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Chapter 20: Antimicrobial Drugs
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  1. Chapter 20: Antimicrobial Drugs

  2. What are antibiotics? • Definition: chemicals produced by one microorganism to kill or inhibit the growth of other microorganisms • Now included the semi-synthetic antibiotics • Effective against bacteria • Antibacterial drugs – largest group of antibiotics • General terms used to include other microbes are antimicrobial drugs or antimicrobials • Difference between disinfectants/antiseptics and antimicrobial drugs

  3. Antibiotic spectrum • Broad vs. narrow spectrum antibiotics • Benefits and problems with each

  4. Microbes that produce antibiotics: • Bacteria: Bacillus and Streptomyces • Fungi: Cephalosporium and Penicillium

  5. How do antibiotics work? 1. must kill pathogen and not kill host 2. fewest sides effects in host; highest toxicity in pathogen 3. exploit differences between the pathogen and the host

  6. Modes of action of the antibiotics: 1. Inhibition of cell wall synthesis • cell wall is weakened by these when cell is growing • ex. penicillin(s) and cephalosporins • low toxicity to humans

  7. Modes of action of the antibiotics: 2. Inhibition of protein synthesis • binding to 70S ribosome • differences between 70S and 80S ribosomes • ex. chloramphenicol, erythromycin, streptomycin, tetracyclines • host mitochondria may also be affected

  8. Modes of action of the antibiotics: 3. Increase permeability of plasma membrane • ex. polymyxin B – used topically • can have high toxicity in humans

  9. Modes of action of the antibiotics: 4. Inhibit synthesis of RNA/DNA • can be very toxic • ex. quinolones – DNA

  10. Modes of action of the antibiotics: 5. Inhibition of metabolic pathways • ex. sulfanilamide – folic acid pathway • low toxicity because of the absence of this pathway in humans

  11. Antagonism vs. synergism of 2 or more antibiotics • Antagonism: • Ex. Tetracycline  penicillin (Why?) • Synergism: • Ex. TMP-SMZ (SMX) trimethoprim and sulfamethoxazole

  12. Prophylaxis – preventative use of antibiotics Ex. of their use: 1. before surgery – i.e. appendix removal 2. before dental work in heart patients 3. in AIDS patients to prevent many infections

  13. Factors affecting antimicrobial activity in vivo – In the environment A. metabolic state of pathogen Ex. Mycobacterium tuberculosis B. distribution of drug is different in different tissues Ex. blood/brain barrier and necrotic tissue C. location of pathogen Ex. Chlamydia inside host cells D. interfering substances Ex. low pH in stomach; binding to proteins in body, etc.

  14. Factors affecting antimicrobial activity in vivo – Concentration of antibiotics in body A. absorption, inactivation, excretion B. distribution of the drug – systemic vs. local vs. topical C. variability – dosing flutuations, how long antibiotic lasts in the body.

  15. Antiviral drugs • Nucleotide analogs (look similar to the bases + sugars of DNA) Ex. AZT – looks like thymine; acyclovir – looks like guanine • Enzyme inhibitors Ex. reverse transcriptase inhibitor – important in controlling HIV infection • Interferons – naturally produced by our immune systemsEx. alpha, beta, and gamma; prevents further infection

  16. Antifungal drugs • Targets for antifungal drugs??? • Possible side effects??? • Ex. amphotericin B and imidazole affect sterol production • Griseofulvin – binds to keratin in skin cells, treats skin fungal infections

  17. Antibiotic resistance (also called drug resistance) What is happening? As microbes are exposed to drugs, the ones with defenses against them survive

  18. Microbial defense mechanisms against antibiotics • Change receptor for drug • Bind to drug and inactivate it, ex. penicillinase (b-lactamase) • Change target site, ex. change ribosome structure • Change metabolic pathway • MDR pump– multi-drug resistance pump

  19. How does drug resistance develop in different microbes? Antibiotics overprescribed and not regulated Many countries do not require a prescription Improper dosage Antibacterial soaps/surfaces, etc. Antibiotics in animals (used as our food source) People insisting on receiving antibiotics, even for viral infections Nosocomial infections and the chronically infected

  20. Antibiotic sensitivity tests • Kirby-Bauer test – zones of inhibition • Minimal inhibitory concentration test

  21. The End