Aminoglycoside
Aminoglycoside antibiotics, aminoglycosides short, belong to the group of the oligosaccharide antibiotics, with combinations of amino sugar - and cyclohexane - blocks. They form a large, still growing group of about 200 water-soluble antibiotics. Excretion is with a short half -life of about two hours mainly through the kidneys.
Streptomycin was the first aminoglycoside antibiotic that was discovered in 1944 by the group of Selman Waksman. Subsequently, many similar substances from actinomycetes were isolated mainly of the genera Streptomyces and Micromonospora.
By convention, the aminoglycoside antibiotics from the genus Streptomyces are designated with the suffix - mycin, while those who are named in the genus Micromonospora with the suffix - micin.
Mechanism of Action
The aminoglycoside antibiotics are highly bactericidal by inhibition of protein synthesis in dividing and non-dividing pathogens by couple to the 30S subunit of the ribosome and cause reading errors of the mRNA. This defective proteins are formed, which lose their biological function. In consequence, for example, incorporated defective proteins in the cell membrane of the bacterium, which results in lysis of the pathogen.
Important representatives
- Amikacin
- Apramycin
- Geneticin ( G418)
- Gentamicins
- Kanamycin
- Netilmicin
- Neomycin
- Paromomycin
- Spectinomycin
- Streptomycin
- Tobramycin
Application & administration
The spectrum of activity includes mainly the Gram negative enteric bacteria and Pseudomonas aeruginosa and the Gram positive staphylococci. Aminoglycosides are ineffective against anaerobic bacteria, because they are captured by an oxygen-consuming process in the cell. Nor do they act against streptococci and Haemophilus species.
Example, they are in serious infections such as meningitis ( meningitis) and endocarditis ( endocarditis) used, as well as frequently against pulmonary infections (Pseudomonas aeruginosa, see above) in the context of an existing cystic fibrosis.
Aminoglycosides are not absorbed and therefore must be administered parenterally for systemic infections. You obtain a good distribution in the extracellular space and cross the placenta, but they pass through the cell walls of the host organism and thus are hardly poor tissue penetration, with an existing meningitis, they are moderately liquorgängig.
The problem is the rapid development of resistance, which can occur under a aminoglycoside. You will be given therefore usually in combination with other antibiotics (especially β -lactam antibiotics).
Side effects
Because of their narrow therapeutic systemic aminoglycosides must be very carefully dosed and therefore are typically intensive medical antibiotics. Aminoglycosides accumulate in the kidney and the inner ear, where they act especially on highly toxic ( nephrotoxicity, ototoxicity ). Other possible side effects include respiratory paralysis, allergies or blood formation disorders. In once- daily dosing, the ratio of desired to undesired effect is particularly favorable. This is related, that it is at the aminoglycosides to concentration-dependent antibiotics, which work well when the peak levels are well above the minimum inhibitory concentration of the pathogen, but the trough levels are very low (< 1μg/ml ). The side effects, however, are aggravated when high trough levels come about, as would be the case with more frequent administration. This is because that accumulates in the affected especially organs kidney and inner ear, the drug and will only be released back into the blood when the peripheral levels are low, this is not the case because the trough levels are high, as the active agent remains in organs and damages them. Therefore, it is important to make an Talspiegelbestimmung before further delivery.
Some aminoglycosides ( neomycin, kanamycin ) are displayed because of its nephrotoxicity and ototoxicity exclusively for the treatment of local infections (skin, mucosa, eye).