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Antimicrobial Drugs

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Title: Antimicrobial Drugs


1
Chapter 20
  • Antimicrobial Drugs

2
Antimicrobial Drugs
  • Chemotherapy The use of drugs to treat a
    disease
  • Antimicrobial drugs Interfere with the growth of
    microbes within a host
  • Antibiotic Substance produced by a microbe
    that, in small amounts, inhibits another
    microbe
  • Selective toxicity A drug that kills harmful
    microbes without damaging the host

3
  • 1928 Fleming discovered penicillin, produced
    by Penicillium.
  • 1940 Howard Florey and Ernst Chain performed
    first clinical trials of penicillin.

Figure 20.1
4
Table 20.1
5
Table 20.2
6
The Action of Antimicrobial Drugs
  • Broad-spectrum
  • Superinfection
  • Bactericidal
  • Bacteriostatic

7
The Action of Antimicrobial Drugs
Figure 20.2
8
The Action of Antimicrobial Drugs
Figure 20.4
9
Antibacterial Antibiotics Inhibitors of Cell
Wall Synthesis
  • Penicillin
  • Natural penicillins
  • Semisynthetic penicillins

10
Penicillins
Figure 20.6
11
Antibacterial Antibiotics Inhibitors of Cell
Wall Synthesis
  • Penicillin
  • Penicilinase-resistant penicillins
  • Extended-spectrum penicillins
  • Penicillins ?-lactamase inhibitors
  • Carbapenems
  • Monobactam

12
Antibacterial Antibiotics Inhibitors of Cell
Wall Synthesis
Figure 20.8
13
Antibacterial Antibiotics Inhibitors of Cell
Wall Synthesis
  • Cephalosporins
  • 2nd, 3rd, and 4th generations more effective
    against gram-negatives

Figure 20.9
14
Antibacterial Antibiotics Inhibitors of Cell
Wall Synthesis
  • Polypeptide antibiotics
  • Bacitracin
  • Topical application
  • Against gram-positives
  • Vancomycin
  • Glycopeptide
  • Important "last line" against antibiotic
    resistant S. aureus

15
Antibacterial Antibiotics Inhibitors of Cell
Wall Synthesis
  • Antimycobacterium antibiotics
  • Isoniazid (INH)
  • Inhibits mycolic acid synthesis
  • Ethambutol
  • Inhibits incorporation of mycolic acid

16
Antibacterial Antibiotics Inhibitors of Protein
Synthesis
  • Chloramphenicol
  • Broad spectrum
  • Binds 50S subunit, inhibits peptide bond
    formation
  • Aminoglycosides
  • Streptomycin, neomycin, gentamycin
  • Broad spectrum
  • Changes shape of 30S subunit

17
Antibacterial Antibiotics Inhibitors of Protein
Synthesis
  • Tetracyclines
  • Broad spectrum
  • Interferes with tRNA attachment
  • Macrolides
  • Gram-positives
  • Binds 50S, prevents translocation
  • Erythromycin
  • Gram-positives
  • Binds 50S, prevents translocation

18
Antibacterial Antibiotics Inhibitors of Protein
Synthesis
  • Streptogramins
  • Gram-positives
  • Binds 50S subunit, inhibits translation
  • Synercid
  • Gram-positives
  • Binds 50S subunit, inhibits translation
  • Oxazolidinones
  • Linezolid
  • Gram-positives
  • Binds 50S subunit, prevents formation of 70S
    ribosome

19
Antibacterial Antibiotics Injury to the Plasma
Membrane
  • Polymyxin B
  • Topical
  • Combined with bacitracin and neomycin in
    over-the-counter preparation

20
Antibacterial Antibiotics Inhibitors of Nucleic
Acid Synthesis
  • Rifamycin
  • Inhibits RNA synthesis
  • Antituberculosis
  • Quinolones and fluoroquinolones
  • Ciprofloxacin
  • Inhibits DNA gyrase
  • Urinary tract infections

21
Antibacterial Antibiotics Competitive Inhibitors
  • Sulfonamides (Sulfa drugs)
  • Inhibit folic acid synthesis
  • Broad spectrum

Figure 5.7
22
Figure 20.13
23
Antifungal DrugsInhibition of Ergosterol
Synthesis
  • Polyenes
  • Amphotericin B
  • Azoles
  • Miconazole
  • Triazoles
  • Allylamines

Figure 20.15
24
Antifungal DrugsInhibition of Cell Wall Synthesis
  • Echinocandins
  • Inhibit synthesis of ?-glucan
  • Cancidas is used against Candida and Pneumocystis

25
Antifungal DrugsInhibition of Nucleic Acids
  • Flucytocine
  • Cytosine analog interferes with RNA synthesis
  • Pentamidine isethionate
  • Anti-Pneumocystis may bind DNA

26
Antifungal DrugsInhibition of Microtubules
(Mitosis)
  • Griseofulvin
  • Used for superficial mycoses
  • Tolnaftate
  • Used for athlete's foot action unknown

27
Antiviral DrugsNucleoside and Nucleotide Analogs
Figure 20.16a
28
Antiviral DrugsNucleoside and Nucleotide Analogs
Figure 20.16b, c
29
Antiviral DrugsEnzyme Inhibitors
  • Protease inhibitors
  • Indinavir
  • HIV
  • Inhibit attachment
  • Zanamivir
  • Influenza
  • Inhibit uncoating
  • Amantadine
  • Influenza
  • Interferons prevent spread of viruses to new
    cells
  • Viral hepatitis

30
Antiprotozoan Drugs
  • Chloroquine
  • Inhibits DNA synthesis
  • Malaria
  • Diiodohydroxyquin
  • Unknown
  • Amoeba
  • Metronidazole
  • Damages DNA
  • Entamoeba, Trichomonas

31
Antihelminthic Drugs
  • Niclosamide
  • Prevents ATP generation
  • Tapeworms
  • Praziquantel
  • Alters membrane permeability
  • Flatworms
  • Pyantel pamoate
  • Neuromuscular block
  • Intestinal roundworms

32
Antihelminthic Drugs
  • Mebendazole
  • Inhibits nutrient absorption
  • Intestinal roundworms
  • Ivermectin
  • Paralyzes worm
  • Intestinal roundworms

33
Disk-Diffusion Test
Figure 20.17
34
E Test
Figure 20.18
35
  • MIC Minimal inhibitory concentration
  • MBC Minimal bactericidal concentration

36
Broth Dilution Test
Figure 20.19
37
Figure 20.20
38
Antibiotic Resistance
  • A variety of mutations can lead to antibiotic
    resistance.
  • Mechanisms of antibiotic resistance
  • 1. Enzymatic destruction of drug
  • 2. Prevention of penetration of drug
  • 3. Alteration of drug's target site
  • 4. Rapid ejection of the drug
  • Resistance genes are often on plasmids or
    transposons that can be transferred between
    bacteria.

39
Antibiotic Resistance
  • Misuse of antibiotics selects for resistance
    mutants. Misuse includes
  • Using outdated, weakened antibiotics
  • Using antibiotics for the common cold and other
    inappropriate conditions
  • Use of antibiotics in animal feed
  • Failure to complete the prescribed regimen
  • Using someone else's leftover prescription

40
Effects of Combinations of Drugs
  • Synergism occurs when the effect of two drugs
    together is greater than the effect of either
    alone.
  • Antagonism occurs when the effect of two drugs
    together is less than the effect of either alone.

41
Effects of Combinations of Drugs
Figure 20.22
42
The Future of Chemotherapeutic Agents
  • Antimicrobial peptides
  • Broad spectrum antibiotics from plants and
    animals
  • Squalamine (sharks)
  • Protegrin (pigs)
  • Magainin (frogs)
  • Antisense agents
  • Complementary DNA or peptide nucleic acids that
    binds to a pathogen's virulence gene(s) and
    prevents transcription
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