Generic name of drug: Micronomicin Sulfate Injection Product name: English name: micronomicin sulfate injection Chinese Pinyin: Liusuan Xiaonuomeisu Zhusheye The main component of this product is micronomicin sulfate, and its chemical name is O-2- amino -2,3,4,5- tetradeoxy -5- (methylamino) -2-d- erythro-hexyl. -L- arabinopyranosyl -( 1→6)-2- deoxy-d-streptamine sulfate. Its chemical structural formula is: molecular formula: c20h41n5o7.5/2h2so4 molecular weight: 708.76. This product is a colorless or almost colorless clear liquid. Pharmacology and Toxicology 1. Pharmacology: This product is aminoglycoside antibiotics. The antibacterial spectrum is similar to that of gentamicin, and it has antibacterial effect on gram-negative bacteria such as Escherichia coli, aerogenes, Klebsiella, Proteus mirabilis, some indole-positive Proteus, Pseudomonas aeruginosa, some Neisseria, some Serratia pigmentosa and Shigella. Among gram-positive bacteria, staphylococcus aureus (including production? Lactamase strain) is sensitive to this product; Streptococcus (including pyogenic streptococcus, pneumococcus, fecal streptococcus, etc.) are resistant to this product. Anaerobic bacteria (Bacteroides), mycobacterium tuberculosis, rickettsia, viruses and fungi are also resistant to this product. This product is stable to aminoglycoside acetyltransferase AAC(6') produced by bacteria, so it still has antibacterial activity to bacteria resistant to kanamycin, gentamicin, amikacin and ribomycin due to the production of this enzyme. The minimum inhibitory concentration of this product is 0.1~ 6.25mg/L. The mechanism of action of this product is to bind to the 30S subunit of bacterial ribosome and inhibit the synthesis of bacterial protein. 2. Toxicology: Acute toxicity: LD50 of this product for intravenous injection is 78.9mg/kg, and LD50 for intramuscular injection is 28619.7 mg/kg. Chronic toxicity: male healthy Wistar rats (weighing 200±20g) were tested. The results showed that the animals could survive for 30 days even after intramuscular injection of this product (156 mg/kg). Although animals sometimes suffer from malaise and loss of appetite 7 ~10 days after injection, the reaction improved at the later stage of injection, and the activity returned to normal after drug withdrawal. Nephrotoxicity: The research results of the Pharmacology Department of Nanjing Medical College show that the nephrotoxicity of this product is slight. When given in a large dose (156 mg/kg), only the renal epithelial cells have obvious vacuolation, and other animals have no special lesions. After using this product, the hearing and vestibular function of dolphins and rats (10) have not changed, and the animals are put to cochlear implantation. In the other three, only a few cochlear hair cells were necrotic (10, 10, 17 respectively). Pharmacokinetics This product is well absorbed by intramuscular injection. After intramuscular injection of 60mg and 120mg, the plasma peak concentration (Cmax) was 4.671.00 mg/L and 9.60 3.86 mg/L, respectively, and the time to peak (tmax) was 0.67 hours and 0.75 hours, respectively, and the blood elimination half-life (t/kloc) ) 2.34 hours and 2.63 hours respectively. This product was dripped at a constant speed of 60mg/ hour. The average blood concentration in half an hour was about 2.54 mg/L, the peak blood concentration (Cmax) was 4.75 0.65 mg/L, and the blood elimination half-life (t 1/2? ) about 2.5 hours. This product is widely distributed in various body fluids and tissues after absorption, but its concentration in bile juice is low. This product is mainly excreted in urine, and 60 ~ 70% of the dosage is excreted 6 ~ 8 hours after administration. When renal function declines, the amount of urine excretion decreases. This product can enter fetal umbilical cord and amniotic fluid, but the concentration is only half of the maternal concentration; The concentration in milk is about 15% of the maternal concentration. No active metabolites were found in urine. Indications This product is mainly used for respiratory tract, urinary tract, abdominal cavity and traumatic infection caused by gram-negative bacilli such as Escherichia coli, Klebsiella, Proteus, Enterobacter, Serratia, Pseudomonas aeruginosa, etc. It can also be used for septicemia. Usage and dosage intramuscular injection or intravenous drip after dilution. Adult intramuscular injection: 60 ~ 80 mg once, 120 mg if necessary, 2 ~ 3 times a day; Intravenous drip: 60mg at a time, add sodium chloride injection 100ml and drip at a constant speed, and finish dripping at 1 hour. Children are given drugs in 2 ~ 3 times according to their body weight of 3 ~ 4 mg/kg. Adverse reactions1.Common hearing loss, tinnitus or ear fullness (ototoxicity), hematuria, significantly decreased urination times or urine volume, loss of appetite, extreme thirst (nephrotoxicity), unsteady gait, dizziness (ototoxicity, vestibular influence), nausea or vomiting (ototoxicity, vestibular influence, nephrotoxicity). 2. Rare allergic reactions such as vision loss (optic neuritis), dyspnea, lethargy, extreme weakness (neuromuscular block), rash, hemogram changes, liver function changes, digestive tract reactions and injection site pain, induration, phlebitis, etc. 3. Anaphylactic shock is rare. Contraindications1.It is forbidden for those who are allergic to this product or other aminoglycosides and bacitracin, or those who have deafness or other deafness caused by the use of streptomycin. 2. People with renal failure are prohibited. Precautions1.Use with caution in patients with renal insufficiency, abnormal liver function, vestibular function or hearing loss, dehydration, myasthenia gravis or Parkinson's disease and elderly patients. 2. The medication time should generally not exceed 14 days. If medication must be continued, the hearing organ and renal function should be closely monitored. 3. Cross allergy. Patients who are allergic to aminoglycoside antibiotics such as streptomycin and gentamicin may be allergic to this product. 4. When conditions permit, the blood drug concentration should be monitored during the course of treatment, and the dosage should be adjusted accordingly. If the blood drug concentration cannot be determined, the dosage should be adjusted according to the measured creatinine clearance rate, especially for patients with renal dysfunction, premature infants, newborns, infants or elderly patients, shock, heart failure, ascites or severe water loss. 5. This product is generally only for intramuscular injection; After dilution, it can be intravenously dripped; But it can't be injected intravenously to avoid neuromuscular block and respiratory inhibition. 6. Long-term use of this product may lead to excessive growth of drug-resistant bacteria. 7. Patients should be given enough water to reduce renal tubular damage. Pregnant women and lactating women take medicine 1. This product can enter fetal umbilical cord and amniotic fluid, and its concentration is about half that of the mother, so it is forbidden for pregnant women. 2. The concentration of this product in milk is about 15% of the maternal concentration, so lactating women should stop breastfeeding when using this product. Children's medication Premature infants, newborns and infants should use this product with caution. If this product is used, the dosage should be adjusted according to the blood concentration or creatinine clearance rate. Elderly patients should use drugs according to the reduction of renal function. This product is prohibited for elderly patients. Drug interaction1.This product can increase ototoxicity, nephrotoxicity and neuromuscular blockade when used in the same way as other aminoglycosides or after continuous local or systemic application. Hearing loss may occur, and it may still progress to deafness after stopping taking drugs; Hearing impairment may be restored or permanent. Neuromuscular block can lead to skeletal muscle weakness, respiratory depression or respiratory paralysis (apnea), and anticholinesterase drugs or calcium salts are helpful to restore the block. 2. This product combined with neuromuscular blocking drugs can aggravate neuromuscular blocking effect, leading to muscle weakness, respiratory depression or respiratory paralysis (apnea). Combined with plasma substitute drugs such as dextran, sodium alginate, diuretics such as itaconic acid, furosemide, capreomycin, cisplatin, vancomycin, etc., or successively applied locally or systemically, ototoxicity and nephrotoxicity may be increased, and hearing damage may occur, and deafness may still develop after drug withdrawal, and hearing damage may be restored or permanent. 3. Local or systemic use of this product with cefotaxime may increase nephrotoxicity. 4. This product can be used together with polymyxin, or applied locally or systemically successively, because it can increase nephrotoxicity and neuromuscular block, which can lead to skeletal muscle weakness, respiratory depression or respiratory paralysis (apnea). 5. This product should not be combined with other nephrotoxicity or ototoxicity or applied successively, so as not to aggravate the nephrotoxicity or ototoxicity. 6. This product should not be combined with amphotericin B, cefotaxime sodium, nitrofurantoin sodium, sulfadiazine sodium and tetracycline hydrochloride (all of which are injections), because there may be incompatibility. 7. Synergy can often be obtained when this product is used with β lactams (cephalosporins or penicillins). 8. Mixing this product with β-lactams (cephalosporins or penicillins) can lead to mutual inactivation, and it must be dripped in different bottles when it needs to be used together. Excessive long-term or large-dose use of this product can cause proteinuria, tubular urine, irreversible hearing loss and neuromuscular block. Due to the lack of specific antagonists, symptomatic therapy and supportive therapy are mainly used.