Pharmacology 14: Aminoglycosides Flashcards
Suffix for Streptomyces
-mycin (ie. Neomycin)
Suffix for micromonospora
-micin (ie. Gentamicin)
Streptomycin
Prototypic aminoglycoside, part of the Streptomyces classification
Oral
Kanamycin
Topical or oral dosing
Streptomyces
Amikacin
A derivative of kanamycin
Neomycin
Mainly a topical drug but may be given orally
Netilimicin
Broad Spectrum
Why are Gentamycin, Tobramycin and Amikacin the most widely used drugs of the aminoglycoside class ?
Lower toxicity and broader spectrum of coverage
Are aminoglycosides polar or non-polar ? What does this imply about their ability to cross the lipid membrane ?
They are highly polar and charged. This makes it difficult for them to pass the lipid membrane w/o some form of transport
This is accomplished by an energy-dependent active bacterial transport mechanism that requires oxygen and an active proton motive force.
– For this reason, aminoglycosides work poorly in anaerobic and acidic environments such as abscesses.
MOA for Aminoglycosides
Inhibition of bacterial protein synthesis through irreversible binding to the 30S bacterial ribosome.
Why do beta-lactams and vancomycin show additive effects when used in conjunction with aminoglycosides ?
Aminoglycosides must get past the cell wall to be effective. Drugs like beta-lactams and vanco inhibit cell wall synthesis making it easier for aminoglycosides to go about their business.
Mechanism of Action at low doses of amino glycosides
misreading of mRNA during elogation leading to the incorporation of incorrect proteins into the bacterial proteins making them functionally useless
Mechanism of action at high doses of aminoglycosides
complets inhibition of protein elongation causing the Ribosome-mRNA complex to be stopped at the start codon
Where do aminoglycosides have significant toxicity within the body ?
Ears (Ototoxicity)
Kidneys (Nephrotoxicity)
Against which class of bacteria are aminoglycosides often used ?
Enterobacteriaceae (Pseudomonas aeruginosa)
Why might you use Tobramycin or Amikacin instead on Gentamycin ?
Gentamycin resistance has become prevalent in many care settings. The other two drugs are functionally similar but may be more effective in treating gentamycin resistant strains.
What are the three ways in which aminoglycosides inhibit bacterial protein productions ?
- Block initiation
- Block elongation
- Cause incorrect AA’s to be inserted in to the growing protein.
What causes resistance due to lack of accumulation of AG’s in the bacterium ?
Most often the presence of efflux pumps
What causes resistance due to modification of aminoglycosides to inactive molecules ?
Bacterial enzymes
Acetyltransferases
Nucleotidyltransferases
Phosphotransferase
Modification inhibits AG’s ability to bind the ribosome
What causes resistance due to the inability of AG’s to bind ribosome w/o being previously modified by bacterial enzymes ?
Mutation of the bacterial ribosome so that recognition site for AG’s is no longe the same.
