Chapter 21 Pharmacology

1. Chapter 21Pharmacology

2. Drug administration • External • local, topical • Intravenous (IV) • into vein • fastest • Intramuscular (IM) • injection in muscle • Oral (PO) • absorbed through intestines • slow Figure 21.2

3. Drug distribution • Barriers to drug • Cell membranes • protein-lined pores • transport systems • Drug-binding proteins • prevents drug from entering tissue • slows Figure 21.3

4. Eliminating Drugs • Two methods of elimination • Metabolically converted to other compound • In liver • Metabolic product usually inactive • Exit the body • Secreted in urine • Some secreted in bile

5. Side Effects and Allergies • Selective toxicity • Inhibit or kill microorganism • No harm to human cells • Side effects • Danger must be weighted against benefit

6. Drug resistance • Natural resistance • lack target • not able to enter cell • broad spectrum • drug effective against many • narrow spectrum • drug effective against few organisms Figure 21.5

7. Drug resistance • Acquired resistance • Mechanisms • enzymes destroy drug • beta lactamase • change target • penicillin-binding protein • prevent entry or pump out • membrane transport system Figure 21.6 Penicillin-resistant S. aureus

8. Drug resistance • Beta lactamase • produced by penicillin-resistant microorganisms • cuts the beta-lactam ring • prevents penicillin from blocking cell wall synthesis

9. Drug resistance • Acquired resistance • Genetics • mutations • plasmids • Slowing resistance • reduce non-essential medical use • limit non-medical use • combined therapy

10. Drug Dosage: Disc diffusion • Kirby-Bauer method • inoculate plate • add discs containing drug • incubate • measure zones of inhibition where bacteria did not grow Figure 21.7

11. Drug Dosage: Broth Dilution • Broth-dilution method • serially dilute drug • inoculate • obtain tube with the minimal amount of drug to prevent growth • Minimum inhibitory concentration (MIC) • Minimum bactericidal concentration (MBC) Figure 21.8

12. Drug Dosage: Serum killing • Serum killing power • drug-containing serum • test to see if kills microorganism

13. Targets of antimicrobial drugs Prokaryotic cells • Cell wall synthesis • destroy peptidoglycan • prevent synthesis • Cell membrane • damage membranes • Nucleic Acids • enzymes • unique to prokaryotic Figure 21.10

14. Targets of antimicrobial drugs • Protein synthesis • interfere • ribosome • prokaryotic different than eukaryotic • tRNA • Metabolism • folic acid synthesis • para-aminobenzoic acid (PABA) Figure 21.11

15. Targets of antimicrobial drugs Eukaryotic cells • Cell membrane • Nucleic acid synthesis • Folic acid synthesis Figure 21.10

16. Pencillins • Inhibit cell wall synthesis • Gram-positive cells • source • antibiotic • semisynthetic • examples • penicillin V • methicillin • ampicillin Figure 21.12

17. Cephalosporins • Inhibit cell wall synthesis • Gram-positive cells • Gram-negative cells • third generation • Source • antibiotic • semisynthetic • more resistant to beta-lactamase Figure 21.13

18. Sulfonamides • Sulfa drugs • first antimicrobial • less effective now • extensive use • microbial resistance • used in combination • inhibit folic acid synthesis Figure 21.13

19. Chloramphenicol • Broad spectrum • Gram-positive • Gram-negative • Rickettsiae • Chlamydiae • Mycoplasmas • Action • inhibits peptide bond formation • Rare complications • Aplastic anemia • Gray baby syndrome Figure 21.13

20. Tetracyclines • Broad spectrum • Action • block entry of tRNA into ribosome • widely used • not for • children • pregnant women Figure 21.13

21. Aminoglycosides • Gram-negative • Action • inhibit protein synthesis • bind 30S subunit • limited use • toxicity • inner ear • microbial resistance • Streptomycin Figure 21.13

22. Erythromycin • Macrolide family • Gram-positive • strep throat • respiratory • Action • inhibit protein synthesis • bind 50S subunit Figure 21.13

23. Quinolones • Broad spectrum • few side effects • slow drug resistance • Action • block DNA replication • Topoisomerase • Ciprofloxacin Figure 21.13

24. Antimycobacterial • Mycobacterium • difficult to treat • cell wall causes resistance • grow very slowly • antibiotic resistance • intracellular pathogen • Isoniazid • Rifampin • Ethambutol Figure 21.15

25. Antifungal • Eukaryotic cell • more similar to human cells • Examples • Nystatin • cytoplasmic membrane • Imidazoles • inhibit sterol synthesis Figure 21.16

26. Anti-fungal • Amphotericin B • disrupts cell membrane • Flucytosine • synthetic pyrimidine analogue • Griseofulvin • effective against ringworm of skin • topic creams • prevents cell division Figure 21.16

27. Anti-parasitic • Mebendazole • interferes with glucose uptake • Metronidazole • obligate anaerobic bacteria • protozoa parasites • use cell energy • Chloroquine • some resistance • unknown mechanism Figure 21.17

28. Anti-viral • Few antivirals • difficult to kill virus without affecting host cells • Amantadine • influenza A virus • Acyclovir • herpesviruses • nucleoside analog • interferes DNA synthesis • Ribavirin • nucleoside analog • interferes RNA synthesis Figure 21.18

29. Anti-viral • Anti-HIV agents • reverse transcriptase inhibitors • AZT • delavirdine • nevirapine • protease inhibitors • indinavir • nelfinavir • ritonavir Figure 21.19