d4: antimicrobial drugs II (protein synthesis inhibitors)
Terms in this set (17)
what do we mean by selective inhibition of bacterial protein synthesis?
these drugs act by selectively blocking the protein synthesis of bacteria (prok) while having relatively little effect on the protein synthesis of humans (eukaryotes)
the selectivity results from?
differences in the structure and function of ribosomes in prokaryotic vs eukaryotic organisms
drugs that affect the 30S subunit
aminoglycosides and tetracyclines
drugs that affect the 50S subunit
macrocodes, chloramphenicol, and clindamycin
linezoid - mechanism
it's a synthetic antimicrobial drug that binds to the bacterial 23S ribosomal RNA of the 50S subunit
this prevents what?
the formation of the 70S initiation complex which starts protein synthesis
there is no ____ with all other protein synthesis inhibitors work on the _____ step in bacterial protein synthesis (ahminoglycosides, tetracyclines, and macroclides)
mutation in the linezolid binding site on 23S ribosomal RNA
linezoid's bacterial spectrum? has activity against
gram + such as methicillin resistant S. aureus (MRSA), penicillin resistant S. pneumonia (PRSP) and vancomycin-resistant enterococcus (VRE). also moderately active against Mycobacterium tuberculosis
what about gram -?
these are intrinsically resistant because they possess efflux pump, which actively pump out linezolid out of the cell faster than it can accumulate
- 100% bioavailable after oral admin (IV prep is also available)
- half life of 4-6 hours
- is metabolized by oxidat metabolism yielding two inactive metabolites - not an inhibitor of CYP isoenzymes
linezolid's side effects?
1) inhibition of mitochondrial protein synthesis
2) inhibition of monoamine oxidase
inhibition of mitochondrial protein synthesis
mitochondrial ribosomes resemble that of bacterial ribosomes. this causes
(low platelet count), particularly when the drug is administered for longer than 2 weeks
what else can occur?
anemia and neutropenia
and optic and peripheral neuropathy and lactic acidosis (prolonged therapy, >month)
inhibition of monoamine oxidase
may lead to
if given concomitantly w/ selective serotonin uptake inhibitors (antidepressant paroxetine)
may enhance BP when taken along with pseudoephedrine (nasal decongestant) or large quantities of tyramine-containing foods (wine, beer, cheese, and yogurt)
linezolid's clinical uses? 3 things
reserve antibiotic used as a drug of last resort
against potentially intractable infections
2) hospital acquired or community acquired
pneumonia, both complicated and uncomplicated skin and skin structure infections
caused by susceptible gram + bacteria
3) off label use for multi drug resistant TB