Aminoglycosides Flashcards
What was the first discovered aminoglycoside and when?
Streptomycin, discovered in 1944.
What is the source of aminoglycosides?
Derived from Actinomycetes, e.g., Streptomyces griseus.
What is the mechanism of action of aminoglycosides?
They inhibit protein synthesis by binding to the 30S ribosomal subunit.
What type of bacteria are aminoglycosides primarily effective against?
Aerobic Gram-negative bacteria.
What are the major toxicities of aminoglycosides?
Ototoxicity (hearing loss, balance issues) and nephrotoxicity (kidney damage).
Why do aminoglycosides have a narrow therapeutic index?
Because the difference between an effective dose and a toxic dose is small.
What are some examples of Gram-negative bacteria targeted by aminoglycosides?
E. coli, Pseudomonas, Klebsiella.
Are aminoglycosides bactericidal or bacteriostatic?
Bactericidal; they actively kill bacteria by interfering with protein synthesis.
What are aminoglycosides composed of?
Amino sugars (e.g., 2-deoxystreptamine) and hexose rings connected by glycosidic bonds.
What are the key structural components of aminoglycosides?
Streptidine, Streptose, N-Methyl-L-glucosamine, and Streptobiosamine.
Why do aminoglycosides have poor oral bioavailability?
They are highly polar, preventing absorption from the gut.
How are aminoglycosides usually administered?
Parenterally (IV/IM) or topically, due to poor oral absorption.
What is the significance of aminoglycosides being strongly basic?
Their basic nature helps them bind to bacterial ribosomes and affects drug interactions.
Which aminoglycoside has a unique structure that makes it effective against tuberculosis and plague?
Streptomycin.
What are the key chemical groups in streptomycin?
Streptidine, Streptose, and N-Methyl-L-glucosamine.
How do aminoglycosides enter bacterial cells?
They passively diffuse through porin channels, then actively transport across the cytoplasmic membrane using oxygen-dependent mechanisms.
Why are aminoglycosides ineffective against anaerobic bacteria?
Because their active transport requires oxygen, which anaerobes lack.
Which ribosomal subunit do aminoglycosides bind to?
The 30S ribosomal subunit.
How do aminoglycosides disrupt protein synthesis?
They interfere with the initiation complex, cause mRNA misreading, and break polysomes into monosomes.
What is the post-antibiotic effect (PAE) of aminoglycosides?
Bacterial growth remains suppressed even after drug levels drop below MIC, allowing once-daily dosing.
Why is once-daily dosing of aminoglycosides effective?
Because of their concentration-dependent killing and post-antibiotic effect.
What is the most common mechanism of resistance to aminoglycosides?
Enzymatic inactivation via plasmid-mediated transferase enzymes.
How do bacterial transferase enzymes confer resistance to aminoglycosides?
They modify the drug through acetylation, phosphorylation, or adenylation, preventing its binding to the 30S ribosomal subunit.
How does decreased drug uptake contribute to aminoglycoside resistance?
Bacteria alter porin channels or reduce active transport, preventing the drug from entering the cytosol.
