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Ch 20 Antimicrobial Drugs

Ch 20 Antimicrobial Drugs. SLOs. Antimicrobial Drugs. Chemotherapy: The use of drugs to treat a disease. Antimicrobial drugs: Interfere with the growth of microbes within a host. Antibiotic : Of biological origin. Produced by a microbe, inhibits other microbes.

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Ch 20 Antimicrobial Drugs

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  1. Ch 20Antimicrobial Drugs

  2. SLOs

  3. Antimicrobial Drugs • Chemotherapy: The use of drugs to treat a disease. • Antimicrobial drugs: Interfere with the growth of microbes within a host. • Antibiotic: Of biological origin. Produced by a microbe, inhibits other microbes. • Chemotherapeutic agent: synthetic chemicals • Today distinction blurred  many newer "antibiotics" are biological products that are • chemically modified or • chemically synthesized

  4. The History of Chemotherapy • Paul Ehrlichand Sahachiro Hata developedSalvarsan (Arsphenamine) against syphilis in 1910: The concept of chemotherapy to treat microbial diseases was born. • Sulfa drugs (sulfanilamide) discovered in 1932  against Gram+ bacteria

  5. The History of Chemotherapy cont. 1928: Fleming discovered penicillin 1940: Howard Florey and Ernst Chain performed first clinical trials of penicillin. Fig 20.1

  6. Activity Spectrum: Broad-spectrum vs. narrow- spectrum

  7. The Action of Antimicrobial Drugs Foundation Fig 20.2

  8. Inhibition of Protein Synthesis by Antibiotics • Figure 20.4

  9. Antibacterial AntibioticsInhibitors of Cell Wall Synthesis: Penicillin Natural and semisynthetic penicilins contain β-lactam ring Natural penicillins produced by Penicillium are effective against Gram + cocci and spirochetes Semisynthetic penicillins: made in laboratory by adding different side chains onto β-lactam ring  penicillinase resistant and broader spectrum of activity

  10. Penicillin cont. Penicillinase (β-lactamase): bacterial enzyme that destroys natural penicillins Penicillinase resistantpenicillins: methicilin replaced by oxacilin and nafcilin due to MRSA Extended-spectrum penicilins: Ampicilin, amoxicilin; new: carboxypenicilins and ureidopenicillins (also good against P. aeruginosa) Fig 20.8

  11. Vancomycin • Glycopeptide from Streptomyces • Inhibition of cell wall synthesis • Used to kill MRSA • Emerging Vancomycinresistance: VRSA and VRE

  12. Antiviral Drugs Anti HIV Drugs: See Chapter 19! Anti Herpes Drugs: Acyclovir and newer derivatives Selectively inhibit herpes virus replication. Acyclovir conversion to nucleotide analog only in virus infected cells  very little harm to uninfected cells! Fig 20.16

  13. Mechanism of Action of Acyclovir Fig 20.16

  14. Antifungal, Antiprotozoan and Antihelminthic Drugs More difficult to find point of selective toxicity! Why? Features of Chemotherapeutic Drugs Selective toxicity: Drug kills pathogens without damaging the host. Therapeutic index: ratio between toxic dose and therapeutic dose – or ratio of LD50 to ED50High therapeutic index  less toxic Antimicrobial action – Bacteriostatic vs. bactericidal Tissue distribution, metabolism, and excretion – BBB; Unstable in acid; half-life duration

  15. Antibiotic Assays to Guide Chemotherapy Agar Disk Diffusion Method determines susceptibility of an organism to a series of antibiotics: Kirby-Bauer test More sophisticated methods available for clinical labs

  16. Drug Resistance Penicillin G resistance of S. aureus from 3% to > 90% Multidrug-resistant S. aureus = MRSA or “super-bug” Vancomycin-resistance = ______ Multi drug resistant TB = MDR-TB Evolution of drug resistance: • Vertical evolution due to spontaneous mutation • Horizontal evolution due to gene transfer ??

  17. Antibiotic Resistance • A variety of mutations can lead to antibiotic resistance • Mechanisms of antibiotic resistance • Enzymatic destruction of drug • Prevention of penetration of drug • Alteration of drug's target site • Rapid ejection of the drug • Resistance genes are often on plasmids or transposons that can be transferred between bacteria.

  18. Resistance to Antibiotics Foundation Fig 20.20

  19. Antibiotic Resistance Misuse of antibiotics selects for resistance mutants. Misuse includes • Using outdated or weakened antibiotics • Using antibiotics for the common cold and other inappropriate conditions • Using antibiotics in animal feed • Failing to complete the prescribed regimen • Using someone else's leftover prescription • ….. the end

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