What Are the Most Common Side Effects of Nitrofurantoin?

Since Dodd and Stillman confirmed the antibacterial effect of nitrofuran compounds in 1944, 5-nitro-2 substituted furan derivatives have developed into an important class of anti-infective drugs, and drugs with such structures are also called nitrates. Furans. Such drugs mainly include furazolidone, furantoin, and furacillin. Due to the genotoxic and carcinogenic effects of furazolidone, the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) have banned its use in humans and animals in 2005. Nitrofurans are mainly used to treat urinary tract infections, intestinal bacterial infections, skin wound infections, and as food additives to prevent intestinal infectious diseases in poultry. However, nitro heterocyclic compounds have cell mutagenicity and animal carcinogenic toxicity, which has caused great attention in clinic.

Nitrofuran drugs

1 Nitrofuran

1.1 Drug effects

It is a powerful antibacterial agent and bactericide, and has curative effects on inflammation of the urinary system such as nephritis, nephritis, bladder inflammation, urethritis, vaginitis, and prostatitis. The exact mechanism of furantoin's antibacterial effect is not fully understood, and it is generally considered to be a multiple mechanism intervention. Its metabolite, flavin protein, enters the bacteria and causes complex multiple reactions to destroy the cell's core ribosomal proteins, respiration, pyruvate metabolism, and other macromolecular substances, and directly mediates the destruction of DNA and breaks the DNA chain; by inhibiting the bacteria's body A variety of enzymes, which interfere with the oxidoreductase system in bacteria, mainly inhibit bacterial coenzyme A and block their metabolism of carbohydrates; they can destroy the bacterial wall to form changes in osmotic pressure of bacteria, which together play a role in killing bacteria and inhibiting bacterial reproduction. effect. Furanotoin is absorbed from the intestine into serum and body tissues and does not reach therapeutic concentrations. 75% is rapidly metabolized by the liver, 25% is excreted from the urine in its original form, and the elimination half-life of furantoin is 0.5h -1h. If taken with food, its bioavailability can be increased by about 40%, and gastrointestinal reactions can be reduced.

1.2 Adverse reactions

Common adverse reactions are nausea, vomiting, anorexia and other gastrointestinal symptoms. The exact mechanism is not clear, it may be related to its limited application in the treatment of urinary tract infections and low blood concentration. Many research reports at home and abroad show that furantoin is also very sensitive to MRSA. The Australian Adverse Reactions Advisory Committee (ADRAC) received a total of 18 cases of peripheral neuropathy caused by furantoin from 1978 to 2001, of which 15 were elderly women at a dose of 100mg / d-400mg / d (average 250mg / d). Peripheral neuropathy occurred from 3 weeks to> 12 months, and only 4 patients recovered in August 2001. It is also believed that furantoin is prone to axonal degeneration sensory neuropathy when used more than 20g, and symptoms can be partially improved after discontinuation of the drug. GFR less than 12ml / min is more likely to occur. At present, there have been cases of long-term use of furantoin in the treatment of interstitial pneumonia.The New Zealand Adverse Reaction Monitoring Center has received reports of acute and chronic pulmonary adverse reactions caused by furantoin. Typical allergic reactions occur 1 to 2 weeks after medication. Chronic This may occur after 6 months of treatment, and most occur in older women who have been treated with furantoin for a year or more. Therefore, patients with long-term furantoin should be monitored for lung function. ADRAC has received 576 suspicious reports of furantoin, of which 142 (25%) are related to its effects on the lungs. Forty-six of these patients have been on long-term furantoin. Pulmonary fibrosis or interstitial pneumonia can be confirmed by chest X-ray, CT scan, tissue biopsy, or autopsy. Although early glucocorticoid therapy may be effective, it is easy to be ignored in clinical practice. If patients have difficulty breathing or cough, hypersensitivity, or special discomfort, they need to be treated in time. Furantoin has a killing and inhibiting effect on most Gram-positive and negative bacteria such as Escherichia coli, Streptococcus saprococcus, Enterococcus and Proteus. It is absorbed orally, mainly absorbed from the distal small intestine, and excreted quickly. Excreted in the urine, is conducive to the treatment of urinary tract infections. Although the peak blood concentration was only 1 mg / L after 100 mg, the drug concentration in urine was> 32 mg / L, which lasted at least 4 hours. James tested the minimum inhibitory concentration of clinically isolated urinary tract infection pathogens in vitro, MIC <64 ng / L. Therefore, furantoin has a strong antibacterial effect in the urethra, and is mainly used to treat infections caused by acute and recurrent urinary susceptible bacteria. Because of its low blood concentration and no obvious side effects on the fetus, it can be used in pregnant women. A large number of epidemiological investigations have shown that furantoin in pregnant women does not affect fetal development. It is reported abroad that patients with furantoin rarely develop polyneuritis, but numbness or tingling can occur in any part of the body, and the drug should be discontinued at this time. This medicine can cause hemolytic anemia. Although there are few clinical data in China, it can be seen that it can also cause polyneuritis.

2 Nitrofuran

2.1 Drug effects

It is the earliest bactericide used in furans. This product is characterized by good bactericidal and bacteriostatic effects on Gram-negative and positive bacteria. It can also kill protozoa, especially on penicillin, chloramphenicol, and chain. Strains resistant to mycin, chlortetracycline, and sulfa. However, due to the toxicity of this product, large doses can lead to the development of polyneuronic neuritis. Therefore, you should take special caution when taking furacillin. Generally used as a topical medicine, abroad, this product is combined with hydrocortisone acetate and local anesthetics to make ointments, which are used for local antibacterial, anti-inflammatory and analgesic analgesia. The antibacterial effect of this product, Dod et al. Believe that it can reversibly prevent the function of the oxidase system in the bacteria, make the bacteria unable to survive, and can produce bacteriostatic effects for a long time at a certain concentration. In addition to being ineffective against Pseudomonas aeruginosa, it is sufficient to kill most of the common pathogens that cause wound infections, and rarely produces drug resistance. Infiltration of the urinary catheter with furacicillin can effectively prevent the urinary system caused by indwelling catheters The occurrence of infection and high temperature and high pressure disinfection did not affect the antibacterial activity and content of furacillin on the urinary catheter. Furacin can be used topically to treat and prevent wound infections such as pyoderma, and degree burns, skin grafts and donor site infections. Treatment of acute bacillary dysentery with furancillin solution enema, the abdominal pain is not significantly reduced, and the antidiarrheal effect is significant.

2.2 Adverse reactions

The adverse reactions of clinical application of furacillin are: gastrointestinal reactions, accounting for 51%, mainly nausea and vomiting, and nervous system reactions are rare. Topical adverse reactions are mainly skin hypersensitivity and rare. Lan Lidong et al reported that 1 case had a hypersensitivity reaction with furancillin solution in the mouth, showing itching of the skin, lumpy papules appearing throughout the body and fused into slices, and there were many chests and arms. The mechanism of the hypersensitivity may be: the first application of the drug, the drug enters the human body as an allergen, stimulates B lymphocytes to produce IgE antibodies, and sensitizes the body. Short-term allergens re-enter the body and bind to the corresponding Ig receptors on the mast cell and basophil granulocyte membranes, activating the cells, resulting in increased cell membrane permeability, basophil granules excreted, and histamine, hypersensitivity for several minutes A large number of acid granulocyte chemokines are released, leading to hypersensitivity reactions. In clinical application, we should pay attention to individual patient differences and take preventive measures.

3 Nitrofuran

3.1 Drug effects

Furazolidone, also known as teratrine, is a nitrofuran antibacterial agent, which has a certain antibacterial effect on Gram-positive and negative bacteria. Cocci, Salmonella, Shigella, some Proteus, Aerobacter, Vibrio cholerae, etc. have antibacterial effect, and also have antibacterial effect on piriformis and Trichomonas. Furazolidone is rarely absorbed orally through the gastrointestinal tract, only 5% of the dose, and can maintain a high concentration in the intestine, so it is often used clinically to treat the intestinal tract caused by salmonella, dysentery, typhoid, and vibrio cholerae infection.

It is mainly used for bacillary dysentery and enteritis, and can also be used for typhoid fever, paratyphoid fever, piriformis and vaginal trichomoniasis. It has a therapeutic effect on gastritis and gastric and duodenal ulcers. In recent years, furazolidone has become more widely used. According to domestic and foreign reports, it has achieved good results in the treatment of esophagitis, gastritis, and peptic ulcers, especially in the treatment of peptic ulcers. Furazolidone not only has a good short-term ulcer healing effect, Moreover, it has long-term effects that other anti-ulcer drugs do not have; in addition to its killing effect on Helicobacter pylori, it also has the effect of inhibiting gastric acid secretion, protecting gastric mucosa, and regulating autonomic nerve function. Furazolidone retention enema has better curative effect on bacterial dysentery.

3.2 Adverse reactions

Furazolidone causes clinical symptoms of neurotoxicity and mental disorders. Central nervous system toxicity is mainly manifested as headache, dizziness, blurred vision, eye pain, weakened or disappeared response to light in both eyes, fundus optic disc congestion, blurred borders, retinal edema, double Tinnitus, hearing loss, etc. Peripheral nervous system toxicity is mainly manifested as paresthesia, decreased sensation, and limb pain. The distal end is heavier than the proximal end. There will be varying degrees of "glove sock-type" sensation decline, acupuncture sensations at the ends, skin sensitivity to pain, walking and Numbness pain is obvious when grasping objects, those with severe illness cannot walk, severe pain in both lower limbs, fear of wind, sagging feet, muscle atrophy, can not hold chopsticks, tendon reflexes weaken or disappear; electrophysiological changes manifest as neurogenic damage, The main reason is that the nerve conduction speed is slowed down, and the sensory nerve conduction speed is more common. The lower limbs are heavier than the upper limbs, and the nerve action potential amplitude is reduced. Mental disorders are mainly manifested as excitement, insomnia, dreaming, energetic, increased activity, talking too much, panic, perverse behavior, hallucinations and vision. At present, the causes of furazolidone-induced neurological diseases and mental disorders are not clear. There are three statements: (1) There is a theory that furazolidone can interfere with bacterial sugar metabolism, but also inhibits the enzyme system related to sugar metabolism in the body, making sugar Disturbances in metabolism occur, the energy source of nerve tissue is blocked, and motor fibers and sensory fibers are involved, leading to the occurrence of peripheral nerve inflammation. (2) Some scholars believe that furazolidone can inhibit the enzymatic process of producing acetyl-CoA from pyruvate, hinder pyruvate from entering the tricarboxylic acid cycle, interfere with sugar metabolism, lead to accumulation of pyruvate and lack of energy in nerve tissues, thereby generating neurotoxicity. symptom. (3) Another argument is that furazolidone is not only an antibacterial drug, but also an effective monoamine oxidase inhibitor. After oral furazolidone, a metabolite produced by the intestinal flora is called 2-hydroxyl Ethylhydrazine (HEH), HEH has a significant inhibitory effect on monoamine oxidase (MAO). By inhibiting MAO, the degradation of monoamine transmitters is reduced. After taking furazolidone for 1-3 days, the levels of norepinephrine and serotonin in the brain increased by 60% -70%, and dopamine increased by 20%. Therefore, some people think that the occurrence of mental disorders is probably related to the inhibition of MAO by furazolidone and the change of the concentration of monoamine transmitters in the brain.

Clinical application of nitrofuran drugs

Nitrofurans are mainly used to treat urinary tract infections, intestinal bacterial infections, skin wound infections, and as food additives to prevent intestinal infectious diseases in poultry. However, nitro heterocyclic compounds have cell mutagenicity and animal carcinogenic toxicity, which has caused great attention in clinic.

Summary of nitrofurans

Although nitrofuran drugs have broad application prospects due to their broad antibacterial spectrum and resistance to drug resistance. However, its adverse reactions still need clinical attention. In order to avoid side effects, topical application in the future may become a research hotspot.

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