Bactericidal drug, at least under aerobic conditions, this property is reduced under anaerobic and hyperosmolar conditions. To exert its mechanism of action, it is actively transformed through the bacterial membrane, irreversibly binds to one or more specific receptor proteins of the 30S subunit of bacterial ribosomes and interferes with the initiation complex between the mRNA and the 30S subunit. . DNA can be misread, leading to the production of non-functional proteins; the polyribosomes separate and are not capable of synthesizing proteins , which implies an accelerated transport of aminoglycosides and increases the rupture of the cytoplasmic membranes of the bacteria and the consequent cell death.
Composition
Each bulb contains 100 mg of tobramycin sulfate.
Pharmacokinetics
It is fully and rapidly absorbed after intramuscular administration. Widely distributed in the extracellular fluid; the initial redistribution to tissues is 5 to 15% with accumulation in the cells of the renal cortex; it also crosses the placenta. High concentrations appear in the urine; however, in bronchial secretions, cerebrospinal fluid, bile, subarachnoid space, ocular tissue and aqueous humor the concentration is low. It is not metabolized. It is widely excreted in unchanged form by glomerular filtration, so that high concentrations appear in the urine. Approximately 53 to 98% of a single intravenous dose is excreted in the urine in 24 hours. However, when kidney function is compromised, an accumulation of significance and subsequent toxicity can appear rapidly if the dose is not adjusted. The plasma half-life is longer in newborns because the immature renal system is unable to excrete this drug rapidly; during the first days, the half-life can exceed 5 or 6 hours. Also in the elderly there is evidence of aprolonged half- life . In patients with severe burns, the half-life can be significantly shortened.
Indications
Use similar to gentamicin with higher activity against Acinetobacter strains and Pseudomona aeruginosa species, but less active against other gram-negative germs. In general, most strains resistant to gentamicin are also resistant to tobramycin. It is indicated in septicemia, severe lower respiratory infections, severe CNS infections, intra-abdominal infections (includes peritonitis), complicated urinary tract infections, and skin and bone infections , caused by E. coli, Enterobacter spp., Klebsiella, P. aeruginosa , Staphilococcus aureus, Proteus spp., Serratia marcences, Providencia spp and Citrobacter spp.
Contraindications
Intrathecal administration. Hypersensitivity to aminoglycosides. Myasthenia gravis.
Precautions
Children: neonates have prolonged renal elimination and risk of toxicity. Older adults: have a higher risk of ototoxicity / nephrotoxicity; renal function should be monitored and the dose adjusted accordingly. DR and DH: increase the risk of nephrotoxicity and ototoxicity (plasma concentrations should be measured). In case of cystic fibrosis and burns, higher doses and shorter administration intervals are required, it is preferred to measure plasma concentrations. Dehydration, hypovolemia, heart failure: increased risk of nephrotoxicity. Administer with caution in cases of: infant botulism, parkinsonism, VIII cranial nerve impairment. Obesity: estimate the dose based on the ideal weight plus the correction factor, it is preferred to measure plasma concentrations. Caution in patients with muscle weakness (risk of neuromuscular block).
Adverse reactions
Common: nephrotoxicity, ototoxicity (bilateral and permanent deafness), paresthesia, seizures, dizziness, nausea, vomiting, ataxia, unsteadiness to walk. Occasional: hypersensitivity (skin rash), fever, headache, tremor, eosinophilia, hypotension, arthralgia, anemia, liver disorders (elevated TGP, TGO, bilirubin, alkaline phosphatase and cholinesterase). Rare:neuromuscular blockage (respiratory depression, muscle weakness), hypomagnesemia in prolonged treatment, colitis associated with antibiotics, stomatitis and very rarely central neurotoxicity (encephalopathy, lethargy, confusion, hallucinations). Additionally, tobramycin contains sodium metabisulfite, which can cause allergic reactions, as well as anaphylactic shock and life-threatening asthmatic episodes in susceptible individuals. The prevalence of patients who may develop an allergic reaction to sulfite is unknown and should be relatively low, but it is more frequent in asthmatics. Other adverse effects that have been related to tobramycin include increased serum bilirubin, decreased plasma levels of calcium, magnesium, sodium and potassium, anemia, granulocytopenia, leukopenia, thrombocytopenia,
Interactions
Avoid simultaneous use with ototoxic, nephrotoxic and neurotoxic drugs. Indomethacin increases serum tobramycin levels in neonates. Concurrent use with anticoagulants may increase the hypothrombinemic effect. With bisphosphonates, the risk of hypocalcemia is usually increased. Together with botulinum toxin, the risk of neuromuscular blockage can be increased. Antagonism is usually established if used with neostigmine or pyridostigmine.
Posology
It is recommended to calculate the dose in relation to the estimated ideal weight; It is administered IM or IV slowly (in no less than 3 min) or by IV infusion of 20 min to 2 h, in 50 to 100 mL of 0.9% sodium chloride or 5% glucose. In adults the dose is 3 to 5 mg / kg / day every 6-8 hours, for 7 to 10 days, depending on the severity. Sometimes it is necessary to administer 8-10 mg / kg / day in equal divided doses to achieve therapeutic plasma concentrations in patients with cystic fibrosis. In children older than one week of age, the dose is 6 to 7.5 mg / kg / day in 3 divided doses over 7 to 10 days. In preterm infants and term infants the dose is 2 mg / kg every 12 h. The average duration of the treatments is 7-10 days, although in complicated infections this period can be extended and in this case, It is necessary to monitor the auditory, renal and vestibular functions, since the toxicity increases after 10 days of continuous treatment. Mild to moderate urinary tract infections: 2-3 mg / kg / day IM in a single daily dose. Extended interval schedule of administration (once daily dose): see introduction to aminoglycosides.