ABs- inhibitors of Protein synthesis Flashcards
what are the 7 ABs that act by protein synthesis inhibition?
Aminoglycosides, Tetracyclines, Chloramphenicol, Clindamycin, Erythromycin (macrolides), Quinupristin/ dalfopristin, and Linezolid
what is the only AB that binds to the 30s part of the ribosome
Tetrecyclines, but some Aminoglycosides bind to 30s too!
Aminoglycoside MoA cidal or static
bind to 30s or 50s, inhibit tRNA attachment, and polysome breakdown
cidal
Tetracylcline MoA, static or CIdal
Tetracycline bind to 30s blocking tRNA binding to mRNA
static
Aminoglycoside spectrum?
Aminoglycosides are effective against GRAM NEG only! especially pseudomonas
How can Aminoglycosides be used to treat Gram pos?
Aminoglycoside + B lactam= effective against Gram +
the 6 aminoglycoside drugs
streptomycin, kanamycin, gentamicin, tobramycin, amikacin, neomycin
Clinical use of streptomycin
Streptomycin = drug resistant TB.
Use penicillin + streptomycin to treat endocarditis (outdated)
Kanamycin clinical use
Kanamycin NOT used in the US
Gentamicin, Tobramycin, and Amikacin uses?
Gram neg infections, septicemia, meningitis, endocarditis, pneumonia
possible use against gram + w B lactams
Neomycin uses?
Neomycin effective for topical tx of burns, wounds, infected dermatoses and oral use for prep for bowl surgery
Aminoglycoside absorption, distrib, metabolism/ excretion
Aminoglycosides are given IV and IM. Poor distribution, don’t enter CNS, renal excretion
Aminoglycoside Toxicity
Aminoglycosides are DOSE RELATED!!
Aminoglycoside toxicities
Aminoglycosides cause ototoxicity (cochlear hair death), Nephrotoxicity and Neuromuscular blockage
What is important for treat pts with myaesthenia Gravis
Aminoglycosides cause neuromuscular blockage- muscle weakness and respiratory depression
What are the 3 concentration dependent drugs
Aminoglycosides, quinolones, and daptomycin
what are the 3 Time dependent drugs
B lactams, Vancomycin, and quinolones (quinolones also Time dependent)
what do ahminoglycosides exhibit
aminoglycosides exhibit a post antibiotic effect- actions occur long after the drugs have cleared the blood
tetracylines bind to what part of the ribosome? are static or cidal?
tetracyclines bind to 30s part of ribosome and are STATIC
what is the specificity of tetracyclines
tetracyclines accumulate preferentially in bacteria through an energy dependent transporter lacking in mammalian cells
What are tetracyclines effective against
rickettsiae, mycoplasma, chlamydia and protozoa
GRAM - and GRAM + . 1st BROAD spectrum AB
tetracyclines are now considered a what due to resistance and toxicities
tetracyclines are 2nd line of defense for acne, outpatient mycoplasma, urethritis
resistance to tetracyclines are due to what
tetracyclines resistance are due dec influx, INC efflux, DEC binding to ribosomes
what don’t you use Tetracyclines with
dont admin tetracyclines with MILK or antacids
what is a concern with the distribution of Tetracyclines
Tetracylines are sequestered in the bone with some penetration into CNS
Tetracyclines are what concern for the mouth
Tetracyclines causes yellowing browning of the teeth, don’t admin in the pregnant or young!
are tetracyclines photosensitive?
whats a special toxicity of tetracyclines?
YES tetracyclines are photosensitive!
tetracyclines= fanconi syndrome: renal tubular dysfunction after admin outdated tetracyclines
What is a newer Tetracycline agent that is static and binds to 30s part of ribosome
Tigecycline: monocycline and Glycylcycline
Tigecycline spectrum? and what is the difference between tigecycline and tetracyclines?
Tigecycline is BROAD spectrum effective against gram - and gram + including anaerobes. Tigecycline is not effected by the same resistance mechanisms as tetracycline
Tigecycline is used against what bacteria
Tigecycline used against bacteria resistant to B lactams, vancomycin, and tetracyclines
what is a limiting toxicity of Tigecycline
Tigecycline causes nausea
what is the clinical use of Tigecycline
Tigecycline is used for complicated intra abdominal and skin and skin structure infections
What is a nitrobenzene analog that has very limited clinical use
Chloramphenicol
Chloramphenicol is very limited clinically why?
Chloramphenicol causes a fatal side effect: aplastic anemia
What is chloramphenicol’s spectrum
Chloramphenicol is BROAD spectrum effective against Gram - and Gram +
What is Chloramphenicol used for when tetracyclines are ineffective
Chloramphenicol is used to treat rikettsial infections when tetracyclines are ineffective
What is the resistance of chloramphenicol
Chloramphenicol resistance develops due to acetylation of the drug, dec uptake, change in ribosome structure
what is the fatal toxicity of chloramphenicol
Aplastic anemia!
What is the other serious toxicity of chloramphenicol
Chloramphenicol is responsible for Gray Baby syndrome- bc neonates can’t glucoronidate chloramphenicol which accumulates inhibition of mitochondrial protein synthesis- abdominal destination, cyanosis = high mortality
what are the 3 macrolides
erytrhomycin, azithromycin, clarithromycin
Spectrum of macrolides?
macrolides are effective against what?
Static some cidal against gram +
Macrolides effective against Mycoplasma pneumonia, Legionnaires, Chlamydial infections, other respiratory infections, pneumoniae
middle ear and sinus infections in children
What are the resistance to Macrolides
Macrolide resistance from methylation of 50s ribosome, enhanced efflux pump, chromosome mutations of 50s, macrolide hydrolysis by esterases
What is used the least out of the 3 macrolides
Erythromycin is the least used bc has the shortest half life, narrowest spectrum and least desirable effects
What is a semisynthetic Erythromycin analog that binds to the 50s ribosomal subunit
Ketolide - Telithromycin
Ketolide- Telithromycin spectrum: What infection specifically?
Broad spectrum. TX of RTI, community acquired pneumonia
and effective against Macrolide resistant strains
What is the toxicity warning of Telithromycin
Liver Toxicity= Ketolide
Clindamycin spectrum
Clindamycin effective against Gram + bacteria and anaerobes: S pyogenes
What two drugs are for anaerobic infections
Clindamycin and Metronidazole
What is Clindamycin used to treat specifically?
Clindamycin used to treat Penicillin resistant infections and gram + anaerobes
what is the specific toxicity that comes with Clindamycin use, making it a rarely used AB
Clindamycin causes pseudomembraneous colitis by toxin form from C difficile. C difficile is resistant to Clindamycin
If a pseudomembraneous colitis develops from use of Clindamycin then what do you treat this C difficile infection with?
Metronidazole
The combo of what two drugs is effective against mainly gram + organisms and is bactericidal
Quinopristin/ dalfopristin
Quinopristin/ dalfopristin is used specifically to treat what infections
VRE and MRSA type infections
What AB is Broad spectrum against gram + (staph, strep, enterococcus) and has poor activity against gram - and anaerobes
Linezolid
What is Linezolid specifically used to treat?
VRE and MRSA infections
What inhibits isoleucyl tRNA synthetase and is bacteriocidal
Mupirocin
What is Mupirocin effective against
Gram + and some gram -. Skin infections including MRSA
