Post on 30-May-2018
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AMINOGLYCOSIDESAMINOGLYCOSIDES
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Streptomycin Neomycin Kanamycin
Amikacin GentamicinTobramycin Sisomycin Netilmicin
AminoglycosidesAminoglycosides
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Are amino sugars bound by glycosidicbridges to a hexose nucleus
They are used widely against gram-negative enteric bacteria (bacteremia andsepsis, in combination with vancomycin ora penicillin for endocarditis for thetreatment of tuberculosis)
AminoglycosidesAminoglycosides
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Have a hexose ring, either streptidine or 2-deoxystreptamine to which various aminosugars are attached by glycosidic linkages
They are water-soluble Stable in solution More active at alkaline than at acidic pH
AminoglycosidesAminoglycosides
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Mechanism of ActionMechanism of Action
Irreversible inhibitors of protein synthesis Generally bactericidal and their efficacy in
several cases can be greatly enhanced bythe concomitant use of cell wall inhibiting
-lactams and glycopeptides Activity: primarily directed toward gram-
negative bacilli and mycobacteria
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1. Interference with the initiation complex ofpeptide formation
2. Misreading of mRNA, which causesincorporation of incorrect amino acids intothe peptide, resulting in a nonfunctional ortoxic protein
3. Breakup of polysomes into nonfunctionalmonosomes
* Occurs more or less simultaneously, overalleffect is irreversible and lethal for the cell
Protein synthesis is inhibited byProtein synthesis is inhibited byaminoglycosides in 3 waysaminoglycosides in 3 ways
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Ribosomal mutations Reduced intracellular transport Plasmid-mediated aminoglycosides-
modifying enzymes (acethyltransferases,aenyltransferases andphosphotransferases)
Mechanism of ResistanceMechanism of Resistance
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Poorly absorbed orallyDo not penetrate well into the CNS,
bronchial secretions or certain microbialcells but are effective intracellularly in the
treatment of tuberculosis, plaque,brucellosis, and tularemia
Administered in high parenteral dosesNormal elimination half-lives are 2-3 hrs.
which can be extended to 24-100 hrs. inend-stage renal diseaseExcreted primarily by glomerular filtration
PharmacokineticsPharmacokinetics
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Parental aminoglycosides currentlyavailable include amikacin, gantamicin,kanamycin, netilmicin, streptomycin andtobramycin
Kanamycin and neomycin are available fororal use for gastointestinal infections
Aminoglycosides are indicated forinfections caused by gram-negativeaerobic bacteria
Often combined with a penicillin orcephalosporin for various infections
General therapeutic usesGeneral therapeutic uses
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Renal toxicity and both auditory andvestibular ototoxicity
Nephrotoxicity is caused by inhibition ofanintracellular lysosomal phospholipase inthe renal proximal tubules resulting inaminoglycoside accumulation andsubsequent reduced glomerular filtration,reduces water and Na transport, reducedmitochondrial respiration and reducedprotein synthesis resulting in renalnecrosis
Adverse effectsAdverse effects
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Nephrotoxicity of aminglycosides isincreased by vancomycin, cephalosporinand methoxyflurane
Loop diuretics increase auditory toxicity
Drug interactionsDrug interactions
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Produced by Streptomyces griseus Mainly used as a second-line agent for
treatment of tuberculosis Given intramuscularly or intravenously Used only in combination with other agents
to prevent emergence of resistance Given intramuscularly in combination with
an oral tetracycline Most serious toxic effect is disturbance of
vestibular function-vertigo and loss ofbalance
A.A.StreptomycinStreptomycin
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B. GentamicinB. Gentamicin
Isolated from Micromonospora purpurea Effective against both gram-negative
organism Inhibits in vitro many strains of staphylococci
and coliforms and other gram-negativebacteria
Active alone, but also as a synergisticcompanion with -lactam antibiotics
In combination with vancomycin or apenicillin produces a potent bactericidaleffect, which in part is due to enhanceduptake of drug that occurs with inhibition of
cell wall synthesis
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C. TobramycinC. Tobramycin
Has an antibacterial spectrum similar tothat gentamicin
Given intramuscularly or intravenously Adverse reaction: ototoxic and nephrotoxic
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E. Neomycin andE. Neomycin andKanamycinKanamycin Active against gram-negative and gram-
positive bacteria and some mycobacteria Poorly absorbed from the GIT Limited to topical and oral use Neomycin is too toxic for parenteral use Adverse reaction: nephrotoxicity and
ototoxicity
Auditory function is affected more thanvestibular
Deafness has occurred
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endend
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