Aminoglycoside

Mechanism of action

Aminoglycosides work by binding to the bacterial 30S bacteriostatic or bacteriocidial agents.

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

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 gentamicin.

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

Experimentation with Aminoglycosides as a treatment in Cystic Fibrosis has shown some promising results. In about 10% of Cystic Fibrosis cases, it is caused by a mutation in the genetic code that leads to early termination of elongation in protein synthesis, leading to a truncated and non-functioning CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) protein. It is believed that Gentamicin distorts the structure of the ribosome-RNA complex, leading to a mis-reading of the codon. The misreading causes the ribosome to "skip" over the stop sequence, leading to normal elongation and production of the CFTR protein. The treatment is still experimental, but promising.

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, hearing loss and tinnitus are irreversible, so care must be taken not to achieve a sufficiently high dose. Concomitant administration of a 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]}

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).