© 2004 wadsworth – thomson learning chapter 21 pharmacology

© 2004 Wadsworth – Thomson Learning

Chapter 21Chapter 21PharmacologyPharmacology


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• transport systems

– Drug-binding proteins

• prevents drug from entering tissue

• slows

Figure 21.3


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


Side Effects and Allergies

• Selective toxicity– Inhibit or kill microorganism– No harm to human cells

• Side effects– Danger must be weighted against benefit


Drug resistance

• Natural resistance– lack target– not able to enter cell– broad spectrum

• drug effective against many

– narrow spectrum• drug effective against

few organismsFigure 21.5


Drug resistance• Acquired resistance

– Mechanisms• enzymes destroy

drug– beta lactamase

• change target– penicillin-binding

protein

• prevent entry or pump out

– membrane transport system

Figure 21.6Penicillin-resistant S. aureus


Drug resistance

• Beta lactamase– produced by

penicillin-resistant microorganisms

– cuts the beta-lactam ring

– prevents penicillin from blocking cell wall synthesis


Drug resistance

• Acquired resistance– Genetics

• mutations• plasmids

– Slowing resistance• reduce non-essential medical use• limit non-medical use• combined therapy


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


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


Drug Dosage: Serum killing

• Serum killing power– drug-containing serum

• test to see if kills microorganism


Targets of antimicrobial drugsProkaryotic cells• Cell wall synthesis

– destroy peptidoglycan– prevent synthesis

• Cell membrane– damage membranes

• Nucleic Acids– enzymes

• unique to prokaryotic

Figure 21.10


Targets of antimicrobial drugs• Protein synthesis

– interfere• ribosome

– prokaryotic different than eukaryotic

• tRNA

• Metabolism– folic acid synthesis

• para-aminobenzoic acid (PABA) Figure 21.11


Targets of antimicrobial drugs

Eukaryotic cells• Cell membrane• Nucleic acid

synthesis• Folic acid synthesis

Figure 21.10


Pencillins

• Inhibit cell wall synthesis– Gram-positive cells– source

• antibiotic• semisynthetic

– examples• penicillin V• methicillin• ampicillin

Figure 21.12


Cephalosporins• Inhibit cell wall

synthesis– Gram-positive cells– Gram-negative cells

• third generation

– Source• antibiotic• semisynthetic

– more resistant to beta-lactamase Figure 21.13


Sulfonamides• Sulfa drugs

– first antimicrobial– less effective now

• extensive use• microbial resistance

– used in combination– inhibit folic acid

synthesis

Figure 21.13


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


Tetracyclines• Broad spectrum• Action

– block entry of tRNA into ribosome

• widely used– not for

• children• pregnant women

Figure 21.13


Aminoglycosides• Gram-negative• Action

– inhibit protein synthesis

• bind 30S subunit

• limited use– toxicity

• inner ear

– microbial resistance

• StreptomycinFigure 21.13


Erythromycin• Macrolide family

– Gram-positive– strep throat– respiratory

• Action– inhibit protein

synthesis• bind 50S subunit

Figure 21.13


Quinolones• Broad spectrum• few side effects• slow drug resistance• Action

– block DNA replication• Topoisomerase

• Ciprofloxacin

Figure 21.13


Antimycobacterial• Mycobacterium

– difficult to treat• cell wall causes

resistance• grow very slowly• antibiotic resistance• intracellular pathogen

– Isoniazid– Rifampin– Ethambutol

Figure 21.15


Antifungal• Eukaryotic cell

– more similar to human cells

• Examples– Nystatin

• cytoplasmic membrane

– Imidazoles• inhibit sterol

synthesis

Figure 21.16


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


Anti-parasitic• Mebendazole

– interferes with glucose uptake

• Metronidazole– obligate anaerobic

bacteria

– protozoa parasites

– use cell energy

• Chloroquine– some resistance

– unknown mechanism

Figure 21.17


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


Anti-viral• Anti-HIV agents

– reverse transcriptase inhibitors

• AZT• delavirdine• nevirapine

– protease inhibitors• indinavir• nelfinavir• ritonavir

Figure 21.19

© 2004 wadsworth – thomson learning chapter 21 pharmacology

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