ANTIBIOTICS

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ANTIBIOTICS

• From the Greek
• anti - against
• bios - life

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Chemotherapy

• Paul Ehrlich
• Use of chemical agent to kill bacteria and not
  harm the host
• Search for the Magic bullet
• Developed an arsenic compound that killed the
  bacteria that causes syphilis
• Compound was called salvarsan but was quite toxic
  to the host

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Antibiotics

• Natural compounds produced by microorganisms that
  inhibit the growth of other microbes
• Majority of antibiotics come from Streptomyces
  bacteria and molds
• Over 100 different antibiotics
• Antibiotics generally have two names
• Brand name created by the drug company
• Generic name based on the chemical structure or
  class of antibiotics

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Famous penicillin picture
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Alexander Fleming

• Discovered penicillin by accident in 1928
• A mold contaminating a plate of Staphylococcus
  aureus showed anti-bacterial properties
• The mold was identified as a member of genus
  Penicillum, hence the name for the naturally
  produced antibiotic
• Fleming won the Nobel prize in 1945 for this
  discovery, shared with Howard Florey and Ernst
  Chain

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Penicillin

• Wonder drug
• Killed bacteria with few side effects on the
  patient
• SELECTIVE TOXICITY

• Penicillin was NOT the first anti-bacterial
  compound
• Penicillin was the FIRST natural compound that
  kills bacteria
• Antibiotic
• Not made in the lab

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Spectrum of Activity

• Broad spectrum antibiotics
• Effect both G and G- bacteria
• Tetracycline

• Narrow spectrum antibiotics
• Effects fewer types of pathogens
• More selective?
• Penicillin best against G bacteria

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How do antibiotics work?
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Cell Wall Synthesis

• Penicillin
• Prevents synthesis of the peptidoglycan
  components of the cell wall
• Targets actively growing cells
• Very little toxicity to human cells

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Inhibition of protein synthesis

• Broad spectrum of activity all bacteria have to
  make proteins
• Difference in ribosome size in bacteria accounts
  for selective toxicity
• Chloramphenicol, erythromycin (G), streptomycin,
  tetracyclines

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Injury to plasma membrane

• Changes to permeability of membrane causes loss
  of metabolites
• Polymyxin B

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Inhibition of nucleic acid synthesis

• Inhibition if either DNA replication or mRNA
  synthesis
• Toxicity problems
• Rifampin mRNA blocker
• Nofloxacin and ciprofloxacin DNA synthesis
  blockers

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Inhibition of synthesis of essential metabolites

• Block enzyme activity
• Competitive inhibition of enzyme activity
• PABA (para-aminobenzoic acid) competition
• Sulfonamides

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Metabolite Inhibition

• Sulfonamide

• P-aminobenzoic acid

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Commonly used antibiotic types

• Penicillins
• Cephalosporins
• Animoglycosides
• Macolides
• Sulfonamides
• Fluoroquinolones
• Tetracyclines
• Polypeptides

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Penicillin

• Destroys the cell wall of bacteria
• Best against G bacteria during active growth
• Examples
• Penicillin G
• Penicillin V
• Ampicillin
• Amoxicillin

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Cephalosprorins

• Similar to penicillin - interferes with cell wall
  formation
• Used when patient is allergic to penicillin
• Examples
• Cefadroxil
• Cephapirin
• Cephalexin
• Cephalothin

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Aminoglycosides

• Inhibition of protein synthesis in bacteria
• Some toxic reactions possible in kidney and liver
• Examples
• Gentamicin
• Streptomycin
• Neomycin

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Macrolides

• Interfere with bacterial protein synthesis
• Commonly given to patients that are sensitive to
  penicillin
• Gastrointestinal discomfort is a common side
  effect
• Examples
• Azithromycin
• Erthromycin

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Sulfonamides

• Very early antimicrobial substance
• Commonly called sulfa drugs
• Developed in the 1930s in Germany
• Mode of action is enzyme inhibition
• Allergy to sulfa is common

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Fluoroquinolones

• Large class of semi-synthetic broad spectrum
  antibiotics
• Inhibition of bacterial DNA replication
• Few side effects, well tolerated
• Examples
• Ciprofloxacin
• Norfloxacin

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Tetracycline Antibiotics

• Members of this group of antibiotics are produced
  by Streptomyces group of bacteria
• Inhibition of protein synthesis
• Used commonly to treat acne
• Examples
• Tetracycline
• Deoxycycline

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Penicillin
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Penicillinase
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Cephalosporin and Penicillin

• Cephalosporin
• Produced from a fungus
• Similar in action to penicillin
• More active against G- bacteria
• More resistant to penicillinase

• Penicillin
• Produced from fungus
• Inhibits cell wall synthesis
• Effective against mostly G bacteria
• Penicillinase sensitivity

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Cephalosporin and Penicillin
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Adverse reactions

• Toxicity
• Allergy
• Disruption of natural flora
• Yeast infections

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Antibiotic Resistance(A BIG problem)

• Resistance is acquired by mutation
• R (resistance) plasmids acquired by bacterial
  conjugation
• How to limit resistance
• Take all your pills, dont stop when you feel
  better
• Use antibiotics only when necessary
• NEVER take antibiotics for viral infection alone

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Nosocomial Infections

• Infections acquired while in a health care
  facilities
• CDC estimates 2 million people per year get these
  infections
• 90,000 deaths per year

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Nosocomial Infections
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Antiviral Drugs

• Limited in number
• Targets for these drugs are viral reproduction
• Nucleotide analogs are the most commonly used
  agents disrupt viral nucleic acid replication
• Acyclovir

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Nucleotide analog
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Sensitivity Testing