Folate & B12- Fitz Flashcards Preview

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Flashcards in Folate & B12- Fitz Deck (15):
1

Leucovorin

reduced form of folate

provides folate to normal tissues, as mech to surpass inhibition of DHFR (MTX therapy)

Some cancer cells cannot uptake because do not have functional REDUCED FOLATE CARRIER needed for uptake

2

Methotrexate

Competitive inhibitor of Dihydrofolatreductase inhibitor

3

What is a source of primary resistance of methotrexate?

Reduced expression or mutation of the RFC.

Need to give higher dose MTR, also administer Leucovorin, to decrease toxicity to normal cells (Leucovorin rescue)

4

Describe rescue therapy in regards to MTX administration

Reduced expression/mutation in RFC of cancer cells (primary resistance to low does MTX)

Need to increase MTX dosage to overcome resistance

Also give leucovorin to allow normal cells with functional RFC to bypass drug induced inhibition of DHFR

5

What are the two major folate transporters?

Reduced folate carrier (RFC)

Folate Receptor - only on some tissues, transports folates when they are present at very low concentrations

6

What makes some leukemias and gynecological and epithelia cancers more sensitive to folate inhibitors?

Over expression of folate receptor

7

Adding of what molecule causes more potent binding to folate-dependent enzymes, and prevents the drug from leaving the cell?

Adding of polyglutamates by FPGS

8

Mechanism of action of Pemetrexed and Pralatrexate?

Antagonists of thymidylate synthase and purine synthesis

9

Why is polyglutamating considered selective toxicity?

Because tumor cells are more capable of polyglutamating, this increases the concentration of the drug in CANCER cells, rather than our normal cells

10

Increased homocysteine levels are diagnostic of what?

Vitamin B12 deiciency

11

What are the major funcitons of Folate and Vit. B12?

**Required for DNA synthesis and maintenance of neurons and RBCs

12

Folate Reactions

Carbon donor in thymidylate and purine synthesis

13

Vit B12 Reactions

Critical cofactor in the generation of THF from livers stores of methylTHF

14

What is the most prominent sign of Folate and B12 deficiency?

Megaloblastic Anemia

*can be caused by folic acid deficiency in alcoholics

15

MOA of Trimethoprim and Sulfamethoxazole?

Selective bacterial folic acid inhibitor

Sulfa- blocks dihydropteroate synthase

Act synergistically