Friday, April 3, 2009

Antibiotic Mechanisms

Antifungals
Binds to ergosterol in fungal membranes, disrupting membrane permeability and transport functions, thereby allowing cations and macromolecules to leak out of the cell

Aztreonam
Binds to PCP's, inhibits peptidoglycan synthesis and is bactericidal for gram negative (no effect on gram pos and anaerobes) B-lactam resistant

Cephalosporins
B-lactam Bactericidal...Binds to PCP's and inhibits murein synthesis and cell wall production

Clindamycin
Binds to 50s subunit of bacterial ribosomes and suppresses protein synthesis by disrupting formation of 70s initiation complex and inhibits translocation step of peptide bond synthesis...gram + cocci and most anaerobes

Erythromycin
Inhibits protein synthesis by binding reversibly to 50s ribosomal subunits ...specifically inhibits translocation step of protein synthesis, where tRNA/amino acid complex moves from the acceptor site to the peptidyl site on the ribososmes

Gentamicin
Aminoglycoside bactericidal...enters by oxygen dependent active transport, binds to 30s and inhibits protein synthesis...interferes with initiation complex, induces misreading of mRNA, and breaks up polysomes...synergistics with B-lactams

Imipenem
B-lactam, binds to PCP's (many of which are transpeptidases for murein wall synthesis)...autolytic enzyme activation..broadest spectrum of all antibiotics

INH
Inhibits mycobacterial cell wall synthesis (specifically mycolic acids)

Metronidazole
Bioactivation of drug's nitro base by ferridoxin leads to cytotoxic agents which are bacteriocidal

Nafcillin
Penicillinase-resistant PCN...binds to PCP's inhibits cell wall synthesis..bulky nature prevents B-lactamase function

Neomycin
Enters by oxygen dependent active transport, binds to 30s and inhibits protein synthesis by interfering with initiation complex, misreading mRNA, breaks up polysomes

Nitrofurantoin
Bacteriostatic...urinary antiseptic...best if urine is acidic

Penicillin
Binds to PCP's which inhibits cell wall synthesis...autolytic enzyme activation leads to bactericidal activity on dividing bacteria

Rifampin
Inhibits DNA-dependent RNA polymerase of Mycobacteria by interacting with its B subunit...this suppresses RNA chain initiation

Quinolones
Inhibits DNA topoisomerase II (DNA gyrase)...bactericidal
Sulfa
Bactriostatic, structural analog of PABA and a competetive antagonist for dihydropteroate synthetase

Tetracycline
Bacteriostatic, bacteriocidal only at high concentrations...passively diffuses through hydrophilic channels and then an energy dependent active transport pumps the drug through the inner cytoplasmic membrane. Humans lack active transport and therefore are protected...drug then binds to 30s and prevents access of the aminoacyl tRNA to its acceptor site on the mRNA

Trimethoprim
Inhibits dihydrofolate reductase, thus preventing folic acid synthesis and therfore decreased production of thymine, purines, and amino acids and interferes with nucleic acid production.

Vancomycin
Binds with high affinity to D-alanyl-D-alanine portion of cell wall precursors and prevents polymerization of peptidoglycans. Bactericidal for dividing gram positives

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