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Pharmacological properties

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 relative to streptococcus spp. (including streptococcus pneumoniae), enterobacter spp. streptomycin is inactive with respect to anaerobic bacteria, spirochaetaceae, rickettsia spp., proteus spp., pseudomonas aeroginosa.

It exhibits a bactericidal effect due to binding to the 30S subunit of the bacterial ribosome, which subsequently leads to inhibition of protein synthesis.

Pharmacokinetics It is poorly absorbed in the digestive tract and is almost completely excreted through the intestines, it is used only parenterally. Streptomycin with i / m administration is rapidly and completely absorbed into the blood. WITHmax it is noted in the blood after 1–2 hours. After a single administration in an average therapeutic dose, the antibiotic is determined in the blood for 6–8 hours. High concentrations of the drug are created in the lungs, kidneys, liver, and extracellular fluid. The drug has a weak tropism for adipose and bone tissue. Does not penetrate the intact BBB. It crosses the placenta and is excreted in breast milk. The drug binds to blood proteins by 10%. With normal excretory function of the kidneys with repeated injections, it does not cumulate in the body. Not metabolized. T½ is 2–4 hours. It is excreted mainly by the kidneys (95%) unchanged. Excretion of the drug slows down in case of impaired renal function, while its concentration in the body increases and adverse reactions (neurotoxic) can develop.

Indications

Treatment of newly diagnosed pulmonary tuberculosis and tuberculous lesions of other organs. For patients previously treated with streptomycin, before re-appointment, it is advisable to conduct a laboratory determination of the sensitivity to streptomycin of mycobacteria secreted by them.

Infectious and inflammatory processes of various localization, which are caused by gram-positive and gram-negative microorganisms that are sensitive to the drug: with pneumonia caused by Klebsiella, with endocarditis, plague, tularemia, brucellosis.

Application

Streptomycin is administered intramuscularly, in the form of aerosols, intratracheally. in adults, the drug is also used intracavernosally. before starting therapy with streptomycin, it is necessary to exclude the patients hypersensitivity to the antibiotic by conducting a skin test, and procaine (when used as a solvent).

With intramuscular administration, the 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 people over the age of 60, the daily dose usually does not exceed 0.75 g.

The daily dose for children aged 1-3 months - 10 mg / kg 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 based on 15–20 mg / kg body weight, but not more than 0.5 g / day for children (up to 12 years old) and not more than 1 g / day for adolescents (12–18 years )

In the treatment of tuberculosis, the daily dose is usually administered once. With poor tolerability of the drug, the daily dose can be divided into 2 injections. 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 i / m administration, the drug is dissolved in water for injection, 0.9% solution of sodium chloride or 0.25-0.5% solution of procaine at the rate of 4 ml of solvent per 1 g of the drug. Rr prepare ex tempore.

Intratracheally for adults, the drug is administered 0.5–1 g in 5–7 ml of 0.9% solution of sodium chloride or 0.5% solution of procaine 2-3 times a week.

For use in the form of an aerosol, adults are administered 0.5–1 g of Streptomycin, for this administration the drug is dissolved in 4–5 ml (with warm-wet inhalation in 25–100 ml) of 0.9% sodium chloride solution. For children over 1 month of age with this route of administration, the drug is prescribed from the same calculation as with the / m introduction.Depending on the indications, other medications compatible with streptomycin may be included in the solution for inhalation.

An intracavernous preparation is administered by insufflation in the form of a fine powder or instillation of 10% solution (the solvent is 0.9% solution of sodium chloride) in a surgical hospital once a day in a total dose of not more than 1 g, regardless of the number of caverns and method introduction.

In patients with hypertension and coronary artery disease, drug treatment, regardless of the route of administration, begins with reduced (up to 0.25 g) doses. With good tolerance, doses can be increased to normal.

In patients with impaired renal excretory function, as well as in patients with liver damage, the daily dose of the drug must be reduced. When clearance of endogenous creatinine is 50-60 ml / min, the dose should not exceed 0.5 g; 40-50 ml / min - not more than 0.4 g / day.

Contraindications

Diseases of the auditory and vestibular apparatus caused by neuritis of the viii pair of cranial nerves and after suffering otoneuritis, severe forms of cardiovascular and renal failure, cerebrovascular accident, obliterating endarteritis, hypersensitivity to streptomycin and / or other aminoglycosides, myasthenia gravis, botulism, and tendency . intracavernous administration is contraindicated in cases of non-closure of the pleural cavity at the site of catheter insertion, and root localization of the cavity.

Side effects

On the part of the immune system: hypersensitivity reactions, including skin rash (including urticaria), hyperemia, itching, dermatitis (including exfoliative), fever, joint and muscle pain, eosinophilia, Quinckes edema, in rare cases - anaphylactic reactions, including anaphylactic shock.

From the central and peripheral nervous system: blockage of the VIII pair of cranial nerves and related vestibular disorders (including dizziness, nausea, vomiting, unstable gait), hearing impairment (including tinnitus and ringing, hearing loss, deafness), headache, peripheral neuritis, optic neuritis, amblyopia, scotoma, oppression of neuromuscular transmission (including difficulty breathing, apnea, weakness, drowsiness, loss of consciousness), peripheral polyneuropathy, paresthesia (including facial paresthesia), s road cuts soft muscles; very rarely - a blockade of neuromuscular conduction up to respiratory arrest, especially in patients with neuromuscular diseases (myasthenia), or in the postoperative period against the background of the residual effect of non-depolarizing muscle relaxants.

From the urinary system: impaired renal function, including proteinuria, hematuria, azotemia.

On the part of the cardiovascular system: pain of a pressing nature in the region of the heart, tachycardia, hypotension.

From the digestive system: diarrhea.

Local reactions: reactions at the injection site, including redness, itching, and pain.

From the hemopoietic system: increased bleeding, aplastic anemia, agranulocytosis, pancytopenia, leukopenia, thrombocytopenia, hemolytic anemia.

special instructions

With prolonged use of streptomycin, nephrotoxicity phenomena can be noted, therefore, during the treatment, urinalysis should be performed at least 1 time per month. renal dysfunctions are reversible and usually quickly disappear after timely discontinuation of the drug.

The likelihood of developing a nephrotoxic phenomenon is higher in patients with impaired renal function, as well as when prescribing high doses or when used for a long time.

Violation of the functions of the vestibulo-cochlear apparatus depends on the dose of the drug, the duration of its use, the age of the patient.

During treatment with Streptomycin, it is necessary to control the functions of the auditory (by conducting caloric tests and audiometry) and the vestibular apparatus.The earliest signs of impaired function of the vestibulo-cochlear apparatus are hearing loss in high frequency sounds.

With an untimely termination of the drug, deafness may develop.

Children should not exceed the recommended dose of streptomycin, since there is information about the occurrence of signs of central nervous system depression (characterized by stupor, sometimes coma and respiratory depression) in children under 6 months of age who have been prescribed a dose that exceeds the maximum allowable.

During pregnancy and breastfeeding. During pregnancy, streptomycin is contraindicated, since it crosses the fetoplacental barrier and can cause ototoxicity in the fetus.

During treatment, breast-feeding should be discontinued, since the drug passes into breast milk.

Children. The drug is used in children aged 1 month. In children under 2 years of age, streptomycin is prescribed only for health reasons.

The ability to influence the reaction rate when driving vehicles and working with other mechanisms. During treatment with the drug, some patients may experience adverse reactions from the central nervous system (see ADVERSE EFFECTS), so you should refrain from driving vehicles and engaging in other potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions.

Interactions

With simultaneous use with other aminoglycosides, polymyxins, capreomycin, vancomycin, cyclosporine, ethacrylic acid, mannitol, the risk of developing nephro- and ototoxic effects of the drug increases.

In / in the introduction of indomethacin reduces the renal clearance of streptomycin, increasing its concentration in the blood.

The drug enhances the side effects of oto- and nephrotoxic drugs, muscle relaxants, methoxyflurane, reduces the effectiveness of anti-asthenia drugs, it is not prescribed simultaneously with diuretics and against the background of dehydration therapy.

Incompatibility. Mixing Streptomycin in the same syringe with penicillin antibiotics (carbenicillin, etc.) and cephalosporins is not allowed.

Use only recommended solvents.

Overdose

It is manifested by increased side effects and blockade of neuromuscular conduction, up to respiratory arrest.

Treatment: injected in / in a solution of calcium chloride and SC prozerin; with the development of apnea, they are transferred to mechanical ventilation.

Storage conditions

In the original packaging at a temperature not exceeding 25 ° C.

Tags: Streptomycin