Professional Documents
Culture Documents
Fading Miracle?
Ehrlich’s Magic Bullets
Fleming and Penicillin
Chemotherapy
• The use of drugs to treat a disease
Figure 20.6
Penicillinase ( Lactamase)
Figure 20.8
Semisynthetic Penicillins
• Penicilinase-resistant penicillins
• Carbapenems: very broad
spectrum
• Monobactam: Gram negative
• Extended-spectrum penicillins
• Penicillins + -lactamase inhibitors
Other Inhibitors of Cell Wall
Synthesis
• Cephalosporins
– 2nd, 3rd, and 4th
generations
more effective
against gram-
negatives
Figure 20.9
Other Inhibitors of Cell Wall
Synthesis
• Polypeptide antibiotics
– Bacitracin
• Topical application
• Against gram-positives
– Vancomycin
• Glycopeptide
• Important "last line" against
antibiotic resistant S. aureus
Other Inhibitors of Cell Wall
Synthesis
• Antibiotics
effective against
Mycobacteria:
interfere with
mycolic acid
synthesis or
incorporation
– Isoniazid (INH)
– Ethambutol
Inhibitors of Protein Synthesis
• Broad spectrum, toxicity problems
• Examples
– Chloramphenicol (bone marrow)
– Aminoglycosides: Streptomycin,
neomycin, gentamycin (hearing, kidneys)
– Tetracyclines (Rickettsias & Chlamydia; GI
tract)
– Macrolides: Erythromycin (gram +, used in
children)
Injury to the Plasma Membrane
Figure 5.7
Antifungal Drugs
• Fungi are
eukaryotes
• Have unique
sterols in their cell
walls
• Pathogenic fungi
are often outside
the body
Antiviral Drugs
• Viruses are composed of nucleic
acid, protein capsid, and host
membrane containing virus proteins
• Viruses live inside host cells and
use many host enzymes
• Some viruses have unique
enzymes for DNA/RNA synthesis or
protein cutting in virus assembly
Figure 20.16a
Antiviral Drugs
Nucleoside and Nucleotide Analogs
Figure 20.16a
Analogs Block DNA Synthesis
Figure 20.16b, c
Antiviral Drugs
Enzyme Inhibitors
• Inhibit assembly
– Indinavir (HIV)
• Inhibit attachment
– Zanamivir (Influenza)
• Inhibit uncoating
– Amantadine (Influenza)
Antiviral Drugs
Enzyme Inhibitors
• Protozoa are
eukaryotic cells
• Many drugs are
experimental and
their mode of
action is unknown
Antihelminthic Drugs
• Helminths are
macroscopic
multicellular
eukaryotic
organisms:
tapeworms,
roundworms,
pinworms,
hookworms
Antihelminthic Drugs
• Prevent ATP generation (Tapeworms)
• Alters membrane permeability
(Flatworms)
• Neuromuscular block (Intestinal
roundworms)
• Inhibits nutrient absorption (Intestinal
roundworms)
• Paralyzes worm (Intestinal
roundworms)
Measuring Antimicrobial
Sensitivity
• E Test
• MIC: Minimal
inhibitory
concentration
Measuring Antimicrobial
Sensitivity: Disk Diffusion
Antibiotic Resistance
Figure 20.20
Antimicrobial Resistance
• Relative or complete lack of
effect of antimicrobial against a
previously susceptible microbe
• Increase in MIC
Mechanisms of Antibiotic
Resistance
• Enzymatic destruction
of drug
• Prevention of
penetration of drug
• Alteration of antibiotic
or target site
• Rapid ejection of the
drug
Antibiotic Selection for
Resistant Bacteria
What Factors Promote
Antimicrobial Resistance?
• Antisense agents
– Complementary DNA or peptide
nucleic acids that binds to a
pathogen's virulence gene(s) and
prevents transcription