Aminoglycosides

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  1. The aminoglycosides are among the most active antibiotics against aerobic gram-negative bacilli, including Pseudomonas aeruginosa
  2. There are eight drugs in this class, but clinically relevant are genatmicin, tobramycin, and amikacin.
  3. Bind to 30s ribosome (erythromycin binds 50s ribosome)
  4. Penetrate CSF poorly
  5. Metabolism does not occur in the host and is excreted in the urine by glomerular filtration
  6. Toxicity:
    1. ototoxicity related to high-peak levels( can produce irreversible hearing loss and vestibular damage)
    2. nephrotoxicity in up to 20% ( enhanced by hypovolemia, hypokalemia, hypomagnesemia, preexistent renal disease, old age, concurrent treatment with other nephrotoxic agents)
      1. Cylindrical casts in the urine, proteinuria, and inability to concentrate are early signs of toxicity, followed by serum rise of creatinine
    3. neuromuscular blockade ( aminoglycosides should be avoided in myasthenia gravis)
  7. Once-daily dosing based on body weight is equivalent to divided-dose regimens in efficacy and toxicity, but less costly and time consuming.
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