Abstract: Fluoroquinolones have been widely used in clinic because of their broad antibacterial spectrum and strong antibacterial activity. However, due to the characteristics of the drug itself and the existence of irrational drug use and drug abuse, a series of adverse reactions have been caused. Common skin allergies and photosensitivity reaction, central nervous system reaction, circulatory system reaction, digestive system reaction, urinary system reaction, respiratory system reaction, cartilage toxicity, liver toxicity, reproductive toxicity, Achilles tendinitis and local irritation, etc. And human health has caused some damage. Therefore, health care workers and veterinary workers should master the characteristics of adverse reactions of fluoroquinolones and avoid the harm caused by them, thus ensuring the health of humans and animals. Key words: fluoroquinolones; adverse reactions; toxicity fluoroquinolones (FQNS or FQS) drugs are third-generation quinolone antibiotics that were developed in the 1980s as they are located at the 6-position of the quinolone naphthyridine ring. The fluorine atom was introduced and the piperazine ring was attached to the 7-position. Therefore, they are collectively referred to as fluoroquinolones and are a series of novel fluorine-substituted quinolone derivatives. The antibacterial spectrum of this type of drug is significantly larger than that of the first and second generations, and its antibacterial activity is also significantly enhanced. It is effective against staphylococcus, pneumococcus, certain anaerobic bacteria, and mycoplasma, and is particularly effective against Pseudomonas aeruginosa. Almost suitable for clinical common bacterial infections. According to the principle of naming international non-proprietary medicines, the new drugs were all named "-oxacin" to indicate their pharmacological similarities and group relationships. The word-building component is transliterated in China as "Sandstar". FQNS drugs have good absorption, high tissue concentration, long half-life, antibacterial spectrum and other advantages, has become a common medicine for human and veterinary clinics. The main varieties are Norfloxacin, Pefloxacin, Enoxacin, Ofloxacin, Ciprofloxacin, Lomefloxacin, Fleroxacin, Enrofloxacin, Danofloxacin mesylate, Sarafloxacin hydrochloride, Mar bofloxacin, Orbifloxacin And difloxacin hydrochloride (Difloxacin hydrochloride), among them, enrofloxacin, dalfloxacin mesylate, sarafloxacin hydrochloride and difluoxacin hydrochloride are animal special drugs. Any drug has side effects, FQNS is no exception, and due to the widespread use of FQNS drugs, often accompanied by unreasonable drug use and drug abuse, the adverse reactions (ADR) problems caused by the use of fluoroquinolones The more people pay attention to. The adverse reactions of fluoroquinolones mainly occur in humans, and the response of animals is not great. However, the drug residues after animal drugs are transmitted through the food chain can also cause human adverse reactions and affect human health. Therefore, attention should be paid to it. This article reviews the common adverse reactions of FQNS drugs and summarizes them as follows:

1 Skin allergic reactions and photosensitivity reactions After the use of FQNS drugs, animals with a low incidence of skin allergic reactions (including erythema, pruritus, rubella, and rash) (78 weeks) were exposed to ultraviolet light for a prolonged period, and tumor growth was observed. Except for lomefloxacin, almost all skin tumors are benign. At present, the impact of short-term antibacterial therapy on the human body remains unclear, but it is strongly advocated that exposure to sunlight or artificial ultraviolet light should be avoided when using FQNS drugs. The order of phototoxicity of FQNS drugs was Clinfloxacin>Lomefloxacin>Serfloxacin>Trovafloxacin>Enoxacin>ofloxacin, ciprofloxacin, moxifloxacin, gatifloxacin. 1].

2 Central nervous system adverse reactions Adverse reactions to the central nervous system during FQNS drug therapy are a common complication, and the mechanism of CNS toxicity is not yet clear. The total incidence of adverse reactions in the nervous system was 11.8%. Symptoms showed altered consciousness, convulsions, epileptic seizures, transient vision impairment, headache dizziness, and sleep disturbances. One patient was given oral norfloxacin 400 mg/time for 4 times a day for chronic cholecystitis and took the drug once in the evening. The next morning he caused general muscle tremors, especially for the upper extremities, slow movements, difficulty in writing, and indifferentness. Language, low voice, increased limb muscle tone, manifested as tremor paralysis group; otherwise reported that ofloxacin injection also showed the same symptoms [2]. It was reported in the literature that if ciprofloxacin (100 mL) was used in the treatment of suppurative tonsillitis with an amount of 20 g/L, aphasia appeared 5 minutes later and disappeared 2 hours after discontinuation. The next day, 80 mL was used again, and the same symptoms reappeared 30 minutes later [3]. Patients of different ages and genders were given ciprofloxacin 0.2 g to 0.5 g orally twice a day. The results were the fastest 1 d. At the slowest 5 d, the hands were shaken. The words increased, the food was restless, and other clothes were worn indiscriminately. symptom. The Canadian Adverse Drug Reactions Bulletin reported that a 22-year-old woman took moxifloxacin for sinusitis. After taking the first dose, the patient experienced fatigue and lethargy. The symptoms disappeared after 2 days, but after 4 days, the left eye was treated. Loss of vision, she consulted an ophthalmologist and continued to take the drug for 6 days. The report stated that her visual acuity was unlikely to recover. Animals show uneasiness or neurological symptoms. The acute neurotoxicity symptoms in chicks are screaming, turning, and finally the head and neck, and the two limbs are stiff and cramps. Cats and dogs can also induce epilepsy.

3 Adverse reactions in the circulatory system Although these reports are rarely reported, they should also be highly regarded. After use, thrombocytopenia, lymphocyte and neutropenia can be reduced, and hemolytic anemia and aplastic anaemia can be produced. The main symptoms are elevated or decreased blood pressure, tachycardia, bradycardia, circulatory failure, atrial fibrillation, myocardial infarction, and severe cardiac arrest. Ansari et al. reported that in a 54-year-old female patient, fainting occurred after treatment with gatifloxacin for acute sinusitis, and a significant QT interval was found in the heart, and the QT interval returned to normal after discontinuation. The adverse reaction sequence of this system was ciprofloxacin>ofloxacin>norfloxacin>lomerfloxacin>pefloxacin>floxacin>enoxacin>sparfloxacin [4]. Therefore, cardiac patients and elderly hypertensive patients should be used with caution.

4 Adverse reactions of the digestive system The common adverse reactions that people use FQNS drugs for treatment are gastrointestinal symptoms. Most of them occur during oral administration. Intravenous administration also occurs from time to time. The main manifestations are anorexia, nausea (1.5% to 2%), abdominal distension. , diarrhea, vomiting (3% to 5%), but there are differences in the incidence of these adverse reactions, the average incidence of 5%, up to 10% to 13.4%. This response is often dose-related, oral dose of less than 600 mg / d, lower incidence of gastrointestinal reactions, when the dose is greater than 800 mg / d, the higher the incidence. The most serious case is gastrointestinal bleeding. The order of the drugs that produce adverse reactions to the digestive system was ciprofloxacin> norfloxacin> fenofloxacin> pefloxacin> fleroxacin> enoxacin [5]. It is particularly important for adverse reactions to the digestive system in animal production. The extremely strong bactericidal activity against Gram-negative bacteria can destroy the mutual inhibition of the flora of the gastrointestinal tract, affect the feed utilization ratio, and reduce the rate of weight gain. It can lead to a series of serious gastrointestinal reactions, such as oral doses of norfloxacin 2 g/kg in chickens. After 1 h, there was a decrease in feed intake and watery diarrhea. According to reports, norfloxacin poisoning caused by 1 day old chicks caused diarrhea, mucosal bleeding, liver yellow crisp [6].

5 urinary system adverse reactions Urinary system nephrotoxicity reaction is rare, kidney damage manifested as urea nitrogen and serum creatinine value increased; high-dose application may occur crystalline urine, proteinuria, hematuria, serum creatinine and urea nitrogen increased, severe edema Interstitial nephritis and even secondary renal failure. There have been reports of ciprofloxacin-induced hematuria, acute renal failure, renal biopsy of allergic interstitial nephritis, and acute urinary retention induced by pefloxacin. Allan et al. reported that the first case of acute lymphoblastic leukemia patients received chemotherapy for 4 weeks after oral administration of ciprofloxacin. Therefore, those with poor renal function should be used cautiously, and elderly people should be used cautiously due to the different degrees of liver and kidney function.

6 Respiratory system adverse reactions reported in this area are few, mainly bronchospasm, asthma, dyspnea, etc., the mechanism is that FQNS drugs can produce singlet oxygen under light and oxygen conditions, singlet oxygen can cause cell membrane lipids. Peroxidative damage, cell rupture, and inhibition of the cell's antioxidant defense mechanisms cause lung damage. Xu Yougui et al. reported that patients with chronic obstructive pulmonary disease suffered from coughing, cyanosis, and dyspnea after taking ciprofloxacin. The cause of the disease was a further cause of bronchospasm on the basis of the original pathology. The sputum was not easy to cough up, and the mucus plugs were widely used to snagged. Bronchial and main bronchial obstructive pulmonary syndrome.

7 Cartilage toxicity In many animal experiments, FQNS drugs have shown toxic effects on immature articular cartilage (ankle complex), especially FQNS drugs also have effects on neonatal or young animal axillary hyperplasia, and there are no corresponding cartilage joints in adult. reaction. Pathological changes showed that the articular cartilage of young animals had blisters, crevices, erosions, chondrocyte aggregation, and non-inflammatory exudation of the joints, thereby affecting cartilage development and inhibiting growth. Some systematic animal research data show that FQNS drugs have the phenomenon of interrupting long bone growth in rats, so it is presumed that these drugs may have chondrotoxic effects on children and uninfused adolescents and affect growth and development. However, in recent years, more and more data at home and abroad have confirmed that many children have no cartilage or joint damage after receiving quinolones. Since the safety of this class of drugs for children has not yet been established, the use of this class of drugs in children should still be avoided, but some indications may be considered in the absence of other more effective and safe antibiotics. The drug can be weighed against the pros and cons.

8 Hepatotoxicity Animals with long-term high doses may have significant hepatotoxicity, especially severe intravenous infusion, hepatic swelling, cholestasis, and even hepatocyte necrosis. FQNS is used clinically. The human body may have elevated biochemical indicators of liver function. Staining of the sclera and skin may also be seen. Occasionally, hepatitis, bile retention, or liver failure may occur. In the presence of norfloxacin, ofloxacin, and ciprofloxacin. Rarely; but ciprofloxacin had 4 outbreaks of hepatic failure in the initial stage of the market, including 2 deaths. The incidence of bile retention intravenous (V1 phase clinical) was 1 in 100 000 cases, orally 0.81 per 100,000 cases. The most serious is trovafloxacin. In 1997, 7 000 pre-approved clinical trials did not show significant liver toxicity. However, approximately 2 million patients received treatment after being listed in 1998, 150 had hepatotoxic symptoms, and at least 14 were acute. Liver failure, 4 of which received liver transplantation and the other 5 died. Hepatotoxicity has been shown to be related to the difluorophenyl group of the parent ring N1 [7]. Hepatic damage manifested as elevated liver function tests, elevated serum transaminases and alkaline phosphatase, and reversal after discontinuation. The order of these reactions was ciprofloxacin>ofloxacin>norfloxacin, and there were fewer reports of other drugs in this area. Therefore, you can't take FQNS drugs for a long time, otherwise it will cause liver damage.

9 The reproductive toxicity of FQNS differs in its reproductive toxicity. After 2 weeks of dosing with pefloxacin 50 mg/kg?, the rate of sperm distortion in mice increased, and the dose increased 10 times, causing testicular atrophy. However, Maoer reported that ofloxacin 270 mg/kg for 26 consecutive weeks does not cause morphological and reproductive changes in male genitalia. The toxicity of high-dose FQNS to the fetus was also obvious. During the period of pregnancy, the rabbits were treated with 160 mg/kg. The daily mortality of ofloxacin was significantly increased compared with the control group. Therefore, when used for treatment or emergency prevention, the course of treatment should not exceed 1 week, and care must be taken with young animals and pregnant animals. Studies have shown that the risk of malformations in pregnant women receiving FQNS drugs (ciprofloxacin, ofloxacin, norfloxacin) does not increase. However, the incidence of miscarriage in women using FQNS drugs appears to have an increasing trend compared with women who received non-teratogenic agents. The literature reports that ofloxacin can cause genital itching, vaginal secretions, abdominal pain, etc. [8]. In addition, FQNS can be secreted into breast milk. Breastfeeding women should stop breastfeeding and should not be used for pregnant women.

10 Achilles tendon Achilles tendinitis and Achilles tendon tear are rare adverse reactions. Most of them are taking Peifloxacin. About half of them are bilateral. If using corticosteroids together, it is more dangerous. Severe cases can cause Achilles tendons. fracture. In Europe, 31 patients with 100 medications had tears associated with Achilles tendons, which could be restored after drug withdrawal (2 weeks to 2 months). No hospitalization or surgery was needed. The French Drug Administration reported in 1992 that 1,050 cases of FQNS caused Achilles tendinitis. The earliest signs were congestion and edema. Achilles tendon lesions were also thought to be related to Mg2+ deficiency. A comparison of the toxicity of ten FQNS drugs to Achilles tendon in rats showed that fleroxacin and pefloxacin were the largest; followed by lomefloxacin, levofloxacin, and sulffloxacin; enoxacin was the smallest, and norfloxacin was the least No toxic reaction with ciprofloxacin [7].

11 Local irritant injections may cause phlebitis, local tissue edema and other reactions. The local irritations are related to the injection speed and drug concentration. Decreasing the drug concentration and slowing down the administration may reduce the occurrence of local irritations. With the wide application of FQNS drugs, FQNS drugs will also occur some uncommon, special adverse reactions, such as parotid glands and breast enlargement, etc., easily ignored. Therefore, the majority of medical personnel should have a profound understanding and proficiency in the characteristics of FQNS adverse drug reactions, not only to ensure that patients use this drug safely, effectively, and reasonably, but also to help capture early signs of adverse drug reactions of FQNS, early detection and early treatment. To avoid or reduce the harm caused by FQNS drug adverse reactions to patients.

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