Aminoglycoside

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Aminoglycosides are a group of antibiotics that are effective against certain types of bacteria. They include amikacin, gentamicin, kanamycin, neomycin, netilmicin, paromomycin, streptomycin, tobramycin and apramycin. Those which are derived from Streptomyces genus are named with the suffix -mycin, while those which are derived from Micromonospora are named with the suffix -micin.

1 Mechanism of action
2 Spectrum of activity
3 Toxicity
4 Routes of administration
5 External links

[edit] Mechanism of action

Aminoglycosides work by binding to the bacterial 30S ribosomal subunit (some work by binding to the 50s subunit), inhibiting the translocation of the peptidyl-tRNA from the A-site to the P-site and also causing misreading of mRNA, leaving the bacterium unable to synthesize proteins vital to its growth. But their exact mechanism of action is not fully known. There is no significant relationship between the dose administered and the resultant plasma level in blood. TDM, therapeutic drug monitoring, is necessary to obtain the correct dose. These agents exhibit a post-antibiotic effect, where there is no or very little drug levels detectable in blood, but there still seems to inhibit bacterial re-growth. This is due to strong, irreversible binding to the ribosome, and remains intracellular long after plasma levels drop. This allows a prolonged dosage interval.

Blocks initiation of protein synthesis, blocks translation, and incorporates incorrect amino acid into chain.

[edit] Spectrum of activity

Aminoglycosides are useful primarily in infections involving aerobic, Gram-negative bacteria, such as Pseudomonas, Acinetobacter, and Enterobacter. In addition, some Mycobacteria, including the bacteria that cause tuberculosis, are susceptible to aminoglycosides. The most frequent use of aminoglycosides is empiric therapy for serious infections such as septicemia, complicated intraabdominal infections, complicated urinary tract infections, and nosocomial respiratory tract infections. Usually, once cultures of the causal organism are grown and their susceptibilities tested, aminoglycosides are discontinued in favor of less toxic antibiotics.

Streptomycin was the first effective drug in the treatment of tuberculosis, though the role of aminoglycosides such as streptomycin and amikacin has been eclipsed (because of their toxicity and inconvenient route of administration) except for multiple drug resistant strains.

Infections caused by Gram-positive bacteria can also be treated with aminoglycosides, but other types of antibiotics are more potent and less damaging to the host. In the past the aminoglycosides have been used in conjunction with beta-lactam antibiotics in streptococcal infections for their synergistic effects, particularly in endocarditis. One of the most frequent combinations is Ampicillin (a beta-lactam, or penicillin-related antibiotic) and Gentamicin. Often, hospital staff refer to this combination as "amp and gent" or more recently called "pen and gent" for penicillin and gentamycin.

Aminoglycosides are mostly ineffective against anaerobic bacteria, fungi and viruses.

[edit] Toxicity

The toxicity of these agents are dose-related, and therefore every individual can get these side effects provided the dose is sufficiently high enough. Because of their potential for ototoxicity and nephrotoxicity (kidney toxicity), aminoglycosides are administered in doses based on body weight. Vestibular damage and hearing loss are irreversible, so care must be taken not to achieve a sufficiently high dose. Concomitant administration of a cephalosporin may lead to increased risk of nephrotoxicity while administration with a loop diuretic increases the risk of ototoxicity. Blood drug levels and creatinine are monitored during the course of therapy, as there is a highly variable dose to plasma level in blood. Serum creatinine measurements are used to estimate how well the kidneys are functioning and as a marker for kidney damage caused by these drugs. They may react with and prolong the actions of neuromuscular agents. Impaired renal function necessitates a reduced dose.^{[citation needed]}

[edit] Routes of administration

Since they are not absorbed from the gut, they are administered intravenously and intramuscularly. Some are used in topical preparations for wounds. Oral administration can be used for gut decontamination (e.g. in hepatic encephalopathy).