Folinic acid , also known as leucovorin , is a drug used to reduce the toxic effects of methotrexate and pyrimethamine. It is also used in combination with 5-fluorouracil to treat colorectal cancer, can be used to treat folate deficiency that causes anemia, and methanol poisoning. This is taken by mouth, injection into the muscle, or injection into the blood vessels.
Side effects may include difficulty sleeping, allergic reactions, or fever. Use in pregnancy or breastfeeding is generally considered safe. When used for anemia it is recommended that pernicious anemia as a cause must be ruled out first. Folinic acid is a form of folic acid that does not require activation by dihydrofolate reductase to be beneficial to the body.
Folinic acid was first made in 1945. This is the List of Essential Medicines of the World Health Organization, the most effective and safe medicines needed in the health system. In the UK the NHS costs around 4.62 pounds per 30mg bottle.
Video Folinic acid
Medical use
Folic acid is given following methotrexate as part of a total chemotherapy plan, where it can protect against bone marrow suppression or gastrointestinal mucosal inflammation. There is no noticeable effect on pre-existing methotrexate nephrotoxicity. Folinic acid can be taken as a pill (oral) or injected into a vein (intravenous) or muscle (intramuscular).
Although not specifically the antidote for methotrexate, folinic acid can also be useful in the treatment of acute methotrexate overdose. Different dosing protocols are used, but the folinic acid should be dimmed to a methotrexate level of less than 5 × 10 -8 M.
In addition, folinic acid is sometimes used to reduce the side effects of methotrexate in patients with rheumatoid arthritis. This includes the reduction of nausea, abdominal pain, abnormal liver blood tests, and mouth sores.
Folinic acid is also used in combination with a 5-fluorouracil chemotherapy agent in treating colon cancer. In this case, folinic acid is not used for "rescue" purposes; rather, it enhances the 5-fluorouracil effect by inhibiting thymidylate synthase.
Folic acid is also sometimes used to prevent the toxic effects of high-dose antimicrobial dihydrofolate reductase inhibitors such as trimethoprim and pyrimethamine. It may be prescribed in the treatment of toxoplasmosis retinitis, in combination with folic acid antagonists primethamine and sulfadiazine.
It has been studied for use in Down syndrome, but the benefits have not been proven.
Maps Folinic acid
Side effects
Folic acid should not be given intrathecally. This can produce severe adverse effects or even death.
Drug interactions
Fluorouracil: Folic acid may increase the toxicity associated with fluorouracil if both are administered together. Some adverse effects have occurred, especially in elderly patients, including severe enterocolitis, diarrhea, and dehydration.
Sulfamethoxazole-trimethoprim: Potential drug interactions exist with concurrent use of sulfamethoxazole-trimethoprim and folinic acid. Folinic acid has been shown to reduce the effectiveness of sulfamethoxazole-trimethoprim in the treatment of Pneumocystis jirovecii (formerly known as Pneumocystis carinii), a common cause of pneumonia in AIDS patients.
Action mechanism
Folinic acid is a 5-formyl derivative of tetrahydrofolic acid. It is readily converted into other reduced folic acid derivatives (eg, 5.10-methylenetetrahydrofolate, 5-methyltetrahydrofolate), thus having vitamin activity equivalent to folic acid. Because it does not require the action of dihydrofolate reductase for conversion, its function as a vitamin is not affected by the inhibition of this enzyme by drugs such as methotrexate. This is the classic view of folinic acid rescue therapy. In the 1980s, however, folinic acid was found to reactivate the dihydrofolate reductase itself even when methotrexate was present. Although the mechanism is not very clear, methotrexate and dihydrofolate polyglutamination in malignant cells is considered to play an important role in the selective reactivation of dihydrofolate reductase by folate in normal cells.
Folinic acid, therefore, allows for some purine/pyrimidine synthesis to occur in the presence of inhibition dihydrofolate reductase, so some normal DNA replication processes may proceed.
Folic acid has dextro and levorotary isomers, only the latter being pharmacologically useful. Thus, levoleucovorin was approved by the FDA in 2008.
History
Folinic acid was found as a growth factor required for the bacterium Leuconostoc citrovorum in 1948, by Sauberlich and Baumann. This produces it called the "citrovorum factor," which means the growth factor citrovorum. It has an unknown structure, but is found to be a derivative of folate that must be metabolized in the liver before it can support the growth of L. citrovorum. The synthesis of the citrovorum factor by liver cells in culture is finally achieved from pteroylglutamic acid in the presence of appropriate ascorbic acid concentrations. The simultaneous addition of sodium formation to the system resulted in increased activity of the citrovorum factor in the cell supernatant (producing, as is now known, 5-formyl derivatives), and from this method preparation of a large number of factors, its structure as levo-folinic acid (5-formyl tetrahydrofolic acid ) finally concluded.
Name
Folic acid should be distinguished from folic acid (vitamin B 9 ). However, folinic acid is a vitamin for folic acid, and has vitamin full activity of this vitamin. Levofolinic acid and its salts are 2S form of molecule. They are the only form of molecule known to be biologically active.
These are generally given as calcium or sodium salts (calcium folinate (INN), sodium folinate, calcium leukovorin, leucovorin sodium).
References
External links
- US. National Drug Library: Drug Information Portal - Folinic Acid
Source of the article : Wikipedia
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