What Is Nalidixic Acid?
Nalidixic acid is 7-methyl-1-ethyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid and is a pale yellow crystalline powder. Soluble in chloroform, slightly soluble in alcohol and strong lye, almost insoluble in water and ether.
- Chinese name
- Nalidixic acid
- English name
- Nalidixic acid
- nickname
- Nalidixic acid
- Chemical formula
- C12H12N2O3
- Molecular weight
- 232.23500
- CAS Registry Number
- 389-08-2
- Melting point
- 227-229 ° C
- Boiling point
- 413.1ºC
- Water soluble
- 0.1 G / L (23 ºC)
- Density
- 1.331 g / cm3
- Exterior
- White to off-white powder
- Flash point
- 203.6ºC
- Nalidixic acid is 7-methyl-1-ethyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid and is a pale yellow crystalline powder. Soluble in chloroform, slightly soluble in alcohol and strong lye, almost insoluble in water and ether.
Brief introduction of nalidixic acid compounds
Nalidixic acid basic information
- Chinese name: Nalidixic acid
- Chinese alias: 7-methyl-1-ethyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid; naphthyridone acid;
- English name: nalidixic acid
- English alias: uriben; 1,8-Naphthyridine-3-carboxylic acid, 1-ethyl-1,4-dihydro-7-methyl-4-oxo-; 1-ethyl-1,4-dihydro-7-methyl-4 -oxo-1,8-naphthyridine-3-carboxylic acid; uroman; uropan; NOGRAM; Urisal; nalix; 1-Ethyl-1,4-dihydro-7-methyl-4-oxo-1,8-naphthyridine-3- carboxylic Acid; Nalidixic acid; poleon; negram; cybis; uroneg;
- CAS number: 389-08-2
- Molecular formula: C 12 H 12 N 2 O 3
- Structural formula:
- Molecular weight: 232.23500
- Exact mass: 232.08500
- PSA: 72.19000
- LogP: 1.42300 [1]
Nalidixic acid properties
- Appearance and properties: white to off-white powder
- Density: 1.331 g / cm 3
- Melting point: 227-229 ° C (lit.)
- Boiling point: 413.1ºC at 760 mmHg
- Flash point: 203.6ºC
- Water solubility: 0.1 G / L (23 ºC)
- Stability: stable, incompatible with strong oxidants
- Storage conditions: 0-6ºC [1]
Nalidixic acid safety information
- Symbol: GHS07
- Signal Word: Warning
- Hazard statement: H302
- Cautionary statement: P301 + P312 + P330
- Customs code: 2933990090
- WGK Germany: 2
- Danger category code: R40; R42 / 43; R63
- Safety instructions: S22-S36 / 37-S45-S24
- RTECS number: QN2885000
- Dangerous goods mark: Xn [1]
Nalidixic acid molecular structure data
- 1. Molar refractive index: 60.07
- 2. Molar volume (m / mol): 174.4
- 3. Isometric Zhang Rong (90.2K): 484.1
- 4. Surface tension (dyne / cm): 59.3
- 5. Polarizability (10cm): 23.81 [2]
Nalidixic acid calculated chemical data
- 1. Hydrophobic parameter calculation reference value (XlogP): None
- 2.Number of hydrogen-bonded donors: 1
- 3.Number of hydrogen bond acceptors: 5
- 4.Number of rotatable chemical bonds: 2
- 5.Number of tautomers: 5
- 6. Topological molecular polar surface area 70.5
- 7.Number of heavy atoms: 17
- 8.Surface charge: 0
- 9.Complexity: 378
- 10.Number of isotope atoms: 0
- 11. Determine the number of atomic stereocenters: 0
- 12. Uncertain number of atomic stereocenters: 0
- 13. Determine the number of chemical bond stereocenters: 0
- 14. Uncertain number of chemical bond stereocenters: 0
- 15. Number of covalent bond units: 1 [2]
Nalidixic acid production method
- 2-amino-5-methylpyridine is prepared from 2-methylpyridine, and then it is condensed with ethyl orthoformate and diethyl malonate to form N- (2-methyl-5-aminopyridine) methylene malonate Diethyl acid, which is then cyclized at 260-270 ° C and then added to a dilute solution of sodium hydroxide for hydrolysis to obtain 7-methyl-1,8-naphthyridin-4-hydroxy-3-hydroxy acid. Finally, it is N-alkylated with ethyl bromide and isomerized to form nalidixic acid. [1]
Nalidixic acid uses
- Quinolones. [1]
Nalidixic acid pharmacopoeia standard
() Nalidixic acid source (molecular formula) and standard
- This product is 7-methyl-1-ethyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid. Calculated on dry basis, containing C12H12N2o3 shall not be less than 98.0%. [3]
Naphthyridine acidic
- This product is light yellow crystalline powder; almost odorless and slightly bitter. Dissolved in chloroform, slightly soluble in ethanol, very slightly soluble in ether, almost insoluble in water; soluble in sodium hydroxide or sodium carbonate solution. [3]
Nalidixic acid
The melting point of this product (Appendix VI C) is 226 to 231 ° C. [3]
Nalidixic acid check
- Clarity of the solution
- Take 1.0g of this product and add 10ml of sodium carbonate test solution to dissolve, the solution should be clear.
Loss on drying <br Take this product and dry it to constant weight at 105 , and the weight loss should not exceed 0.5% (Appendix L).
Ignition residue <br /> Take 1.0g of this product and inspect it according to law (Appendix N). The residual residue should not exceed 0.2%.
Heavy metals < br Take the residue left under the item of burning residue and inspect it in accordance with law (Appendix H second method). The content of heavy metals must not exceed 20 parts per million. [3]
Nalidixic acid identification
- (1) Take about 10mg of this product, add 1ml of water and 1ml of sulfuric acid to dissolve, add about 10mg of vanillin, heat and boil for 2 minutes, the solution changes from yellow to red, and a yellow precipitate precipitates.
(2) Take this product, add 0.4% sodium hydroxide solution to make a solution containing 5g per 1ml, and measure it by spectrophotometry (Appendix IV A). It has maximum absorption at the wavelengths of 258 and 332nm. [3]
Determination of nalidixic acid
- Take about 0.3g of this product, accurately weigh, place in a conical flask with a stopper, add 25ml of sodium hydroxide titration solution (0.1mol / L), tightly stopper, shake to dissolve, add a few drops of phenolphthalein indicator solution, use Titrate hydrochloric acid (0.1 mol / L), and correct the results of the titration with a blank test. Each 1ml of sodium hydroxide titration solution (0.1mol / L) is equivalent to 23.22mg of C12H12N2O3. [3]
Nalidixic acid category
- Antibacterials. [3]
Nalidixic acid dose
- Oral once 0.5 1g 1.5 3g a day [3]
Nalidixic acid
- Pregnant women, young children and those with liver and kidney dysfunction should be used with caution; newborns should not use it. [3]
Nalidixic acid storage
- Keep tightly closed.
Nalidixic acid preparation
- Nalidixic acid tablets [3]
Nalidixic acid pharmacology and toxicology
- This product is the first generation of quinolone antibiotics, and has antibacterial activity against some strains of Escherichia coli, Klebsiella, Proteus, Shigella, Salmonella, Enterobacter and Haemophilus influenzae. It also has antibacterial activity against Neisseria gonorrhoeae, but has no antibacterial activity against Gram-positive cocci such as Pseudomonas, Acinetobacter and Staphylococcus. This product is a bactericide, and its pH has no effect on its effect. [4]
- Moderate photosensitivity caused by the drug
Nalidixic acid kinetics
- After oral administration, it is rapidly absorbed from the gastrointestinal tract, and part of it is metabolized in the liver to hydroxylated naphthyl acid, which is similar to nalidixic acid, and is rapidly excreted by the kidneys. This product is excreted in the urine as a prototype and metabolites. Other metabolites include glucuronic acid and dicarboxylic acid derivatives combined with nalidixic acid, hydroxylated nalidixic acid. Hydroxynalidixic acid accounts for 30% of the biological activity of the drug in the blood and 85% of the activity in the urine
- Drug-bound plasma proteins
- The peak concentration in plasma 2 hours after oral administration of 1 g is 20-50 mg / L, and the blood elimination half-life (t1 / 2?) Is about 1 to 2.5 hours. The plasma protein binding rate of nalidixic acid was 93%, and the plasma protein binding rate of hydroxylated nalidixic acid was 63%. The peak concentration (Cmax) in urine was 150 to 200 mg / L 3 to 4 hours after the administration, and t1 / 2 was about 6 hours. About 4% of this product is excreted in feces and can also be secreted from milk. The product can penetrate the placental barrier. [4]
Nalidixic acid indication
- This product is suitable for urinary tract infections caused by sensitive Gram-negative bacilli, such as Escherichia coli, Klebsiella, Proteus, Enterobacter and so on. Because Escherichia coli is more common in those who are resistant to it, the drug should be selected based on drug sensitivity results. [4]
Nalidixic acid usage dosage
- Adult dosage is 0.5 to 1 g each time, 3 times a day, and the course of treatment is 1 to 2 weeks. [4]
Nalidixic acid adverse reactions
- 1. Gastrointestinal reaction: nausea, vomiting, diarrhea, abdominal pain.
- 2. Central nervous system reaction: lethargy, weakness, headache, dizziness and dizziness.
- 3. Allergic reactions: rash, pruritus, urticaria, angioedema, eosinophilia, joint pain with joint stiffness and swelling, and other allergic reactions. Photosensitive reactions can occur when directly exposed to sunlight.
- 4. Other: rare cholestasis, paresthesia, metabolic acidosis, thrombocytopenia, granulocytopenia, or hemolytic anemia. [4]
Nalidixic acid contraindications
- Patients who are allergic to this product and have a history of convulsions are contraindicated. [4]
Nalidixic acid matters needing attention
- 1. Use this product with caution in patients with liver disorders, renal insufficiency, epilepsy and severe cerebral arteriosclerosis.
- 2. This product should be taken with food and drink, and should not be taken with antacids.
- 3 Moderate or severe photosensitivity can occur when taking this product. Avoid excessive exposure to sunlight. If photosensitivity occurs, discontinue the drug.
- 4 Glucose-6-phosphate dehydrogenase (G-6PD) deficiency patients taking this product, occasionally a hemolytic reaction may occur.
- 5. Those who take this product continuously for more than 2 weeks should monitor blood, liver and kidney function. [4]
Nalidixic acid for pregnant and lactating women:
- When the dosage of this product reaches 6 times the human dosage, it has teratogenic effect on rats. This product can prolong pregnancy during 4 times the clinical dose. However, appropriate, well-controlled studies have not been conducted in pregnant women. This product, like other quinolone drugs, can cause joint cartilage damage in immature animals and should not be used in pregnant women. This product can be secreted through milk, and because of the potential for serious adverse effects of such drugs on newborns, infants and young children, nursing mothers should avoid using this product or stop breastfeeding during application. [4]
Nalidixic acid for children
- The safety and effectiveness of the product in infants under 3 months have not been determined. Toxicity studies have shown that this product and related drugs can cause cartilage damage and other joint lesions in most of the immature animals tested. Therefore, this product is not suitable for adolescents and children under 18 years of age. [4]
Nalidixic acid for elderly patients
- Elderly patients often have renal dysfunction, because the product is mainly excreted through the kidney, it is necessary to reduce the application. [4]
Nalidixic acid interaction
- 1. The combination of the product and theophylline can cause the latter's blood concentration to increase, and the adverse effects of theophylline appear. Therefore, the concentration of theophylline should be monitored and the dosage should be adjusted when combined.
- 2. This product interferes with the metabolism of caffeine, which can lead to reduced caffeine clearance and prolonged plasma t1 / 2.
- Pyelonephritis
- 4. This product should not be used in combination with furantoin, the two antagonize each other.
- 5. Multivitamins, or other iron- and zinc-containing preparations and antacids containing aluminum or magnesium can reduce the oral absorption of this product, resulting in a decrease in urine concentration. Do not take them at the same time. If you can't avoid it, take at least the interval between taking the product 2 hours.
- 6. Combined with cyclosporine, it can increase its blood concentration. It is necessary to monitor the cyclosporine blood concentration and adjust the dose.
- 7. Combined with melphalan will increase gastrointestinal toxicity. [4]
Nalidixate overdose
- Overdose of this product may cause mental disorders, convulsions, increased intracranial pressure, metabolic acidosis, nausea, vomiting and lethargy. Due to the rapid excretion of the drug, the duration of the reaction is short (2 to 3 hours). If an overdose of the drug is found early, vomiting or gastric lavage should be performed to promote gastric emptying. If the drug has been absorbed, it can increase the amount of fluid replacement to accelerate excretion, and carefully observe the changes in the condition. Treat symptomatically and supportively. [4]
Nalidixic acid treatment case
- Pyelonephritis (pyelonephritis) refers to inflammation of the renal pelvis, most of which are caused by bacterial infections, usually accompanied by inflammation of the lower urinary tract, which is not easily distinguished clinically. According to the clinical course and disease, pyelonephritis can be divided into acute and chronic phases. Chronic pyelonephritis is an important cause of chronic renal insufficiency. Western medicine recommends the use of antibiotics for adjuvant treatment of pyelonephritis, penicillins: penicillin V, ampicillin, chloramphenicol, and amikacin. And quinolone drugs, such as nalidixic acid.
- Acute pyelonephritis lesions can be unilateral or bilateral, localized or extensive, and can be mild or severe, with only those involving the pelvis mucosa. In severe cases, the kidney is swollen, and mucosal congestive ulcers are seen on the cut surface, and small abscesses are formed. If there is obstruction, the kidney is widened. In a few severe patients, necrosis of the renal nipples and cones can be seen. Necrotic tissue is discharged with the urine and is called necrotizing papillitis. Microscopically, renal interstitial edema and neutrophil infiltration can be seen under the microscope. . Chronic pyelonephritis The renal pelvis and calves have chronic inflammation. Enlargement and deformity of the renal pelvis, scar formation in the renal cortex and papilla, shrinkage of the kidneys compared to normal, often asymmetric lesions on both sides, deformation of the renal medulla, enlargement of the renal pelvis and mucosa and ureteral wall, severe renal atrophy in severe cases.
Clinical manifestations of nalidixic acid
- (1) Acute pyelonephritis This disease can occur at various ages, but it is most common in women of childbearing age. The onset of illness is mainly caused by the following symptoms. 1. General symptoms of high fever and chills, body temperature is mostly between 38 to 39 , but also up to 40 . The heat type is different, it is generally relaxation type, and it can also be intermittent or retentive. With headache, sore body, but sweating when the fever retreats.
- 2. Patients with urinary symptoms have low back pain, mostly dull pain or soreness, to varying degrees, and a few have abdominal cramping energy, which radiates along the ureter toward the bladder. At the time of physical examination, the upper ureter point (the outer edge of the rectus abdominis and the umbilical flat line) Crossing point) or rib waist point (cross point of the psoas major muscle and the twelve ribs) with tenderness and positive renal palpitation. Patients often have urinary bladder irritation symptoms such as frequent urination, urgency, and dysuria. In the morning, a sexual infection may precede systemic symptoms. Children's urinary system symptoms are often not obvious. In addition to systemic symptoms such as high fever, onset of seizures and seizures are common.
- 3. Gastrointestinal symptoms may include loss of appetite, nausea, and vomiting, and individual patients may have mid-upper or total abdominal pain.
- (2) Chronic pyelonephritis symptoms are milder than the acute phase, and can sometimes manifest asymptomatic urine. More than half of the patients had a previous history of acute pyelonephritis, followed by symptoms such as fatigue, low fever, anorexia, and backache and back pain, accompanied by lower urinary tract irritation such as frequent urination, urgency, and dysuria. Acute episodes also appear from time to time. In the past, those who had a disease course of more than six months or one year were regarded as chronic pyelonephritis. In recent years, it has been proposed that scars formed in the renal pelvis and renal pelvis. Intravenous pyelography, the deformation of the renal pelvis, hydronephrosis, and the appearance of the kidneys are not smooth, or the size of the two kidneys is different Called chronic pyelonephritis. There may be impairment of renal tubular function, such as reduced concentration, hypotonicity, low specific gravity urine, increased nocturia, and renal tubular acidosis. In the later stages, glomerular function impairment can occur, with azotemia up to uremia. Renal hypertension is mostly caused by chronic pyelitis. It is generally believed that patients with hyperreninemia and the release of some vasoconstrictor peptides are related to diseases such as vascular sclerosis and stenosis. In a few patients, hypertension was improved after one side of the kidney was removed.
- Single cells in petri dishes
Nalidixic acid treatment
- (A) general treatment
- The purpose is to relieve symptoms, prevent recurrence, and reduce renal parenchymal damage. Patients should be encouraged to drink more water and urinate frequently to reduce the medulla osmotic pressure, improve the body's phagocytic function, and flush out the cells in the bladder. Patients should generally be encouraged to drink more water and urinate frequently to reduce the osmotic pressure of the medulla and improve the phagocytic function of the body. Have fever and other symptoms of systemic infection should stay in bed. Taking 1 g of sodium bicarbonate 3 times a day can alkalinize urine, reduce bladder irritation and irritation, and enhance the efficacy of aminoglycoside antibiotics, penicillin, erythromycin and sulfonamide, nalidixic acid, etc. So that the efficacy of tetracycline and furanidine is reduced. Those with predisposing factors should be treated, such as kidney stones and ureteral deformities. Anti-infection treatment is best performed in urine bacterial culture and drug sensitivity tests.
- (Two) anti-infective treatment
- 1. The main bacteria causing urinary tract infection due to acute pyelonephritis are Gram-negative bacteria, of which E. coli is the main. For the first episode of acute pyelonephritis, you can choose 2 tablets of compound sulfamethoxazole (SMZ-TMP), 2 times a day, or 0.5 g of pipic acid, 3 to 4 times a day, 0.2 g of norfloxacin, 3 times a day. The course of treatment is 7 to 14 days. Severe infection with sepsis should be administered intravenously. Select sensitive drugs according to the results of urine culture. For example, cefoperazone and amikacin toxin are more than 90% sensitive to Staphylococcus, Klebsiella, Proteus, Pseudomonas aeruginosa, and E. coli. The former is 1 to 2 g, once every 8 to 12 hours, and the latter is 0.4 g, once every 8 to 12 hours. Fluoroquinolones are more than 80% sensitive to Proteus, Citrobacter and Klebsiella. Piperacillin, ampicillin, and furoxetine are 100% sensitive to group D enterococci. Usage, the former 2 1-2, once every 6 o'clock; the latter 0.1g, 3 times a day. Fungal infection with ketoconazole 0.2g, 3 times a day. Or fluconazole 50mg, 2 times a day.
- Acute pyelonephritis in newborns, infants, and children under 5 years of age is mostly associated with urinary tract malformations and dysfunction, so it is not easy to eradicate, but some functions
- Pyelonephritis
- 2. The author of acute pyelonephritis with acute pyelonephritis should be treated according to acute pyelonephritis. Authors with repeated episodes should use urine bacterial culture and determine the bacterial type to determine whether the recurrence is relapse or reinfection.
- Relapse: means that the strain becomes negative after treatment, but recurs within 6 weeks after discontinuation, and the pathogenic bacteria are exactly the same as the previous infection. Common causes of recurrence are anatomical or functional abnormalities of the urinary tract, causing poor urinary flow. Can be confirmed by intravenous pyelography or retrograde pyelography, if there are obvious anatomic abnormalities, surgery needs to be corrected. If the obstruction factor is difficult to be removed, the appropriate antibacterial agent is selected for 6 weeks according to the drug sensitivity. Improper selection of antibiotics or insufficient dosage and course of treatment often leads to recurrence. Drugs can be selected according to drug sensitivity and treated for 4 weeks. Because of scar formation, poor blood flow, and insufficient antibacterial concentration in the lesion, a larger dose of bactericidal antibacterials such as vanillin, ampicillin, oxybenzyl penicillin, and B gene closomycin can be tried for 6 weeks .
- If the urinary sensation occurs 3 or more times within one year, it is also called recurrent urinary sensation. Long-range low-dose treatment can be considered. Generally choose low-toxicity antibacterial drugs, such as compound sulfamethoxazole or furantantin one tablet per night, take 1 year or longer, about 605 patients with bacteriuria turned negative. For men who have recurrence due to prostatitis, they should be treated with chronic prostatic prostatitis at the same time. They should choose fat-soluble antibacterial drugs such as compound sulfamethoxazole; ciprofloxacin 0.5g, twice a day; The course of treatment should be as long as 3 months. If necessary, surgically remove the diseased (proliferative, tumor) prostate.
- If urinary bacteria continue to be positive after two courses of adequate antibacterial therapy, long-range low-dose therapy can be considered. Generally, the combination of Xinnuoming or Furan once a night can be taken for 1 year or longer, about 60% of patients with negative bacteria.
- Re-infection: refers to the infection caused by the invasion of the urinary tract by another pathogenic bacterium that is different from the previous one after the bacteriuria turns negative, and it usually reappears 6 weeks after the bacteriuria turns negative. Women with recurrent urinary sensations, 85% are reinfected, can be treated according to the treatment method of the first episode, and patients are advised to pay attention to the prevention of urinary sensations. At the same time, a comprehensive inspection should be performed to remove any susceptible factors.
Nalidixic acid specifications
- 0.25g
Nalidixic acid storage
- Keep sealed.