What Is Chloramphenicol?
Chloramphenicol is white or colorless needle-like or flaky crystals, melting point 149.7 ~ 150.79C, easily soluble in methanol, ethanol, propanol and ethyl acetate, slightly soluble in ether and chloroform, insoluble in petroleum ether And benzene. Chloramphenicol is extremely stable, and its aqueous solution will not lose its effect after boiling for 5h. Chloramphenicol molecule contains para-nitrophenyl group, propylene glycol and dichloroacetamide group. Because chloramphenicol has 2 asymmetric carbon atoms, chloramphenicol has 4 optical isomers, of which only the L-isomer has antibacterial ability. [1]
- CAS number: 56-75-7
- MDL number: MFCD00078159
- EINECS number: 200-287-4
- RTECS number: AB6825000
- BRN number: 2225532
- PubChem number: [2]
- 1. Properties: white or yellowish with green needle-like crystals.
- 2. Density (g / mL, 25/4 ): 1.474
- 3. Relative vapor density (g / mL, air = 1): not determined
- 4. Melting point (ºC): 150.5-151.5 (149.7-150.7 ). Sublimation under high vacuum.
- 5. Boiling point (ºC, normal pressure): Not determined
- 6. Boiling point (ºC, 5.2kPa): Not determined
- 7. Refractive index: Not determined
- 8. Flash point (ºC): Not determined
- 9. Specific rotation (º): 19.5 ° (c = 6, EtOH).
- 10. Spontaneous ignition point or ignition temperature (ºC): Not determined
- 11. Vapor pressure (kPa, 25ºC): Not determined
- 12. Saturated vapor pressure (kPa, 60ºC): Not determined
- 13. Combustion heat (KJ / mol): Not determined
- 14. Critical temperature (ºC): Not determined
- 15. Critical pressure (KPa): Not determined
- 16. Logarithm of oil-water (octanol / water) partition coefficient: not determined
- 17. Upper explosion limit (%, V / V): Not determined
- 18. Lower explosion limit (%, V / V): Not determined
- 19. Solubility: slightly soluble in water (2.5mg / ml, 25 ), slightly soluble in propylene glycol (150.8mg / ml), easily soluble in methanol, ethanol, butanol, ethyl acetate, acetone, insoluble in ether, Benzene, petroleum ether, vegetable oil. [2]
- 1. Molar refractive index: 72.55
- 2. Molar volume (m3 / mol): 208.8
- 3. Isometric Zhang Rong (90.2K): 595.5
- 4. Surface tension (dyne / cm): 66.1
- 5. Polarizability (10-24cm3): 28.76 [2]
- 1. Hydrophobic parameter calculation reference value (XlogP): None
- 2.Number of hydrogen-bonded donors: 3
- 3.Number of hydrogen bond acceptors: 5
- 4.Number of rotatable chemical bonds: 5
- 5.Number of tautomers: 2
- 6. Topological molecular polar surface area 115
- 7.Number of heavy atoms: 20
- 8.Surface charge: 0
- 9.Complexity: 342
- 10.Number of isotope atoms: 0
- 11. Determine the number of atomic stereocenters: 2
- 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]
- Customs Code: 2941400000
- Dangerous Goods Transport Code: 2811
- WGK Germany: 3
- Danger category code: R45
- Safety instructions: S53-S45
- RTECS number: AB6825000
- Dangerous goods mark: T
- Countries around the world have conducted a lot of research on the production methods of chloramphenicol, and they are summarized as follows:
- (1) p-nitroacetophenone method;
- (2) Styrene method;
- (3) cinnamyl alcohol method;
- (4) p-nitrocinnanol method;
- (5) p-nitrobenzaldehyde method. The p-nitroacetophenone method is used in our country.This method involves nitrification of ethylbenzene; oxidation; bromination; salt formation; hydrolysis; acetylation; addition; reduction; decomposition; disassembly; dichloroacetylation to obtain chloramphenicol. .
- The synthesis uses p-nitroacetophenone as a raw material, brominates to form p-nitro--bromoacetophenone, forms a salt with cyclohexamethylenetetramine, and hydrolyzes p-nitro--aminobenzene with hydrochloric acid. Ethyl ketone hydrochloride, acetylated with acetic anhydride, and then condensed with formaldehyde, methylolated to obtain p-nitro--acetamino--hydroxyphenylacetone, reduced with aluminum isopropoxide to obtain (±) suaraose Type-1-p-nitrophenyl-2-acetaminopropanediol, hydrolyzed to remove the acetyl group, and neutralized with a base to obtain (±) suarose-1- p-nitrophenyl-2-aminopropanediol (amino Material), and then resolved by the induced crystallization method to obtain D (-)-sucrose amino group, and finally obtained by dichloroacetylation.
- For the treatment of infections caused by typhoid, dysentery, Escherichia coli, influenza bacillus, brucella, pneumococcus, etc. [2]
- Column Active Phase Temperature (° C) Retention Index (I) References
- Packed column SE-30 2310. Perrigo and Peel, 1981
- Column Active Phase Temperature (° C) Retention Index (I) References
- Methyl Silicone 2310. Ardrey and Moffat, 1981
- Chloramphenicol antibiotics can act on the 50S subunit of bacterial ribonucleoproteins and hinder protein synthesis. They are bacteriostatic broad-spectrum antibiotics.
- The 70S ribosome of bacterial cells is the main cellular component of protein synthesis. It includes 50S and 30S subunits. Chloramphenicol reversibly interacts with
- 1 description of necessary first aid measures
- General advice: Ask your doctor. Present this safety data sheet to the doctor present.
- Inhalation: If inhaled, remove patient to fresh air. If not breathing, give artificial respiration. Ask your doctor.
- Skin contact: Rinse with soap and plenty of water. Ask your doctor.
- Eye contact: Wash eyes with water as a precaution.
- Ingestion: Never give anything by mouth to an unconscious person. Rinse mouth with water. Ask your doctor.
- 2 Major symptoms and effects, acute and delayed effects
- Nausea, headache, vomiting
- 3 Instructions and instructions for timely medical treatment and special treatment required
- No data available [3]
- 1 Fire extinguishing medium
- Fire extinguishing method and fire extinguishing agent
- Extinguish with water spray, alcohol-resistant foam, dry powder or carbon dioxide.
- 2 Special hazards arising from the substance or mixture
- Carbon oxides, nitrogen oxides, hydrogen chloride gas
- 3 Advice for firefighters
- If necessary, wear self-contained breathing apparatus to fight fire.
- 4 Further information
- No data
- 6. Leak emergency treatment
- 1 Protective measures for workers, protective equipment and emergency procedures
- Use personal protective equipment. Avoid dust formation. Avoid breathing vapor, fumes or gases. Ensure adequate ventilation.
- Personnel are evacuated to a safe area. Avoid breathing dust.
- 2 Environmental protection measures
- Where safety is ensured, measures can be taken to prevent further leakage or spillage. Do not allow product to enter drains.
- 3 Methods and materials for containment and cleaning up of spilled chemicals
- Do not generate dust during collection and disposal. Sweep and shovel. Put in a suitable closed container for processing.
- 4 Reference to other sections
- Refer to Section 13 for disposal.
- 7. Handling and storage
- 1 Precautions for safe operation
- Avoid exposure: Special instructions are required before use. Avoid the formation of dust and aerosols.
- Provide appropriate exhaust equipment where dust is generated.
- 2 Conditions for safe storage, including any incompatibilities
- Store in a cool place. Keep container tightly closed in a dry and well-ventilated place.
- Sensitive to light
- 3 Specific uses
- No data
- 8. Exposure controls and personal protection
- 1 Allowable concentration
- Maximum allowable concentration
- 2 Exposure controls
- Appropriate technical controls
- Handle in accordance with good industrial hygiene and safety practices. Wash hands before breaks and at the end of work.
- Personal protective equipment
- Eye / face protection
- Safety glasses with protective side shields meet the requirements of EN166 Please use official standards such as NIOSH (US) or EN 166 (EU)
- Detection and approval of equipment for eye protection.
- Skin protection
- Gloves and gloves must be inspected before use.
- Please use appropriate methods to remove gloves (do not touch the outer surface of the gloves), and avoid any skin parts to contact this product.
- After use, please handle the contaminated gloves carefully in accordance with relevant laws and regulations and effective laboratory regulations and procedures. Wash and dry your hands
- The protective gloves chosen must comply with the EU's 89/686 / EEC regulations and the EN 376 standard derived from them.
- Full contact
- Material: Nitrile
- Minimum layer thickness of 0.11 mm
- Solvent penetration time: 480 min
- Dermatril® (KCL 740 / Z677272, size M) tested
- Splash protection
- Material: Nitrile
- Minimum layer thickness of 0.11 mm
- Solvent penetration time: 480 min
- Dermatril® (KCL 740 / Z677272, size M) tested
- , Test method EN374
- If used in a solvent or mixed with other substances, or under conditions other than those specified in EN374, please contact the supplier of the EC approved gloves. This recommendation is only advisory and must be evaluated by an industrial hygienist who is familiar with the specific situation our customers plan to use. This should not be interpreted as providing approval for any specific use case method.
- Body protection
- The type of impervious clothing and protective equipment must be selected according to the concentration and amount of dangerous substances in the specific workplace.
- Respiratory protection
- If the risk assessment shows that air-purifying respirators are required, please use full-face multifunctional particulate respirators N100 (US) or P3 (EN143) respirators as candidates for engineering control. If the gas mask is the only way to protect, use a full-face supply air mask. Respirators use respirators and parts that have been tested and passed government standards such as NIOSH (US) or CEN (EU). [3]
- 1 Information on toxicological effects
- Acute toxicity
- LD50 Oral-Rat-2,500 mg / kg
- Half-lethal dose (LD50) intraperitoneally-rat-1,811 mg / kg
- Half-lethal dose (LD50) intraperitoneally-mouse-1,100 mg / kg
- Skin irritation or corrosion
- No data
- Eye irritation or corrosion
- No data
- Respiratory or skin irritation
- Prolonged or repeated exposure causes individual allergic reactions
- Germ cell mutagenicity
- Laboratory tests show mutagenic effects
- Cell Mutation-In Vitro-Rat-Liver
- DNA damage
- Cell Mutation-In Vivo-Mice-Intraperitoneal
- Cytogenetic analysis
- Carcinogenicity
- This product is or contains a component that is listed as a possible carcinogen by IARC, ACGIH, EPA, and NTP
- Possible human carcinogen
- IARC: 2A-Group 2A: May be carcinogenic to humans (Chloramphenicol)
- Reproductive toxicity
- No data
- Specific target organ system toxicity (single exposure)
- No data
- Specific target organ system toxicity (repeated exposure)
- No data
- Aspiration hazard
- No data
- Potential health effects
- May be harmful if inhaled. May cause respiratory irritation.
- Ingestion is harmful if swallowed.
- Absorption through the skin can be harmful. May cause skin irritation.
- Eyes may cause eye irritation.
- Signs and symptoms after exposure
- Nausea, headache, vomiting
- Additional information
- Registration of Toxic Effects of Chemical Substances: AB6825000
- 1 Ecotoxicity
- Toxicity to daphnia and other aquatic invertebrates
- EC50-Daphnia magna (Water flea)-345 mg / l-48 h
- 2 Persistence and degradability
- No data
- 3 Potential bioaccumulative
- No data
- 4 Mobility in soil
- No data
- 5 Evaluation of PBT and vPvB results
- No data
- 6 Other adverse effects
- No data
- The product passes the remaining and non-recyclable solution to a licensed company for disposal. Compatible with or mixed with flammable solvents, burned in chemical incinerators with post-combustion treatment and scrubbing effects. Contaminated containers and packaging are disposed of as unused products.
- Source (name), content (potency)
- This product is D-threo-(-)-N- [- (hydroxymethyl) --ihydroxy-p-nitrophenethyl] -2,2-dichloroacetamide. Calculated based on dry products, C11H12Cl2N2O5 should be 98.0% to 102.0%.
- Character
- This product is white to slightly yellowish green needle-like, long plate-like crystal or crystalline powder; bitter.
- This product is easily soluble in methanol, ethanol, acetone or propylene glycol, and slightly soluble in water.
- Melting point
- The melting point of this product (Appendix VIC of Part Two of the 2010 Pharmacopoeia) is 149 to 153 ° C.
- Specific rotation
- Take this product, weigh it accurately, add absolute ethanol to dissolve and quantitatively dilute it to make a solution containing about 50mg per 1ml, and measure it according to the law (Appendix VI E of the Pharmacopoeia Part II of 2010 Edition). °.
- Identify
- (1) Take 10mg of this product, add 1ml of diluted ethanol to dissolve, add 3ml of 1% calcium chloride solution and 50mg of zinc powder, heat in a water bath for 10 minutes, pour the supernatant, add about 0.1ml of benzoyl chloride, immediately Shake vigorously for 1 minute, add 0.5 ml of ferric chloride test solution and 2 ml of chloroform, shake, and the water layer is purple. If the same method is used, but no zinc powder is added, the color shall not be developed.
- (2) In the chromatogram recorded under the content determination item, the retention time of the main peak of the test solution should be consistent with the retention time of the main peak of the reference solution.
- (3) The infrared light absorption spectrum of this product should be consistent with the control spectrum (Figure 507 of "Infrared Spectra of Drugs").
- an examination
- Crystallinity
- Take a little of this product and check it according to law (Appendix D of Part II of the Pharmacopoeia 2010), and it should meet the requirements.
- PH
- Take this product, add water to make a suspension containing 25mg per 1ml, and measure it according to law (Appendix VI H of the second edition of the Pharmacopoeia 2010), the pH value should be 4.5 ~ 7.5.
- relative substance
- Accurately weigh the appropriate amount of this product, add an appropriate amount of methanol (1ml of chloramphenicol plus 1ml of methanol) to dissolve, and then quantitatively dilute with mobile phase to make a solution containing 0.5mg per 1ml, shake well, as the test solution; Accurately weigh the appropriate amount of chloramphenicol diol reference substance and p-nitrobenzaldehyde reference substance, add the appropriate amount of methanol (1ml of methanol per 10mg of chloramphenicol diol substance) to dissolve, and make quantitative dilution with mobile phase to make 1ml A mixed solution containing 5 g of chloramphenicol diol and 3 g of p-nitrobenzaldehyde was used as an impurity reference solution. According to the chromatographic conditions under the content determination item, take 10 l of the impurity reference solution and inject it into the liquid chromatograph, adjust the detection sensitivity, so that the peak height of the chloramphenicol diol peak is about 25% of the full range; the precise amount is taken for the test product 10 l each of the solution and the impurity reference solution were injected into the liquid chromatograph and the chromatograms were recorded. Calculated by peak area based on the external standard method, chloramphenicol-containing diols should not exceed 1.0% and p-nitrobenzaldehyde should not exceed 0.5%.
- remaining solvent
- 1 ethanol and chlorobenzene
- Take about 0.5g of this product, accurately weigh it, place it in a 10ml measuring bottle, add dimethyl sulfoxide to dissolve and dilute to the mark, shake well, and use it as a stock solution for the test product. Precisely measure 2ml and place it in the headspace bottle. Add 1ml of dimethyl sulfoxide, shake well, and seal it as the test solution: accurately weigh about 36mg of chlorobenzene and about 500mg of ethanol, put it in a 100ml measuring flask, add dimethylsulfoxide to dilute to the mark, and shake well. As the reference stock solution; precisely measure 1ml of the reference stock solution and place it in the headspace bottle, and then add 2ml of dimethyl sulfoxide precisely, shake, and seal it as the system suitability test solution; precisely measure 1ml of the reference stock solution and place it on top In an empty bottle, add 2ml of the test stock solution precisely, shake well, and seal it as the reference solution. According to the residual solvent determination method (the second method of Appendix P of the 2010 Pharmacopoeia, the second method), the capillary column with 6% cyanopropylphenyl-94% dimethylpolysiloxane (or similar polarity) as the fixing solution is Chromatographic column: start temperature is 40 ° C, maintain for 10 minutes, then increase to 200 ° C at a rate of 10 ° C per minute, and maintain for 4 minutes; inlet temperature is 250 ° C; detector temperature is 300 ° C; headspace bottle equilibration The temperature was 85 ° C and the equilibration time was 45 minutes. Samples were taken from the headspace of the system suitability test solution, and the elution order was: ethanol, chlorobenzene, and the resolution between the chromatographic peaks should meet the requirements. Take the reference solution headspace sample and calculate the results of several consecutive injections. The relative standard deviation must not exceed 5.0%. Take the test solution and the control solution for headspace injection, record the chromatogram, and calculate the peak area by the standard addition method. Both should meet the requirements.
- Loss on drying
- Take this product and dry it to constant weight at 105 ° C, and the weight loss shall not exceed 0.5% (Appendix L of Pharmacopoeia Part II of 2010 Edition).
- Residue on ignition
- Must not exceed 0.1% (Appendix N of Part Two of the 2010 Pharmacopoeia).
- Assay
- It was determined by high performance liquid chromatography (Appendix VD of Part Two of the Pharmacopoeia, 2010 Edition).
- Chromatographic conditions and system suitability tests
- Use octadecylsilane bonded silica as a filler; use 0.01 mol / L sodium heptane sulfonate buffer solution (take 6.8 g of potassium dihydrogen phosphate, dissolve with 0.01 mol / L sodium heptane sulfonate solution and dilute to 1000 ml Add 5ml of triethylamine, mix well, adjust the pH to 2.5 with phosphoric acid)-methanol (68:32) as the mobile phase; detection wavelength is 277nm; take chloramphenicol reference substance, chloramphenicol glycol reference substance Add an appropriate amount of p-nitrobenzaldehyde reference substance, add an appropriate amount of methanol (1ml of chloramphenicol plus 1ml of methanol) to dissolve, dilute with mobile phase to make a solution containing 50g per 1ml, and take 10l into the liquid chromatograph. Record the chromatogram. The resolution of each adjacent peak should meet the requirements.
- Assay
- Accurately weigh an appropriate amount of this product, add an appropriate amount of methanol (1ml of chloramphenicol plus 1ml of methanol) to dissolve, and quantitatively dilute with mobile phase to make a solution containing about 0.1mg per 1ml, shake well, and accurately take 10l into the liquid Chromatograph, record the chromatogram; also weigh the appropriate amount of chloramphenicol reference substance and measure it in the same way. Calculate the peak area according to the external standard method, that is, [4]
Chloramphenicol mechanism of action
- Chloramphenicol is absorbed from the upper intestine,
- Most of chloramphenicol's metabolism in the body is combined with glucuronic acid. Its original drug and metabolites are quickly excreted through the urine. The effective original drug with an oral dosage of 5% to 15% is excreted into the urine by glomerular filtration. Can reach effective antibacterial concentration, can be used to treat urinary system infections. Renal dysfunction should be reduced when used.
The main uses of chloramphenicol
- It is a broad-spectrum bacteriostatic antibiotic. It is the first choice for treating typhoid and paratyphoid. It is one of the effective drugs for treating anaerobic infections. It is secondly used for the treatment of various infectious diseases caused by sensitive microorganisms. Due to serious adverse reactions, fewer and fewer are used.
Clinical application of chloramphenicol
- Chloramphenicol has been widely used in the treatment of various sensitive bacterial infections.
- Methanesulfomycin and chloramphenicol are the same type of antibiotics. Only the nitro group on the benzene ring of chloramphenicol is replaced by a methylsulfone group. Its antibacterial spectrum is similar to that of chloramphenicol. Methanesulfomycin is mainly excreted from the kidney, and the active concentration in urine is higher than that of chloramphenicol, so the dose should be reduced when renal function is poor. Although there are also hematological toxicities, they are all reversible changes and there is no aplastic anemia. Some countries believe that its efficacy is better than chloramphenicol, but China believes that its efficacy is not better than chloramphenicol.
Chloramphenicol pharmacological properties
- Chloramphenicol is a broad-spectrum bacteriostatic agent. Fat soluble
- Chloramphenicol generally has a stronger effect on Gram-negative bacteria than Gram-positive bacteria. Sensitive bacteria include Enterobacteriaceae (such as E. coli, Enterobacter aerogenes, Klebsiella, Salmonella, etc.) and anthrax, pneumococcus, streptococcus, listeria, staphylococcus, etc. Chlamydia, Leptospira, and Rickettsia are also sensitive to this product. This product also has a considerable effect on anaerobic bacteria such as Clostridium tetanus, perfringens, actinomycetes, lactobacillus, clostridium, etc. But it is not effective against Pseudomonas aeruginosa, Mycobacterium tuberculosis, viruses, fungi, etc.
- Bacteria have a slowly developing resistance to chloramphenicol, which mainly produces acetyltransferases. Obtained by plasmid delivery. Some strains of certain bacteria (Pseudomonas aeruginosa, Proteus, Klebsiella, etc.) are also resistant to chloramphenicol because they change the permeability of the bacterial cell wall, making it impossible for chloramphenicol to enter the bacteria.
Chloramphenicol pharmacokinetics
- Chloramphenicol
- This product is widely distributed in systemic tissues and fluids after intravenous administration, and has a higher concentration in liver and kidney tissues, and the rest are lung, spleen, myocardium, intestine, and brain tissues. It can enter the cerebrospinal fluid through the blood-cerebrospinal fluid barrier. When there is no inflammation of the meninges, the cerebrospinal fluid drug concentration is 21% to 50% of the blood concentration. When the meninges are inflamed, the blood concentration can reach 45% to 89%. Infant patients can reach 50% to 99%. It can also enter the fetal circulation through the placental barrier, and the fetal blood drug concentration can reach 30% to 80% of the maternal blood drug concentration. It can also enter the aqueous humor and vitreous fluid through the blood-eye barrier, and can reach the therapeutic concentration. Still secreted into milk, saliva, ascites, pleural fluid and synovial fluid.
- The apparent distribution volume (Vd) is 0.6 to 1 L / kg. The protein binding rate is about 50% to 60%. Blood elimination half-life (t1 / 2b) is 1.5 to 3.5 hours for adults, renal function impairment is 3 to 4 hours, and severe liver impairment is prolonged (4.6 to 11.6 hours), and within two weeks of birth The elimination half-life (t1 / 2b) of neonatal blood is 24 hours, 12 hours for 2-4 weeks, and 4 hours for infants older than 1 month. 90% of the free drugs in the liver are combined with glucuronic acid into inactive chloramphenicol monoglucuronide. Within 24 hours, 5% to 10% were excreted by the glomerulus through filtration and 80% were excreted by the renal tubules as inactive metabolites. Dialysis has no significant effect on the clearance of this product.
Chloramphenicol adverse reactions
- The main adverse reaction was the inhibition of bone marrow hematopoietic function.
- Typhoid
- One is the reversible reduction of various types of blood cells, in which granulocytes first decrease, and this response is related to the dose and the course of treatment. Once found, the drug should be stopped in time and can be resumed;
- The second is irreversible aplastic anemia. Although rare, it has a high mortality rate. This reaction is allergic and has no direct relationship with the dose course. May be related to the inhibition of chloramphenicol in bone marrow hematopoietic cells by the same 70S ribosomes as bacteria.
- In order to prevent toxic reactions in the hematopoietic system, abuse should be avoided, and blood images should be checked frequently when applied. Chloramphenicol can also produce gastrointestinal reactions and secondary infections. In addition, a small number of patients may develop allergic reactions such as rash and angioedema, but they are relatively mild. Cyclic failure (gray infant syndrome) can occur in newborns and premature infants at excessive doses. This is due to their liver dysgenesis and poor excretion capacity, which limits the metabolism and detoxification of chloramphenicol, resulting in drug accumulation in the body. Therefore, premature babies and newborns under two weeks should be avoided.
- [Precautions]
- Including chloramphenicol, sulfomycin and odorless chloramphenicol. Chloramphenicol is a broad-spectrum antibiotic. It is less commonly used because of its greater toxicity to the blood system. Use its eye drops topically to prevent eye infections. Note: The main adverse reactions are granulocyte and thrombocytopenia, aplastic anemia, etc. Long-term use can cause optic neuritis, ataxia, and double infection. Sometimes there is a gastrointestinal reaction. Newborns can cause gray baby syndrome, so it is contraindicated. Mental patients can cause severe reactions and are therefore disabled. Intramuscular injections can cause serious reactions. The antibacterial spectrum of methanesulfomycin is similar to that of chloramphenicol, and it does not show aplastic anemia. However, when renal function is poor, the dose should be reduced. Children can take odorless chloramphenicol.
Chloramphenicol drug interactions
- Compatibility Note: This product injection, when it is in strong alkaline and strong acid solution, is easily destroyed and ineffective.
- (1) The antibacterial action mechanism of macrolides and lincomycin antibiotics is similar to that of chloramphenicol, which can replace or prevent the combination of chloramphenicol and the 50s subunit of the bacterial ribosome, so the same use can occur Antagonism should not be combined.
- (2) Chloramphenicol is a bacteriostatic agent that inhibits the synthesis of bacterial proteins and interferes with the bactericidal effect of penicillin-type fungicides. The use of both drugs should be avoided.
- (3) Chloramphenicol can antagonize vitamin B6, increase the body's need for B6, and can also antagonize the hematopoietic effect of vitamin B12.
- (4) Chloramphenicol can inhibit the drug metabolism enzymes of liver microsomes and can affect the efficacy of other drugs, such as significantly prolonging the anesthesia time of sodium pentobarbital in animals.
- (5) This product is equivalent to certain drugs that inhibit bone marrow, such as colchicine, butapine and penicillamine, which can increase toxicity.
Chloramphenicol dosage
- 1. Oral: 0.5g for adults, once every 6 hours. A larger first dose can be used for treating typhoid fever. Patients should continue to apply for 2-3 days after normal body temperature to prevent recurrence. The highest dose does not exceed 26g. Children per day per kilogram of body weight 25 50mg, divided dose once every 6 hours. Intramuscular injection or intravenous drip: 1 day volume: 0.5-1g, divided into 2 injections. Dilute with liquid. One chloramphenicol (250mg) should be diluted with at least 100ml.
- 2. Eye drops: 1-2 drops each time, 3-5 times daily. Ear drops: 2-3 drops each time, 3 times daily. Note: Chloramphenicol injection (containing solvents such as ethanol, glycerol or propylene glycol) ), It should be extracted with a dry syringe and shaken while diluting to prevent precipitation of crystals.
- 3. The symptoms should be reduced or discontinued as appropriate after the symptoms subsided.
Chloramphenicol indication
- Chloramphenicol
- 1. Typhoid and other Salmonella infections: The drug of choice for typhoid and paratyphoid caused by sensitive strains is generally not suitable for gastroenteritis infected by Salmonella. If the disease is serious, it may still be used when combined septicemia is possible.
- 2. Ampicillin-resistant Haemophilus influenzae type B meningitis or Streptococcus pneumoniae, Neisseria meningitidis meningitis, and sensitive gram-negative meningitis meningitis in patients allergic to penicillin. This product can be used as one of the drugs of choice.
- 3 Brain abscesses, especially otogenic, are often a mixed infection of aerobic and anaerobic bacteria.
- 4 Severe anaerobic infections, such as those caused by Bacteroides fragile, are particularly suitable for those with lesions involving the central nervous system. They can be used in combination with aminoglycoside antibiotics to treat abdominal infections and pelvic infections to control coexisting aerobic and anaerobic bacteria. infection.
- 5. No other low-toxic antibacterial drugs can be used to treat various serious infections caused by sensitive bacteria, such as sepsis and lung infections caused by Haemophilus influenzae, Salmonella and other Gram-negative bacilli, often with aminoglycosides. joint.
- 6. Rickettsia infection can be used for the treatment of Q fever, Rocky Mountain spotted fever, and endemic typhus.
Chloramphenicol precautions
- 1. Due to the possibility of irreversible bone marrow suppression, this product should avoid repeated treatment.
- 2. Patients with impaired liver and kidney function should avoid using this product. If it must be used, it should be applied in a reduced amount. When possible, monitor the blood concentration to make the peak concentration below 25mg / L and the trough concentration below 5mg / L. If the blood concentration exceeds this range, the risk of bone marrow suppression can be increased.
- 3 Peripheral hemograms should be checked regularly during treatment. Long-term therapists must check reticulocyte counts and bone marrow tests if necessary in order to find dose-related reversible bone marrow suppression in time. However, full blood tests can not predict usually after treatment is completed Aplastic anemia occurred.
- 4 Disturbance to diagnosis: When urinary glucose is measured by the copper sulfate method, patients using chloramphenicol may produce false positive reactions.
- Medication for pregnant and lactating women
- Because chloramphenicol can penetrate the placental barrier, it may cause toxic reactions to premature and term neonates, and "grey infant syndrome" occurs. Therefore, this product should not be used during pregnancy, especially at the end of pregnancy or during childbirth.
- This product is secreted from breast milk, which may cause adverse reactions in lactating infants, including severe bone marrow suppression. Therefore, this product is not suitable for breastfeeding women, and breastfeeding should be suspended when necessary.
- Medication for children
- Due to immature liver enzyme system and poor renal excretion function in newborns, the excretion of the drug from the kidney is slower than that in adults. Therefore, chloramphenicol used in newborns may cause high blood concentrations and toxic reactions (grey infant syndrome). Therefore, this product is not suitable for newborns. When there are indications that this product must be used, it should be used under conditions of monitoring blood concentration if necessary.
- Medication for elderly patients
- Most of the elderly patients' tissues and organs are degraded, their functions are reduced, and their autoimmune function is also reduced. Chloramphenicol can cause serious adverse reactions, so they should be used with caution.
Chloramphenicol poisoning
- Chloramphenicol (L-mycin) is a broad-spectrum antibacterial drug, which has a stronger effect on gram-negative bacteria than on gram-positive bacteria; it also has antimicrobial effects on anaerobic bacteria, chlamydia, mycoplasma, and rickettsia. Oral absorption is rapid and complete, with a plasma protein binding rate of about 60%, a half-life of 1.5 to 3.5 hours, and a volume distribution of 0.92 L / kg. Can enter the cerebrospinal fluid through the blood cerebrospinal fluid barrier, can also enter the fetal circulation through the blood placental barrier, can also be distributed to milk, saliva, pleural fluid, ascites and synovial fluid. The most suitable therapeutic drug concentration range is 5-20 g / ml, beyond this range can increase the risk of causing bone marrow suppression. Adults usually use 1-2 g / d in 3 to 4 doses; or intravenously after dilution, 1 to 2 g / d in 2 doses. When this medicine is applied when liver and kidney dysfunction is used, the dosage should be adjusted.
- Clinical manifestation
- 1. Nausea, vomiting, lack of appetite, glossitis, and stomatitis may occur when taken orally. This medicine may cause jaundice, liver fat infiltration, and even acute severe hepatitis.
- 2. Hematopoietic system toxicity:
- (1) The dose-related is reversible myelosuppression, and clinical anemia, leukocytes, and thrombocytopenia occur.
- (2) Severe and irreversible aplastic anemia is irrelevant to the dose, and a few develop into granulocytic leukemia. The majority of patients with aplastic anemia develop after oral chloramphenicol, and the incubation period can be as long as several weeks to several months, with bleeding tendency, infection and anemia. Some patients with congenital glucose-6-phosphate dehydrogenase deficiency can develop hemolytic anemia.
- 3. Nervous system damage: Peripheral neuritis, optic neuritis, and visual impairment can progress to optic atrophy, which can cause toxic psychosis: severe insomnia, hallucinations, suspicion, mania, depression, etc.
- 4. Allergic reactions are rare, and there may be various rashes, solar dermatitis, and angioedema. Topical application can cause contact dermatitis. Occasional anaphylactic shock has been reported.
- 5. Grey infant syndrome can occur when preterm infants or newborns are given large doses of chloramphenicol (more than 25mg / kg daily): bloating, vomiting, progressive paleness, cyanosis, microcirculation disorders, temperature rise, breathing irregular. Similar performance can also occur when the dosage is 100 mg / kg in adults or older children.
- treatment
- The main points of treatment for chloramphenicol poisoning are:
- 1. Those who take large doses orally should induce vomiting, gastric lavage, catharsis, and fluid replacement to promote their excretion.
- 2. When chloramphenicol is used in excess, there is no specific antidote, and dialysis therapy cannot clear the drug, and symptomatic and supportive treatment is the main.
- 3. Give oxygen to newborns when circulatory failure occurs, and actively treat circulatory failure.
- 4. When dose-related bone marrow suppression occurs, the drug should be discontinued immediately and treated accordingly, which is generally reversible.
- 5. Peripheral neuritis, bleeding tends to stop early, and treatment with vitamin B6 and multivitamins is often reversible. After the drug is discontinued when toxic psychiatric symptoms occur, no special treatment is required, and the symptoms usually disappear within 2 to 7 days.
- 6. Discontinue the drug promptly when an allergic reaction occurs, give anti-allergic treatment, and treat glucocorticoid with severe jaundice [3] .