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13 Cards in this Set
- Front
- Back
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Aminoglycoside penetration into gram negative bacteria
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1. Diffuse through porin proteins/LPS
2. Bind to cation-binding sites on bacterial membrane (think about the absorption here...) 3. Energy-dependent transport across cytoplasmic membrane: REQUIRES O2/ATP |
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What is the mechanism of the Aminoglycosides?
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Acts at the 30S ribosome (different site than tetracycline)
3 ways: -Can't add aatRNAs to the complex -Blocks the translation of already started proteins -Misreading of mRNA - mutated proteins --> apoptosis |
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Aminoglycoside resistance
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Enzymatic alteration (acetylation, phosphorylation, adenylation) of the drugs; amakacin is more resistant than others (this is different than the resistance to Streptomycin in Tb!)
Decreased penetration into bacteria Decreased binding to ribosomes |
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What is the absorption of the Aminoglycosides?
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Parenterally; doesn't absorb from the GI tract (polar cations)
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What is the distribution of the Aminoglycosides?
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Primarily in ECF
High concentrations reached in the renal cortex, inner ear (think about the adverse effects!) |
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Aminoglycoside metabolism
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minimal alterations - think about the fact that they're excreted unchanged in the urine.
T1/2 = 2-3 hr. |
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Aminoglycoside excretion
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Glomerular filtration after the parenteral dose
Majority is excreted unchanged inside urine |
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Aminoglycoside unique information
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Strong post-antibiotic effect: lots of antibacterial activity even after the concentration is below the MIC
1 dose/day Combine well with anti beta-lactam drugs. |
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Aminoglycoside adverse effects
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Ototoxicity
Nephrotoxicity Teratogenic to fetuses |
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Mechanism of Aminoglycoside ototoxicity
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Destruction of vestibular, auditory sensory hair cells
Increased formation of ROS in hair cells --> apoptosis |
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Mechanism of Aminoglycoside nephrotoxicity
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-Retention of Aminoglycoside in proximal tubular cells
-Increased formation of ROS --> apoptosis --Gentamycin, tobramycin are particularly bad for this |
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What are some examples of aminoglycosides?
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Streptomycin
Kanamycin Gentamicin Netilmicin Tobramycin Amikacin (synthetic) |
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Clinical uses of aminoglycosides
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Gram negative aerobes: pseudomonas aeruginosa, enterobacter, klebsiella
Bacterial endocarditis |
