Gentamycin

General characteristics. Structure:

Active agent: Gentamycini sulfas (in terms of gentamycin) – 80 mg.

Pharmacological properties:

Pharmacodynamics. A bactericidal antibiotic of a broad spectrum of activity from group of aminoglycosides. Communicates with 30S in subunit of ribosomes and breaks protein synthesis, interfering with formation of a complex of transport and information RNA, at the same time there is a wrong reading of a genetic code and formation of nonfunctional proteins. Possesses bactericidal action - in big concentration reduces barrier functions of cellular membranes and causes death of microorganisms.
Gram-negative microorganisms - Proteus spp are highly sensitive to gentamycin (the minimum overwhelming concentration (MOC) less than 4 mg/l). (including indolpositive and indolnegative strains), Escherichia coli, Klebsiella spp., Salmonella spp., Shigella spp., Campylobacter spp.; gram-positive microorganisms - Staphylococcus spp. (including penitsillino-resistant); are sensitive at MPK of 4-8 mg/l - Serratia spp., Klebsiella spp., Pseudomonas spp. (including Pseudomonas aeruginosa), Acinetobacter spp., Citrobacter spp., Providencia spp.
Rezistentna (MPK more than 8 mg/l) - Neisseria meningitidis, Treponema pallidum, Streptococcus spp. (including Streptococcus pneumoniae and strains of group D), Bacteroides spp., Clostridium spp., Providencia rettgeri.
In a combination with the penicillin (including with benzylpenicillin, ampicillin, karbenitsilliny, Oxacillinum) operating on synthesis of a cell wall of microorganisms shows activity concerning Enterococcus faecalis, Enterococcus faecium, Enterococcus durans, Enterococcus avium, practically all strains of Streptococcus faecalis and their versions (including. Streptococcus faecalis liguifaciens, Streptococcus faecalis zymogenes), Streptococcus faecium, Streptococcus durans.
Resistance of microorganisms to gentamycin develops slowly, however the strains steady against Neomycinum and Kanamycinum can show stability as well to gentamycin (incomplete cross stability). Does not affect mushrooms, viruses, the elementary.

Pharmacokinetics. It is soaked up quickly and completely. Time necessary for achievement of the maximum concentration - 0,5-1,5 h, the size of the maximum concentration after intramuscular introduction of 1,5 mg/kg makes 6 mkg/ml, therapeutic concentration in blood remain during 8-12 h.
Communication with proteins of plasma - low (to 10%). Distribution volume adults - 0,26 l/kg, at children have 0,2-0,4 l/kg. It is found in therapeutic concentration in a liver, kidneys, lungs, in pleural, pericardiac, synovial, peritoneal, ascitic and lymphatic liquids, urine, in the pus separated from wounds, granulations. Low concentration are noted in fatty tissue, muscles, bones, bile, breast milk, watery moisture of an eye, a bronchial secret, a phlegm and cerebrospinal fluid.
In therapeutic concentration at adults practically does not get through a blood-brain barrier, at meningitis its concentration in cerebrospinal fluid increases. Gets through a placenta.
Is not exposed to metabolism. An elimination half-life adults - 2-4 h, at children aged from 1 week up to 6 months have 3-3,5 h.
It is removed generally by kidneys in not changed look; in insignificant quantities - with bile. At patients with normal function of kidneys for the first days 70-95% are removed, at the same time in urine concentration more than 100 mkg/ml are created. At patients with reduced glomerular filtering removal considerably decreases.
It is removed at a hemodialysis - in each 4-6 h concentration decreases by 50%. Peritoneal dialysis is less effective - for 48-72 h 25% of a dose are removed.
At repeated introductions kumulirut, mainly in lymphatic space of an inner ear and in proximal departments of renal tubules.

Indications to use:

The bacterial infections caused by sensitive microflora:
- infections of upper and lower respiratory tracts (including bronchitis, pneumonia, pleura empyema);
- the complicated urogenital infections (including pyelonephritis, cystitis, an urethritis, prostatitis, gonorrhea, an endometritis);
- infections of bones and joints (including osteomyelitis);
- infections of skin and soft tissues;
- abdominal infections (peritonitis, pelviperitonitis);
- infections of the central nervous system (including meningitis);
- sepsis;
- wound fever, burn infection;
- average otitis.

Route of administration and doses:

Intramusculary. For intramuscular introduction contents of a bottle are dissolved in 2 ml of water for injections.
Daily dose at moderately severe diseases for adults with normal function of kidneys - 3 mg/kg/days. Frequency rate of introduction - 2-3 times a day. 
At the heavy course of diseases a daily dose - 5 mg/kg, frequency rate - 3-4 times a day; after improvement of a state the dose is reduced to 3 mg/kg. To patients with infectious and inflammatory diseases of urinary tract and holes -
molar function of kidneys appoint 1 time a day in a dose of 120-160 mg within 7-10 days; at gonorrhea - 240-280 mg once.
Premature - 6 mg/kg/days, frequency rate of introduction - 2 times; to children from 1 month to 2 years - 6 mg/kg/days, frequency rate of introduction - 3 times; to children 2 years are more senior appoint 3-5 mg/kg/days, frequency rate of introduction - 3 times.
Patients with disturbance of secretory function of kidneys and to elderly patients, and also at a serious burn disease for the adequate choice of the mode of dosing need definition of concentration of gentamycin in plasma.
The interval between introduction of average doses of gentamycin (in hours) is determined by a formula: 
interval (ch) = concentration of creatinine (mg / 100 ml) x 8.
At the heavy course of infections purpose of smaller single doses with bigger frequency rate is recommended; decrease in size of a single dose has to be multiple to the relation calculated by the stated above interval formula to the size of a normal interval between introductions (8 h). The dose has to be picked up so that the maximum concentration did not exceed 12 mkg/ml (decrease in risk of development nefro-, from - and a neurotoxicity).
At hypostases, ascites, obesity the dose is defined on "ideal" or Sukhoi to body weight. 
At a renal failure and carrying out a hemodialysis the recommended doses after the session adult - 1-1,7 mg/kg (depending on weight of an infection), to children - 2-2,5 mg/kg.

Features of use:

With care apply gentamycin at parkinsonism, a myasthenia, renal failures. At use of gentamycin it is necessary to control functions of kidneys, acoustical and vestibular devices.

At external use of gentamycin for a long time on the big surfaces of skin it is necessary to consider a possibility of resorptive action, especially at patients with a chronic renal failure.

Side effects:

From the alimentary system: nausea, vomiting, increase in activity of hepatic transaminases, hyperbilirubinemia.

From system of a hemopoiesis: anemia, leukopenia, granulocytopenia, thrombocytopenia.

From an urinary system: oliguria, proteinuria, microhematuria, renal failure.

From TsNS and peripheral nervous system: headache, drowsiness, disturbance of neuromuscular conductivity, decrease in hearing, vestibular frustration, irreversible deafness.

Allergic reactions: skin rash, an itch, a small tortoiseshell, fever, it is rare - a Quincke's edema.

Interaction with other medicines:

At simultaneous use with aminoglycosides, Vancomycinum, cephalosporins, Acidum etacrynicum strengthening from - and nephrotoxic action is possible.

At simultaneous use with indometacin decrease in clearance of gentamycin, increase in its concentration in a blood plasma is noted, at the same time the risk of development of toxic action increases.

At simultaneous use with means for an inhalation anesthesia, opioid analgetics the risk of development of neuromuscular blockade increases, up to development of an apnoea.

At simultaneous use of gentamycin and "loopback" diuretics (furosemide, Acidum etacrynicum) concentration in gentamycin blood in this connection the risk of development of toxic side reactions increases increases.

Contraindications:

Hypersensitivity to gentamycin (including to other aminoglycosides in the anamnesis), neuritis of an acoustical nerve, a heavy chronic renal failure with an azotemia and uraemia, newborns (up to 1 month). 
Use at pregnancy Use of drug at pregnancy and during breastfeeding is possible if the expected advantage for mother exceeds potential risk for a fruit and the child.

Overdose:

Symptoms: decrease in neuromuscular conductivity (apnoea).

Treatment: the adult in/in antikholinesterazny HP (Prozerin), and also calcium drugs enter (5–10 ml of 10% of solution of Calcii chloridum, 5–10 ml of 10% of solution of calcium of a gluconate). Before Prozerin's introduction previously in/in enter atropine in a dose of 0,5-0,7 mg, expect increase of pulse and in 1,5–2 min. enter into 1,5 mg (3 ml of 0,05% of solution) of Prozerin. If the effect of this dose was insufficient, enter repeatedly the same dose of Prozerin (at emergence of bradycardia do an additional injection of atropine). To children administer the calcium drugs. In hard cases of respiratory depression IVL is necessary. It can be removed by means of a hemodialysis (is more effective) also peritoneal dialysis.

Storage conditions:

In the place protected from light at a temperature from 10 to 25 °C. To store in the places unavailable to children. 
Period of validity 2 years. Not to use after the period of validity specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Solution for intramuscular and intravenous administration of 40 mg/ml in ampoules on the I ml or 2 ml.

5 ampoules in a blister strip packaging. 10 ampoules with the application instruction in a box. 1 - 2 blister strip packagings with the application instruction in a pack or 100 blister strip packagings and 50 application instructions in a box or a box "for a hospital".