Antibacterial Agents: Protein Synthesis Flashcards
Name the three binding sites on a ribosome
Where new charged tRNA molecules first attach, where growing peptide chain is held, where uncharged tRNA molecules leave
How many ribosomal subunits do bacteria have
50S + 30S subunits
What is the start codon in bacteria called?
F-Met
What antibacterial agents act on the 30S subunit?
Aminoglycoside antibiotics and tetracyclines
What antibacterial agents act on the 50S subunit?
Chloramphenicol and macrolides
Give two examples of aminoglycosides drugs?
Streptomycin and Gentamicin
Describe Aminoglycosides’ mechanism of action.
Prevent initiation by preventing binding of start codon, cause misreading of codons along mRNA and interferes with translocation of tRNA from A to P site
What type of bacteria do aminoglycosides have activity against?
Gram -ve aerobic bacilli
Why are aminoglycosides not absorbed in the GIT
Highly polar - don’t readily cross cell membranes
How are aminoglycosides administered?
Topically (I.V. or I.M.)
Where are aminoglycosides mainly distributed?
To the extracellular fluid (do not cross BBB)
Do aminoglycosides undergo metabolism?
No
How are aminoglycosides exctreted?
Glomerular filtrartion
What type of aminoglycoside is toxic and why?
Neomycin. It is nephrotoxic
What are aminoglycosides clinical uses?
G -ve bacillary infections, bacterial endocarditis, TB, plague, conjunctiva or external ear infections
What are the side effects of aminoglycosides?
Ototoxicity, neuromuscular transmission inhibition, paralysis, nephrotoxicity, contact dermatitis, bone marrow depression and hemolytic toxicity
What are the main mechanisms of resistance of aminoglycosides?
Membrane impermeabilization, bacterial expression of drug inactivating enzymes (plasmids), inhibitors of cell wall synthesis and alteration of receptor protein on 30S subunit by mutations
What are tetracyclines?
Bacteriostatic antibiotics (30S)
What is tetracyclines mechanism of action?
Bind irreversibly to 30S - competes with tRNA for A site
Prevents elongation of polypeptide chain
What type of bacteria do tetracyclines act on?
G+ve/G-ve bacteria, spirochaetes and protozoa - wide spectrum
How are tetracyclines administered?
Orally and by I.V.
Where are tetracyclines distributed?
Everywhere
How are tetracyclines metabolized?
Undergo 2nd generation metabolism in the liver
How are tetracyclines excreted?
Kidneys in urine and doxycycline glucuronide is excreted via bile
What are tetracyclines clinal uses?
Peptic ulcer disease, Lymes disease, cholera, mycoplasma pneumoniae, chlamydia, acne and chronic hynonatraemia
What are tetracyclines side effects?
GIT disturbances, photosensitivity, deposition in calcified tissues, hepatotoxicity, vestibular dysfunction, Fanconi syndrome, pseudotumor cerebri and hematologic toxicity
How is bacteria resistant to tetracyclines?
Efflux pumps, enzymatic inactivation and ribosomal protection
