21 - Antimicrobial Medications
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What is Salvarsan?
- First documented chemical used as an antimicrobial.
- Discovered by Paul Erlich in treatment of syphillis
Who discovered penicillin and how?
- Alexander Flemming
- Accidentlly while working with staphyloccoccus.
- Noticed there were no colonies growing near a mold contaminant...thought the colonies were "melting."
When and what was the first antibiotic tested on humans?
- Treatment of wounded soldiers for staphylococcus aureus infections
What is Penicillin G?
The first alteration of penicillin, broadened its spectrum
What is MRSA?
Methicillin Resistant Staphyloccocus Aureus
Where do most modern antibiotics come from?
Organisms living in the soil
How are commerical antibiotics produced?
- Strain inoculated into broth medium
- Incubated until maximum ideal concetration is reached
- Drug extracted from medium
- Extensively purified
Sometimes altered to achieve new characteristics, ie capsules, liquid.
What is theapeutic index?
- Lowest does toxic to patient divided by dose typically used for treatment.
- High therapeutic index = less toxic to patient
What are the 2 antimicrobial actions?
- Bacteriostatic - inhibits further bacterial growth, but doesn't kill the bacteria
- Bacteriocidal - kills bacteria
What are the 2 spectrums of activity for antimicrobials?
- Narrow Spectrum - Works on narrow range of organisms only. EX - Gram positive OR negative
- Broad Spectrum - Works on broad range of organisms; causes disruption of normal flora
What is a drugs half-life?
- Time it takes for the body to eliminate one half the original dose in serum
- Dictates frequency of dosage
Synergistic, Antagonistic, and Additive effects of drugs on each other:
- Synergistic - One drug enhances performance of another
- Antagonistic - One drug interferes with effect of another
- Additive - When added drug does not effect another drug
What are the adverse effects of antimicrobial drugs?
- Allergic Reactions - often life threatening
- Toxic Effects - Aplastic anemia, body cannot make R or WBC's.
- Supression of normal flora - When normal flora is diminished, other organisms have an opportunity to move in
- Antimicrobial resistance - Microogranisms can come immune to antibiotics
What are the "Mechanisms of Action" of antimicrobial drugs?
- Inhibition of cell wall synthesis (do not effect humans or other eurkaryotes)
- Inhibition of protien synthesis (ribosomes)
- Inhibition of nucleic acid synthesis (nucleus)
- Inhibition of metabolic pathways (mitochondria)
- Interference with cell membrane integrity
What are natural penicillins?
- Narrow spectrum
- Effective against gram + and - cocci
What are broad spectrum penicillins?
- Penicillins that has a modified side chain
- Effective against gram + and -
How does vancomycin work?
- Inhibits formation of glycan chain
- Must be given intravenously due to poor absorption in digestive tract
- Important in treating infections caused by penicillin resistant gram + organisms
What are cephalosporins?
Broad range of antibiotics that are resistant to beta lactams
What is Bacitracin?
- Common ingredient in non-prescription first aid ointments
- Highly toxic
- Can only use topically
Which antibiotics inhibit protien synthesis?
How does streptomycin work?
Causes misreading of mRNA
How do tetracyclins work?
- Blocks attachment of tRNA to ribosome
- Causes discoloration of teeth if taken as a young child
How does ciprofloxacin (a fluoroquinolones) work?
Inhibits action of DNA enzyme
What does inhibiting the metabolic pathway do?
Inhibit the production of folic acid
What is polymixin B?
- Common ingredient in first aid ointments
- Can bind to eukaryotic cells (humans)
- Limited to topical use
What is MIC?
- Minimum Inhibitory Concentration
- Smallest effective dose
How is MIC determined?
- By examining strains ability to grow in broth containing different concentrations of test drug
- Serial Dilution - Test tubes inpregnanted
- Disc Diffusion Method - Discs impregnated with antibiotic and placed on plate
- E-test - Strips impregnated with antibiotic
What are the 2 types of "Acquisition of Resistance?"
- Spontaneous Mutation - Natural alteration of existing genes, relatively rare
- Acquisition of New Genes - Occurs most commonly by conjugation
What are some emerging examples of antimicrobial resistance?
- Enterococci - some strains now resistant to vancomycin, Termed - "Vancomycin Resistant Enterococcus" or "VRE"
- MRSA - strain of staphylococcus arueus now resistant to Methicillin
- Streptococcus pneumoniae - some strains have gained resistance to penicillin
What is the mechanism of action for antiviral drugs?
Viral uncoating - prevents severity and duration of disease
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