Transcript Pharmacology

Chapter 21
Pharmacology
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Drug administration
• External
– local, topical
• Intravenous (IV)
– into vein
– fastest
• Intramuscular (IM)
– injection in muscle
• Oral (PO)
– absorbed through
intestines
Figure 21.2
– slow
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Drug distribution
• Barriers to drug
– Cell membranes
• protein-lined pores
• transport systems
– Drug-binding
proteins
• prevents drug from
entering tissue
• slows
Figure 21.3
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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
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Side Effects and Allergies
• Selective toxicity
– Inhibit or kill microorganism
– No harm to human cells
• Side effects
– Danger must be weighted against benefit
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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
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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
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Drug resistance
• Beta lactamase
– produced by
penicillin-resistant
microorganisms
– cuts the betalactam ring
– prevents penicillin
from blocking cell
wall synthesis
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Drug resistance
• Acquired resistance
– Genetics
• mutations
• plasmids
– Slowing resistance
• reduce non-essential medical use
• limit non-medical use
• combined therapy
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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
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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)
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Drug Dosage: Serum killing
• Serum killing power
– drug-containing serum
• test to see if kills microorganism
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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
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Targets of antimicrobial drugs
• Protein synthesis
– interfere
• ribosome
– prokaryotic different
than eukaryotic
• tRNA
• Metabolism
– folic acid synthesis
• para-aminobenzoic
acid (PABA)
Figure 21.11
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Targets of antimicrobial drugs
Eukaryotic cells
• Cell membrane
• Nucleic acid
synthesis
• Folic acid synthesis
Figure 21.10
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Pencillins
• Inhibit cell wall
synthesis
– Gram-positive cells
– source
• antibiotic
• semisynthetic
– examples
• penicillin V
• methicillin
• ampicillin
Figure 21.12
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Cephalosporins
• Inhibit cell wall
synthesis
– Gram-positive cells
– Gram-negative cells
• third generation
– Source
• antibiotic
• semisynthetic
– more resistant to betalactamase
Figure 21.13
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Sulfonamides
• Sulfa drugs
– first antimicrobial
– less effective now
• extensive use
• microbial resistance
– used in combination
– inhibit folic acid
synthesis
Figure 21.13
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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
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Tetracyclines
• Broad spectrum
• Action
– block entry of tRNA
into ribosome
• widely used
– not for
• children
• pregnant women
Figure 21.13
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Aminoglycosides
• Gram-negative
• Action
– inhibit protein
synthesis
• bind 30S subunit
• limited use
– toxicity
• inner ear
– microbial resistance
• Streptomycin
Figure 21.13
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Erythromycin
• Macrolide family
– Gram-positive
– strep throat
– respiratory
• Action
– inhibit protein
synthesis
• bind 50S subunit
Figure 21.13
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Quinolones
•
•
•
•
Broad spectrum
few side effects
slow drug resistance
Action
– block DNA replication
• Topoisomerase
• Ciprofloxacin
Figure 21.13
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Antimycobacterial
• Mycobacterium
– difficult to treat
• cell wall causes
resistance
• grow very slowly
• antibiotic resistance
• intracellular pathogen
– Isoniazid
– Rifampin
– Ethambutol
Figure 21.15
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Antifungal
• Eukaryotic cell
– more similar to
human cells
• Examples
– Nystatin
• cytoplasmic
membrane
– Imidazoles
Figure 21.16
• inhibit sterol
synthesis
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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
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Anti-parasitic
• Mebendazole
– interferes with glucose
uptake
• Metronidazole
– obligate anaerobic
bacteria
– protozoa parasites
– use cell energy
• Chloroquine
– some resistance
– unknown mechanism
Figure 21.17
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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
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Anti-viral
• Anti-HIV agents
– reverse transcriptase
inhibitors
• AZT
• delavirdine
• nevirapine
– protease inhibitors
• indinavir
• nelfinavir
• ritonavir
Figure 21.19
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