Chem Basis - AGNs 3
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What is an aminoglycoside?
Molecule made from amino-modified sugars derived from Streptomyces genus
Why does Gentimin end in –micin rather than –mycin like other aminoglycosides?
It is derived from the Microsmonospora species of the Streptomyces genus
What is the MOA of Aminoglycosides?
- Protein synthesis inhibitors
- Bind to 30s ribosome causing mRNA misreads
- Halt growth
- Cationic nature creates fissure in the outer membrane, causing cell leakage
Are Aminoglycosides bactericidal or static?
The bactericidal nature of Aminoglycosides is attributable to what characteristic?
- Cationic nature
- Creates fissure in the outer membrane, causing cell leakage (Na, K, etc.)
What is the benefit of the cationic nature of aminoglycosides?
- Creates fissure in the outer membrane
- Causes cell leakage
- Results in bactericidal activity
- Increases cellular uptake
Why are aminoglycosides more active against aerobes than anaerobes?
They need energy to be transported into the cell
By what routes are AGs usually given?
IV, IM or topically (only two are oral: Kanamycin and Neomycin)
Are oral AGs absorbed systemically?
Why are AGs poor for outpatient therapy?
They are not absorbed by the GI and so usually are given IV or IM
What is Tobrex?
Tobramycin’s opthalamic preparation
What is Tobradex
Tobramycin’s combo opthalamic preparation with dexamethasone
Which AG would you use for a severe case of meningitis in a neonate?
Dosing for AGs need to be adjusted under what conditions?
Dosing of AG should be adjusted in renal disease based on Creatinine Clearance and serum levels.
Are AGs useful against Neisseria?
Only moderately sensitive and should not be treated with AG alone
What is the general spectrum of AGs?
- Aerobic and G-
- Pseudomonas aeruginosa
- E. Coli
- H. influenzae
Would you use and AG for severe P. aeruginosa sepsis?
Yes, in combination with a broad spectrum B-lactam
Can AGs be used against G+ infections, like Staphylococcus epidermidis?
Yes, but more effective and less toxic drugs are usually used
Can Aminoglycosides be used to treat streptococcal infection?
- Yes, in combination with B-lactams for synergistic effects
- Alone, Streptococci and Staphylococci are usually resistant
Are aminoglycosides effective against S. pneumonia (community acquired pneumonia)?
What type of interaction do AGs have with Vancomycin?
Generally, what types of organisms are AGs ineffective against?
Fungi, Viruses and Anaerobes
The activity of Aminoglycosides is similar to what other drugs?
The development of resistance to what drugs has helped maintain usefulness of Aminoglycosides?
The use of higher AG dosing had what effects on its characteristics?
Increased efficacy and decreased toxicity
What are aminoglycosides mainly used for?
- Empirically treatment of serious infections including:
- Complicated urinary tract infections (pyelonephritis)
- Complicated intra-abdominal infections
- Hospital acquired respiratory tract infections
Are AGs first line therapies, why or why not?
No, because of the risk of oto/nephrotoxicity and Neuromusclar blockade
Once a culture is obtained of a bug being treated by an AG, what should you do?
Change antibiotic to a more narrow spectrum if possible
Why do AGs cause Oto- and Nephrotoxicity?
+ charge causes them to accumulate in the Ear and Kidneys
The resulcatance to use Ags, due to their toxicity, has lead to the use of other broad spectrum antibiotics, what effect has this had on antimicrobial treatment?
Lead to antibiotic resistant strains such as Golden Staph and superbugs
What are the three mechanism of resistance to AGs?
- 1) Ribosmal mutation
- 2) Decreased permeability/inactivation of energy-dependant drug uptake mechanism
- 3) Enzyme production
What types of enzymatic reactions do resistant bacteria use to inactivate Aminoglycosides?
What is the action of bacterial Phosphotransferases on Aminoglycosides?
- Phosphorylates the 3”-0H group
What is the action of bacterial Nucleotidyltransferases on Aminoglycosides?
- Adenylate the 4”-0H group, 2’-OH and 4’-0H
What is the action of bacterial Aminoacetyltransferases on Aminoglycosides?
- Acetylate the 2”-OH, 6”-NH2 and 3-NH2
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