Aminoglycoside Ototoxicity Risk Factors and Prevention

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Questions and Answers

Which aminoglycoside has the broadest spectrum of activity?

  • Paromomycin
  • Gentamicin (correct)
  • Streptomycin
  • Framycetin

What contributes to the basic nature of aminoglycoside antimicrobials?

  • The chemical structure of apramycin
  • The aminocyclitol group
  • Hydroxyl groups on the sugar moieties
  • Amino sugars attached to the aminocyclitol ring (correct)

Which aminoglycoside has synergistic activity toward selected gram-positive organisms?

  • Neomycin (correct)
  • Kanamycin
  • Amikacin
  • Tobramycin

What is characteristic of the chemical structure of aminoglycosides?

<p>Amino sugars attached to the aminocyclitol ring in glycosidic linkage (D)</p> Signup and view all the answers

What is the recommended method for obtaining evidence-based withdrawal recommendations for apramycin in the US?

<p>Contacting the Food Animal Residue Avoidance Databank (FARAD) (A)</p> Signup and view all the answers

What is the elimination half-life of apramycin in calves?

<p>~4–5 hours (A)</p> Signup and view all the answers

How is apramycin primarily excreted from the body?

<p>Unchanged in the urine (A)</p> Signup and view all the answers

What is the recommended dosage of apramycin for swine?

<p>22.5 mg/kg, PO, every 24 hours for 7 consecutive days (C)</p> Signup and view all the answers

How does spectinomycin primarily interfere with bacteria?

<p>Interferes with protein synthesis (D)</p> Signup and view all the answers

What percentage of spectinomycin can be recovered unchanged in the urine over 24–48 hours?

<p>~80% (C)</p> Signup and view all the answers

What is the main site of action for aminoglycosides?

<p>Bacterial ribosome (C)</p> Signup and view all the answers

What effect does low oxygen tension have on the efficacy of aminoglycosides?

<p>Diminishes their transfer into bacteria (B)</p> Signup and view all the answers

Which type of microorganisms are aminoglycosides principally effective against?

<p>Gram-negative organisms (B)</p> Signup and view all the answers

What is the pKa range of aminoglycoside drugs?

<p>8-10 (C)</p> Signup and view all the answers

What is the driving force for the transfer of aminoglycosides into bacteria?

<p>Membrane potential (C)</p> Signup and view all the answers

In what environment is the efficacy of aminoglycosides markedly curtailed?

<p>Anaerobic environment (B)</p> Signup and view all the answers

What process is required for aminoglycosides to reach the bacterial ribosome?

<p>Active transport process (C)</p> Signup and view all the answers

What can interfere with the transport of aminoglycosides into bacteria?

<p>Divalent cations located in the LPS, cell wall, or membrane (B)</p> Signup and view all the answers

Which type of antimicrobials commonly demonstrate synergism when used in combination with aminoglycosides?

<p>Beta-lactams (penicillins and cephalosporins) (A)</p> Signup and view all the answers

What effect does an alkaline pH have on the passive movement of aminoglycosides across bacterial cell membranes?

<p>Facilitates it (C)</p> Signup and view all the answers

Which ribosomal subunit is irreversibly bound by aminoglycosides?

<p>30S subunit (D)</p> Signup and view all the answers

Which type of organisms can aminoglycosides be less effective against at low concentrations?

<p>Gram-positive organisms (C)</p> Signup and view all the answers

What is the main reason aminoglycosides are relatively ineffective against facultative anaerobes in a low-oxygen environment?

<p>Oxygen is necessary for active transport of the drug into the microbe. (C)</p> Signup and view all the answers

What is the main factor that leads to indirectly proportional changes in the concentration of an aminoglycoside?

<p>Dehydration (D)</p> Signup and view all the answers

In which body compartment do aminoglycosides accumulate as ionization increases?

<p>Extracellular fluid (B)</p> Signup and view all the answers

What is the main reason for administering aminoglycosides via once-daily treatment?

<p>To minimize adaptive resistance (C)</p> Signup and view all the answers

Why are aminoglycosides contraindicated for short dosing intervals, including continuous infusions?

<p>To minimize adaptive resistance (C)</p> Signup and view all the answers

What is the main reason that aminoglycosides are relatively ineffective against obligate anaerobic bacteria and fungi?

<p>Lack of active transport into the microbe in low-oxygen environments (C)</p> Signup and view all the answers

What is the main route of excretion for aminoglycosides?

<p>Via glomerular filtration in the kidneys (C)</p> Signup and view all the answers

In which body compartment do aminoglycosides reach therapeutic concentrations?

<p>In the synovial, pleural, and peritoneal fluids (D)</p> Signup and view all the answers

What is the most common method of administering aminoglycosides?

<p>Slow intramuscular injection (B)</p> Signup and view all the answers

What complication may arise from excessive accumulation of aminoglycosides in tubular cells?

<p>Tubular cell necrosis (A)</p> Signup and view all the answers

What is the main reason that once-daily treatment with aminoglycosides is indicated?

<p>To prevent adaptive resistance (D)</p> Signup and view all the answers

Which of the following is a mechanism of resistance to aminoglycoside antimicrobials that is plasmid or chromosomally mediated?

<p>Increased production of outer cell membrane protein, H1 (C)</p> Signup and view all the answers

In which bacterial species does impaired transport across the cell membrane occur as a mechanism of nonplasmid-mediated resistance to aminoglycosides?

<p>Clostridium perfringens (C)</p> Signup and view all the answers

Which of the following is a characteristic of streptomycin and dihydrostreptomycin?

<p>Resistance limited by narrow spectra (D)</p> Signup and view all the answers

Under which condition will the efficacy of aminoglycosides be reduced?

<p>Decreased pH (A)</p> Signup and view all the answers

What is the most frequently observed phenomenon in P aeruginosa and other gram-negative bacilli, where bacterial cells develop a reversible resistance to aminoglycosides if they survive the initial ionic binding?

<p>Adaptive resistance (B)</p> Signup and view all the answers

Which aminoglycoside has the broadest spectrum among the group?

<p>Amikacin (B)</p> Signup and view all the answers

Which bacteria are still susceptible to streptomycin and dihydrostreptomycin?

<p>Actinomyces bovis and Pasteurella spp (A)</p> Signup and view all the answers

What happens to adaptive resistance after multiple daily dosing or constant rate infusions?

<p>It persists (B)</p> Signup and view all the answers

What is the effect of once-daily dosing on adaptive resistance?

<p>It reduces adaptive resistance (A)</p> Signup and view all the answers

Which mechanism of resistance increases in P aeruginosa mutants, resulting in resistance to gentamicin?

<p>Increased production of outer cell membrane protein, H1 (B)</p> Signup and view all the answers

Which bacterial species are sensitive to streptomycin?

<p>Mycobacterium tuberculosis, Salmonella spp, E coli, Proteus spp, and Acinetobacter spp (A)</p> Signup and view all the answers

What is the most common route of excretion for aminoglycosides?

<p>Renal excretion (D)</p> Signup and view all the answers

Which phase of elimination reflects the gradual release of the antimicrobial from renal intracellular binding sites?

<p>Gamma phase (C)</p> Signup and view all the answers

What is the recommended peak concentration of aminoglycosides for efficacy?

<p>$10-12$ times the MIC (D)</p> Signup and view all the answers

What is the ideal time to collect a trough concentration for safety monitoring?

<p>Just before the next dose (D)</p> Signup and view all the answers

How should the dosage regimen of aminoglycosides be altered to minimize nephrotoxicity?

<p>By administering lower doses at more frequent intervals (D)</p> Signup and view all the answers

In cases of renal failure, what should be done with the treatment interval for aminoglycosides?

<p>It should be increased (C)</p> Signup and view all the answers

What is the recommended action if plasma creatinine concentrations are increased in cases of renal failure?

<p>Increase the treatment interval (D)</p> Signup and view all the answers

What should be done to assure that 10 times the MIC is achieved at peak concentrations?

<p>Increase the dose rate and frequency (B)</p> Signup and view all the answers

What is the preferred number of time points to monitor when administering aminoglycosides intravenously?

<p>$2$ time points (peak and trough concentrations) (D)</p> Signup and view all the answers

When should trough concentrations generally be collected?

<p>Just before the next dose (B)</p> Signup and view all the answers

What is the most common method of excretion for aminoglycosides?

<p>Renal excretion (C)</p> Signup and view all the answers

What factor determines how half-life will vary?

<p>Volume of the extracellular fluid compartment (D)</p> Signup and view all the answers

What is the order of aminoglycosides from most ototoxic to least ototoxic?

<p>Gentamicin, sisomicin, neomycin, netilmicin (C)</p> Signup and view all the answers

Which drug has been shown to decrease the risk of aminoglycoside ototoxicity in people?

<p>N-acetylcysteine (D)</p> Signup and view all the answers

What is the effect of aminoglycosides on muscle weakness and respiratory arrest?

<p>Causes muscle weakness and respiratory arrest (B)</p> Signup and view all the answers

What is the mechanism behind the neuromuscular blockade caused by aminoglycosides?

<p>Competitive inhibition of acetylcholine release (C)</p> Signup and view all the answers

Which drug antagonizes the neuromuscular blockade caused by aminoglycosides?

<p>Neostigmine (D)</p> Signup and view all the answers

What adverse effect may be aggravated by aminoglycosides when administered to animals under halothane anesthesia?

<p>Cardiovascular depression (D)</p> Signup and view all the answers

What laboratory finding is a noteworthy adverse effect associated with aminoglycosides?

<p>Proteinuria (D)</p> Signup and view all the answers

What happens if aminoglycosides are administered with loop-acting diuretics, especially furosemide?

<p>Enhanced nephrotoxicity (A)</p> Signup and view all the answers

What do high concentrations of carbenicillin, ticarcillin, and piperacillin do to aminoglycosides?

<p>Inactivate them (A)</p> Signup and view all the answers

Which of the following is true about withdrawal intervals for aminoglycosides in production animals?

<p>Aminoglycosides are not prohibited from extralabel use in production animals in the US. (A)</p> Signup and view all the answers

Which can enhance the antibacterial efficacy of aminoglycosides?

<p>Beta-lactam antimicrobials (A)</p> Signup and view all the answers

What should veterinarians be aware of regarding the withdrawal times for aminoglycosides used in an extralabel fashion in production animals?

<p>Withdrawal times vary depending on the specific drug used. (D)</p> Signup and view all the answers

What is the primary concern associated with aminoglycoside nephrotoxicity?

<p>Renal failure due to acute tubular necrosis (C)</p> Signup and view all the answers

How can nephrotoxicity be detected in animals undergoing aminoglycoside treatment?

<p>Increased fractional sodium excretion (A)</p> Signup and view all the answers

What role does mitochondria play in aminoglycoside-induced ototoxicity?

<p>Prominent role in ototoxicity (C)</p> Signup and view all the answers

Which animals are particularly sensitive to the toxic vestibular effects of aminoglycosides?

<p>Cats (B)</p> Signup and view all the answers

What characteristic reflects permanent damage and loss of the hair cells in the organ of Corti due to aminoglycoside-induced ototoxicity?

<p>Loss of high-frequency hearing (C)</p> Signup and view all the answers

In renal insufficiency, what alteration is generally made to the interval between doses of aminoglycosides?

<p>Prolonged interval (A)</p> Signup and view all the answers

What is the driving force for the transfer of aminoglycosides into proximal tubular epithelial cells?

<p>Active uptake due to lower pH (A)</p> Signup and view all the answers

What should be considered for treatment to minimize aminoglycoside nephrotoxicity?

<p>[N-acetylcysteine] treatment (D)</p> Signup and view all the answers

What is necessary for kidneys to eliminate accumulated aminoglycosides?

<p>Drug-free period before next dose (B)</p> Signup and view all the answers

What is indicative of aminoglycoside nephrotoxicity based on laboratory tests?

<p>Increased BUN and creatinine concentrations (A)</p> Signup and view all the answers

In cases of excessive accumulation, what complication may arise from aminoglycosides in tubular cells?

<p>Tubular necrosis and injury (B)</p> Signup and view all the answers

What contributes to the reduction of toxicity and negative impact on efficacy while treating renal insufficiency with aminoglycosides?

<p>Decreasing plasma drug concentrations below recommended levels (B)</p> Signup and view all the answers

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