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Related Concept Videos

Inhibitors of Bacterial Protein Synthesis01:25

Inhibitors of Bacterial Protein Synthesis

Aminoglycosides constitute a highly potent class of bactericidal antibiotics that exert their antimicrobial effects by targeting the bacterial ribosome, specifically disrupting protein synthesis. These polycationic molecules consist of amino-modified sugars linked via glycosidic bonds to an aminocyclitol core such as 2-deoxystreptamine or streptamine. Their strong positive charges facilitate tight binding to the negatively charged phosphate backbone of ribosomal RNA (rRNA), primarily at the 16S...
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Estimation of k and VD of Aminoglycosides

Aminoglycosides are a class of antibiotics used to treat various bacterial infections. Clinicians must determine the elimination rate constant (k) and volume of distribution (VD) to optimize therapeutic efficacy and minimize toxicity. The k value represents the rate at which the drug is removed from the body, and the VD reflects the degree to which the drug distributes into body tissues. Accurately estimating these parameters allows healthcare professionals to tailor drug dosing to individual...
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Drug Accumulation During Multiple Dosing: Intermittent IV Infusions

Intermittent intravenous (IV) infusion is a method of drug administration where medications are delivered over short infusion periods followed by intervals of no drug delivery. This approach helps to prevent sustained high drug concentrations in the bloodstream, reducing the risk of adverse effects associated with prolonged exposure. Unlike continuous infusion, steady-state concentrations may not be achieved during a single dosing cycle but can be reached through repeated...
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Gentamicin, an aminoglycoside antibiotic, is commonly administered via intermittent intravenous infusion to treat severe infections. An intermittent one-hour infusion of gentamicin, administered at eight-hour intervals, allows for precise control of plasma drug concentrations, minimizing toxicity while ensuring therapeutic efficacy. Pharmacokinetic principles govern the dynamics of plasma concentrations and can be mathematically described using specific equations.The plasma drug concentration...
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Amphotericin B is a broad-spectrum antifungal agent that exploits structural differences between fungal and mammalian cell membranes. Its amphipathic structure—featuring a hydrophobic polyene-lactone ring and a hydrophilic region containing mycosamine and carboxylic acid groups—enables selective binding to ergosterol, a sterol predominantly found in fungal plasma membranes. This selective interaction underlies the drug’s antifungal activity, although weak binding to cholesterol contributes to...
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Drug toxicities can be stratified into pharmacological, pathological, or genotoxic based on their mechanisms. The incidence and severity of these toxicities generally increase with the drug's concentration in the body and exposure time.Pharmacological toxicity is evident when the therapeutic effects of drugs overshoot into adverse reactions in a predictable, dose-dependent manner. Central nervous system (CNS) depression from barbiturates is a classic example, with effects escalating from...

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Trans-Tympanic Drug Delivery for the Treatment of Ototoxicity
09:52

Trans-Tympanic Drug Delivery for the Treatment of Ototoxicity

Published on: March 16, 2018

Aminoglycoside induced ototoxicity.

O'Neil W Guthrie1

  • 1Duke University, Department of Biology, Developmental, Cell and Molecular Biology (DCMB) Group, French Family Science Center, Durham, NC 27708-0338, USA. owg@duke.edu

Toxicology
|June 3, 2008
PubMed
Summary

Aminoglycoside antibiotics can cause hearing loss. While animal studies show promise for otoprotective strategies, their effectiveness in humans requires further investigation.

Area of Science:

  • Ototoxicity research
  • Pharmacology
  • Neuroscience

Background:

  • Aminoglycosides are widely used, cost-effective bactericidal antibiotics.
  • Otoxicity, specifically sensorineural hearing loss and vestibular dysfunction, is a significant dose-limiting side effect.
  • Cellular damage in the cochlea, involving hair cell and neuron degeneration, is linked to iron-aminoglycoside complexes and reactive oxygen species (ROS).

Purpose of the Study:

  • To explore the development of otoprotective strategies against aminoglycoside-induced ototoxicity.
  • To evaluate the potential of otoprotective interventions in preventing cochlear damage.

Main Methods:

  • Review of animal experiments investigating otoprotective agents against aminoglycoside toxicity.
  • Analysis of mechanisms underlying aminoglycoside-induced ototoxicity, including the role of iron and ROS.

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The Mouse Round-window Approach for Ototoxic Agent Delivery: A Rapid and Reliable Technique for Inducing Cochlear Cell Degeneration
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The Mouse Round-window Approach for Ototoxic Agent Delivery: A Rapid and Reliable Technique for Inducing Cochlear Cell Degeneration

Published on: November 26, 2015

Cochlear Implant Surgery and Electrically-evoked Auditory Brainstem Response Recordings in C57BL/6 Mice
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Cochlear Implant Surgery and Electrically-evoked Auditory Brainstem Response Recordings in C57BL/6 Mice

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Last Updated: Jul 4, 2026

Trans-Tympanic Drug Delivery for the Treatment of Ototoxicity
09:52

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Published on: March 16, 2018

The Mouse Round-window Approach for Ototoxic Agent Delivery: A Rapid and Reliable Technique for Inducing Cochlear Cell Degeneration
12:21

The Mouse Round-window Approach for Ototoxic Agent Delivery: A Rapid and Reliable Technique for Inducing Cochlear Cell Degeneration

Published on: November 26, 2015

Cochlear Implant Surgery and Electrically-evoked Auditory Brainstem Response Recordings in C57BL/6 Mice
09:06

Cochlear Implant Surgery and Electrically-evoked Auditory Brainstem Response Recordings in C57BL/6 Mice

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Main Results:

  • Animal studies have demonstrated encouraging evidence for protecting cochlear hair cells and neurons from aminoglycoside toxicity.
  • The precise mechanisms of aminoglycoside-induced ototoxicity involve ROS potentiation by iron-aminoglycoside complexes.

Conclusions:

  • Otoprotective strategies show promise in preclinical animal models for mitigating aminoglycoside-induced ototoxicity.
  • Translating these protective effects to human ototoxicity remains a critical, unresolved challenge in the field.