Lecture 4 Aminoglycosides/Synercid/Linezolid Flashcards
What are the 2 “core structures” of the aminoglycosides?
streptidine; 2-deoxystreptamine
Aminoglycosides (AGs) are bacterio______
cidal
AG mechanism:
binds the ____ of the ____ ribosomal subunit in the ____ site, interfering with formation of the _______ _____
16sRNA; 30s
A; initiation complex
AG mechanism:
inhibits translation by preventing translocation of the _____ from the ____ to the ____ site, causing premature ______
peptidyl-tRNA;
A, P;
termination
AG mechanism:
Impairs the _____ mechanism, causing _____ mutations which end up forming _____ proteins.
proofreading; frameshift
nonsense
AG mechanism:
Nonsense proteins damage the _____ _____, increasing ____, and allowing more AGs to enter
cell membrane;
permeability
Entry of the _____ly charged AGs through the outer membrane involves the displacement of ____ and ____ ions that form ____ _____ with phosphates of phospholipids in the membrane, increasing permeability
positive;
Mg, Ca;
salt bridges
Passage of AGs through the cytoplasmic membrane is an ______ transport process and requires _____.
active; O2
AG Resistance:
- _______
- _______
- ______
Metabolism, ribosome mutations, altered uptake
AG resistance–> metabolism:
Bacteria can _____, _____, or _____ AGs, inactivating them. These genes responsible can be transferred to other _____
adenylate, acetylate, phosphorylate;
bacteria
AG side effects:
Irreversible _____ and reversible ______.
ototoxicity; nephrotoxicity
AG side effects:
Ototoxicity/Nephrotoxicity is increased with concurrent use of other ototoxic drugs such as vancomycin and ______ diuretics. Compromised ______ function also increases risk
loop;
renal
How to monitor ototoxicity:
How to monitory renal toxicity:
serial audiograms;
creatinine clearance
____-like effects are less common with AG use but can occur with large ____
Curare; large
Generally, AG’s are used for severe (Gram +/Gram -) (Aerobic/Anaerobic) bacterial infections
Gram -; aerobic
AG’s are synergistic with ______. However, these should not be administered within the same _____, due to a chemical rxn that inactivates both drugs.
Penicillin (and other beta lactams)
compartment
____ is the AG that is most often used to treat Tb.
Streptomycin (although not much anymore)
_____ is the most important of the AGs, according to his notes
Gentamycin
AG-resistant strains are common in hospitals, but _____ has retained activity against these strains and is the drug of choice for _____ infections
Amikacin; nosocomial
What is Synercid a mixture of?
Quinupristen, dalfopristin
Quinupristin and dalfopristin separately are bacterio_____. Synercid is bacterio____
static;
cidal
Quinu- and dalfopristin are derived from ______. _____ lacks suitable solubility for reliable dsoes
pristinamycin; pristinamcyin
Both Quinu- and dalfo- bind the __s RNA
23
Dalfopristin binds and inhibits ____ ____
peptidyl transferase
Quinupristin binds and blocks the ____ _____
ribosomal tunnel
Quinupristin and dalfopristin belong to the _____ family
streptogramins
Synercid is used for vancomycin resistant enteroccus ____ bacteremia and UTIs as well as skin infections caused by _____
faecium;
MRSA
The most common resistance to quinupristin is due to adenine _____ of the A2058 ____s rRNA. This renders synercid _______
methylation; 23s
bacteriostatic
75% of clearance of Synercid is through _____ excretion
biliary (Fecal matter)
Streptogramins inhibit ______
CYP3A4 (cyp for warfarin, cyclosporine, NNRTIs)
______ is an example of an oxazolidinone
linezolid
Linezolid mech:
binds the ____s rRNA of the ____s ribosomal subunit
23s; 50s
Linezolid mechanism:
binds the 50s ribosomal subunit before formation of the _____ ribosome; ie before interaction of the 50s ribosomal subunit, the 30s ribosomal subunit, and _____-tRNA
70s;
fMet-
Linezolid is typically only used to treat Vanc resistant _______ and nosocomial pneumonia/skin infections caused by ______
enterococcus faecium;
MRSA
Resistance to linezolid is due to ____ mutations of the _____ ____ of the 23s rRNA
point;
binding site
Side effects of linezolid include thrombo_______, bone marrow ______, and peripheral ______
cytopenia; supression; neuropathy
Linezolid is a reversible, non-selective inhibitor of _________
monamine oxidase
Linezolid can interact with adrenergic and serotonergic agents, causing ______
serotonin syndrome
Patients taking linezolid should not consume large quantities of food containing ______ in order to avoid a significant _____ response
tyramine;
pressor
