Streptomycin

General characteristics. Structure:

Active ingredient: sulfate streptomycin (in terms of streptomycin) - 0,5 g and 1,0 g.

Pharmacological properties:

Pharmacodynamics. An antibiotic of a broad spectrum of activity from group of aminoglycosides. It is formed in the course of life activity of radiant mushrooms of Streptomyces globisporus or other types of Streptomyces spp. In low concentration has bacteriostatic action: getting in a microbic cell, contacts specific proteins receptors on 30S subunit of a bacterial ribosome, breaking formation of the initiating complex "template-RNA + 30S ribosome subunit" that leads to disintegration of polyribosomes thereof there are defects when reading information from DNA, defective proteins are synthesized that as a result leads to a stunt and development of a microbic cell. In higher concentration streptomycin renders bactericidal effect (damages cytoplasmic membranes, causing death of a microbic cell). Possesses a wide range of antimicrobic action. It is active concerning Mycobacterium tuberculosis, the majority of gram-negative bacteria (Escherichia coli, Klebsiella spp. (including Klebsiella pneumoniae), Proteus spp., Salmonella spp., Shigella spp., Yersinia spp. (including Yersinia pestis), Brucella spp., Francisella tularensis, Haemophilus ducreyi, Haemophilus influenzae, Neisseria gonorrhoeae, Neisseria meningitidis, some gram-positive microorganisms (Staphylococcus spp., Corynebacterium diphtheriae). It is moderately active concerning Streptococcus spp. (including Streptococcus pneumoniae), Enterococcus spp. In a combination with benzylpenicillin or Vancomycinum streptomycin is effective in treatment of the endocarditis caused by Enterococcus faecalis or Streptococcus of the viridans group. It is steady in the subacidic environment, but easily collapses in solutions of acids and alkalis when heating. Secondary stability of bacteria develops quickly. Streptomycin is inactive concerning anaerobic bacteria, this. Spirochaetaceae, Rickettsia spp., Pseudomonas aeruginosa.

Pharmacokinetics. After intramuscular introduction streptomycin is quickly and completely soaked up from the place of an injection. Time of achievement of the maximum concentration in blood – 0,5-1,5 h, the maximum concentration in blood after introduction of 1 g in oil – 25-50 mkg/ml. Communication with proteins of plasma – less than 10%. It is distributed in all body tissues (except brain tissue), including in extracellular liquid, liquid of abscesses, a pleural exudate, in ascitic, pericardiac, synovial, lymphatic and peritoneal liquids. High concentration are created in kidneys, a liver, lungs; low - in bone and fatty tissue. Distribution volume adults – 0,26 l/kg, at children have 0,2 – 0,4 l/kg, at newborns at the age of less than 1 week and with a body weight less than 1500 - to 0,68 l/kg, at the age of less than 1 week and with a body weight more than 1500 - to 0,58 l/kg, at patients with a mucoviscidosis – 0,3-0,39 l/kg. Does not get through the unimpaired blood-brain barrier. Gets through a placenta and into breast milk. Is not exposed to metabolism. An elimination half-life (T1/2) adults – 2-4 h, at newborns have 5-8 h, children of more advanced age have 2,5-4 h. Final T1/2 – more than 100 h (release from intracellular depots). At patients with a renal failure of T1/2 varies depending on insufficiency degree – to 100 h, patients with a mucoviscidosis have 1-2 h, at patients with burns and a hyperthermia can be shorter in comparison with average values owing to the increased clearance. It is removed by kidneys (95%) in not changed look by glomerular filtering.

Indications to use:

- tuberculosis of various localization, including tubercular meningitis (as a part of a combination therapy);
- venereal granuloma;
- tularemia, brucellosis, plague;
- a bacterial endocarditis (only in combination with benzylpenicillin or with Vancomycinum);
- acute bacterial intestinal infections, infections of urinary tract (after establishment of sensitivity of the activator).

Route of administration and doses:

Intramusculary.
Contents of a bottle are dissolved in sterile water for injections or in 0,9% solution of sodium of chloride or in 0,25-0,5% solution of Procainum (Novocaine) at the rate of 4 ml of solvent on 1 g of streptomycin. Solution is prepared just before introduction.
Adult: a single dose at intramuscular introduction – 0,5-1 g, daily – 1 - 2 g. The maximum daily dose of streptomycin for the adult – 2 g. At bad portability, the patient with body weight less than 50 kg, and also to persons are more senior than 60 years – a daily dose of 750 mg.
To children: aged up to 3 months – in a dose at the rate of 10 mg/kg/days, aged from 3 up to 6 months – 15 mg/kg/days, from 6 months to 2 years – 20 mg/kg/days, for children up to 13 years and teenagers – 15-20 mg/kg/days, but no more than 500 mg/days – for children up to 13 years and 1 g/days – for teenagers.
Maximum doses of streptomycin to children of different age:
2-4 years - one-time - 150 mg, daily - 300 mg;
5-6 years - one-time - 175 mg, daily - 350 mg;
7-9 years - one-time - 200 mg, daily - 400 mg;
9-14 years - one-time - 250 mg, daily - 500 mg;
14 years - one-time 500 mg, daily - 1 g are more senior.
The pulmonary tuberculosis and other bodies - a daily dose of 15 mg/kg (but no more than 1 g) is entered 1 time a day, at bad portability - into 2 receptions; duration of treatment is 3 months and more (in parallel with reception of other antitubercular drugs).

Bacterial endocarditis:

streptococcal etiology (the caused Streptococcus spp., sensitive to penicillin) – streptomycin is entered into combinations with benzylpenicillin within 2 weeks: in the first week – on 1 g 2 times a day; within the second week – on 500 mg 2 times a day; to patients 60 years – on 500 mg 2 times a day within 2 weeks are more senior;

enterokokkovy etiology - streptomycin is entered into combinations with benzylpenicillin within 6 weeks: in the first 2 weeks – on 1 g 2 times a day; within the next four weeks – on 500 mg 2 times a day (duration of a course of treatment can be reduced at the ototoxicity phenomena).

Tularemia – on 0,5-1 g 2 times a day within 7-14 days till 5-7th day of lack of febrile temperature.

Plague, brucellosis – on 1 g 2 times a day not less than 7-10 days.
At a venereal granuloma, acute bacterial intestinal infections and infections of urinary tract – the daily dose is divided into 2-4 introductions, course duration – at least 10 days (should not exceed 14 days).
At a renal failure the daily dose of streptomycin should be reduced. At clearance of creatinine from 50 to 60 ml/min. the dose should not exceed         500 mg/days; at clearance of creatinine from 40 to 50 ml/min. – no more than 400 mg/days.
For patients with arterial hypertension and coronary heart disease an initial dose – 250 mg/days, at good tolerance a dose of a uvelichiv.

Features of use:

During treatment it is necessary at least 1 time a week to control function of kidneys, an acoustical nerve and vestibular mechanism.
The probability of development of nephrotoxicity is higher at patients with a renal failure, and also at purpose of high doses or for a long time (at this category of patients daily control of function of kidneys can be required).
At unsatisfactory audiometric tests the dose of drug is reduced or stop treatment.
In the absence of positive clinical dynamics it is necessary to remember a possibility of development of resistant microorganisms. In similar cases it is necessary to cancel treatment and to begin performing the corresponding therapy.
To children till 1 year streptomycin is appointed only on zhiznenny ״ to indications.
During administration of drug it is necessary to be careful at control of vehicles, mechanisms and when performing other potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions.

Side effects:

From a nervous system: a headache, drowsiness, weakness, peripheral neuritis, neuritis of a facial nerve (a burning sensation in a face or an oral cavity, numbness, a pricking), neuromuscular blockade at simultaneous introduction with muscle relaxants (breath difficulty, a night apnoea, an apnoea), neurotoxic action (twitching of muscles, paresthesias, epileptic seizures).
From sense bodys: ototoxicity (a hearing loss, a ring, buzz or feeling of "congestion" in ears, decrease in hearing up to irreversible deafness), vestibular and labyrinth disturbances (a diskoordination, dizziness, nausea, vomiting, instability).
From an urinary system: nephrotoxicity (significant increase or reduction of frequency of an urination, oliguria, polyuria, thirst, anorexia, nausea, vomiting).
From the alimentary system: nausea, vomiting, diarrhea, abnormal liver function (increase in activity of "hepatic" transaminases, hyperbilirubinemia).
Allergic reactions: itch, dermahemia, rash, Quincke's disease, fever.
Local reactions: a hyperemia and pain in an injection site.
If any of the side effects specified in the instruction are aggravated, or you noticed any other side effects which are not specified in the instruction, report about it to the doctor.

Interaction with other medicines:

Mixing in one syringe with antibiotics of a penicillinic row and cephalosporins is inadmissible. At simultaneous use with other nefro-and ototoksichny drugs (including with other aminoglycosides, polymyxins, kapreomitsiny) the risk of development from - and nephrotoxic action increases.
Streptomycin shows a synergism at simultaneous use with a beta laktamnymi antibiotics (penicillin and cephalosporins).
Streptomycin reduces efficiency of anti-myasthenic drugs.
Metoksifluran increases risk of development of side effects of streptomycin.
Drugs for an inhalation anesthesia (galogensoderzhashchy hydrocarbons), opioid analgetics, transfusion of large amounts of blood with citrate preservatives as anticoagulants and other medicines blocking neuromuscular transmission – at simultaneous use with streptomycin strengthening of neuromuscular blockade is possible.
Intravenous administration of indometacin reduces renal clearance of streptomycin, increasing concentration in blood and increasing T1/2.

Contraindications:

Hypersensitivity (including to other aminoglycosides in the anamnesis), a heavy chronic renal failure with an azotemia and uraemia, organic lesions of the VIII pair of cherepnomozgovy nerves, pregnancy.
If at you one of the listed diseases, before drug use surely consult with the doctor. 
Use at pregnancy At pregnancy streptomycin is contraindicated as it gets through a placental barrier and can have nephrotoxic and ototoksichesky effect on a fruit of the person.
In the period of a lactation (breastfeeding) it is applied with care (streptomycin gets into breast milk in low concentration and is badly soaked up from digestive tract).

Overdose:

Symptoms: toxic reactions (a hearing loss, an ataxy, dizziness, frustration of an urination, thirst, anorexia, nausea, vomiting, a ring or feeling of a mortgaging in ears, disturbance of breath up to its stop).
Treatment: for lifting the siege of neuromuscular transmission and its effects – carrying out a hemodialysis or peritoneal dialysis; reception of inhibitors of cholinesterase, calcium salts; artificial ventilation of the lungs; other symptomatic and maintenance therapy.

Storage conditions:

In the dry place at a temperature from 15 to 25 °C. To store in the places unavailable to children. 
Period of validity 3 years. Not to apply after the period of validity specified on packaging.

Issue conditions:

According to the recipe

Packaging:

In bottles till 0:25; 0,5 and 1 g