ABX III- protein synth inhib Flashcards
what does the small rRNA subunit do?
and the large?
small (30s): has decoding function– it reads the mRNA
large (50s): form the A and P sites for the amino-acid bearing tRNA. it has the peptidyl transferase function (links the aa onto the nascent protein) and also has theexit tunnel through which the growing peptide chain passes out of the ribosome
effect of prot synth inhib on bacteria?
inhibits growth but doesn’t kill them– bacteriostatic EXCEPT aminoglycosides be at low concentrations they cause misreading of mRNA leading to incorporation of wrong aa into nascent prot —> cell death
all prot synth inhibs are bacteriostatic except…
aminoglycosides, which at small concentrations cause misreading of mRNA leading to incorporation of wrong aa into nascent prot —> cell death
Aminoglycosides
mech:
use:
adverse effects:
Aminoglycosides
mech: binds 30 s at decoding site —> at low conc: incorporation of incorrect aa
at high conc: inhibits prot synth
use: serious ifxns with GNR (including P. aeruginosa
used in combo with cell wall synth inhibs for serious ifxn with some GP bact (Staph, enterococcus, A/B strep and Listeria but NOT S. pneumoniae)
streptomycin = used for M. Tb
adverse effects: can be sig – ie limit use to serious ifxn, nephrotoxicity (usually reversible), ototoxicity (common, often reversible), neuromuscular blockade
aminoglycosides mech:
mech: binds 30 s at decoding site —> at low conc: incorporation of incorrect aa
at high conc: inhibits prot synth
aminoglycosides use:
use: serious ifxns with GNR (including P. aeruginosa
used in combo with cell wall synth inhibs for serious ifxn with some GP bact (Staph, enterococcus, A/B strep and Listeria but NOT S. pneumoniae)
streptomycin = used for M. Tb
aminoglycoside adverse effects:
adverse effects: can be sig – ie limit use to serious ifxn, nephrotoxicity (usually reversible), ototoxicity (common, often reversible), neuromuscular blockade
tetracyclines
mech:
use:
advers Rxns:
tetracyclines
mech: binds 30s t A site, blocks aminoacyl-tRNA binding
use: Staph, Strep and enteric GNRs
advers Rxns:
atypical orgs: Mycoplasma pneumoniae, borrelia burgdorferi, chlamydia species, ricketsia species, ehrlichia chafeensis
anaplasma phagocytophilum
glycylcyclines are effective agst MRSA and VRE and are reserved for such resistant orgs
adverse Rxns:
well tolerated, but GI upset common and BAD FOR GROWING TEETH (avoid in pregnant women and children under 8)
tetracyclin mech
mech: binds 30s t A site, blocks aminoacyl-tRNA binding
tetracyclin uses
Staph, Strep and enteric GNRs
advers Rxns:
atypical orgs: Mycoplasma pneumoniae, borrelia burgdorferi, chlamydia species, ricketsia species, ehrlichia chafeensis
anaplasma phagocytophilum
glycylcyclines are effective agst MRSA and VRE and are reserved for such resistant orgs
tetracycline adverse Rxns
adverse Rxns:
well tolerated, but GI upset common and BAD FOR GROWING TEETH (avoid in pregnant women and children under 8)
chloramphenicol
mech:
use:
adverse Rxns
chloramphenicol
mech: blocks 50 S at A site and transpeptidation site, blocking transpeptidation
use: rarely in dvpd nations, used for Typhoid fever (salmonella typhi), bacterial meningitis, ricketsia species and anaerobic bacteria
adverse Rxns: uncommon but sig toxicity limits, hematopoietic suppression (minor - severe/death), most often hemolytic anemia (suppression of RBCs), gray- baby syndrome due to reduced drug excretion in neonates can be fatal
chloramphenicol mech
mech: blocks 50 S at A site and transpeptidation site, blocking transpeptidation
chloramphenicol use
use: rarely in dvpd nations, used for Typhoid fever (salmonella typhi), bacterial meningitis, ricketsia species and anaerobic bacteria
chloramphenicol adverse rxns
adverse Rxns: uncommon but sig toxicity limits, hematopoietic suppression (minor - severe/death), most often hemolytic anemia (suppression of RBCs), gray- baby syndrome due to reduced drug excretion in neonates can be fatal
lincosamides
mech
use
adverse rxns
lincosamides
mech: binds 50s at A and P binding site/blocks transpeptidation
use: infection with anerobes, TSS and necrotizing fasciitis (in combo with cell wall inhib)
second line monotherapy forstaph and strep
adverse rxns: can be sig– limits use to serious rxns, C diff is associated with pseudomembranous colitis
lincosamides
mech
lincosamides
mech: binds 50s at A and P binding site/blocks transpeptidation
lincosamides use:
use: infection with anerobes, TSS and necrotizing fasciitis (in combo with cell wall inhib)
second line monotherapy forstaph and strep
lincosamides adverse rxns:
adverse rxns: can be sig– limits use to serious rxns, C diff is associated with pseudomembranous colitis
macrolides
mech:
use:
adverse rxns:
macrolides
mech: binds 50 s exit tunnel, blocking elongation of peptide
use: Resp tract Ifxn bc good activity agst Strep, Staph, Haemophilus, bordetella pertussis, legionella pneumophila and chlamydia ifxns
adverse rxns: well tolerated, some GI upset, reversible cholastic hepatitis
macrolides
mech:
macrolides
mech: binds 50 s exit tunnel, blocking elongation of peptide
macrolides use:
use: Resp tract Ifxn bc good activity agst Strep, Staph, Haemophilus, bordetella pertussis, legionella pneumophila and chlamydia ifxns
macrolides adverse rxns:
adverse rxns: well tolerated, some GI upset, reversible cholastic hepatitis
Mechanisms of acquired Abx resistance
- inactivation of ABX (drug destruction via lactamases, or drug modification by enzymes that modify drug to reduce affinity to target)
- Change in the target (mutate genes at Abx target/acquisition of new genes that alter/replace target)
- efflux of abx (pump abx out of bact,)
