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41 Cards in this Set
- Front
- Back
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What are Antimetabolites?
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Structural analogs of compounds that are required by cells for intermediary metabolism
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How does the cell specificity of many of the antimetabolites compare to that of the alkylating agents?
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Antimetabolites are more specific - often for S phase
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Why do the antimetabolites target cells in S phase?
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Because they inhbiit nucleic acid syntheis, and S phase is when that is occurring - DNA synthesis.
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For what types of tumors do the Antimetabolites have the greatest effectiveness?
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Those with rapid cell proliferation
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What are the 4 general classes of Antimetabolite drugs?
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1. Folate analogs
2. Pyrimidine analogs 3. Purine analogs 4. Misc analogs |
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What is the folate analog to know?
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Methotrexate
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What are the 2 Pyrimidine analogs to know?
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-Fluorouracil
-Cytarabine |
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What is the Purine analog?
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Mercaptopurine
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What is the misc antimetabolite?
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Hydroxyurea
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What is the folate analog again?
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Methotrexate
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What is Methotrexate's mechanism?
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Binds DHFR and inhibits formation of THF
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What is THF needed for?
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Thymidine synthesis.
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What would happen if you blocked ALL of the THF production?
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You'd kill all the normal cells too
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So how do you prevent high doses of MTX from killing all the cells in the body?
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By following with Leucovorin to rescue host cells.
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How does MTX circulate?
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Bound to Albumin
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So what should you avoid giving to patients on MTX?
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Other drugs that will displace MTX from albumin
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What is a side effect unique to MTX? How is it prevented?
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It crystallizes and causes Renal Tubular Necrosis; alkalinize urine to prevent.
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What are 2 indications for MTX?
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-Acute lymph leukemia
-Choriocarcinoma |
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How does Leucovorin rescue following the high doses of MTX that are needed for inhibiting all DHFR work?
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Leucovorin is already-reduced folate and doesn't NEED dhfr.
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What are the 2 pyrimidine analogs again?
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-5-fluorouracil
-Cytarabine |
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What are the pyrimidines?
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Cytosine
Uracil Thymidine |
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How does 5-fluoruracil's mechanism go? (3 steps)
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1. Activated in cells to FUTP
2. F-UTP inhibits RNA synthesis 3. FdUMP interferes w/ Thymidylate synthesis ultimately DNA sythesis |
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What is Fluorouracil indicated for?
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Broad spectrum
esp colon cancer |
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How is 5-FU given for basal cell carcinoma?
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As a topical cream
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What is Cytarabine?
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A cytidine analog
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What is Cytarabine's mechanism? (2 steps)
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-Competes with Cytidine for all 3 phosphorylation steps to dCTP
-Cytarabine-3P competes with dCTP for incorp into DNA and causes DNA chain termination. |
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What is a unique side effect of Cytarabine in addition to the typical se's of anticancer drugs?
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Neurotoxicity
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What cancer is Cytarabine indicated for treated?
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AML
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What is the purine analog antimetabolite?
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Mercaptopurine
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What is the mechanism of Mercaptopurine?
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Converted in cells to Ribonucleotide that inhibits RNA and DNA synthesis
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Txmt indication for Mercaptopurine:
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Acute leukemias
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Unique side effect of Mercaptopurine:
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Jaundice
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What enzyme metabolizes Mercaptopurine to an inactive compound?
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TMPT
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What will happen to the patient if homozygous for having no active TPMT? What % of patients are this?
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They will die; this is <1%
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What if a patient is heterozygous and has 1 active copy of TPMT?
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Use a lower dose of mercaptopurine as their metabolizing capacity is decreased.
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What is the cause of different amounts of TPMT in different people?
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Genetic polymorphisms
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What is the miscellaneous antimetabolite?
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Hydroxyurea
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What is the mechanism of Hydroxyurea?
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It inhibits ribonucleotide reductase thus blocks DNA synthesis
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What is the cell cycle effect of blocking DNA synthesis by Hydroxyurea?
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It ARRESTS the cells at the G1-S interface which is VERY sensitive to irradiation!
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So what is Hydroxyurea used as?
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A radiosensitizing agent
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What is the major indication for Hydroxyurea?
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Granulocytic leukemia
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