Week 4 - Protein Synthesis Inhibitors Flashcards
What are the inhibitors of the 30S subunit?
aminoglycosides and tetracycline
What are the inhibitors of the 50S subunit?
linezolid, macrolides, chloramphenicol, clindamycin, quinupristin/dalfopristin
What drugs inhibit initiation?
linezolid, aminoglycosides
What drugs inhibit elongation?
aminoglycosides, tetracycline, macrolides, chloramphenicol, clindamycin, quinuspristin/dalfopristin
What drugs inhibit termination?
aminoglycosides
What drugs produce a side effect due to interference with mitochondrial ribosomes? What is this side effect?
drugs: linezolid, tetracycline, chloramphenicol
- bone marrow suppression is the side effect
What drug binds the P-site on the 50S?
Linezolid
How do aminoglycosides prevent mRNA synthesis?
bind to the 30S ribosome and freeze the initiation complex
What is the mechanism of action for Linezolid?
bacteriostatic – binds 50S on the 23S rRNA to prevent formation of of the initiation complex
What is the spectrum for linezolid?
Gram +, MRSA and Vanco-resistant Enterococci
Adverse effects of linezolid:
bone marrow suppression, Serotonin Syndrome if taken with SSRI (hallucinations, increase heart beat, agitation, nausea) due to inhibition of monoamine oxidase
What are the aminoglycosides?
gentamicin, amikacin, tobramycin, neomycin, streptomycin (GNATS)
What is the mechanism of action for aminoglycosides?
bactericidal – prevent formation of initiation complex, cause misreading of mRNA, induces early termination
Spectrum of aminoglycosides:
gram - aerobes because they need a lot of energy get into the cell, and anaerobes have no oxidative phosphorylation
Why would you treat with a cell wall inhibitor and an aminoglycoside?
to treat an anaerobe, need to break down cell wall for easier time getting into cell
What is the spectrum of amikacin?
broader because it is less susceptible to enzyme inactivation, can treat Pseudomonas
What antibiotics are concentration-dependent killers?
aminoglycosides, fluoroquinolones
What antibiotics are time-dependent killers?
beta-lactams and vanco
Adverse effects of aminoglycosides:
tubular necrosis: nephrotoxicity (drug retained in renal cortex) , ototoxic, pregnancy class D (due to hearing loss) neomycin - can cause allergic rxn in triple antibiotics
What drug is administered by IV?
aminoglycosides
*also excluded from CSF
Mechanism of action for Tetracyclines:
bacteriostatic – bind 30S preventing attachment of aminoacyl-tRNA
What drugs are tetracyclines?
tetracycline, doxycycline, minocycline
What is the spectrum for tetracyclines?
broad, but resistance has led to treating only: B. burfdorferi, H. pylori, Mycoplasma pneumoniae
Adverse effects for tetracyclines
forms chelates with metal ions - decreases absorption (don’t take with antacids)
GI irritation, photosensitivity, discolor teeth, inhibit bone growth in kids
-don’t give to preggo
What drug would be used to treat Lyme’s disease?
doxycycline – can be effective for treating other tick borne disease at the same time
What bacteria exhibits a persister phenotype that is tolerant to drugs?
B. burgdorferi (Lyme’s)
Mechanism of action for chloramphenicol:
bacteriostatic – binds 50S, prevents peptide bond formation, peptidyltransferase can’t associate with AA substrate
Spectrum for chloramphenicol:
extended, but limited use due to side effects
Adverse effects of chloramphenicol:
Toxic, bone marrow suppression, aplastic anemia, Gray baby syndrome – don’t use for prego
What is gray baby syndrome?
babies have decreased renal function, high levels of drug build up, leads to cardiovascular and respiratory collapse
What are the macrolides?
erythromycin, azithromycin, clarithromycin
Mechanism for macrolides
bacteriostatic – inhibit translocation by binding 23S rRNA of the 50S subunit
Spectrum for macrolides:
broad coverage of respiratory pathogens, Chlamydia
What would you use to treat Mycoplasma?
doxycycline, azithromycin, levofloxacin
no cell wall so no beta lactams
Adverse effects for macrolides:
GI discomfort, hepatic failure, prolonged QT interval, inhibits action of Cyp450 enzymes
**clarithromycin - don’t give to prego
Mechanism for Clindamycin
bacteriostatic – blocks translocation at 50S
Spectrum for Clindamycin:
gram + including anaerobic, treats acne
Adverse effects of clindamycin:
hypersensitivity, GI issues (blood in stool), Superinfection with C. diff
What drugs are the streptogramins?
quinupristin/dalfopristin
Mechanism for streptogramins
combo action is bactericidal for some organisms, bind 50S to inhibit translocation
Spectrum for quinupristin/dalfopristin
should be reserved for infections caused by multiple drug-resistant Gram + bacteria
Adverse effects for streptogramins:
arthralgias, myalgia (pain), inhibits Cyp450 enzymes, likely to have significant drug interactions
What drugs will have increased efflux as the resistance mechanism?
Tetracyclines, macrolides, quinopristin/dalfopristin
What drugs will have decreased uptake as the resistance mechanism?
aminoglycosides, chloramphenicol
What drugs will have altered target as the resistance mechanism?
Linezolid, aminoglycosides, quinupristin/dalfopristin, tetracyclines
What drugs will have enzymatic inactivation of drug as the resistance mechanism?
Aminoglycosides (amikacin most resistant), chloramphenicol, tetracyclines, macrolides, clindamycin, quinupristin/dalfopristin, metronidazole
Drugs reserved fro MRSA and VRE
5th generation cephalosporin, vancomycin, daptomycin, quinupristrin/dalfopristin, linezolid
Don’t use in newborns (can’t glucoronidate)
Chloramphenicol (Gray baby), Sulfonamides (Kernicterus jaundice)
Don’t use in children
Tetracycline, Fluoroquinolones (arthropathy)
Don’t use during pregnancy
Chloramphenicol, Sulfonamides, Tetracycline, Fluoroquinolones, Aminoglycosides, Clarithromycin
Reserved for MRSA & VRE
5th gen. cephalosporins, vancomycin, daptomycin, quinipristin/dolfapristin, linezolid
