Antibiotic therapy Flashcards
aminoglycosides
What are the most commonly used in feline medicine
Parenteral and topical gentamicin
Parenteral amikacin
Topical neomycin
What is the mechanism of action of aminoglycosides
They block the production of proteins by binding to the small and in some cases, large ribosomal subunits of bacteria, where they interfere with the proofreading process of amino acid assembly
Which pharmacological effect can be deduced from their mechanism of action
The binding of these drugs is strong and irreversible giving an antibacterial effect long after the blood levels have dropped (this is known as a post-antibiotic effect)
- This means thatt the dosage interval can be quite prolonged
- They are concentration dependent
What is the spectrum of action of aminoglycosides
They are primarily effective against gram-negative aerobes, although some gram-positive organisms may be susceptible
They have not activity against obligate anaerobes as they require oxygen for transport into bacterial cells
They are bactericidal, concentration-dependent antibiotics
What class of antibiotics can be used concurrently to aminoglycosides to have a synergistic antiibacterial activity
Co-administration with beta-lactam is often used parenterally in animals with serious infection (e.g., sepsis)
How resistance to aminoglycosides can develop
The development of resistance is mediated via one or a combination of three mechanisms:
- Decreased bacterial penetrability
- Plasmid-associated production of enzymes that inactivate the drug - Alteration of receptor sites on bacterial ribosomes
What are the principal pharmacokinetics facts about aminoglycosides
They mus be administered parenterally because oof their poor absorption from the GI tract
Toxicity may result if large amounts of topical preparations are applied to damaged skin and mucous membranes
They are not lipid soluble, therefore they do not tend to penetrate tissues well
Aminoglycosides are eliminated unchanged rapidly in the urine by glomerular filtration and tubular excretion (urine concentration much higher than blood concentration)
- It is recommended that they are not used in animal with renal dysfunction
What is the main toxicity of aminoglycosides
Aminoglycosides tend to accumulate in the renal tubular cells and the cells of the inner ear, which may cause cell necrosis
- All of the sensory cells of the inner ear are susceptible, however those required for hearing seem to be more affected than those involved in balance regulation
- Thus, topical solutions should always be used with caution, especially if the integrity of the tympanic membrane is questionable or the animal has reduced renal function
Which monitoring should be performed in animals treated with injectable aminoglycosides
Monitoring of tubular function (urine specific gravity, presence of glycosuria, proteinuria, renal casts) should be performed regularly
Indicators of glomerular filtration, such as plasma urea and creatinine may also be monitored, however they are less accurate indicators of aminoglycosides toxicity
What are the clinical consequences of the potential renal toxicity of aminoglycosides
They should not be administered concurrently with other drugs that are known to cause renal tubular dysfunction (e.g., amphotericin B)
Renal toxicity appears to be enhanced by the administration of smaller, more frequent doses, than an equivalent total dose given once daily
Co-administration of diuretics (especially furosemide) enhances the nephro- and ototoxic effects of aminoglycosides
