Take methotrexate, folic acid to make up so! . . . you "drugs" know.

Don't want to miss Jiemei's push? Poke the blue word "medical rheumatism and nephropathy channel" to pay attention to us, and click the "··" menu in the upper right corner, and select "set as star" to know the clinical medication knowledge! Methotrexate is the most commonly used drug in the treatment of rheumatoid arthritis (RA). It has the advantages of definite curative effect, low price and convenient use.however, methotrexate also has many adverse reactions, such as gastrointestinal discomfort, slight increase of transaminase, oral mucositis, skin ulcer and pancytopenia.studies have shown that folic acid supplementation can reduce or prevent adverse reactions caused by methotrexate, such as mucosal damage, gastrointestinal reactions and pancytopenia. Therefore, it is recommended that methotrexate combined with folic acid be used in the treatment of RA to ensure drug safety.1 then, why do patients taking methotrexate take folic acid? Folic acid is a water-soluble vitamin B, which is essential for the growth and reproduction of human cells.folic acid is converted into dihydrofolate by folate reductase, and then tetrahydrofolate (an important coenzyme for purine nucleotide and pyrimidine deoxynucleotide synthesis in vivo) is produced by dihydrofolate reductase.tetrahydrofolate combines with a variety of one carbon units (such as CH3, CH2, CHO, etc.) to form tetrahydrofolate coenzymes, transfer one carbon unit, and participate in a variety of important reactions in vivo and the synthesis of nucleic acids and amino acids.Fig. 1 folic acid physiological function dihydrofolate reductase is a key enzyme in vivo that catalyzes the reduction of dihydrofolate to tetrahydrofolate with physiological activity.because the structure of dihydrofolate reductase inhibitor is similar to the substrate of dihydrofolate reductase, it can combine with dihydrofolate reductase, prevent or inhibit the combination of normal substrate and enzyme, inhibit its activity, so that dihydrofolate can not be reduced to tetrahydrofolate, and the transfer of one carbon unit in the biosynthesis process of purine nucleotide and thymine nucleotide is blocked, which interferes with DNA and DNA Protein synthesis, produce cytotoxicity.methotrexate is a dihydrofolate reductase inhibitor similar to folic acid in chemical structure.it has a strong and lasting inhibitory effect on dihydrofolate reductase. The binding capacity of dihydrofolate reductase to the enzyme is 106 times greater than that of folic acid. It has a competitive inhibitory effect with folic acid and reduces the production of tetrahydrofolate.adding folic acid can directly provide tetrahydrofolate coenzyme to cells, avoid the inhibitory effect of methotrexate and reduce its cytotoxic effect. However, MTX supplementation did not reduce the adverse effects of MTX.2 how to take folic acid? Since the affinity of dihydrofolate reductase to methotrexate is much greater than that to folic acid or dihydrofolate, the effect of methotrexate on the reduction of dihydrofolate to tetrahydrofolate cannot be reversed by high dose folic acid.a randomized controlled trial comparing folic acid 10mg / week and 30mg / week in reducing methotrexate toxicity showed that high-dose folic acid did not improve gastrointestinal discomfort, hemocytopenia and elevated transaminase response.therefore, China's "expert consensus on the application of methotrexate in rheumatic diseases (2018)" (hereinafter referred to as "China consensus") recommends that 5 mg folic acid be supplemented 24 hours after the application of methotrexate. When the dosage of methotrexate is higher, the appropriate increase of folic acid dose can be considered.(the oral dose of methotrexate in the treatment of RA is usually 7.5 ~ 20mg / week, and the initial dose is 7.5 ~ 15mg / week. The dosage should be adjusted according to the patient's condition and treatment response.) 3 how do pregnant / lactating women take folic acid? Methotrexate has been reported to cause stillbirth and / or congenital malformations. Therefore, China's consensus emphasizes that both men and women should stop using methotrexate for at least three months before conception, and that methotrexate should be banned during pregnancy and lactation.China's guidelines for supplementation of folic acid during perinatal period (2017) recommends that for women who are taking drugs that increase the risk of fetal neural tube defects (including methotrexate), it is recommended to supplement 0.8-1.0 mg folic acid daily from the time of possible pregnancy or at least 3 months before pregnancy until the third month of pregnancy. in 2016, the British Society of Rheumatology and the British Association of rheumatic health professionals issued the guidelines on medication during pregnancy and lactation, which suggested that any dose of methotrexate should be avoided during pregnancy and should be discontinued three months before pregnancy; women who received low-dose methotrexate treatment within three months before pregnancy should supplement folic acid (5mg / D) during pregnancy and the whole pregnancy, and it is not recommended that breast-feeding patients should be given folic acid (5mg / D) Methotrexate was used. 4 how to give first aid when methotrexate overdose? Calcium folinate is a calcium salt with reduced folate structure. After entering the human body, it is converted into methylenetetrahydrofolate and N10 formyltetrahydrofolate. It can be reduced from dihydrofolate blocked by methotrexate to tetrahydrofolate from the bypass, so that normal DNA and protein biochemical reactions can continue, so as to play a rescue role and effectively neutralize the toxic reaction of methotrexate. therefore, when methotrexate is overdose, calcium folinate should be given as soon as possible, preferably within 1 hour after administration. with the increase of the interval between methotrexate and calcium folinate, the detoxification effect of folic acid decreased. 5 what are the precautions when taking medicine? ▎ methotrexate methotrexate may damage sperm and have adverse effects on the fetus. Therefore, both men and women should take contraceptive measures during the period of taking medicine and at least 3 months after stopping the drug; it can inhibit blood coagulation function and be alert to bleeding; it can lead to photosensitive reaction, and avoid excessive exposure to sunlight or sunlight without protection during the medication; it can cause elevated blood uric acid level, gout or Patients with hyperuricemia should increase the dosage of anti gout drugs; it may cause central nervous system symptoms (such as fatigue and dizziness), and should avoid driving or operating dangerous machines; during the medication, alcohol or alcoholic drinks should be avoided; when combined with butazone and sulfonamides, the competition with protein binding may cause the increase of serum methotrexate concentration The appearance of toxic reaction. live vaccination is prohibited during the use of methotrexate or within 3 months after the administration. regular monitoring of blood routine, liver and kidney function, lung function, etc. ▎ taking folic acid for a long time may cause gastrointestinal symptoms such as fear of eating, nausea, abdominal distension. the urine may turn yellow during medication. folic acid can reduce the absorption of theophylline and reduce its antiasthmatic effect. if combined, theophylline should be taken with folic acid at an interval of 1 hour. during the folic acid intake period, you can eat more foods rich in folic acid, such as dark green vegetables, citrus fruits, beans, nuts, animal liver, etc., to develop a healthy lifestyle. References: [1] guidelines for the diagnosis and treatment of rheumatoid arthritis in China (2018). [2] Chinese expert consensus on the application of methotrexate in rheumatic diseases (2018). [3] British Society of Rheumatology and British Association of rheumatic health professionals, [4] expert consensus on high-dose methotrexate calcium folinate rescue therapy for malignant tumors (2019). [5] supplement of folic acid to prevent neural tube defects during pregnancy (2017)