Anti-Metabolites Flashcards
What is the main function of methotrexate?
Impairs folic acid intake by tumor cells; Inhibits formation of FH4
What is Folic acid’s role as an antidote to methotrexate?
MTXs affinity to DHFR is greater than folic acid’s. Used for toxicity prevention in patients.
What is folinic acid’s role as an antidote to methotrexate?
Competes with MTX for transport into human target tissue cells
What is glucarpidase’s role as an antidote to methotrexate?
Converts MTX to its inactivate metabolites to glutamate. Provides a non-renal pathway to MTX elimination.
Describe MTX effect?
Immunosuppresive
Discuss MTXs renal toxicity?
MTX has a hydroxyl-metabolite which mechanically blocks the kidney; seen at high doses.
Discuss the use of Pyrimidine Antagonists
Not a rescue therapy. 5-FU can be potentiated by using folinic acid because it allows 5-FU to bind to its target.
Describe 5-FU IV bolus dose.
Incorporated into cellular RNA; More myelosuppression
Describe 5-FU IV contiunous infusion dose.
Incorporated into cellular DNA; More skin toxicity
Describe Cytarabine and Gemcitabine
Pyrimidine Antagonists that require intracellular activation. Once they are in the cell, they are added onto an elongating DNA strand. Proofreading enzymes are unable to remove them.
What happens to Cytarabine once its in the cell?
Its phosphorylated to the nucleotide triphosphate.
What happens to Gemcitabine once its in the cell?
Incorporated into the cell through the formation of gemcitabine-disphosphate.
Which purine antagonist is more potent? 6-MP or 6-TG
6-TG is more potent and is NOT metabolized by xanathine oxidase.
What is the MOA for allopurinol?
Blocks Xanathine Oxidase, leading to the build-up of 6-MP. Causes high risk for severe bone marrow suppresion; Anti-gout drug.
Discuss Hydroxyurea
Analog of urea; Inhibits ribonucleotide reductase. In sickle cell disease it stimulates the production of HbF.
