Aminoglycosides Flashcards
Describe the mechanism of action of the aminoglycosides.
They irreversibly bind to the 30S ribosomal subunit of susceptible bacteria, resulting in inhibition of protein synthesis.
Which are the aminoglycosides we should know that are still used clinically?
- streptomycin
- gentamicin
- tobramycin
- amikacin
- plazomicin
What are the main mechanisms of resistance to the aminoglycosides?
- synthesis of AG modifying enzymes (plasmid-mediated)
- altered AG uptake (loss of porin channel, efflux pumps)
- change in ribosomal binding site/target modification
In terms of SOA, what is the main thing to know about gentamicin?
It targets a wide variety of gram negatives, particularly pseudomonas!
How do tobramycin and gentamicin differ?
Tobramycin is more active against psuedomonas and slightly less active against other gram negatives.
Factors that impact Postantibiotic Effect (PAE):
- organism
- drug concentration
- duration of drug exposure
- antimicrobial combinations
Describe some of the reasons behind using extended-interval dosing.
- concentration-dependent bactericidal activity
- post-antibiotic effect (PAE)
- adaptive resistance
- minimize toxicities (nephrotoxicity, ototoxicity)
- cost savings
- efficacy
Explain the concept of adaptive resistance.
Adaptive resistance describes how bacteria become resistant to antibiotics. Decreased drug uptake occurs in bacteria that survive the initial, suboptimal AG dose. An increased drug-free time may protect the bactericidal activity of AGs.
Why does nephrotoxicity happen with the AGs?
It is related to the intracellular accumulation of drug in the renal cortex. Uptake of AGs into the proximal tubule cells is saturable at clinically achieved concentrations. Therefore, continuous infusion of AGs results in higher renal cortical concentrations and an increased risk of toxicity.
