Q. 1. Classify, m/a toxic effect, adverse effect and bacterial spectrum of Aminoglycoside (S19)Discus antimicrobial spectrium and adverse effect of aminoglycoside
Systemic aminoglycosides Streptomycin , Amikacin Gentamicin, Sisomicin, Kanamycin, Netilmicin, Tobramycin , Paromomycin,
Topical aminoglycosides Neomycin , Framycetin
Mechanism Penetration to bacterial cell wall: Transport of the aminoglycoside through through porin channels. Transport carrier mediated which is linked to the electron transport chain. Penetration is dependent upon maintenance of a polarized membrane and on oxygen dependent active processes.
Protein synthesis inhibition Binding of aminoglycoside to 30S-50S juncture causes distortion of mRNA codon recognition resulting in misreading of the code: one or more wrong amino acids are entered in the peptide chain and/or peptides of abnormal lengths are produced. Different aminoglycosides cause misreading at different levels depending upon their selective affinity for specific ribosomal proteins.
Toxic effect Ototoxicity: This is the most important dose and duration of treatment related adverse effect. The vestibular or the cochlear part may be primarily affected Cochlear damage: It starts from the base and spreads to the apex; hearing loss affects the high frequency sound first Vestibular damage:
Headache is usually first to appear, followed by nausea, vomiting, dizziness, nystagmus, vertigo and ataxia
Nephrotoxicity: It manifests as tubular damage resulting in loss of urinary concentrating power, low g.f.r., nitrogen retention, albuminuria
Neuromuscular blockade: All aminoglycosides reduce ACh release from the motor nerve endings. They interfere with mobilization of centrally located synaptic vesicles to fuse with the terminal membrane (probably by antagonizing Ca2+) as well as decrease the sensitivity of the muscle endplates to ACh. Spectrum E. coli, Klebsiella pneumoniae, Enterobacter, H.influenzae, Proteus, Serratia and Pseudomonas aeruginosa. Many strains of Brucella, Campylobacter, Citrobacter, Fransisella and Yersinia are also sensitive. Limited number of gram-positive bacteria are susceptible, especially Staph. aureus, Strep. faecalis and some Listeria,