Colchicine, also known as colchicine, was originally an alkaloid extracted from colchicine in Liliaceae, hence the name. Colchicine in China is mostly extracted from bulbs of Liliaceae plant Lijiang River in Shā rotto Katakuri.
Colchicine has a long history in the treatment of gout, especially in the treatment of acute gout. Therefore, many gout patients should be very familiar with this drug. Gouty joints are swollen, so it may have become a habit to eat a piece of colchicine immediately.
The mechanism of colchicine in treating acute gout attack is to control local pain, swelling and inflammatory reaction of joints by inhibiting chemotaxis, adhesion and phagocytosis of inflammatory cells and inhibiting the release of inflammatory factors. However, it should be noted that colchicine only has anti-inflammatory and analgesic effects, and does not affect the formation, dissolution and excretion of urate, so it does not reduce serum uric acid.
Colchicine and non-steroidal anti-inflammatory drugs (such as etoricoxib, celecoxib, meloxicam, loxoprofen, diclofenac sodium, etc.). ) is a first-line drug for the treatment of acute gout. Short-term glucocorticoid anti-inflammatory therapy should be considered when there are contraindications or poor therapeutic effects.
If the single drug treatment effect is not good, you can choose the combination of the above drugs, such as colchicine+non-steroidal anti-inflammatory drugs, or colchicine+glucocorticoid; Non-steroidal anti-inflammatory drugs+glucocorticoid will increase the adverse reactions of gastrointestinal tract, so be careful. When necessary, highly selective cyclooxygenase -2 inhibitors should be selected, such as etoricoxib, celecoxib and meloxicam. These NSAIDs have little effect on gastrointestinal mucosa.
Why should colchicine be used in small doses? This is because the therapeutic window of colchicine is very narrow, and its therapeutic dose is very close to poisoning. People with mild poisoning reaction may have diarrhea, nausea and vomiting. In severe cases, bone marrow suppression, aplastic anemia and peripheral neuropathy may occur. The toxic reaction of colchicine is mainly related to its excessive dose. The existing research shows that there is no difference in the effectiveness of low-dose colchicine and high-dose colchicine in treating gout. Therefore, at present, guidelines at home and abroad suggest using small doses of colchicine to treat gout, which can significantly reduce the occurrence of adverse reactions.
Guidelines for the diagnosis and treatment of hyperuricemia and gout in China (20 19) recommend that the first dose of colchicine 1mg, 1h, and then 0.5mg qd or bid. Use as soon as possible after onset 12h, and the curative effect will be obviously reduced after 36 hours. In order to prevent gout attack, it is suggested that a small dose of colchicine (0.5~ 1.0mg/d) should be used for at least 3~6 months.
Colchicine is a good medicine for treating gout, which can make the pain and inflammation of more than 90% patients begin to subside within 12 hours and disappear within 24~48 hours. But the common side effects of colchicine are diarrhea, abdominal pain and nausea. If diarrhea is severe, stop using it. Some patients said that they began to have diarrhea after eating colchicine, and then they thought about life in the toilet.
The occurrence of colchicine adverse reactions may also be related to drug interaction. Colchicine is the substrate of CYP3A4 and P- glycoprotein. When CYP3A4 or P- glycoprotein inhibitor exists, the concentration of colchicine in blood will increase. Therefore, patients who are using P- glycoprotein or powerful CYP3A4 inhibitors (such as erythromycin, clarithromycin, cyclosporine, diltiazem, etc.). ) and drugs metabolized by CYP3A4 (such as simvastatin and other lipid-lowering drugs) should use colchicine with caution or reduce the dose.
For patients with renal insufficiency, it is suggested to adjust the dosage of colchicine according to glomerular filtration rate (eGFR). See table 1 for the recommended maximum dose.
The application of colchicine should also be adjusted according to the general situation, weight, age and combined medication of patients, and close observation should be made to guard against colchicine poisoning.
Besides treating gout, colchicine has many clinical applications, such as familial Mediterranean fever. Familial Mediterranean fever (FMF) is a spontaneous autosomal recessive genetic disease with unknown etiology, which is characterized by recurrent fever and peritonitis. A few cases show pleurisy, arthritis, skin lesions and pericarditis. Colchicine is the only drug used to treat familial Mediterranean fever. Can be used for life, and can prevent and reduce recurrence and prevent renal amyloidosis.
In dermatology, it has good curative effect on papular dermatosis, cutaneous vasculitis, immune bullous disease, allergic dermatosis, endocrine, metabolic and nutritional dermatosis.
Cardiovascular system, 20 15ESC recommended it as the first-line treatment of pericardial diseases; 20 14AHA/ACC/HRS recommended it to prevent postoperative atrial fibrillation (grade Ⅱ b).
In addition, it has obvious therapeutic and preventive effects on fibrosis diseases such as primary liver fibrosis, pulmonary fibrosis, renal fibrosis, alcoholic cirrhosis and primary biliary cirrhosis. Others include anti-tumor; Used for Behcet's disease, keloid, etc.
The pharmacological action of colchicine is complex, although it has certain curative effect on many difficult diseases in clinic, but some specific mechanisms are still unclear and need further study.
In recent years, some encouraging studies show that colchicine can reduce the risk of cardiovascular events (including recurrence, cardiac arrest, stroke or angioplasty) in patients with myocardial infarction. In fact, atherosclerosis is an inflammatory process to a great extent. It is speculated that the mechanism of colchicine reducing cardiovascular events in patients lies in inhibiting this inflammatory process. These results also confirmed that dealing with inflammation can reduce the risk of cardiovascular diseases, which also ignited people's research enthusiasm in the field of anti-inflammatory treatment of coronary heart disease. It should be noted that these studies are only in some high-risk groups of cardiovascular risk, and the use of low-dose colchicine can bring cardiovascular benefits, but it is uncertain whether it will benefit other groups.
In a word, colchicine is a highly effective anti-gout drug with a long history. Recent research shows that it can reduce the risk of cardiovascular events in patients with myocardial infarction, which has aroused great concern. The therapeutic dose is very close to the toxic dose, but it is usually safe to use at low dose. Of course, some patients will have adverse reactions of diarrhea after taking it. For the elderly, low weight, liver and renal insufficiency, it is necessary to adjust the dose and closely observe the reaction after taking the medicine.