PROTEIN SYNTHESIS INHIBITORS Work by targeting bacterial ribosome Mammalian (eukaryotic) cells have 80S ribosomes composed of 60S

and 40S subunits Bacteria (prokaryotic) cells have 70S ribosomes composed or 50S and 30S subunits
AMINOGLYCOSIDES Streptomycin Gentamicin Tobramycin Amikacin Netilmicin Neomycin Kanamycin TETRA-CYCLINES Tetracycline Doxycycline Minocycline Demeclocycline Oxytetracycline CHLORAMPHENICOL Chloramphenicol MACROLIDES Erythromycin Clarithromycin Azithromycin LINCOSAMIDES Clindamycin Lincomycin

AMINOGLYCOSIDES Bactericidal Inhibit protein synthesis All bind irreversibly to the 30S ribosomal subunit and interfere with protein synthesis in susceptible bacteria Used to treat infections caused by several aerobic gram-negative bacteria Given parenterally Mechanisms of Resistance: o Plasmid-mediated synthesis of aminoglycoside inactivating enzymes such as acetyltransferase, nucleotidyltransferase and phosphotransferase which modify and inactivate these drugs o Changes in the 30S ribosomal subunit resulting in decreased affinity between the drug and 30S subunit o Decreased membrane permeability

TETRACYCLINES Large group of related agents Effective against both aerobic and anaerobic gr (+) and (-) bacteria, rickettsiae, mycoplasma and chlamydiae Can cross placenta but have poor CNS penetration

Mechanisms of Resistance: o Resistance usually results from acquisition of an R-factor which may code for the following: Active efflux mechanism that pumps drug out of the microorganism Loss of cytoplasmic transport proteins which are required for entry into susceptible organisms Changes in membrane permeability to the drug

CHLORAMPHENICOL Broad spectrum antibiotic Inhibits protein synthesis in bacteria by binding to the 50S ribosomal subunit Remains an important drug for life-threatening infections such as meningitis, typhoid fever Mechanism for Resistance o Resistance to gram (-) bacteria to this drug is usually caused by a plasmid acquired by conjugation which may code for the ff: o R-factors coding for Acetyl-CoA transferase which inactivates chloramphenicol o Decreased ability to penetrate the organism Side effects: o Anemia o Gray baby syndrome o Nausea, vomiting, diarrhes and perineal irritation

MACROLIDES Characterized by a macrocyclic lactone ring to which sugars are attached Erythromycin drug prototype Mechanisms of Resistance: o Plasmids coding for specific enzymes (erythromycin esterases) which inactivate these drugs o Methylation of an adenine residue on the 23S rRNA binding site leads to decreased affinity for the 50S ribosomal subunit o Defective uptake of the drug by the microbe CLINICAL USES:

Spectrum: anaerobic gram (+) cocci and bacilli Pneumonia Legionnaires disease Pertusis Diphtheria
SIDE EFFECT:

GI side effects: nausea, vomiting, diarrhea Cholestatic hepatitis