12
what is the difference between leucovorin and levo-leucovorin? LEVOleucovorin is the ACTIVE L-isomer of leucovorin - the dose of LEVOleucovorin = 1/2 leucovorin
How dose leucovorin minimize the toxicity of high-dose methotrexate? - leucovorin is a folic acid active form ( folinic acid) - bypass the activation step by dihydrofolate reductase enzyme -
What is a common class side effect ( folate antimetabolites)? - NEPHORTOXOCITIY - hepatotoxicity
Which side effect of folate antimetabolites is dose dependent vs. chronic use? - Nephrotoxicity: DOSE dependent - hepatotoxicity: chronic use
what is the MOA of LEUCOVORIN while used with Fluorourical vs. methotrexate? - Augmentation vs. rescue
which cytotoxic drugs act on the S-phase? - folate antimetabolites - pyrimidine antimetabolites - Topoisomerase I inhibitors
List the common folate antimetabolites drugs? 1- methotrexate 2- pemetrexted 3- pralatrexate
which folate antimetabolite causes dermatological toxicity? PEMEtrexted and Methotrexate ** premeditated with steroid
what are some recommendation to manage PEMEtrexted and PRALAtrexted toxicity? -Give: 1- VitB-12 2- Folic acid ** for PEMEtrexted : dexamethasone 2/2 dermatological side effects
What is the difference in methotrexate dosing in rheumatoid arthritis vs. Cancer? - RA: low- dose/ week vs. Cancer: high-dose/ day
what is the cutoff of high dose methotrexate? 1- >= 500mg/m2/ dose is considered high dose 2- > 1 gram/m2 is considered nephrotoxic
what are some management considerations to minimize the risk of methotrexate when given at high dose >= 500mg/m2/dose? 1- GIVE methotrexate with LEVOleucovorin until methotrexate level is <0.05-0.1 MICROMOLAR 2- HYDRATION 3- IV Na-bicarbonate ( alkalinize the urin) ( folic acid + bicarbonate = alkalinizie)
What are some complications that increases the risk of methotrexate toxicity 2/2 reduction in clearance and build up of the drug? - 3rd spacing ds 1- ascites 2- pleural effusions 3- severe edema
what is the antidote of methotrexate toxicity? Glucarpidase turns methotrexate into inactive metabolites: 1- DAMPA 2- Glutamate
which DDI effect the clearance of methotrexate? 1- NSAIDS ( acid) 2- PPI ( reduce acid) 3- beta lactamease 4- salicylate ( acid) 5- sulfonamide Ab ( sulfa) 6- probenecid ( uric acid reducer)
which folate antimetabolites causes hand-foot syndrome? methotrexate
Methotrexate Boxed Warnings: 1- myelosuppresion: 2-nephrotoxic 3- hepatotoxic 4- pregnancy 5- Tumor lysis syndrom - Myelosuppression: 1- aplastic anemia, stomatitis, interstitial pneumonitis - nephrotoxic: - hepatotoxic Fibrosis/ cirrhosis--->> Ascites/ pleural effusion - Dermatological: SJS and TEN - pregnancy: fetal death and teratogenic - tumor lysis synd
Created by: Smoham38



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