Lecture 2- bacterial protein synthesis inhibitors Flashcards
what are the types of 30S protein synthesis inhibitors? (3)
- tetracyclins
- glycylcycline
- aminoglycosides
types of 50s protein synthesis inhi (3)
- macrolides
- clindamycin
- linezolid
tetracycline MOA
enter organism via passive diffusion and transport protein mech (energy dep)
concentrate intracellularly in susceptible org
drug binds reversibly to 30s subunti of bacterial ribosome–> prevent binding of tRNA to A site of complex–> inhibit bacterial protein synthesis
tetracycline absorption? ROA
good bioavail
best on empty stomach
oral
what decreases tetracycline absorption? (2)
- dairy prod
- containing divalent and trivalent cations
properties of tetracycline (3)
- bacteriostatic ab
- activity against broad spectrum of gram pos, gram neg and atypical bacteria and spirochete bac
- inadequate activity against ps. aeruginosa and proteus
types of tetracycline (3)
- tetracycline
- doxycycline
- minocycline
tetracycline elimination
by kkdney
doxycycline elim
largerly excreted unchanged in bile and urine
minocycline elim
extensively met by liver before excretion
type of glycylcycline (1)
tigecycline
benefits of glycylcycline over tetra (2)
- expanded spectrum of act
- decreased susceptibility to dev of resistance
what are the mechs of tetracyline resistance glycylcycline is designed to overcome? (2)
- resistance mediated by acquired efflux pump
- ribosomal protection
tigecycline MOA
bind to bac 30s ribosome–> block entry to tRNA (similar to minocycline)
why does tigecycline have lower sus to resistance?
it has good binding affinity to ribosomes so its less likely to be dislodged by TET O and TET M proteins
ROA of tigecycline
IV- poor oral bioavail
tigecycline distribution?
- penetrates well into tissue but low plasma conc
- poor option for bloodstream infection
tigecycline elim?
biliary/fecal
what is the spectrum of tigecycline
- MRSA
- multidrug resistant streptococci
- vancomycin resistant enterococci
- extended spectrum beta lactamase gram neg bac
- community acquired pneumonia
tigecycline and tetra SE (4)
- gastric discomfort
- effects of calcified tissues- discolouration of teeth eg. grey, temporary stunting of growth
- hepatotoxicity
- ## phototoxicity
tigecycline and tetra CI (2)
- pregnant
- < 8yo- may cause permanent teeth discolouration
types of aminoglycosides (5)
- gentamicin
- streptomycin
- tobramycin
- amikacin
- neomycin
aminoglycosides MOA
distort structure of ribosom by binding to them and blocking formation of initiation complex, cause misreading of codons, inihibit translocation
aminoglycosides absorption and ROA
poor oral bioavail– parenteral
aminoglycosides clearance
renal, need dose adjustt
which drug has post antibiotic effect (PAE)?
aminoglycosides
what is PAE
even tho drug conc has dropped below MEC, can still see effect mainly coz drug has doen something to bacteria and this bacteria needs to recover
antimicrobial spectrum of aminoglycosides
- broad spectrum
- primarily effective against aerobic gram neg and mycobacteria
wat is aminoglycosides used in combi with
why?
beta lactams for therpay of proven or suspected bacterial infections
- expand spectrum of activity of antimic
- provide synergistic bacterial killing
- prevent emergence of resistance to indv agents
gentamycin indicatiosn
- for serious gram neg bac infection
- more active against gram POS cocci than others when used with betalactam
- combi therapy with penicillin/ceftriaxone to treat enterobacteriaceae
tobramycin indication
- pseudomonas aeruginosa
amikacin indication
- WIDEST spcetrum
- ineffective against majority gram POS
neomycin ROA
oral, topical
neomycni indication
- toxic
- topcial against skin infections
- oral for bowel prep for surgery
aminoglycosides adverse effects
- ototoxicity- hearing
- nephrotox- retention of aminoglycosides by proximal tubular cells
- neuromuscular paralysis
- hypersen
6 NOs of aminoglycosides
- no to protein synthesis- inhibit 30s
- mainly aerobic gram Neg Org
- No to use during pregnancy
- No to CSF penetration
- Nephro and Oto toxicity
- No to oral admin
factors that predispose nephro and oto toxicity
- dose
- duration
- concomitant use of nephrotoxic drugs
- elderly
resistance to aminoglycosides
- increase efflux pumps reduce effective intracellular conc
- gram neg bacteria produce aminoglycosides inactivating enzymes
- some bacteria alter 30s rib subunit
- low level resistance may result from inhibition of aminoglycosides uptake by bacteria
types of macrolides (3)
- erythromycin
- clarithromycin
- azi
classes of 50s inhibitors (3)
- macrolides
- clindamycin
- linelozoid
macrolides MOA
inihibit protein synthesis by reversibly binding to 50s subunut
inhibit translocation
benefits of clari and azi over erythro
- imrpoved acid stability, tissue penetration, braoden spectrum of activity
macrolides ROA
oral and parenteal
good oral bioavail
macrolides indications
ATYPICAL microbes
macrolides SE (3)
- gastric distress and motility
- hepato
- oto
- prolong QT interval
erythromycin ROA
oral, IV
erythromycin indication
against gram pos and neg
treat comm acquired pneumonia
effective against atypical
clarithromycin ROA
oral
clarithromycin indication
most active against both pos and neg
higher activity against atypical bac
benefit of clarithromycin
modified for better GI tolerance compaed to ery
- clari and azi stable in stomach acid and are readily absorbed
azithromycin ROA
oral, IV
azithromycin indication
most avtive against resp infections
macrolide elim
metabolised hepatically
disad of macrolides
poor CSF penetration, not good for CNS infection
macrolides CI
hepatic dysfunction
macrolides resistance- how is it acquired (2)
- acquire oen of a erm gene resulting in ribosomal methylation, reduced binding of macrolides to 50s rib subunit
- increased expression of efflux pump
what class does clindamycin belong in
lincosamide
clindamycin indication
anaerobic infection
clindamycin moA
bind exclusively to 50s subunit of bacterial ribosome and inhibit peptide synthesis
clindamycin indications
- trat infection caused by gram pos including MRSA and streptococcus and penicillin resistance anaerobic bac
- good spectrum of activity agaisnt oral pathogens
what cant clindamycin be used against
CDAD
coz it has high risk for CDAD
clindamycin ROA
IV, oral
good oral bioavail
clindamycin distribution
well into fluids
poor entry into CSF
clindamycin metabolism
hepatic
clindamycin adverse effects
takew ith full glass of water to reduce esophageal irritaiton. do not lie down immediately
skin rash
CDAD
linezolid MOA
bidn to bac 23s ribosomal RNA of 50s subunit–> prevent formation of func 70s initiation complex
antimicrobial activity of linezolid
bactericidal
- against gram pos
- NOT FOR gram neg
wide coverage due to uniqe MOA eg. covers penicillin resistant strains…
linezolid ROA
IV, oral
linezolid distribution
widely distri to body
good penetration into CSF and brain tissue
pro (2) and cons (2) of linezolid
pros
- useful agaisnt many multidrug resistant strains
- can give oral and IV, outpt
cons
- need give over longer period
- need to monitor and take blood count
linezolid adverse
- GI eg. nausea
- bone marrow suppression- monitor blood count
- serotonin syndrome if given with selective serotonicn reuptake inhibitors
