18 Protein Synthesis Inhibiting Antibiotics Duncan Flashcards
What are the antibiotics that inhibit protein synthesis?
Macrolides. Lincosamides (clindamycin). Chloramphenicol. Tetracyclines. Aminoglycosides. Aminocyclitols. Oxazolidinones. Streptogramins
What is Erythromycin primarily effective against?
Gram (+): Streptomyces, Neisseria, Pasteurella
What class of drug is Erythromycin?
Macrolide (macrolactone glycoside): polyketide. 14, 15, of 16 atom lactone ring. 1 or more neutral or amino sugars attached
What is the Polyketide biosynthetic pathway?
Sequentially adds building blocks to extend chain. Pathway synthesizes many different antibiotics. Using different but similar enzymes in the pathway can produce variant antibiotics
What are the Macrolide Features?
1) 14-16 atom ring. 2) 1 oxygen. 3) No nitrogen. 4) Many short side chains. 5) 1 or more sugars
What is good about second generation macrolides?
Imrpove acid stability, BA, more predictable PK. Exampe: Clarithromycin
What are the characteristics of Clarithromycin?
Major drawback to erythromycin is low acid stability (low oral BA). Clarithromycin improves this aspect. Also fewer ADRs, longer half-life, easier dosing. Novel antibiotics with erythromycin-like structures can be developed biosynthetically
What are Azalides?
Like macrolides, but with N in ring. Example: Azithromycin
What are the characteristics of Azithromycin?
15 membered ring, with nitrogen; changes activity and properties significantly. Addition of nitrogen decreases potency (ability to bind to target) but more than counterbalanced by PK/PD effects. Enhanced activity against Gram (-) species
What is the PK/PD of Azithromycin?
Very rapid clearance from the blood; concentrated in the tissues where its needed (more than outweighing the decrease in potency). Low serum concentrations, high infection-site concentration. Prolonged period of action from single dose. Enhanced penetration of outer cell membrane. Generally ineffective against erythromycin-resistant strains
What are third generation macrolides?
Versions to counteract microbial resistance to macrolides. Ketolides: telithromycin
What is the primary use of Ketolides: Telithromycin?
Macrolide-resistant S. pneumoniae
What does the structure of Telithromycin look like?
Ketolides: like macrolides, but with =O replacing the C3 sugar. Telithromycin also has a synthetic hydrophobic side chain
What is some general information on Ketolides (Telithromycin)?
Synthetic hydrophobic side chains provide additional novel ribosome interactions. Result, 10 fold better binding to ribosomes resistant to erythromycin
What are the ADRs associated with Ketek (Telithromycin)?
Liver damage, deaths. Flawed Aventis trials, falsified data