"And the rest" of the Protein synthesis inhibitors Flashcards
How does Chloramphenicol work?
Binds 50s subunit
Inhibits bond formation between peptide and new amino acids (Inhibits peptidyltransferase)
Binding is reversible!
What is the first synthetic antibiotic?
Chloramphenicol
Is chloramphenicol bacteriocidal or bacteriostatic?
Mostly bacteriostatic
It’s bacteriocidal in H influenzae, strep pneumoniae, and neisseria meningitidis
Use of chloramphenicol is limited to what? Why
Use is limited due to toxicity
Use is limited to meningitis and rickettsial infections in patients who can’t take safer drugs because of reisstance or allergies
What causes chloramphenicol resistance?
Plasmid encoded acetyltransferase prevents binding to the ribosome
True or False: Chloramphenicol enters the CNS
True
True or False: Chloramphenicol is safe in pregnancy
False
Enters both breast milk and placenta
What toxicities are associated with chloramphenicol?
Lots! Bone marrow suppression (can be fatal) - aplastic anemia, leukopenia, thrombocytopenia Altered red blood cell maturation Peripheral neuropathy Inhibits microsomal enzymes Hypersensitivity reactions Inhibits CYP enzymes nausea, vomiting, diarrhea, blurring of vision
How do Streptogramins work?
Bind the 50S subunit
Dalfopristin prevents peptide bond formation (inhibits peptidyltransferase, causes early termination)
This changes the 50s subunit to enhance quinupristin binding
Quinupristin inhibits t-RNA synthesis (inhibiting elongation, causing early termination)
What is streptogramins?
Combination product of Dalfopristin (group A) and Quinupristin (Group B)
30 Dalf
70 Quin
Is streptogramins bacteriostatic or bacteriocidal?
The individual agents are bacteriostatic
When given in combination, they’re bacteriocidal
What causes resistance in streptogramins?
Quinupristin: Altered ribosomal binding
Dalfopristin: Increased metabolism
What is streptogramins used for?
vancomycin resistant e. faecium
NOT active against faecalis
How is streptogramins administered?
IV infusion
What toxicities are associated with streptogramins
Inflammation of the veins Muscle aches Diarrhea, nausea Inhibits CYP3A4 Elevates serum transaminase
Which drug elevates serum transaminase
Streptogramins
Which drug causes veinflammation
Streptogramins
What drugs are replacing Streptogramins?
Linezolid and Daptomycin
What is linezolid?
An oxazolidinone
How does Linezolid work?
Binds the P site of the 50s subunit, preventing formation of the 70s unit
Inhibits binding of the met-tRNA
What is Linezolid used for?
Nosocomial pneumonia by:
MRSA
S Aureus
S Pneumoniae
Also skin and skin structure infections (MRSA resistant and sensitive)
Reserved for MULTIPLE-DRUG-RESISTANT strains
How is Linezolid administered?
Oral and IV formulations
How is Linezolid excreted?
Metabolized by non-enzymatic oxidation
True or False: There is no resistance to linezolid
False, thought to have no resistance but has started showing resistance
What toxicities are associated with Linezolid
Nausea Thrombocytopenia, anemia, leukopenia Itching Non-selective MAO inhibitor Peripheral neuropathy
What is Mupirocin?
Topical cream/ointment
How does Mupirocin work?
Inhibits Isoleucyl-tRNA synthase only
Prevents incorporation of isoleucine into proteins only
No cross tolerance with other antibiotics
Can still make peptides that don’t have isoleucine!
True or false: Mupirocin shows no cross tolerance with other antibiotics
True
Is mupirocin bacteriocidal or bacteriostatic?
Bacteriostatic at low concentrations
Cidal at higher
What is Mupirocin used for?
Traumatic skin lesions (Impetigo, s aureus, streptococcus pyrogens)
or nasal colonization with Methicillin resistant s. aureus
What drug is used to treat nasal colonies of MRSA?
Mupirocin
