Antibacterial Agents and Resistance Flashcards
Explain the concept of selective toxicity and its relationship to antimicrobial agents.
Selective toxicity- toxic against bacteria but sparing host cells
What are the desired antimicrobial properties and pharmacologic activities of antimicrobial agents?
Narrow spectrum when pathogen is identified and broad when unidentified. Long half life in the plasma. Bacteriocidal. Wide tissue distribution and penetration of BBB. No interaction with other drugs. Oral and injectable forms.
How are bacteriostatic agents classified according to their activity, target site and chemical structure?
Bacteriostatic just suppress the microbes and wait for immune system to kill them. Needs to have a steady level in the blood for at least a week.
How are bacteriocidal agents classified according to their activity, target site and chemical structure?
Bacteriocidal kill the microbes.
What are the roles of bacterial chromosomal mutations, plasmids, transposons and integrons in the generation of antibiotic resistance mechanisms?
Mutations- a random mutation may give a bacteria immunity and will pass it on in reproduction
Plasmids- horizontal gene transfer by passing plasmids to other bacterial cells
Transposons- can move to chromosome for stability or to the plasmid for mobility
Intergrons- can carry multiple resistance cassettes
What are bacterial targets for antibiotics?
Cell walls
Cell membrane (phosphotidylglcerol or hopanoids)
Protein synthesis with prokaryotic ribosomes
Nucleic acid synthesis with prokaryotic enzymes
Folic acid synthesis which we do not use
What are the major mechanisms of bacterial resistance to antibiotics?
1) Mutation of gene encoding target proteins.
2) Mutation of pores or pumps to prevent up take or allow efflux of antibiotics.
3) Detoxifying enzymes such as beta-lactams or CAT (acetylates to inactivate)
Explain beta-lactams chemical structure, mechanism of action, pharmacokinetics, spectrum of activity, clinical use, toxicity and resistance mechanisms.
All beta-lactams bind penicillin-binding proteins to inhibit cell wall formation. Low oral bioavailability. Can’t penetrate BBB. Ineffective against intracellular bact. Excreted in urine. Penicillin can kill by anaphylactic shock Ampicillin can cause rashes cross-hypersensitivity between other beta-lactams. Can be broken down by beta-lactamase.
Explain glycopeptides chemical structure, mechanism of action, pharmacokinetics, spectrum of activity, clinical use, toxicity and resistance mechanisms.
Large peptide with few monosaccharides. Used on Gram positive beta-lactam resistant bacteria. Binds to peptide ends D-alanyl-D-alanine. Not digested in GI very good. Good for oral ingestion for colitis by Clostridium difficile
How does cylcoserine block cell wall synthesis?
Inhibits reactions involved in incorporation of alanine into the cell wall precursor
How does bacitrin block cell wall synthesis?
Prevents dephosphorylation of phospholipid carrier which prevents regeneration of carrier necessary for synthesis to continue
How do glycopeptides block cell wall synthesis?
Bind to terminal D-ala-D-ala residues to prevent incorporation of subunit into growing peptidoglycan
How do beta-lactams block cell wall synthesis?
Bind to and inhibit enzymes which catalyse binding of glycopeptide subunits
