Interactions, drug aminoglycoside antibiotics

In principle, various targets for therapeutic intervention exist. A successful drug can interact with viral receptors, virally encoded enzymes, viral structural components, viral genes or transcripts, or cellular factors required for viral replication. In recent years, attention has been given to small molecules that can target viral-specific RNA sites and prevent the formation of key RNA-protein and RNA-RNA complexes. Aminoglycoside antibiotics have provided the impetus for this approach as discussed below. 

The phosphate backbone of both DNA and RNA provides a negatively charged template for attracting positively charged species. Drugs that commonly exploit this interaction are the aminoglycoside antibiotics. Examples include neomycin B (6.20) and kanamycin A (6.21) (Figure 6.12). This class of compounds binds rRNA in bacteria to interfere with translation of mRNA into functional proteins. 

Interactions Inhaled anesthetics, especially isoflurane, strongly potentiate and prolong neuromuscular blockade. Aminoglycoside antibiotics and antiarrhythmic drugs potentiate and prolong the relaxant action of neuromuscular blockers to a lesser degree. 

Paradelis AG, Crassaris LG, Karachalios DN, Triantapl llidis CJ. Aminoglycoside antibiotics interaction with trimethaphan at the neuromuscular junctions. Drugs Clin Res (1987)... 

Certain aminoglycoside antibiotics, including gentamicin and streptomycin, have been observed to interact with the acidic mucopolysaccharide heparin, condroitin sulfate, and hylauronic acid with reduction of antibacterial activity. The interaction of aminoglycosides with the acidic mucopolysaccharides has been suggested to result in the accumulation of the drug in the kidney and in the inner ear and to partly account for the well-documented nephrotoxicity and ototoxicity of this group of antibiotics. 

The preferred substrates of acetyltransferases are amino-groups of antibiotics, like chloramphenicol, strepto-gramin derivatives, and the various aminoglycosides. The modification is believed to block a functional group involved in the drug-target-interaction. All acetyltransferases use acetyl-coenzyme A as cofactor. 

Aminoglycosides remain clinically important antibiotics. NMR provided the initial breakthrough in structural understanding of aminoglycoside action on the ribosome, and it remains a powerful tool for the biophysical characterization of drug-RNA interaction. The combined use of NMR, X-ray crystallography, thermodynamic and functional assays, and computational methods is needed to drive forward the development of new aminoglycosides with improved clinical properties. The rich data described above, combined with the application of new synthetic methods, bode well for the future. 

Drugs that may interact with aztreonam include other -lactamase-inducing antibiotics and aminoglycosides. 

---