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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 Figure 21.2 – slow © 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 betalactam 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 Figure 21.8 – serially dilute drug – inoculate – obtain tube with the minimal amount of drug to prevent growth • Minimum inhibitory concentration (MIC) • Minimum bactericidal concentration (MBC) © 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 betalactamase 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 Figure 21.16 • inhibit sterol synthesis © 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 © 2004 Wadsworth – Thomson Learning