Protein Synthesis Inhibitors (Antimicrobials) - 30S Inhibitors Flashcards
what drugs are protein synthesis inhibitors?
gentamicin tobramycin tetracycline doxycycline tigecycline azithromycin erythromycin fidaxomicin chloramphenicol clindamycin linezolid mupirocin
which agents bind to 30S ribosomal subunit
aminoglycosides (gentamicin, neomycin, amikacin, tobramycin, streptomycin –GNATS)
tetracyclines (doxycycline, tetracycline, minocycline)
glycylcycline (tigecycline)
which agents bind to 50S ribosomal subunit
macrolides (azithromycin, erythromycin, clarithromycin)
Chloramphenicol
Clindamycin
Erythromycin
Linezolid (oxazolidinone)
gentamicin route
topical, IV, IM
tobramycin route
topical, IV, IM, nebulized
general MOA of aminoglycosides
active transport across cell membrane into the cytoplasm by oxygen dependent process (so covers aerobes)
AND passive diffusion via porin channels across outer membrane (gram-)
(this is important)
what do aminoglycosides do
bactericidal (bc irreversible binding to 30S and formation of aberrant proteins
what does irreversible binding of 30S by aminoglycosides do
- interferes with initiation complex of peptide formation - blocks
- prevents proofreading of transcript (incorporation of incorrect AA) – miscoding
- blocks movement of ribosomes after single initiation complex resulting in mRNA chain with just one ribosome – block translocation
spectrum of aminoglycosides
aerobic gram - including pseudomonas
what would happen if you gave an aminoglycoside with a cell wall agent for gram+
alone aminoglycoside wouldn’t work, but once cell wall agent destroys cell wall (give first) then aminoglycoside can penetrate
(aka synergy with cell wall agents on gram+ organisms)
how is resistance conferred against aminoglycosides
- production of transferase enzyme that inactivates aminoglycosides
- imapired entry (decreased uptake and altered porins)
- mutation of receptor on 30S ribosomal subunit (prevents aminoglycosides from binding)
absorption of aminoglycosides
poorly absorbed, almost entire dose excreted in feces
when does peak concentration occur in IM
within 30-90min
peak concentration in IV
30-60min
tissue concentration of drug?
low because poorly absorbed
CNS concentration of drug
inadequate even with inflamed meninges
where do aminoglycosides accumulate?
renal cortex, endolymph and perilymph of the inner ear
side effects of aminoglycosides
nephrotoxicity and ototoxicity (ringing of ears)
aminoglycosides and placenta
can cross placental barrier and accumulate in fetal plasma and amniotic fluid
toxicity of aminoglycosides
- since high concentrations in renal cortex, endolymph and perilymph of inner ear, then nephrotoxic and ototoxic
- neuromuscular blockade
- contact dermatitis
what is oto and nephrotoxicity associated with
prolonged high trough levels (not peak levels)
what is neuromuscular blockade associated with
direct intraperitoneal or intrapleural application of a large dose
(cannot get into the CNS but can directly administer)
how are aminoglycosides cleared
renally – excretion is directly proportional to creatinine clearance
why must aminoglycosides be monitored in kidney damage?
excretion is directly proportional to creatinine clearance so if kidney not working, less excretion
describe aminoglycosides dosing
concentration dependent (looking for a high peak) with a post antibiotic effect (continues after drug wears off)
when would once daily dosing be avoided?
- renal impairment because accumlates
- pregnancy (crosses placenta)
- neonates (accumulates in fetal plasma and amniotic fluid)
- bacterial endocarditis
how to monitor aminoglycosides that are dosed once daily
check trough to makes sure the drug is washing out – don’t need to check peak