Q.1. M/A and adverse effect of Chloramphenicol and aminoglycoside (W 15, S17)
M/A Chloramphenicol: Inhibits bacterial protein synthesis by interfering with ‘transfer’ of the elongating peptide chain to the newly attached aminoacyl-tRNA at the ribosome-mRNA complex. It specifically attaches to the 50S ribosome near the acceptor (A) site and prevents peptide bond formation between the newly attached amino acid and the nascent peptide chain without interfering with the aminoacyl-tRNA attachment to the 30S ribosome (the step blocked by tetracycline).
Adverse effect: At high doses, it can inhibit mammalian mitochondrial protein synthesis as well. Bone marrow cells are especially susceptible.
Antimicrobial spectrum: Chloramphenicol is primarily bacteriostatic, though high concentrations have been shown to exert cidal effect on some bacteria, e.g. H. influenzae and N. meningitidis. It is a broad-spectrum antibiotic, active against gram-positive and negative cocci and bacilli, rickettsiae, mycoplasma Aminoglycoside Clasification
Systemic aminoglycosides: Streptomycin, Amikacin, Gentamicin, Kanamycin, Tobramycin,
Topical aminoglycosides Neomycin, Framycetin
M/A aminoglycoside The aminoglycosides are bactericidal antibiotics, all having the same general pattern of action which may be described in two main steps:
Transport of the aminoglycoside through the bacterial cell wall and cytoplasmic membrane: They diffuse across the outer coat of gram-negative bacteria through porin channels. Carrier mediated which is linked to the electron transport chain.
Binding to ribosomes resulting in inhibition of protein synthesis: Streptomycin binds to 30S ribosomes, but other aminoglycosides bind to additional sites on 50S subunit, as well as to 30S-50S interface. They freeze initiation of protein synthesis prevent polysome formation and promote their disaggregation to monosomes so that only one ribosome is attached to each
strand of mRNA. Binding of aminoglycoside to 30S-50S juncture causes distortion of mRNA codon recognition resulting in misreading of the code: wrong amino acids are entered in the peptide chain and/or peptides of abnormal lengths are produced.
Adverse effect Ototoxicity: Hearing defect. The vestibular or the cochlear part may be primarily affected.
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.