Antibiotic workshop Flashcards
Peak plasma levels of
Gross underdosing, a significant problem.
The therapeutic effect of the Beta-lactams is not what?
Strongly peak concentration dependent, depends mainly on the time the drug concentration is maintained above the MIC of the infecting pathogen.
The therapeutic activity of the aminoglycosides is dependent on what?
Peak serum concentrations.
Why are plasma concentrations which exceed 10 times the MIC for a given bacteria more effective than those just above the MIC for aminoglycosides?
Aminoglycoside action is biphasic. Primary phase is a rapid, drug concentration-dependent action; during which the killing-rate is directly related to the initial drug concentration.
What is the second phase of aminoglycoside action independent of?
Independent of the drug concentration and the bactericidal rate is slow. The PAE is prolonged. Surviving bacteria may not begin to metabolise normally for up to 8 hours after all the extracellular aminoglycoside has been washed away.
What does the statement: “The post-antibiotic effect (PBE) of aminoglycosides is prolonged” mean?
Surviving bacteria may not begin to metabolise normally for up to 8 hours after all the extracellular aminoglycoside has been washed away.
Pharmacodynamic and toxicity properties of gentamicin suggest what frequency of administration of what sized doses are best?
Less frequent administration of larger doses can maximise bactericidal activity while minimising the likelihood of oto- and nephro-toxicity.
Once daily dosing results in similar efficacy and decreased risk of toxicity compared to conventional dosing.
Toxicity from gentamicin is related to what?
Duration of treatment, Transient exposure to high aminoglycoside concentrations in the serum and the long washout period with low trough concentration results in less accumulation in the fluids and tissues of the inner ear.
In the kidney, uptake kinetics into the cortex appear saturable. Hence, with a single high-dose injection, the momentary high drug concentrations saturate cortical uptake, resulting in decreased renal accumulation compared with continuous infusion where concentrations remain below those required to saturate uptake.
Why does a single-high dose injection of gentamicin lead to decreased renal accumulation compared with continuous infusions?
In the kidney, uptake kinetics into the cortex appear saturable. Hence, with a single high-dose injection, the momentary high drug concentrations saturate cortical uptake, resulting in decreased renal accumulation compared with continuous infusion where concentrations remain below those required to saturate uptake.
Why are aminoglycosides poorly absorbed through the GI?
High MW, very polar drugs.
Must be parenterally administered in order to achieve therapeutic concentrations.
How is gentamicin usually administered and at was dose/frequency?
IV infusion over 30-60 minutes.
5-7mg/kg a day.
Single daily dose of divided doses every 8 hours.
Peak plasma concentrations following conventional dosing of gentamicin are:
In the range of 5-8mg/L.
Peak concentrations lower than 4mg/L are likely to be ineffective.
Trough concentrations should be less than 2mg/L.
Peak plasma concentrations of gentamicin lower than what are likely to be ineffective?
Lower than 4mg/L
Trough levels of gentamicin are measured before a new dose, if
Maintain on selected dose, no toxicity issues likely below 2mg/L
Trough levels of gentamicin are measured before a new dose, if > 2mg/L what should be done?
Increase the dosing interval beyond 24 hours or reduce dosage.
