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Streptomycin


ACCESSION NB: DB01082 (APRD00412)


TYPE: small molecule


GROUP: approved


DESCRIPTION:
Streptomycin is an aminoglycoside antibiotic produced by the soil actinomycete Streptomyces griseus. It acts by binding to the 30S ribosomal subunit of susceptible organisms and disrupting the initiation and elongation steps in protein synthesis. It is bactericidal due to effects that are not fully understood.

VOLUME OF DISTRIBUTION: Not Available

CATEGORIES:
Anti-Bacterial Agents Protein Synthesis Inhibitors Aminoglycosides

ABSORPTION: Rapidly absorbed after intramuscular injection with peak serum concentrations attained after 1 - 2 hours. Not absorbed in the GI tract.

INDICATION:
For the treatment of tuberculosis. May also be used in combination with other drugs to treat tularemia (Francisella tularensis), plague (Yersia pestis), severe M. avium complex, brucellosis, and enterococcal endocarditis (e.g. E. faecalis, E. faecium).

PHARMACODYNAMICS:
Streptomycin is an aminoglycoside antibiotic. Aminoglycosides work by binding to the bacterial 30S ribosomal subunit, causing misreading of t-RNA, leaving the bacterium unable to synthesize proteins vital to its growth. Aminoglycosides are useful primarily in infections involving aerobic, Gram-negative bacteria, such as Pseudomonas, Acinetobacter, and Enterobacter. In addition, some mycobacteria, including the bacteria that cause tuberculosis, are susceptible to aminoglycosides. Infections caused by Gram-positive bacteria can also be treated with aminoglycosides, but other types of antibiotics are more potent and less damaging to the host. In the past the aminoglycosides have been used in conjunction with penicillin-related antibiotics in streptococcal infections for their synergistic effects, particularly in endocarditis. Aminoglycosides are mostly ineffective against anaerobic bacteria, fungi and viruses.

MECHANISM OF ACTION:
Aminoglycosides like Streptomycin "irreversibly" bind to specific 30S-subunit proteins and 16S rRNA. Specifically Streptomycin binds to four nucleotides of 16S rRNA and a single amino acid of protein S12. This interferes with decoding site in the vicinity of nucleotide 1400 in 16S rRNA of 30S subunit. This region interacts with the wobble base in the anticodon of tRNA. This leads to interference with the initiation complex, misreading of mRNA so incorrect amino acids are inserted into the polypeptide leading to nonfunctional or toxic peptides and the breakup of polysomes into nonfunctional monosomes.

PROTEIN BINDING:
Not Available

TOXICITY:
Nephrotoxic and ototoxic potential. Nephrotoxicity is caused by accumulation of the drug in proximal renal tubular cells, which results in cellular damage. Tubular cells may regenerate despite continued exposure and nephrotoxicity is usually mild and reversible. Streptomycin is the least nephrotoxic of the aminoglycosides owing to the small number of cationic amino groups in its structure. Otoxocity occurs via drug accumulation in the endolymph and perilymph of the inner ear. Accumulation causes irreversible damage to hair cells of the cochlea or summit of the ampullar cristae of the vestibular complex. High frequency hearing loss precedes low frequency hearing loss. Further toxicity may result in retrograde degeneration of the auditory nerve. Vestibular toxicity may result in vertigo, nausea and vomiting, dizziness and loss of balance. LD50=430 mg/kg (Orally in rats with Streptomycin Sulfate); Side effects include nausea, vomiting, and vertigo, paresthesia of face, rash, fever, urticaria, angioneurotic edema, and eosinophilia.

AFECTED ORGANISMS:
Enteric bacteria and other eubacteria