Aminoglycoside Antibiotics Flashcards
Aminoglycoside antibiotics core structure made of whaT?
1,3 diaminocyclitol linked to one or more aminoglcoside rings
Core structures are what?
Streptidine
2-deoxystreptamine
Spectinamine
What do aminoglycosides inhibit
Protein biosynthesis
How do amino-glycosides inhibit protein biosynthesis?
Binding to 30S ribosomal subunit to the 16S rRNA forming the A site
What step of translation does amino-glycodies interfere with?
Formation of initiation complex, causes premature termination
What does aminoglycosides form from its interruption of protein synthesis?
Nonsense proteins
Result of formation of nonsense proteins due to aminoglycosdies?
Cell wall function impaired
Result of impaired cell wall function in aminoglycosides?
More aminoglycosides (AMG) gets in and stops protein synthesis altogether
AMG positively charged or negatively?
Positively
What needs to be displaced to get AMG in through outer membrane?
Mg++ and Ca++ ions
Why does Mg and Ca need to be displaced?
They form salt bridges with phosphates of phospholipids
What type of transport process is passage through cytoplasmic membrane?
Active transport
How many bacterial resistance mechanisms have evolved to combat AMG?
At least 3
What are the 3 mechanisms that resist AMG?
1) Metabolism
2) Altered Ribosomes
3) Altered AMG uptake
How does the metabolism resistance of AMG work?
Bacteria inactivate AMG by acetylation, adenylation, and phosphorylation
Are AMGs metabolized by humans or bacteria?
Bacteria
How does altered ribosome resistance work?
16S rRNA binding site via point mutations
Which bacteria has displayed altered ribosomes in the past?
Mycobacterium tuberculosis
How does Altered AMG uptake resistance work?
Emergence is far less than resistance due to metabolism
Dangers of AMG?
Ototoxic and nephrotoxic
Difference between Ototoxicity and nephrotoxicity in AMG?
Ototoxicity is irreversible while nephrotoxicity is reversible
Risk factors for ototoxicity?
Using other ototoxic drugs
Reduced renal function
Genetic vulnerability
A less common effect that can result from large doses of AMGs?
Curare like effect involving respiratory paralysis
How does one deal with the respiratory paralysis caused by AMG?
Neostigmine
Calcium gluconate
What is the period treatment that AMGs should be discontinued after?
5 days
Spectrum of antibiotics for AMGs?
Gram + and gram -
Primary use for AMGs?
Gram -
What are AMGs usually used in combination with?
Penicillin
How does AMG and Penicillin combo need to be given?
One in each arm to avoid chemical reaction between the two
Streptomycin used to treat what?
Tuberculosis
Most important of the AMGs?
Gentamycin
Which AMG used for nosocomial infections?
Amikacin
Streptogramin is a semisynthetic structure derived from what?
Pristinamycin 1 and pristinamycin 2 taken from Strep pristinaspiralis
Synercid mixture contains what?
30% quinupristin
70% Dalfopristin
Dalfopristin interfere with protein synthesis how?
Interfere with peptide transferase formation of peptide bond between two amino acids
How does Quinupristin work?
Binds n the ribosomal tunnel and blocks it
What provides resistance to Streptogramin?
Mutation of A2062 which gates the tunnel exit
What is Synercid used IV in treatment of?
Vancomycin resistant Enteroccus faecium bacteremia
Skin infection via MRSA
Vanco resistant Enteroccus faecium urinary tract infections
Most common resistance to quinupristin due to?
Adenine methylation of A2058 in 23S rRNA
Streptogramin treatment most likely reserved for what?
Life threatening Gram +
Senesced use selects for resistant forms of?
E. faecialis
E. faecium
S. aureus
Toxicity due to synercid?
None
Does Synercid penetrate blood brain barriers?
No
Where is concentration of Synercid 50X the extracellular fluid concentration?
Macrophage
How is Synercid excreted?
75% biliary excretion
Streptogramins inhibit what enzyme?
CYP3A4
How does linezolid inhibit protein synthesis?
It stops the formation of the 70S initiation complex
What is Linezolid used to treat?
1) Vanco resistant Enterococcus faecium
2) Nosocomial pneumonia caused by MRSA
3) Skin infections caused by MRSA
How is Linezolid taken?
Orally or I.V
When is linezolid taken?
Infections caused by multiple drug resistant Gram +
Where has linezolid resistance been reported?
Enterococcus species
How do organisms develop resistance against linezolid?
Target site modification, G to U substitution in peptidyl transferase center
What can happen if a patient takes linezolid for more than 6 months?
Neuropathy
Half life of linezolid?
4-6 hour
What does Linezolid inhibit non selectively?
Monoamine oxidase
Lienzolid has potential for interaction with whaT?
Adrenergic and serotonergic agents
Patients should avoid consuming what when taking Linezolid?
Food/beverages rich in tyramine
