How does gentamicin cause nephrotoxicity?

Gentamicin (GM) is causing tubular damage through: 1) necrosis of tubular epithelial cells, predominantly in proximal segment and 2) alteration of function of main cellular components involved in transport of water and solutes. The central aspect of GM nephrotoxicity is tubular cytotoxicity.

Why do aminoglycosides cause ototoxicity?

Aminoglycosides appear to generate free radicals within the inner ear, with subsequent permanent damage to sensory cells and neurons, resulting in permanent hearing loss. Two mutations in the mitochondrial 12S ribosomal RNA gene have been previously reported to predispose carriers to aminoglycoside-induced ototoxicity.

How can aminoglycoside antibiotics cause acute kidney injury?

Aminoglycosides are freely filtered across the glomerulus and then partially taken up by, concentrated in, and produce damage to proximal tubular cells. The kidney injury induced by these drugs is related to their preferential accumulation in the kidney cortex.

What is drug induced nephrotoxicity?

Nephrotoxic drugs often induce inflammation in glomerulus, proximal tubules, and surrounding cellular matrix, and then fiberize the kidney tissue. Inflammation that disturb normal kidney functions and induce toxicity includes glomerulonephritis, acute and chronic interstitial nephritis.

Which of the following is a mechanism of aminoglycosides?

There are three mechanisms of aminoglycoside resistance: reduced uptake or decreased cell permeability, alterations at the ribosomal binding sites, or production of aminoglycoside modifying enzymes.

Which antibiotic causes ototoxicity and nephrotoxicity?

The aminoglycoside antibiotic gentamicin can cause both ototoxicity and nephrotoxicity, the severity of which varies with circadian time of daily treatment. However, it is not yet resolved if such drug-induced adverse effects are independent or dependent phenomena.

How do nephrotoxic drugs cause kidney damage?

High metabolic rates of TALH tubular cells increase risk for drug nephrotoxicity. Kidney metabolism of drugs to toxic metabolites and ROS overwhelms local antioxidants and promotes tubular injury. Increased concentrations of potentially nephrotoxic drugs in the medulla and interstitium increase kidney injury.

What are the major toxic effects of aminoglycosides?

The major side effects of aminoglycosides are kidney injury, hearing impairment and vestibular toxicity.

What are the pharmacokinetics of aminoglycosides?

For practical purposes, aminoglycosides are neither protein bound nor biotransformed. The major route of elimination is glomerular filtration, and aminoglycosides undergo some tubular reabsorption. Relevant pharmacokinetic parameters from significant studies have been tabulated.

How can nephrotoxicity of aminoglycosides be reduced?

To minimize the risk of nephrotoxicity, select loading and maintenance aminoglycoside dosages based on estimated creatinine clearance. Also, monitor peak and trough serum aminoglycoside levels, replenish volume, and correct potassium and magnesium abnormalities.