Protein synthesis inhibitors Flashcards
How do AGs work?
They block translocation and termination of peptides
How do tetracyclines work?
They block AA-tRNA
How do macrolide work?
They lock translocation of peptides
How do oxazolidinones (linezolid) work?
Block 50 S binding
CLEan TAG
50s: chloramphenicol, clindamycin, linezolid, erythromycin
30s: tetracyclines and aminoglycosides
Name the aminoglycosides
Gentamicin and tobramycin
What are aminoglycosides good at covering?
aerobic GNRs
What formulary is available for AGs?
Only IV
What are the side effects of aminoglycosides?
Nephrotoxic and ototoxic. Lots of kids given gentamicin develop irreversible hearing loss which is why we don’t often use it.
Describe concentration dependent killing versus time dependent killing
Concentration dependent=Exposure to higher concentration for a short time
Time dependent=Longer exposure with more dosings is more efficient
Which drugs rely on concentration dependent killing?
Aminoglycosides
fluoroquinolones
metronidazole
Which drugs rely on time dependent killing?
penicillins
Extended interval dosing:
Give lots of smaller doses throughout the day to keep toxicity low but remain in efective range
How to tetracyclines work?
They bind to 30S unit and block the aminoacyl tRNA too
What are the major situations in which we would use a tetracycline?
Rocky mountain spotted fever and lyme dz
How do macrolides develop resistance?
23S rRNA nucleotide mutation
Efflux
When do we use macrolides?
Respiratory tract infections
What is unique about the metabolism of macrolides?
They have a very long half life
What are the side effects of macrolides?
Ototoxicity
What do the macrolides cover?
- GPC (staph and strep often resistant)
- mycoplasma
- legionella
- chlamydia, mycobacteria
- H. flu
- –>basically all the atypicals
How does clindamycin work?
Binds to 23S rRNA binding site, preventing peptide bond formation
What drug should you NOT prescribe with clindamycin? Why?
Macrolides–because will have mutual interference
Is clindamycin bacteriostatic or bacteriocidal?
bacteriostatic. Almost all of the protein synthesis inhibitors are bacteriostatic EXCEPT the aminoglycosides
What is clindamycin effective against?
GPC and oral/bowel anaerobes
How does linezolid work?
Prevents 50S from binding the 30S unit
What is linezolid effective against?
VRE, VRSA, MRSA
How do sulfa drugs work?
They inhibit dihydropteorate synthesis
How does trimethoprim work?
Inhibits DHFR
Is bactrim static or cidal?
static
What are the contraindications to bactrim?
erythema multiforme rxn
Pregnancy***
Can cause bone marrow suppression
What is bactrim good for?
S pneumo
H flu, E coli, pneumocystis
How do fluoroquinolones work?
They inhibit DNA gyrase
What are three mechanisms of resistance with fluoroquinolones?
- Reduced binding to DNA topoisomerase (gyrase)
- Protection by QnR protein
- Impaired permeability and drug efflux
Are fluoros cidal or static?
cidal
Cipro is used for:
Uti and STD (mostly gram negative coverage)
–Cipro has better penetration of the urinary tract
Mox/levo is used for:
pneumonia (good gram positive coverage too unlike cipro)
How does metronidazole work?
Damages DNA by forming a nitro radical
What is metronidazole used for?
Anaerobes (bowel, oral)
C difficile infection
Giardia
Amoeba
What are the side effects of metronidazole?
Metallic taste
GI upset
CNS: ataxia/vertigo
teratogen
How does Rifampin work?
Binds to RNA polymerase and inhibits
What is Rifampin good for?
It’s broad spectrum and good for: GP and GN coverage
Mycobacterium especially
How does rifampin resistance develop?
Mutation of the RNA poly binding site. Resistance develops very easily, so never use alone
How do you treat pertussis?
Azithromycin
–can also use bactrim
