Aminoglycoside Toxicosis

Aminoglycoside Toxicosis



Basic Information image



Definition


The aminoglycosides are large molecules with numerous amino acid groups, making them basic polycations that are highly ionized at physiologic pHs. These physical properties are important in their known toxicities: nephrotoxicity, ototoxicity, and neuromuscular blockade.



Epidemiology



Species, Age, Sex


All ages and sexes are affected, but neonates and geriatrics are more at risk because of their reduced renal function.



Risk Factors




• Prolonged aminoglycoside therapy (>7–10 days)


• Acidosis and electrolyte disturbances (hypokalemia, hyponatremia)


• Volume depletion (shock, endotoxemia)


• Concurrent therapy with nephrotoxic drug (eg, nonsteroidal antiinflammatory drugs [NSAIDs]) or diuretics


• Preexisting renal disease


• Elevated plasma trough concentrations



Clinical Presentation



History, Chief Complaint




• Nonoliguric renal failure


• Hearing loss


• Neuromuscular blockade



Physical Exam Findings


Usually related to the original disease for which the aminoglycoside was being administered



Etiology and Pathophysiology


Nephrotoxicity is caused by accumulation of the drug in the renal tubular epithelial cells.



• Aminoglycosides enter the renal tubule after filtration through the glomerulus.


• Cationic aminoglycoside molecules bind to anionic phospholipids on the proximal tubular cells.


• The aminoglycoside is taken into the cell by carrier-mediated pinocytosis and translocated into cytoplasmic vacuoles, which fuse with lysosomes.


• With additional pinocytosis, drug continues to accumulate within the lysosomes.


• The accumulated aminoglycoside interferes with normal lysosomal function, and the overloaded lysosomes eventually swell and rupture.


• Lysosomal enzymes, phospholipids, and the aminoglycoside are released into the cytosol of the proximal tubular cell, disrupting other organelles and causing cell death.


• Neomycin is the most nephrotoxic, and streptomycin and dihydrostreptomycin are the least nephrotoxic.


• Amikacin is often recommended in critical patients over gentamicin because it is considered less nephrotoxic.


Ototoxicity:



• Occurs by the same mechanisms as nephrotoxicity


• Not typically diagnosed in horses because of failure to identify partial hearing losses

• Toxicity varies with the drug


• Vestibular damage (balance): Streptomycin, gentamicin

• Cochlear damage (hearing): Amikacin, kanamycin, neomycin

• Both: Tobramycin

Neuromuscular blockade:



• Rapid IV administration causes bradycardia, reduced cardiac output, and hypotension through an effect on calcium metabolism. These effects are of minor significance.


• Paralysis of skeletal muscles


• A rare effect

• From blockade of acetylcholine at the nicotinic cholinergic receptor

• Most often seen when anesthetic agents are administered concurrently


Diagnosis image



Differential Diagnosis


NSAID-induced and other drug-induced renal failure

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Jul 24, 2016 | Posted by in SMALL ANIMAL | Comments Off on Aminoglycoside Toxicosis

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