What Is Colchicine Toxicity?

Colchicine, an alkaloid, is also called colchicine because it was originally extracted from the lily plant Colchicum. Pure colchicine is yellow needle-like crystals with a melting point of 157 ° C. Soluble in water, ethanol and chloroform. It is bitter and toxic. Colchicine can inhibit mitosis, damage the spindle, and cause chromosomes to stagnate in the middle stage of division. This abnormal division caused by colchicine is called colchicine mitosis. In such mitosis, although the chromosomes are split longitudinally, the cells do not divide and cannot form two daughter cells, thus doubling the chromosomes. Since the American scholar AFBlakeslee and others in 1937 succeeded in using colchicine to double the number of chromosomes of plants such as Datura, colchicine has been widely used in cytology, genetics research, and plant breeding.

China's natural plant resources are very rich. The composition of the plant body is composed of complex chemical components, which mainly include alkaloids, mushrooms, plastids, pupae, flavonoids, awakening, coumarin organic acids, amino acids, monosaccharides, oligosaccharides, polysaccharides, Proteins, enzymes, etc. are generally considered to have medicinal value. And cellulose, chlorophyll, wax, oil, resin, and gum, although they also have a certain economic value, are often removed as impurities when studying plant physiologically active ingredients. ^[1]

The traditional method of extracting colchicine from plants is generally solvent extraction. The advantage of this method is that the instruments and materials are simple and easy to obtain, the method is relatively simple, but the reagent consumption is large. The basic principle of the solvent extraction method is: according to the properties of colchicine, using its difference in solubility in different solvents, separation according to certain steps and methods. According to the different solvents used, traditional extraction methods can be divided into water extraction, acid extraction, and organic solvent extraction. The extracted mixture containing colchicine needs to be further separated and purified by separation methods such as column chromatography, thin layer chromatography (Zhao), and ion exchange chromatography. ^[1]

(1) For mid-term karyotype analysis (higher concentration)

inhibition

Symptoms of poisoning and

Indications for colchicine

(1) Gout

This product may play an analgesic role by reducing white blood cell activity and phagocytosis and reducing lactic acid formation, thereby reducing the deposition of uric acid crystals and reducing the inflammatory response. It is mainly used for acute gout and is ineffective for general pain, inflammation and chronic gout. ^[4]

(2) Anti-tumor

It can inhibit mitosis of cells and has anti-tumor effect, but it is highly toxic and is now rarely used. It has a significant effect on breast cancer, and may also have a certain effect on cervical cancer, esophageal cancer and lung cancer. Some patients' tumors have shrunk, which is conducive to surgical resection. ^[4]

Colchicine dosage

gout

(1) Treatment of acute gout: take the first oral dose of 1mg, and then 0.5mg for 1 to 2 hours until the symptoms are relieved or adverse reactions occur. For the treatment of acute gouty arthritis, it should not exceed 6 mg within 24 hours. It is not necessary to take it within 48 hours after the symptoms are relieved, and to take 0.5-1 mg daily for 72 days after 72 hours.

(2) Prevention of acute onset of gout: 0.5 to 1 mg daily or every other day.

(3) When using allopurinol or uric acid excretion drugs to treat chronic gout, this product can also be given at the same time to prevent seizures. (Note: When using colchicine in the treatment of acute gouty arthritis, it should be avoided with allopurinol, because allopurinol promotes the dissolution of uric acid crystals in the acute episode, which will aggravate the pain symptoms. Allopurin should be taken in the plateau Drugs such as alcohol control uric acid levels.) ^[4]

Colchicine adverse reactions

Colchicine is highly toxic, and common nausea, vomiting, diarrhea, abdominal pain, and gastrointestinal reactions are the precursor symptoms of severe poisoning. Discontinuation of the drug when symptoms occur, renal damage can be seen in hematuria, oliguria, direct inhibition of bone marrow, causing granule Cell deficiency, aplastic anemia.

(1) Digestive tract reaction: It is the most common side effect. Many gout patients experience nausea, loss of appetite, vomiting, abdominal discomfort, and diarrhea after taking colchicine. Some patients are unable to adhere to the medication due to nausea, vomiting or severe diarrhea.

(2) Bone marrow toxicity: It mainly inhibits the hematopoietic function of the bone marrow, leading to leukopenia and aplastic anemia.

(3) Liver damage: can cause abnormal liver function, jaundice in severe cases.

(4) Kidney damage: proteinuria can occur, which generally does not cause renal failure.

(5) Other side effects: including hair loss, skin allergies, and depression.

In order to reduce the side effects of colchicine, you can also use painkillers such as fenbutide and diclofenac in the acute stage. If there is damage to liver and kidney function, you can only use natural anti-inflammatory drugs such as natural astaxanthin (asta), dimethylsulfone (DSM), etc., can improve uric acid excretion rate by 30%. ^[4]

Instructions for colchicine administration

(1) The effects of CNS and sympathomimetic drugs are enhanced.

(2) Can cause reversible vitamin B12 malabsorption.

(3) Gastrointestinal reactions are usually prodromal symptoms of intolerance or poisoning of this product, which should be reduced or discontinued in time.

(4) Combination with hypertension drugs can reduce the antihypertensive effect of the latter.

(5) Simultaneous application of thiazide diuretics and colchicine will affect its anti-gout efficacy.

(6) There are reports in the literature that this product is effective in treating chronic and active hepatitis through immunosuppressive effects.

(7) Pregnant women can cause teratosis, and the elderly are prone to accumulation poisoning, and should be used with caution.

(8) Interfering with the urine 17-hydroxycorticosterone measurement results in an increase in serum ALT and AST, and a false positive result in the urine hemoglobin test.

(9) Bone marrow suppression, gastrointestinal reactions, and paralytic intestinal obstruction. Leakage outside the blood vessel can cause local necrosis (for intravenous injection). ^[4]