Aminoglycoside antibiotics action

Puglisi, Joseph D. Structural basis for aminoglycoside antibiotic action in Many Faces RNA, (8th SmithKline Beecham Pharm. Res. Symp.), ed. by D.S. Eggleston, Ed. Academic Press, San Diego, CA 1998, p. 97. 

Luciferase assay. In this technique, firefly luciferase is used to measure small amounts of adenosine triphosphate (ATP) in a bacterial culture, ATP levels being reduced by the inhibitory action of aminoglycoside antibiotics. This method may find more application in the future as more active and reliable luciferase preparations become available. 

This difference in half-lives in serum and tissues was misinterpreted in the early literature as an accumulation of aminoglycosides in the inner ear and held responsible for their organ-specificity. Such an interpretation is, however, not tenable. Aminoglycoside antibiotics are present in the fluids (perilymph and endolymph) and the tissues of the inner ear at relatively low levels, typically at one-tenth of peak serum levels. The reason for the differential sensitivity of inner ear sensory cells may then be based on the extreme persistence of the drugs or on an intrinsic susceptibility to their actions, notably to the generation of reactive oxygen species as described later. ... 

Inhibition of protein synthesis by aminoglycoside antibiotics, especially by streptomycin, is bactericidal (rev.46)). The antibiotic binds to the smaller ribosomal subunit and leads to the formation of abortive initiation complexes of ribosomes, streptomycin and amino acyl tRNA which progressively trap ribosomes in the form of such biologically irreversible complexes. When protein synthesis is prematurely terminated by puromycin and ribosomes are thus made available for reinitiation of de novo protein biosynthesis, the bactericidal action of streptomycin is accelerated47). Destruction of ribosomes under the influence of primaquine operationally also results in non-occurrence of protein synthesis and in a marked bactericidal effect48, 49 ... 

Other studies [127] have shown that both calcium and magnesium ions increase the resistance of the organism to aminoglycoside antibiotics. The individual antibiotics varied in their response and, by using spheroplasts of the organism, it was concluded that the site of action of the metal ions was either the cell wall or the linkage between cell wall and cytoplasmic membrane. 

In rats, ototoxicity caused by gentamicin or tobramycin was amehorated by melatonin, which did not interfere with the antibiotic action of the aminoglycosides (70). The free radical scavenging agent alpha-lipoic acid has previously been shown to protect against the cochlear adverse effects of systemically administered aminoglycoside antibiotics, and in a recent animal study it also prevented cochlear toxicity after the administration of neomycin 5% directly to the round window membrane over 7 days (71). 

It may also have ANTIPSYCHOTIC activity, dapiprazole hydrochloride dapiprazole. dapitant [inn] (RPR 100893) is a substituted isoindole, a TACHYKININ RECEPTOR ANTAGONIST, selective for the NK,-receptor subtype. It has potential as an ANTIMIGRAINE AGENT, dapsone [ban, inn, usan] is a sulphone with actions similar to SULPHONAMIDES and with ANTIBACTERIAL activity. It can be used as an antileprotic and for infective dermatitis herpetiformis. and is being investigated for the treatment and prevention of Pneumocystis carinii pneumonia (e.g. in AIDS), daptomycin [ban, inn, usan] is an (aminoglycoside) antibiotic. It has antibacterial properties. 

PJL Daniels. Aminoglycoside Antibiotics, Drug Action and Drug Resistance in Bacteria, vol. 2. Baltimore University Park Press, 1975, pp 77-111. 

Aminoglycoside antibiotics produce neuromuscular blockade by inhibiting ACh release from the preganglionic terminal (through competition with Ca ) and to a lesser extent by noncompetitively blocking the receptor. Tetracyclines also can produce neuromuscular blockade, possibly by chelation of Ca. Additional antibiotics that have neuromuscular blocking action, through both presynaptic... 

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