Lecture 6 - Antibacterial Agents Flashcards
What was the compound that Paul Ehrlich came up with?
Compound 606 aka Salvarsan
What was the first real antibiotic?
Penicillin (1928)
What is the definition of an antibiotic?
Chemical that is able to kill or inhibit the growth of bacterial cells
What is the definition of antimicrobial?
All agents that kill all types of microorganisms
What are the two very basic actions carried out by antibiotics?
Bacteriostatic + Bacteriocidal
What is bacteriostatic?
Inhibits the growth of bacteria
What is bacteriocidal?
Kills bacteria
What are the three categories in regards to spectrum of activity?
Narrow - Broad - Moderate
What is the major goal of antibiotic development (what should be one of the most important?
Selective toxicity
What is selective toxicity?
AB is more toxic to the bacterial cells than it is the host cells
What are some basic targets for antibiotics to ensure that they have selective toxicity?
Cell wall + Ribosomes + Bacterial enzymes
What does it mean to use antibiotics in a non-therapeutic manner?
Commonly seen in food animal medicine. This is the practice of using AB to prevent an infection from occurring before it is even present in the animal.
What is bad about the non-therapeutic use of AB’s?
This helps increase the rate in which bacterias become resistant to various antibiotics
What are the five classes of antibiotics?
Inhibition of cell wall synthesis Disruption of cell membrane function Inhibition of protein synthesis Inhibition of nucleic acid synthesis Action as antimetabolite
What are the three AB’s that are inhibitors of cell wall synthesis?
Beta-Lactam
Glycopeptides
Bacitracin
What is the spectrum of activity of beta-lactam?
Varies
Is beta-lactam a -cidal or a -static?
Bactericidal
What is the mechanism of beta-lactam?
Binds/blocks transpeptidase
Prevents peptidoglycan cross-linking
Cell lysis
What is another name for transpeptidase?
Penicillin binding protein
What is the spectrum of activity for glycopeptides?
Narrow - Gram(+) only
Is glycopeptide -cidal or -static?
Bactericidal
What is the mechanism of glycopeptides?
Binds to the pentapeptide chains of NAM
Blocks transglycosylation + transpeptidation of peptidoglycan syn.
Cell lysis
What is the spectrum of activity for Bacitracin?
Broad
What is crucial to know clinically about Bacitracin?
Topical use only, too toxic for systemic use
Is Bacitracin -cidal or -static?
Bactericidal
What is the mechanism for Bacitracin?
Prevents dephosphorylation of bactoprenol
Prevents transport of NAG-NAM monomers
Cell lysis
What antibiotic works through disruption of the cell membrane?
Polymyxins
What is the spectrum for Polymyxins?
Moderate
What does polymyxin work on?
Gram-negative bacteria
What is clinically important to know about polymyxin?
Poor selective toxicity therefore topical use only
What is the mechanism for polymyxin?
Works as a cationic detergent
Increase water uptake into the cell
Cell lysis
What ribosome type is found in bacteria?
70s
What are the subunits of the bacterial ribosome?
30s + 50s
What antibiotics target the 30s subunit of the bacterial ribosome?
Aminoglycosides + Tetracyclines
What antibiotics target the 50s subunit of the bacterial ribosome?
Chloramphenicol
Macrolides
Lincosamides
What is the spectrum of activity for aminoglycosides?
Broad
What should the use of aminoglycosides be limited to?
Enteric infections and sometimes sepsis
Are aminoglycosides -cidal or -static?
Bactericidal
What is the mechanism for aminoglycosides?
Irreversible binding to 30s
Block initiation complex + misreading/premature release of mRNA
Stops protein synthesis h
What is the spectrum of activity for tetracyclines?
Broad
What is clinically important to know about tetracyclines?
Have non-antibacterial uses
Can be used as an anti-inflammatory
Are tetracyclines -cidal or -static?
Bacteriostatic
What is the mechanism of action for tetracylines?
Reversibly bind to ribosome
Prevent attachment of aminoacyl-tRNA to complex
Prevent AA addition to peptide chain
Halt protein syntheiss
What is the spectrum of activity for chloramphenicol?
Broad
What is clinically important to know about the use of chloramphenicol?
Can be toxic; causes aplastic anemia in humans
Is chloramphenicol -cidal or -static?
Bacteriostatic
What is the mechanism of chloramphenicol?
Reversibly binds to ribosome
Inhibits peptidyl transferase
Prevents elongation of peptide chain
Halts protein synthesis
What is the spectrum of macrolides?
Narrow
Are macrolides -cidal or -static?
Bacteriostatic
What is the mechanism for macrolides?
Reversibly binds to ribosome
Inhibits transpeptidation + translocation
Prevention of chain elongation + premature detachment of peptide
Halt protein synthesis
What is the spectrum of activity for lincosamides?
Moderate
What microbes do lincosamides target?
Gram-postive
Anaerobes
Some mycoplasmas
Are lincosamides -cidal or -static?
Bacteriostatic
What is the mechanism of action for lincosamides?
Reversible binds to ribosome
Inhibit transpeptidation + translocation
Similar to macrolides
Halt protein synthesis
What antibiotics target nucleic acid synthesis?
Quinolones + Fluoroquinolones
Rifamycins
Metronidazole
Are quinolones -cidal or -static?
Bactericidal
What is the spectrum of quinolones?
Varies - normally broad
What is the mechanism for quinolones?
Bind to DNA gyrase + topoisomerase IV
Inhibit bacterial replication via interference with DNA supercoiling
Stop DNA/RNA synthesis
What is the spectrum of activity for rifamycin?
Broad
Are rifamycins -cidal or -static?
Bactericidal
What is the mechanism of action for rifamycins?
Inhibits DNA-dependent RNA polymerase
Stops transcription of mRNA
What is the spectrum of activity for metronidazole?
Narrow
What microbes does metronidazole target?
Anaerobes + Protozoans
Is metronidazole -cidal or -static?
Bactericidal
What is the mechanism for metronidazole?
Reduction into active form
Covalently binds to DNA = breakage
Inhibits NA synthesis
What antibiotics are antimetabolites?
Sulfonamides + Diaminopyrimidines
Are the antimetabolite AB’s -cidal or -static?
If used alone they are bacteriostatic
If used together (common) bacteriocidal
What is the mechanism of the antimetabolites?
Interfere with folic acid synthesis
What is the specific mechanism of sulfonamides?
Analog of PABA - compete for the enzyme dihydropteroate synthetase
What is the specific mechanism for diaminopyrimidines?
Analogs of pteridine portion of dihydrofolic acid - inhibit dihyro reductase
Who was the first person to begin to find a compound that would kill infectious microbes?
Paul Ehrlich