Transcript Chapter 16 Cholinesterase Inhibitors

Chapter 86
Aminoglycosides: Bactericidal
Inhibitors of Protein Synthesis
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Aminoglycosides
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Most commonly employed agents
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Gentamicin, tobramycin, amikacin
Narrow-spectrum antibiotics
Bactericidal
Use – aerobic gram-negative bacilli
Can cause serious injury to inner ear and
kidney
Not absorbed from the GI tract
Microbial resistance
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Aminoglycosides
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Adverse effects
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Nephrotoxicity
Ototoxicity
Hypersensitivity reactions
Neuromuscular blockade
Blood dyscrasias
Drug Interactions
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Penicillins, cephalosporins and vancomycin,
ototoxic drugs, nephrotoxic drugs, skeletal muscle
relaxants
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Fig. 86-1. Structural formulas of the major aminoglycosides.
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Fig. 86-2. Mechanism of action of aminoglycosides.
A, Protein synthesis begins with binding of the 50S and 30S ribosomal subunits to messenger RNA (mRNA), followed by attachment of
the first amino acid of the new protein to the 50S subunit. As the ribosome moves down the mRNA strand, additional amino acids are
added to the growing peptide chain. When the new protein is complete, it separates from the ribosome and the ribosomal subunits
separate from the mRNA. B, Aminoglycosides bind to the 30S ribosomal subunit and can thereby (1) block initiation, (2) terminate
synthesis before the new protein is complete, and (3) cause misreading of the genetic code, which causes synthesis of faulty proteins.
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Serum Levels
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Dosing
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Single large dose each day or 2-3 smaller doses
Monitoring of serum levels is common – the
same aminoglycoside dose can produce very
different plasma levels in different patients.
Peak levels must be high enough to kill
bacteria; trough levels must be low enough to
minimize toxicity.
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Gentamicin (Garamycin)
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Used to treat serious infections caused by
aerobic gram-negative bacilli
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Pseudomonas aeruginosa
Escherichia coli
Klebsiella
Serratia
Proteus mirabilis
Adverse effects
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Nephrotoxicity
Ototoxicity
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Fig. 86-3. Plasma gentamicin levels produced with once-daily doses versus divided doses.
The curves depict plasma levels of gentamicin produced with (1) a single large dose administered once a day versus (2) the same daily
total given as three smaller doses spaced 8 hours apart. Plasma levels with both regimens are high enough to produce good
bactericidal effects. The shaded area indicates levels that are low enough to permit washout of the drug from vulnerable cells in the
inner ear. Note that, with once-daily dosing, levels are in the washout range for over 12 hours, versus a total of only 6 hours when
divided doses are used. As a result, ototoxicity is lower with the once-a-day schedule.
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Other Aminoglycosides
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Tobramycin (Nebcin)
Amikacin (Amikin)
Neomycin
Kanamycin (Kantrex)
Streptomycin
Paromomycin (Humatin)
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