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Chapter 21 Pharmacology

Chapter 21 Pharmacology. Drug administration. External local, topical Intravenous (IV) into vein fastest Intramuscular (IM) injection in muscle Oral (PO) absorbed through intestines slow. Figure 21.2. Drug distribution. Barriers to drug Cell membranes protein-lined pores

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Chapter 21 Pharmacology

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  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

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