© 2004 Wadsworth – Thomson Learning Chapter 21 Pharmacology

© 2004 Wadsworth – Thomson Learning Drug administration External –local, topical Intravenous (IV) –into vein –fastest Intramuscular (IM) –injection in muscle Oral (PO) –absorbed through intestines –slow Figure 21.2

© 2004 Wadsworth – Thomson Learning Drug distribution Barriers to drug –Cell membranes protein-lined pores transport systems –Drug-binding proteins prevents drug from entering tissue slows Figure 21.3

© 2004 Wadsworth – Thomson Learning 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

© 2004 Wadsworth – Thomson Learning Side Effects and Allergies Selective toxicity –Inhibit or kill microorganism –No harm to human cells Side effects –Danger must be weighted against benefit

© 2004 Wadsworth – Thomson Learning 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

© 2004 Wadsworth – Thomson Learning 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

© 2004 Wadsworth – Thomson Learning Drug resistance Beta lactamase –produced by penicillin-resistant microorganisms –cuts the beta- lactam ring –prevents penicillin from blocking cell wall synthesis

© 2004 Wadsworth – Thomson Learning Drug resistance Acquired resistance –Genetics mutations plasmids –Slowing resistance reduce non-essential medical use limit non-medical use combined therapy

© 2004 Wadsworth – Thomson Learning 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

© 2004 Wadsworth – Thomson Learning 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

© 2004 Wadsworth – Thomson Learning Drug Dosage: Serum killing Serum killing power –drug-containing serum test to see if kills microorganism

© 2004 Wadsworth – Thomson Learning 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

© 2004 Wadsworth – Thomson Learning Targets of antimicrobial drugs Protein synthesis –interfere ribosome –prokaryotic different than eukaryotic tRNA Metabolism –folic acid synthesis para-aminobenzoic acid (PABA) Figure 21.11

© 2004 Wadsworth – Thomson Learning Targets of antimicrobial drugs Eukaryotic cells Cell membrane Nucleic acid synthesis Folic acid synthesis Figure 21.10

© 2004 Wadsworth – Thomson Learning Pencillins Inhibit cell wall synthesis –Gram-positive cells –source antibiotic semisynthetic –examples penicillin V methicillin ampicillin Figure 21.12

© 2004 Wadsworth – Thomson Learning Cephalosporins Inhibit cell wall synthesis –Gram-positive cells –Gram-negative cells third generation –Source antibiotic semisynthetic –more resistant to beta- lactamase Figure 21.13

© 2004 Wadsworth – Thomson Learning Sulfonamides Sulfa drugs –first antimicrobial –less effective now extensive use microbial resistance –used in combination –inhibit folic acid synthesis Figure 21.13

© 2004 Wadsworth – Thomson Learning 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

© 2004 Wadsworth – Thomson Learning Tetracyclines Broad spectrum Action –block entry of tRNA into ribosome widely used –not for children pregnant women Figure 21.13

© 2004 Wadsworth – Thomson Learning Aminoglycosides Gram-negative Action –inhibit protein synthesis bind 30S subunit limited use –toxicity inner ear –microbial resistance Streptomycin Figure 21.13

© 2004 Wadsworth – Thomson Learning Erythromycin Macrolide family –Gram-positive –strep throat –respiratory Action –inhibit protein synthesis bind 50S subunit Figure 21.13

© 2004 Wadsworth – Thomson Learning Quinolones Broad spectrum few side effects slow drug resistance Action –block DNA replication Topoisomerase Ciprofloxacin Figure 21.13

© 2004 Wadsworth – Thomson Learning Antimycobacterial Mycobacterium –difficult to treat cell wall causes resistance grow very slowly antibiotic resistance intracellular pathogen –Isoniazid –Rifampin –Ethambutol Figure 21.15

© 2004 Wadsworth – Thomson Learning Antifungal Eukaryotic cell –more similar to human cells Examples –Nystatin cytoplasmic membrane –Imidazoles inhibit sterol synthesis Figure 21.16

© 2004 Wadsworth – Thomson Learning 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

© 2004 Wadsworth – Thomson Learning Anti-parasitic Mebendazole –interferes with glucose uptake Metronidazole –obligate anaerobic bacteria –protozoa parasites –use cell energy Chloroquine –some resistance –unknown mechanism Figure 21.17

© 2004 Wadsworth – Thomson Learning 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

© 2004 Wadsworth – Thomson Learning Anti-viral Anti-HIV agents –reverse transcriptase inhibitors AZT delavirdine nevirapine –protease inhibitors indinavir nelfinavir ritonavir Figure 21.19