Aminoglycosides

 generally considered to be bactericidal

 effective against both gram-positive and gram-negative organisms (although best activity
against gram-negative)
o commonly reserved for serious gram-negative infections
 natural products or semisynthetic derivatives of the natural product
o characterised as glycoside substituted 1,3-diaminoinositols
 inhibits protein synthesis by binding to the 16S unit within the 30S ribosomal subunit of
bacteria (near A-site)
o irreversible binding interaction
o conformational change to the A-site
o mis-reading of mRNA leads to formation of nonsense proteins, killing the bacteria
 hydrophilic - water soluble
o multiple ionisable amine functionality with high pKa
o form acid salts at the basic nitrogens
o not absorbed via the oral route
o orally administered aminoglycosides have GItract antibacterial activity
 primary route of elimination is through the kidney
o generally excreted unchanged by glomerular filtration
o patients with renal impairment exhibit potential for nephrotoxicity due to
accumulation in proximal tubular cells
o (also, ototoxicity – potential for hearing loss and loss of balance)
 resistance is associated with N-acetylation, O-adenylation, O-phosphorylation
 incompatibility with β-lactams as nucleophilic amino group of the aminoglycoside initiates
ring-opening of the β-lactam ring