Aminoglycosides

Introduction:

Aminoglycosides comprise a complex group of drugs derived from soil Actinomycetes in the genera Streptomyces and Micromonospora that impairs ribosome function and has antibiotic potential. 

Examples includes Streptomycin, gentamicin, tobramycin, and, amikacin.

Mode of Action:

This complex group of drugs inserts itself on sites on the 30S ribosomal subunit of the prokaryotes and causes the misreading of the mRNA, eventually leading to abnormal proteins. 

Figure: Site of inhibition on the prokaryotic ribosome by the drug aminoglycoside, which has a general effect of blocking the protein synthesis. The blockage action is indicated by X. 

Structure of the drug:

The aminoglycoside class of drugs comprises one or more amino sugars and an aminocyclitol ring, a 6-carbon cyclic ring. 

Figure: The structure of an aminoglycoside: Streptomycin.

 Coloured portions of the molecule are found in all members of this drug class. 

Subgroups and Uses of Aminoglycosides:

The aminoglycoside group of drugs possesses a relatively broad antimicrobial spectrum since they inhibit the synthesis of prokaryotic proteins by binding to one of the ribosomal subunits. Therefore, this group of drugs is mostly used to treat infections generally caused by aerobic gram-negative rods and gram-positive bacteria. 

Streptomycin is one of the oldest known drugs. However, it is gradually being replaced by newer forms of drugs that possess less mammalian toxicity. However, even today, Streptomycin is considered an effective antituberculosis agent and an antibiotic of choice for treating bubonic plague and tularaemia. 

Gentamicin is less toxic and is widely administered for infections caused by gram-negative rods such as Escherichia, Pseudomonas, Salmonella, and Shigella. 

Two relatively new aminoglycosides; amikacin, and tobramycin are also used for gram-negative infections, with tobramycin especially useful for treating Pseudomonas infections in cystic fibrosis patients.

Antimicrobial Resistance 

Since this complex group of drugs works by blocking the protein synthesis in prokaryotes, the microbes usually circumvent these drugs by altering the nature of the protein target. Bacteria can thus become resistant to aminoglycosides when point mutations in ribosomal proteins arise.

Drug toxicity:

Aminoglycosides can directly act on the brain and cause seizures. In addition, this group of drugs may damage nerves (very commonly, the eighth cranial nerve), leading to dizziness, deafness, or motor and sensory disturbances. 

Aminoglycosides such as gentamicin are nephrotoxic and are poorly cleared by damaged kidneys. 

Note: The intake of other drugs must be carefully scrutinized because incompatibilities can result in increased toxicity or failure of one or more of the drugs. For example, the combination of aminoglycosides and cephalosporins increases nephrotoxic effects. 

Article by- SAMPRATI PAREKH (MSIWM049)

References: Talaros Foundations in Microbiology – 8^thEdition