Antimicrobial Drugs and Drug Resistance Flashcards

1
Q

What is Antimicrobial Drugs?

A
  • Used when immunization has not occurred and the immune system has
    difficulty to eliminate infection
    • Useful against bacterial infection, very few antivirals are available
  • These are compounds that kill or control the growth of microorganisms in
    the host
    • These drugs must display selective toxicity or they will cause damage to the host
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2
Q

What is the two broad categories of Antimicrobial Drugs?

A
  1. Synthetic and natural
    • Large number of naturally occurring antibiotics with no clinical use
      • Produced by bacteria and fungi
  2. Can be described based on whether they are:
    • Bacteriostatic or bacteriocidal
    • Broad spectrum or narrow spectrum
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3
Q

Cell Wall Active Antimicrobial Drugs

A
  • Cell wall active agents offer excellent selective toxicity
    • Most widely used class of antibiotics
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4
Q

Beta Lactam Antibiotics

A
  • Largest Class
  • Common feature is the b-lactam ring
  • Naturally occurring: produced by Penicillium and Cephalosporium fungi
  • Example: penicillins and cephalosporins
  • Can be modified in the lab to produce semi-synthetic drugs that have a modified spectrum of activity
  • Susceptible to beta-lactamases
    • Enzyme produced by some bugs to cut and inactivate beta-lactams
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5
Q

Penicillins

A
  • Narrow spectrum of activity
    • Characterized by a five membered ring attached to the beta-lactam component
    • Target transpeptidation in gram positive bacteria
    • Cannot penetrate outer membrane of gram negative bacteria
      • Semi-synthetic penicillin are modified to provide some activity against gram negative bugs
        • Example: ampicillin
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6
Q

Cephalosporins

A
  • Structurally distinct from penicillins
    • Six membered ring is attached to the beta-lactam component
  • Also target transpeptidation of peptidoglycan
  • Many semi-synthetic examples
  • Broader spectrum of activity than penicillin
  • Better resistance against beta lactamases
  • Grouped into generations
    • 1st generation cephalosporin, 2nd generation cephalosporin etc.
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7
Q

Growth Factor Analogs

A
  • Growth factor analogs are structurally similar to growth factors but do not function in the cell
    • Analogs similar to vitamins, amino acids, and other compounds
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8
Q

Growth Factor Analogs (Example: Sulfa Drugs)

A
  • Example: sulfanilamide
  • Inhibit growth of bacteria by inhibiting folic acid synthesis and thus nucleic
    acid synthesis (We can’t synthesis on out own)
  • Often used in combination with another analog→ trimethoprim
    • Combination therapy minimizes the likelihood of resistance
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9
Q

Growth Factor Analogs (Example: Isoniazid)

A
  • Extremely narrow spectrum cell wall active agent
  • Analog of mycolic acid component needed by Mycobacterium spp.
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10
Q

Nucleic Acid Synthesis Inhibitors (Quinolones)

A
  • Synthetic antimicrobials
  • Inhibit DNA gyrase
    • Prevents supercoiling of DNA
  • Active against both Gram-negative and Gram-positive bacteria
  • Example: ciprofloxacin a fluorinated quinolone (fluoroquinolone)
    • Useful against life threatening infections
  • Rifampin: binds to RNA polymerase preventing transcription
  • Actinomycin: Binds to DNA template blocking transcription elongation
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11
Q

Protein Synthesis Inhibitors

A
  • Protein synthesis inhibitors target 70S ribosomes
    • Good selective toxicity
    • Some issues because human cells have 70S ribosomes in the mitochondrial matrix
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12
Q

What are included in Protein Synthesis Inhibitors?

A
  1. Aminoglycosides
  2. Tetracycline
  3. Macrolides
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13
Q

Aminoglycosides

A
  • Bind to the 30S subunit of 70S ribosomes
  • Block translation
  • Narrow spectrum
    • Useful against gram negative bugs
  • Often used as a last resort drug
  • Damaging to the kidneys and ears
  • Examples include streptomycin, gentamycin and neomycin
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14
Q

Tetracycline

A
  • Broad spectrum
  • Produced by species of the Streptomyces genus
  • Bind to the 30S subunit
  • Consist of both natural and modified semisynthetic
    drugs
  • Binds to calcium damaging teeth and bone
    • Shouldn’t be used in children and pregnant
      women
  • Used in veterinary medicine and to promote animal growth
    • Creates problems with resistance
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15
Q

Macrolides

A
  • Broad spectrum of activity
  • Bind to the 50S ribosomal subunit
    • Only inhibits translation of some proteins
    • Some proteins are preferential translated and others are not
      • Creates a detrimental protein imbalance inside of the cell
  • Useful to treat infection in patients with allergies to beta lactam antibiotics
  • Example: erythromycin and azithromycin
    • Produced by Streptomyces spp.
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16
Q

Novel Antibiotics

A
  • Daptomycin
    • Produced by Streptomyces spp.
  • Cyclic lipopeptide
    • Active against Gram-positives
      • Pathogenic Staphylococcal spp. and
        Streptococcal spp.
  • Forms pores in the plasma membrane causing depolarization
    • Cell cannot synthesize necessary biomolecules
      • Cell death occurs
  • Resistance can occur when bacteria alter plasma
    membrane composition
17
Q

Antibiotic Resistance

A
  • Antibiotic resistance occurs when an organism develops a mechanism to elude the activity of an antimicrobial drug that it should otherwise be susceptible to
    • Genes for antibiotic resistance can either be encoded on a plasmid or directly within the genome
  • Resistance is prevalent because of widespread and sometimes incorrect use of antibiotics
    • Medicine, veterinary medicine, agriculture
18
Q

What are the mechanisms and examples?

A
  • Reduced permeability -> Penicillins
  • Inactivation of antibiotic -> Penicillins, Chloramphenicol, Aminoglycosides
  • Alternation of target -> Erythromycin, Streptomycin, Norfloxacin
  • Development of resistant biochemical pathway -> Sulfonamides
  • Efflux -> Tetracyclines, Chloramphenicol, Fluoroquinolones
19
Q

Patterns of Antibiotic Resistance

A
  • Emergence of antibiotic resistance in different species of bacteria
  • Patterns of antimicrobial resistance
20
Q

Preventing Antibiotic Resistance

A
  • Infection prevention -> Void getting sick
  • Rapid and conclusive diagnosis -> Right for treatment but bad for antibiotic resistance
  • Appropriate/prudent use of antibiotics -> Use it when you only need it NO OVERUSE (Prescription)
  • Prevention of transmission - Stay home and be careful