Pharmacological properties
Pharmacodynamics. Streptomycin has a wide spectrum of antimicrobial (bactericidal) activity. It is active against Mycobacterium tuberculosis, most gram-negative: Escherichia coli, Salmonella spp., Shigella spp., Yersinia spp., Klebsiella spp. (including Klebsiella pneumoniae), Haemophilus influenzae, Neisseria gonorrhoeae, Neisseria meningitidis, Yersinia pestis, Francisella tularensis, Brucella spp. and some gram-positive microorganisms: Staphylococcus spp., Corynebacterium diphtheriae. Less active against Streptococcus spp. (including Streptococcus pneumoniae), Enterobacter spp. Streptomycin is inactive against anaerobic bacteria, Spirochaetaceae, Rickettsia spp., Proteus spp., Pseudomonas aeroginosa.
It exerts its bactericidal effect by binding to the 30S subunit of the bacterial ribosome, which subsequently leads to inhibition of protein synthesis.
Pharmacokinetics. Poorly absorbed in the gastrointestinal tract and almost completely excreted by the intestines, used only parenterally. Streptomycin with i / m administration is quickly and completely absorbed into the blood. C max in the blood is observed after 1-2 hours. After a single administration in an average therapeutic dose, the antibiotic is detected in the blood for 6-8 hours. High concentrations of the drug are created in the lungs, kidneys, liver, extracellular fluid. The drug has a weak tropism for adipose and bone tissue. Does not penetrate through an intact blood-brain barrier. Penetrates well through the placenta and into breast milk. The drug binds to blood proteins by 10%. With normal renal excretory function, it does not accumulate in the body with repeated administration. It is not metabolized. T ½ is 2-4 hours. It is excreted mainly by the kidneys (95%) in unchanged form. The elimination of the drug is slowed down in case of impaired kidney function, while its concentration in the body increases and adverse reactions (neurotoxic) may develop.
Indication
Treatment of newly diagnosed pulmonary tuberculosis and tuberculous lesions of other organs. In patients previously treated with streptomycin, before its repeated administration, it is advisable to test the mycobacteria isolated by them after laboratory detection of their sensitivity to streptomycin.
Infectious-inflammatory processes of various localization caused by gram-positive and gram-negative microorganisms sensitive to the drug: pneumonia caused by Klebsiella, endocarditis, plague, tularemia, brucellosis.
Application
Streptomycin is administered intramuscularly, in the form of aerosols, intratracheally. In adults, the drug is also used intracavernously. Before starting therapy with streptomycin, it is necessary to exclude the patient's hypersensitivity to the antibiotic by conducting a skin test, and Procaine (when used as a solvent).
With intramuscular administration, a single dose for adults is 0.5-1 g, the maximum daily dose is 2 g. For patients with a body weight of 50 kg and persons over 60 years of age, the daily dose usually does not exceed 0.75 g.
The daily dose for children aged 1-3 months is 10 mg/kg of body weight, 3-6 months - 15 mg/kg, from 6 months to 2 years - 20 mg/kg. The daily dose for children aged 2-18 years is determined at the rate of 15-20 mg/kg of body weight, but not more than 0.5 g/day for children (up to 12 years) and not more than 1 g/day for adolescents (12-18 years).
In the treatment of tuberculosis, the daily dose is usually administered once. In case of poor tolerance of the drug, the daily dose can be divided into 2 administrations. The duration of treatment depends on the form and phase of the disease and is 2-3 months.
When treating infections of non-tuberculous etiology, the daily dose is administered in 3-4 doses with an interval of 6-8 hours. The duration of treatment is 7-10 days (should not exceed 14 days).
For intramuscular administration, the drug is dissolved in water for injection, 0.9% sodium chloride solution or 0.25-0.5% procaine solution at the rate of 4 ml of solvent per 1 g of the drug. The solution is prepared ex tempore.
Intratracheally, adults are administered the drug at a dose of 0.5-1 g in 5-7 ml of 0.9% sodium chloride solution or 0.5% novocaine solution 2-3 times a week.
For use in the form of an aerosol, adults are administered 0.5-1 g of Streptomycin, for such administration the drug is dissolved in 4-5 ml (for warm-moist inhalation - in 25-100 ml) of 0.9% sodium chloride solution. Children over the age of 1 month with this route of administration the drug is prescribed in the same calculation as with i / m administration. Depending on the indications, other drugs compatible with streptomycin can be included in the inhalation solution.
Intracavernous administration of the drug is carried out by insufflation in the form of a finely dispersed powder or instillation of a 10% solution (solvent - 0.9% sodium chloride solution) in a surgical hospital once a day in a total dose of no more than 1 g, regardless of the number of cavities and the method of administration.
In patients with hypertension and coronary heart disease, treatment with the drug, regardless of the route of administration, begins with reduced doses (up to 0.25 g). With good tolerability, doses can be increased to the usual ones.
In patients with impaired renal excretory function, as well as in patients with liver damage, the daily dose of the drug should be reduced. If the endogenous creatinine clearance is 50-60 ml/min, the dose should not exceed 0.5 g; 40-50 ml/min - no more than 0.4 g/day.
Diseases of the auditory and vestibular apparatus caused by neuritis of the eighth pair of cranial nerves and after otoneuritis, severe forms of cardiovascular and renal failure, impaired cerebral circulation, obliterating endarteritis, hypersensitivity to streptomycin and/or other aminoglycosides, myasthenia gravis, botulism, tendency to bleeding. Intracavernous administration is contraindicated in cases of non-union of the pleural cavity at the catheter insertion site, basal localization of the cavity.
Side effects
On the part of the immune system: hypersensitivity reactions, including skin rashes (including urticaria), hyperemia, itching, dermatitis (including exfoliative), fever, pain in the joints and muscles, eosinophilia, angioedema, in rare cases - anaphylactic reactions, including anaphylactic shock.
From the side of the central and peripheral nervous system: blockade of the VIII pair of cranial nerves and associated vestibular disorders (including dizziness, nausea, vomiting, unsteady gait), hearing impairment (including noise and ringing in the ears, hearing loss, deafness), headache, peripheral neuritis, optic neuritis, amblyopia, the appearance of scotoma, inhibition of neuromuscular transmission (including difficulty breathing, apnea, weakness, drowsiness, loss of consciousness), peripheral polyneuropathy, paresthesias (including facial paresthesias), convulsive contractions of soft muscles; very rarely - blockade of neuromuscular conduction up to respiratory arrest, especially in patients with neuromuscular diseases (myasthenia gravis), or in the postoperative period against the background of the residual effect of non-depolarizing muscle relaxants.
From the urinary system: renal dysfunction, including proteinuria, hematuria, azotemia.
From the side of the cardiovascular system: pressing pain in the heart area, tachycardia, hypotension.
On the part of the digestive system: diarrhea.
Local reactions: reactions at the injection site, including redness, itching, and pain.
From the side of the hematopoietic system: increased bleeding, aplastic anemia, agranulocytosis, pancytopenia, leukopenia, thrombocytopenia, hemolytic anemia.
Special instructions
With prolonged use of streptomycin, nephrotoxicity may occur, so during treatment it is necessary to conduct urine tests at least once a month. Renal dysfunction is reversible and usually disappears quickly after timely discontinuation of the drug.
The likelihood of developing nephrotoxicity is higher in patients with impaired renal function, as well as when prescribing high doses or when used for a long time.
Disturbances in the functions of the vestibulocochlear apparatus depend on the dose of the drug, the duration of its use, and the patient's age.
During treatment with Streptomycin, it is necessary to monitor the functions of the auditory (by conducting a caloric test and audiometry) and vestibular apparatus. Early signs of impaired function of the vestibulocochlear apparatus are a decrease in hearing to high-frequency sounds.
If the drug is discontinued prematurely, deafness may develop.
Children should not exceed the recommended dose of streptomycin, as there is information about the occurrence of signs of CNS depression (characterized by stupor, sometimes coma and respiratory depression) in children under 6 months of age who were prescribed a dose exceeding the maximum permissible.
Pregnancy and breastfeeding. During pregnancy, Streptomycin is contraindicated because it crosses the fetoplacental barrier and can cause ototoxicity in the fetus.
Breastfeeding should be discontinued during treatment, as the drug passes into breast milk.
Children. The drug is used in children from the age of 1 month. In children up to 2 years of age, Streptomycin is prescribed only for vital indications.
Ability to influence the reaction rate when driving vehicles or working with other mechanisms. During treatment with the drug, some patients may experience adverse reactions from the central nervous system (see Side effects), therefore, you should refrain from driving vehicles and engaging in other potentially dangerous activities that require increased concentration of attention and speed of psychomotor reactions.
Interactions
With simultaneous use with other aminoglycosides, polymyxins, capreomycin, vancomycin, cyclosporine, ethacrynic acid, mannitol, the risk of developing nephrotoxic and ototoxic effects of the drug increases.
Intravenous administration of indomethacin reduces the renal clearance of streptomycin, increasing its concentration in the blood.
The drug enhances the side effects of ototoxic and nephrotoxic drugs, muscle relaxants, methoxyflurane, reduces the effectiveness of antimyasthenic drugs, it is not prescribed simultaneously with diuretics and against the background of dehydration therapy.
Incompatibility. It is unacceptable to mix Streptomycin in the same syringe with penicillin antibiotics (carbenicillin, etc.) and cephalosporins.
Only recommended solvents should be used.
Overdose
It manifests itself in increased side effects and blockade of neuromuscular conduction, up to respiratory arrest.
Treatment: administer intravenous calcium chloride solution and subcutaneous proserin; if apnea develops, transfer to mechanical ventilation.
Storage conditions
In the original packaging at a temperature not exceeding 25 °C.
