Drugs Notes

Drugs.pptx Download Drugs.pptx

  

   

 

Antimicrobial Drugs

Learning Objectives	Check Your Understanding
20-1    Identify the contributions of Paul Ehrlich and Alexander Fleming to chemotherapy.	Who coined the term chemotherapy ?
20-2    Name the microbes that produce most antibiotics.	More than half our antibiotics are produced by a certain genus of bacteria. What is it?
20-3    Describe the problems of chemotherapy for viral, fungal, protozoan, and helminthic infections.	Identify at least one reason why it is so difficult to target a pathogenic virus without damaging the host’s cells.
20-4    Define the following terms: spectrum of activity, broad-spectrum antibiotic, superinfection.	Why are antibiotics with a very broad spectrum of activity not as useful as one might first think?
20-5    Identify five modes of action of antimicrobial drugs.	What cellular function is inhibited by tetracyclines?
20-6    Explain why the drugs described in this section are bacteria specific.	One of the most successful groups of antibiotics targets the synthesis of bacterial cell walls. Why does the antibiotic not affect the mammalian cell?
20-7    List the advantages of each of the following over penicillin: semisynthetic penicillins, cephalosporins, and vancomycin.	What phenomenon prompted the development of the first semisynthetic antibiotics, such as methicillin?
20-8    Explain why isoniazid (INH) and ethambutal are antimycobacterial agents.	What genus of bacteria has mycolic acids in the cell wall?
20-9    Describe how each of the following inhibits protein synthesis: aminoglycosides, tetracyclines, chloramphenicol, macrolides.	Why does erythromycin, a macrolide antibiotic, have a spectrum of activity limited largely to gram-positive bacteria even though its mode of action is similar to that of the broad-spectrum tetracyclines?
20-10  Compare polymyxin B, bacitracin, and neomycin in their modes of actions.	Of the three drugs often found in over-the-counter antiseptic creams—polymyxin B, bacitracin, and neomycin—which has a mode of action most similar to that of penicillin?
20-11  Describe how rifamycins and quinolones kill bacteria.	What group of antibiotics interferes with the DNA-replicating enzyme DNA gyrase?
20-12  Describe how sulfa drugs inhibit microbial growth.	Both humans and bacteria need PABA to make folic acid. So, why do sulfa drugs adversely impact only bacterial cells?
20-13  Explain modes of action of current antifungal drugs.	What sterol in the cell membrane of fungi is the most common target for antifungal action?
20-14  Explain modes of action of current antiviral drugs.	One of the most widely used antivirals, acyclovir, inhibits the synthesis of DNA. Humans also synthesize DNA, so why is the drug still useful in treating viral infections?
20-15  Explain modes of action of current antiprotozoan and antihelminthic drugs.	What was the first drug for parasitic infections?
20-16  Describe two tests for microbial susceptibility to chemotherapeutic agents.	In the disk-diffusion test, the zone of inhibition indicating sensitivity around the disk varies with the antibiotic. Why?
20-17  Describe the mechanisms of drug resistance.	What is the most common mechanism that a bacterium uses to resist the effects of penicillin?
20-18  Compare and contrast synergism and antagonism.	Tetracycline sometimes interferes with the activity of penicillin. How?
20-19  Identify three areas of research on new chemotherapeutic agents.	What are defensins?

 

Chapter Summary

Introduction (p. 548)

ASM 3.4: The growth of microorganisms can be controlled by physical, chemical, mechanical, and biological means.

ASM 6.3: Humans utilize and harness microorganisms and their products.

1. An antimicrobial drug is a chemical substance that destroys pathogenic microorganisms with minimal damage to host tissues.
2. Chemotherapeutic agents include chemicals that combat disease in the body.

The History of Chemotherapy (pp. 549–550)

1. Paul Ehrlich developed the concept of chemotherapy to treat microbial diseases; he predicted the development of chemotherapeutic agents, which would kill pathogens without harming the host.
2. Sulfa drugs came into prominence in the late 1930s.
3. Alexander Fleming discovered the first antibiotic, penicillin, in 1928; its first clinical trials were done in 1940.

The Spectrum of Antimicrobial Activity (pp. 550–551)

1. Antibacterial drugs affect many targets in a prokaryotic cell.
2. Fungal, protozoan, and helminthic infections are more difficult to treat because these
   organisms have eukaryotic cells.
3. Narrow-spectrum drugs affect only a select group of microbes—gram-positive cells, for example; broad-spectrum drugs affect a more diverse range of microbes.
4. Small, hydrophilic drugs can affect gram-negative cells.
5. Antimicrobial agents should not cause excessive harm to normal microbiota.
6. Superinfections occur when a pathogen develops resistance to the drug being used or when normally resistant microbiota multiply excessively.

The Action of Antimicrobial Drugs (pp. 551–553)

ASM 2.2: Bacteria have unique cell structures that can be targets for antibiotics, immunity, and phage infection.

1. Antimicrobials generally act either by directly killing microorganisms (bactericidal) or by inhibiting their growth (bacteriostatic).
2. Some agents, such as penicillin, inhibit cell wall synthesis in bacteria.
3. Other agents, such as chloramphenicol, tetracyclines, and streptomycin, inhibit protein synthesis by acting on 70S ribosomes.
4. Antifungal agents target plasma membranes.
5. Some agents inhibit nucleic acid synthesis.
6. Agents such as sulfanilamide act as antimetabolites by competitively inhibiting enzyme activity.

Common Antimicrobial Drugs (pp. 554–567)

Antibacterial Antibiotics: Inhibitors of Cell Wall Synthesis (pp. 554–559)

1. All penicillins contain a β-lactam ring.
2. Natural penicillins produced by Penicillium are effective against gram-positive cocci and spirochetes.
3. Penicillinases (β-lactamases) are bacterial enzymes that destroy natural penicillins.
4. Semisynthetic penicillins are made in the laboratory by adding different side chains onto the β-lactam ring made by the fungus.
5. Semisynthetic penicillins are resistant to penicillinases and have a broader spectrum of activity than natural penicillins.
6. Carbapenems are broad-spectrum antibiotics that inhibit cell wall synthesis.
7. The monobactam aztreonam affects only gram-negative bacteria.
8. Cephalosporins inhibit cell wall synthesis and are used against penicillin-resistant strains.
9. Polypeptides such as bacitracin inhibit cell wall synthesis primarily in gram-positive bacteria.
10. Vancomycin inhibits cell wall synthesis and may be used to kill penicillinase-producing staphylococci.

Antimycobacterial Antibiotics (pp. 559–560)

11. Isoniazid (INH) and ethambutol inhibit cell wall synthesis in mycobacteria.

Inhibitors of Protein Synthesis (pp. 560–562)

12. Chloramphenicol, aminoglycosides, tetracyclines, glycylcyclines, macrolides, streptogramins, oxazolidinones, and pleuromutilins inhibit protein synthesis at 70S ribosomes.

Injury to the Plasma Membrane (p. 562)

13. Lipopeptides polymyxin B and bacitracin cause damage to plasma membranes.

Nucleic Acid Synthesis Inhibitors (pp. 562–563)

14. Rifamycin inhibits mRNA synthesis; it is used to treat tuberculosis.
15. Quinolones and fluoroquinolones inhibit DNA gyrase for treating urinary tract infections.

Competitive Inhibitors of Essential Metabolites (p. 563)

16. Sulfonamides competitively inhibit folic acid synthesis.
17. TMP-SMZ competitively inhibits dihydrofolic acid synthesis.

Antifungal Drugs (pp. 564–565)

18. Polyenes, such as nystatin and amphotericin B, combine with plasma membrane sterols and are fungicidal.
19. Azoles and allylamines interfere with sterol synthesis and are used to treat cutaneous and systemic mycoses.
20. Echinocandins interfere with fungal cell wall synthesis.
21. The antifungal agent flucytosine is an antimetabolite of cytosine.
22. Griseofulvin interferes with eukaryotic cell division and is used primarily to treat skin infections caused by fungi.

Antiviral Drugs (pp. 565–567)

23. Entry inhibitors and fusion inhibitors bind to HIV attachment and receptor sites.
24. Nucleoside and nucleotide analogs, such as acyclovir and zidovudine, inhibit DNA or RNA synthesis.
25. Inhibitors of viral enzymes are used to treat influenza and HIV infection.
26. Alpha interferons inhibit the spread of viruses to new cells.

Antiprotozoan and Antihelminthic Drugs (p. 567)

27. Chloroquine, artemisinin, quinacrine, diiodohydroxyquin, pentamidine, and metronidazole are used to treat protozoan infections.
28. Antihelminthic drugs include mebendazole, praziquantel, and ivermectin.

Tests to Guide Chemotherapy (pp. 567–569)

1. Tests are used to determine which chemotherapeutic agent is most likely to combat a specific pathogen.
2. These tests are used when susceptibility cannot be predicted or when drug resistance arises.

The Diffusion Methods (p. 568)

3. In the disk-diffusion test, also known as the Kirby-Bauer test, a bacterial culture is
   inoculated on an agar medium, and filter paper disks impregnated with chemotherapeutic agents are overlaid on the culture.
4. After incubation, the diameter of the zone of inhibition is used to determine whether the organism is sensitive, intermediate, or resistant to the drug.
5. MIC is the lowest concentration of drug capable of preventing microbial growth; MIC can be estimated using the E test.

Broth Dilution Tests (pp. 568–569)

6. In a broth dilution test, the microorganism is grown in liquid media containing different concentrations of a chemotherapeutic agent.
7. The lowest concentration of a chemotherapeutic agent that kills bacteria is called the minimum bactericidal concentration (MBC).

Resistance to Antimicrobial Drugs (pp. 569–574)

ASM 1.3: Human impact on the environment influences the evolution of microorganisms (e.g., emerging diseases and the selection of antibiotic resistance).

ASM 4.1 Genetic variations can impact microbial functions (e.g., in biofilm formation, pathogenicity, and drug resistance).

1. Many bacterial diseases, previously treatable with antibiotics, have become resistant to antibiotics.
2. Superbugs are bacteria that are resistant to several antibiotics.
3. Drug resistance factors are transferred horizontally between bacteria.
4. Resistance may be due to enzymatic destruction of a drug, prevention of penetration of the drug to its target site, cellular or metabolic changes at target sites, altering the target site, or rapid efflux of the antibiotic.
5. The discriminating use of drugs in appropriate concentrations and dosages can minimize resistance.

Antibiotic Safety (p. 574)

1. The risk (e.g., side effects) versus the benefit (e.g., curing an infection) must be evaluated before antibiotics are used.

Effects of Combinations of Drugs (p. 574)

1. Some combinations of drugs are synergistic; they are more effective when taken together.
2. Some combinations of drugs are antagonistic; when taken together, both drugs become less effective than when taken alone.

The Future of Chemotherapeutic Agents (pp. 574–575)

1. New agents include antimicrobial peptides, bacteriocins, and bacteriophages.
2. Virulence factors rather than cell growth factors may provide new targets.

FDA: The Drug Development Process Links to an external site. 

  How are drugs designed and developed? Links to an external site.