Antibacterial Agents: Protein Synthesis 50s Flashcards
What drugs act on the 50S subunit?
Chloramphenicols and Macrolides
What type of drug is chloramphenicol?
Bacteriostatic, bactericidal at high levels
What is chloromphenicol’s mechanism of action?
Prevents binding of tRNA to A site, prevents transpeptidation process, inhibits protein production, prevents protein production
How is chloramphenicol administered?
Oral, topical and I.V.
How is choloramphenicol absorbed?
Oral drug is abosorbed in GIT (2hrs)
I.V. levels vary (2-3hrs)
Where is chloramphenicol distributed?
Everywhere
How is chloramphenicol metabolized?
It is a prodrug.
Oral prodrug hydrolyzed in small intestine
IV prodrug hydrolyzed in circulation
Active drug metabolized by hepatic glucuronyl transferase
How is chloramphenicol excreted?
Via the renal tubule
What is chloramphenicol used against?
Gram-ve and gram+ve bacteria
aerobic and anaerobic
reserved for life threatening illnesses
What are chloramphenicol’s clinical uses?
Typhoid fever, cholera and bacterial conjunctivitis
What are chloramphenicol’s side effects?
Anemias, Grey baby syndrome, prevents other drugs; metabolism, GIT disturbances, ocular irritation and toxicity and CNS effects
How can bacteria be resistant to chloramphenicol?
Enzymatic inactivation through acetylation by CAT gene, decreased drug permeability, ribosomal protection and presence/increased presence of efflux pumps
Give two examples of Macrolides
Erythromycin and clarithromycin
What type of drug are macrolides?
Bacteriostatic but bactericidal at high concentrations
What is the mechanism of action for macrolides?
Binds to 50s subunit, blocks relocation of tRNA with polypeptide chain from A to P site, inhibits translocation blocking further translation of protein
How are macrolides administered?
Oral and I.V. Food has an affect on uptake
How are macrolides distributed?
Extensive tissue and cellular distribution. Does not cross BBB
How are macrolides metabolized?
In the liver
How are macrolides excreted?
Azithromycin and erythromycin excreted in bile. Clarithromycin excreted in urine
What bacteria are macrolides effective against?
G+ve cocci and bacilli and some G-ve cocci and bacilli
What are macrolides clinical uses?
Whooping cough, community acquired pneumonia, Heliobacter pylori infection, STIs, acute non-specific urethritis, campylobacteriosis, anti-inflammatory effects
What are the side effects of macrolides?
GIT disturbances, ototoxicity, inactivates digoxin, inhibits cytochrome p450, cholestatic jaundice, QTe prolongation
What are mechanisms of resistance against macrolides?
Target modification of a guanine residue, active efflux system, drug inactivation
