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

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

9. Table 20.2

10. The Action of Antimicrobial Drugs
Foundation figure 20.2
Figure 20.2

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

12. The Action of Antimicrobial Drugs
Figure 20.4

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

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

15. Figure 20.13

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

17. 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.

18. 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.

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

20. 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

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

22. Inhibitors of cell wall Synthesis
Ampicillin
Cephalosporin
Bacitracin
Vancomycin

23. Inhibitors of Protein Synthesis
Streptomycin
Tetracycline
Clormphenicol
Erythromycin

24. Plasma membrane
Polymyxin B

25. Inhibitors of Nucleic Acid Synthesis
Rifampin
ciprofloxacin

26. Competitive inhibitors of the Synthesis of Essential Metabolites
Trimethoprim-sulfamethoxozole

27. Antifungal
Amphotericin B
Griseofulvin
Flucytosine

28. Antiviral drugs
Acyclovir
Ganciclovir
Indinavir
Alpha interferon

29. Antiprotozoan Drugs
Chloroquine
Diiodohydroxyquin
Metronidazole

30. Antihelminthic Drugs
Niclosamide

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

32. Nucleoside and Nucleotide Analogs
Figure 20.16b ,c

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

34. Broth Dilution Test
Figure 20.19

35. Resistance to Antibiotics
Figure 20.20

36. From Lab
How do antimicrobials work
How are they tested?

37. Effects of Combinations of Drugs
Figure 20.22

38. 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

39. Disk-Diffusion Test
Figure 20.17

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

41. 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

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