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Aminoglycosides

Antibiotics with amino+sugar molecules linked by glycosidic bond.

  1. Narrow spectrum
  2. Bactericidal
  3. All share common mechanisms, toxicity
  4. Narrow therapeutic index
  5. Exhibit postantibiotic leucocyte enhancement
  6. NO ACTION AGAINST ANAEROBES
     
    i. Active against aerobic gram negative bacteria  

MAO

  1. Three fold mechanism of killing:
    1. Inhibit polysome
    2. Insert wrong amino acids (Misreading of amino acid complexes)
    3. Premature termination of chain elongation

MOR

  1. Bacteria liberate antibiotic inactivating enzymes (DNAs, RNAs, sulphatases etc)
     
    i. Amikacin is most stable aminoglycoside

p/k

  1. No oral absorption
  2. No metabolism
  3. MIC=<2mg/ml
  4. Do not enter blood brain barrier
  5. Eliminated unchanged
    1. C/I renal failure
    2. Or reduce dose

Use

  1. Streptomycin (discovered by Waksman)
     
    DOC
    1. Plague                
    2. Brucellosis                
    3. Rhinoscleroma    
    4. Pelvic infections          
    5. Enterococcal endocarditis
  2. Gentamicin is used in
    1. Staphyloccocal infection
    2. Pseudomonal infection
  3. Paromomycin
    1. Asymptomatic ameobiasis
    2. Past drug-diloxanide furate
  4. Neomycin
    1. Past drug for bowel sterlization
    2. Present drug-lectulose
  5. Toberamycin
     
    i. Antipseudomonal
  6. Spectinomycin
    1. Aminocyclitol antibiotic
    2. Gonnohoea in patients with penicillin allergy
  7. Kanamycin (Semisynthetic amikacin)
  8. Capreomycin
     
    i. MDR TB
  9. Amikacin
     
    i. Gram negative sepsis\
  10. Netilmycin
    1. Broadest spectrum
    2. Most efficacious
    3. Safest 

S/E

  1. Ototoxicity
    1. MC side effect
       
      i. Vestibular
    2. Streptomycin
       
      i. Headache---ataxia, Auditory
    3. KAN (Kanamycin, Amikacin, Neomycin)
       
      i. Loss of high frequency followed by low frequency
       
      ii. Base of hair cells is first affected---apex 
  2. Nephrotoxicity
    1. GTN (Gentamicin, toberamycin, neomycin)
    2. Dilute urine---rise of BUN
    3. Streptomycin---least nephrotoxic 
  3. Neuromuscular m block
     
    a. Neomycin 
  4. Reversed by calcium/neostigmine





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