Antimicrobial Drugs
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Antimicrobal Chemotherapy Terms
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Chemotherapy
• The use of drugs to treat a disease
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Early history of Antimicrobial
Chemotherapeutic Agents
Paul Ehrlich (1910) developed the •
concept of chemotherapy to treat microbial
diseases
•
He predicted the development of •
chemotherapeutic agents which would kill
pathogens without harming the host
In 1930s Sulfa drugs came into
prominence
Gerhard Domagk
Alexander Fleming discovered the •
first antibiotic penicillin in 1929
** its first trials were done in 1940 •
History of antibacterial
Paul Ehrlich articulates the principles of •
chemotherapy in 1894
1910 introduce Salvarsan to treat syphilis •
Alexander Fleming discovered •
penicillin in 1929 •
Penicillium spp •
. •
Synthetic antibiotic = sulfa drug •
Antibiotic/Antimicrobial
• Antibiotic: Chemical produced by a
microorganism that kills or inhibits the
growth of another microorganism
• Antimicrobial agent: Chemical that kills
or inhibits the growth of microorganisms
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The Spectrum of antimicrobial Activity
**it is easy to find or develop drugs that •
effective against prokaryotic cells ,&
that do not affect the eukaryotic cells of
humans
**the problem is difficult when the •
pathogen is eukaryotic (fungus,
protozoan, helminthes)
**viral infection more difficult to treat •
The Spectrum of antimicrobial Activity
**-differ in cell wall •
-differ in fine structure of their •
ribosome
-details of their metabolism •
**resemble the human cell •
**the virus is within the human cells •
• Selective toxicity: A drug that kills harmful
Therapeutic Index
microbes without damaging the host
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 This is defined by Therapeutic Index as a
measure of the degree of selective toxicity.
 The therapeutic index is the ratio of the toxic
dosage to the therapeutic dosage.
 That is, (Lowest dose toxic to patient)  (Dose normally
used for therapy).
 The greater the ratio (or difference) of these
two numbers, the easier it is to find a dosage
that kills the pathogen without harming the
host.
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Drug Dosage (per Kg Body Weight)
Therapeutic Index
Therapeutic Index = Toxic Dose/Therapeutic Dose
Small Ratio
(dangerous)
Most
desirable.
Moderate
Ratio
High Ratio
(safe)
Mechanisms of Antimicrobial
Action
• Bacteria have their own enzymes for
– Cell wall formation
– Protein synthesis
– DNA replication
– plasma membrane
– Synthesis of essential metabolites
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Targets of Antibacterial Drugs
Measuring Antimicrobial Sensitivity
• These tests are used to determine
which chemotherapeutic agent is
most likely to combat a specific
pathogen
• These tests are used when
susceptibility can not be predicted or
when drug resistance arises
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Susceptibility Tests
(cont’d)
Agar diffusion = disk-diffusion test
 Kirby-Bauer Disk Diffusion Test
Sensitive
Intermediate
resistant
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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
• Viruses are reproduce only inside living
cells
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Viral replicative cycle
Attachment === receptors •
Penetration •
Uncoating •
Nucleic acid replication •
(polymerases) •
Assembly •
Release •
Antiviral drugs
Inhibitors of •
Attachment •
Penetration •
Uncoating •
Nucleic acid synthesis •
(polymerases inhibitors) •
Assembly •
Release •
Antifungal Drugs
Inhibitors of •
cell wall synthesis •
plasma membrane = sterols = ergosterol •
interfere with RNA biosynthesis
Anti parasitic drugs
Anti protozoan & anti helminthes drugs •
Inhibit enzymes and proteins •
Inhibit nucleic acid synthesis •
Inhibit nutrient absorbtion •
Alters membrane permeability •
Prevent ATP generation •