Folic acid Fluorouracil

Droperidol Droperidol has pH-dependent incompatibility with many drugs. It is not compatible with nafcillin sodium, fluorouracil, folic acid, frusemide, heparin, methotrexate, or barbiturates. Droperidol should not be stored in PVC bags containing intravenous infusions, although some solutions appear to be stable.157... 

FLUOROURACIL FOLIC ACID Risk of fluorouracil toxicity Folic acid exacerbates the inhibitory effect of fluorouracil on DNA Avoid co-administration... 

Antimetabolites (inhibition of purine and pyrimidine nucleotide synthesis) Methotrexate Folic acid antagonist, inhibits tetrahydrofolate reductase and therefore dTMP synthesis 6-Mercaptopurine Interferes with purine synthesis 5-Fluorouracil Inhibits dTMP synthesis ... 

Folic acid antagonist overdose PO 2-15 mg/day for 3 days or 5 mg every 3 days. Megaloblastic anemia secondary to folate deficiency IM 1 mg/day Colon cancer IV 200 mg/m followed by 370 mg/m fluorouracil daily for 5 days. Repeat course at 4-wk intervals for 2 courses then 4-5 wk intervals or 20 mg/m followed by 425 mg/m fluorouracil daily for 5 days. Repeat course at 4-wk intervals for 2 courses then 4-5 wk intervals. 

Antimetabolites include 5-fluorouracil [51-21-8] (153) and amethopterin [59-05-2] (154), a folic acid antagonist, which produce sterility in female flies when fed at 0.01—0.05% in the diet. 

A depressed uptake of deoxyuridine brought about by a deficiency of vitamin B12 can be reversed as reflected by a reduction in labeled thymidine uptake by the addition of as little as 1 xg of the vitamin. Folic acid added to a concentration of 50 p.g/ml of the culture will correct abnormal results due to folate deficiency and may partially correct abnormal results due to vitamin B12 deficiency. Abnormal results may occur in bone marrow from patients with iron deficiency and from patients being treated with 5-fluorouracil (B7). 

The folic acid-dependent conversion of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP) carried out by thymidylate synthase is an absolute requirement for DNA synthesis. An unusually high demand for uracil (ura) by certain tumor cells suggested that such an inhibitor of this process could have tumor cell selectivity. 5-Fluorouracil (fl5ura) (80), along with 5-fluorocytosine (fl5cyt) (81) and 5-fluoroorotic acid (fl5oro) (82), were synthesized by Heidelberger in 1957 as part of a... 

B Fluorouracil is a prodrug that is metabolized to FdUMP and a triphosphate metabolite. FdUMP binds and interferes with thymidylate synthase, whereas the triphosphate metabolite interferes with RNA function. Leucovorin is a reduced form of folic acid. Leucovorin provides folate cofactors that stabilize the binding of FdUMP and thymidylate synthase, thus enhancing the cytotoxic effects of fluorouracil. 

Folic acid is a nutritional supplement frequently used during periods of deficiency. Folic acid needs increase during chronic diseases, such as malabsorption liver disease, alcoholism, and anticonvulsant or oral contraceptive use. Folic acid supplementation during pregnancy is strongly recommended to prevent neural tube defects to the unborn child. The active form of folic acid, folinic acid, is used in the management of certain medical diseases (e.g., patients taking methotrexate, and 5-fluorouracil). 

Leucovorin is used to reduce the toxicity ( rescue ) of high dose methotrexate in osteosarcoma to counteract the action of folic-acid antagonists such as pyrimethamine or trimethoprim and in combination with 4-fluorouracil to prolong survival in patients with advanced colorectal cancer. In this case, leucovorin enhances the toxicity of 5-fluo-rouracil (5-FU), and the doses of 5-FU should be reduced. 

The antimetabolites are structurally similar to endogenous compounds and are antagonists of folic acid (methotrexate), purines (mercaptopurine, thioguanine), or pyrimidines (fluorouracil, cy-tarabine). Antimetabolites are CCS drugs acting primarily in the S phase of the cell cycle. Their sites of action on DNA synthetic pathways are shown in Figure 55-3. In addition to their cytotoxic effects on neoplastic cells, the anti metabolites also have immunosuppressant actions. Some of the uses of the antimetabolites in neoplastic disease are listed in Table 55-2. 

The formation of thymidylate is specifically blocked by certain analogues of folic acid and by derivatives of 5-fluorouracil these agents have an important use in the treatment of cancer in humans. 

Fluoroquinolones, 12.250, 18.271 Fluorouracil, adverse reactions, 23.476 Folic acid, dietary supplementation, 19.369 safety aspects, 27.407 Formoterol, tolerance, 24.187 Fragrances, contact allergy, 20.149... 

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