inhibitors of protein synthesis I Flashcards
prokaryotic ribosomes are composed of what two subunits
- 50S
- 30S
- combine to form 70S total
Eukaryotic ribosomes are composed of what two subunits
- 60S
- 40S
- combine to form 80S
MOA of macrolides
targets 50S subunit of ribosome
Macrolides prototype
erythromycin
Name the three macrolides
- erythromycin
- clarithromycin
- azithromycin
route of administration of erythromycin
oral, IV
route of administration of Clarithromycin
oral
route of administration of azithromycin
oral, IV
are macrolides bacteriostatic or cidal
bacteriostatic; concentration/organism dependent- cidal activity
coverage of macrolides
G+
*majority of G- organisms are resistant
how do bacteria become resistance to macrolides
- efflux pumps
- methylation of drug binding site (ribosome)
toxicity of macrolides, particularly Erythromycin
- diarrhea
- erythromycin +++; Azithro ++; clarithromycin +: GI adverse effects
- QT prolongation
- erythro +++; Claritho ++; Azithro +
erythromycin is a potent inhibitor of what enzyme that leads to drug interactions
CYP3A4
- therefore, can inhibit the hepatic metabolism of other drugs that require CYP3A4, increasing their serum concentrations and potentially causing toxicity
DOC for urogenital infections due to Chlamydia occuring during pregnancy
Erythromycin
DOC legionnaries’ disease
azithromycin
MOA of Ketolides
block bacterial protein synthesis; has 2 binding sites for the ribosomal RNA, 50S, which increases its affinity
what group is Telithromycin in
Ketolides
coverage of Telithromycin
broad spectrum
- good against respiratory pathogens including erythromycin and penicillin resistant pneumococci: remains on market for community acquired PNA (not first choice)
route of administration of Telithromycin
oral
metabolism of Telithromycin
via CYP3A4
toxicity of Telithromycin
- diarrhea
- hepatotoxicity
MOA of Clindamycin
binds to 50S ribosomal subunit
coverage of Clindamycin
- aerobic G+
- Anaerobic G- and G+ organisms
is Clindamycin bacteriostatic or cidal
either, depends on
- concentration at the site of action
- specific susceptibility of the organism
why is Clindamycin used to treat osteomyelitis
it obtains high concentration in bones
which organisms are extremely susceptible to Clindamycin
- streptococci (except enterococci) and staphylococci (MRSA)
what two Abx are used to treat toxic shock syndrome
- clindamycin
- vancomycin
Clindamycin toxicity
- Pseudomembranous colitis (overgrowth of clostridium difficile)
is Clindamycin safe to use in nursing mothers
NO, crosses the placenta readily and is distributed into breast milk
What two Abx does Streprogramins consist of
- Dalfopristin
- Quinupristin
- Trade name (Synercid)
- combination is bactericidal
MOA of Dalfopristin; Quinupristin (Synercid)
both Abx bind to 50S particles but inhibit different stages of protein synthesis
route of adminstration of Dalfopristin; Quinupristin (Synercid)
IV infusion
Dalfopristin; Quinupristin (Synercid) has been approved for what uses
- Aerobic G+
- penicillin resistant S. pneumoniae
- complicated skin infections due to staph aureus (MSSA and MRSA)
- vancomycin resistant Enterococcus faecium
adverse reactions of Dalfopristin; Quinupristin (Synercid)
- hepatotoxicity
- inhibit P450 drug metabolism system (CYP3A4), many metabolic interactions (warfarin, diazepam)
what group does Linezolid belong to
Oxazolidinones
coverage of Linezolid
aerobic G+ organisms
- bacterial PNA
- vancomycin-resistant enterococcal infections
- MRSA
***new Abx; should be used as alternate agent bc overuse with hasten selection of resistant strains
MOA of Linezolid
- binds to a site on the bacterial 23S ribosomal RNA of the 50S subunit
Linezolid adverse reactions
reversible, non-selective inhibitor of monoamine oxidase (MAO)
*MAO inactivate neurotransmitters
route of administration of Linezolid
IV or oral
*Oral bioavailability is 100%
