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Antimicrobial Drugs

Antimicrobial Drugs. Chemotherapy : Use of chemicals that do not harm the host yet kills others. Chemotherapeutic agent : substance that is used in medicine. Antimicrobial agents: Chemicals used to treat diseases caused by microbes. Antibiotics: Produced by microbes to inhibit others

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Antimicrobial Drugs

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  1. Antimicrobial Drugs • Chemotherapy: Use of chemicals that do not harm the host yet kills others. • Chemotherapeutic agent: substance that is used in medicine. • Antimicrobial agents: Chemicals used to treat diseases caused by microbes.

  2. Antibiotics: Produced by microbes to inhibit others • Synthetic drugs: Antimicrobials made in the lab • Semi Synthetic: synthetic or natural that is modified in the lab.

  3. History of Antibiotics • Paul Ehrlich- Sulfa that stains bacteria may be able to inhibit it as well. Predicted the rise of antimicrobials

  4. 1928 Fleming makes his observation • 1940’s production of penicillin • In order to keep up with microbial resistance we must continually discover new antibiotics, but this is getting harder to do

  5. 1928 – Fleming discovered penicillin, produced by Penicillium. • 1940 – Howard Florey and Ernst Chain performed first clinical trials of penicillin. Figure 20.1

  6. Drug Discovery Figure 20.1

  7. General Properties of antimicrobials • Selective toxicity: Kills microbes not host • Has a spectrum of activity • Broad • Narrow • Which is better? • Why?

  8. Table 20.2

  9. The Action of Antimicrobial Drugs Figure 20.2

  10. Modes of action • Inhibition of cell wall synthesis • Pen • Disruption of cell membrane function • Polymyxins • Inhibition of protein synthesis • Chloramphenicol • Erythromycin • Tetracycline • Streptomycin

  11. The Action of Antimicrobial Drugs Figure 20.4

  12. Inhibition of nucleic acid synthesis • Rifamycin • Inhibitors of enzymatic function of primary metabolism • Competitive inhibition • Noncompetitive inhibition

  13. Competitive Inhibitors • Sulfonamides (sulfa drugs) • Inhibit folic acid synthesis • Broad spectrum Figure 5.7b

  14. Figure 20.13

  15. Side Effects • Toxicity in host • Allergy in host • Disruption of normal microbiota • Birth defects in pregnancy

  16. Resistance of microbes • When microbes no longer respond to an antibiotic • Resistance is acquired by • Non genetic means, basically evasion, grow in an area not exposed to antibiotic • Tuberculosis • Genetic resistance • A change in the chromosome or gain of a plasmid.

  17. 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.

  18. We humans will always have to find or create new antibiotics as microbes become resistant

  19. 8 Attributes of an ideal antimicrobial agent • Solubility in body fluids • Selectively toxic • Toxicity not easily altered • Not allergenic • Stability in body • Resistance not easily acquired • Long shelf life • Reasonable cost

  20. Drugs with all 8 characteristics are very very rare.

  21. Inhibitors of cell wall Synthesis • Ampicillin • Cephalosporin • Bacitracin • Vancomycin

  22. Inhibitors of Protein Synthesis • Streptomycin • Tetracycline • Clormphenicol • Erythromycin

  23. Plasma membrane • Polymyxin B

  24. Inhibitors of Nucleic Acid Synthesis • Rifampin • ciprofloxacin

  25. Competitive inhibitors of the Synthesis of Essential Metabolites • Trimethoprim-sulfamethoxozole

  26. Antifungal • Amphotericin B • Griseofulvin • Flucytosine

  27. Antiviral drugs • Acyclovir • Ganciclovir • Indinavir • Alpha interferon

  28. Antiprotozoan Drugs • Chloroquine • Diiodohydroxyquin • Metronidazole

  29. Antihelminthic Drugs • Niclosamide

  30. What are these drugs, modes of action and side effects?

  31. Nucleoside and Nucleotide Analogs Figure 20.16b ,c

  32. Tests to Guide Chemotherapy • MIC: Minimal inhibitory concentration • MBC: Minimal bactericidal concentration • Antibiogram

  33. Broth Dilution Test Figure 20.19

  34. Resistance to Antibiotics Figure 20.20

  35. From Lab • How do antimicrobials work • How are they tested?

  36. Effects of Combinations of Drugs Figure 20.22

  37. 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

  38. Disk-Diffusion Test Figure 20.17

  39. Future of Chemotherapeutic Agents • Antimicrobial peptides • Broad-spectrum antibiotics • Nisin (lactic acid bacteria) • Magainin (frogs) • Cecropin (moths)

  40. Future of Chemotherapeutic Agents • Antisense agents • Complementary DNA that binds to a pathogen's virulence gene(s) and prevents transcription • Fomivirsen to treat CMV retinitis

  41. Future of Chemotherapeutic Agents • siRNA • Complementary RNA that binds mRNA to inhibit translation Figure 9.14

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