1 Antimicrobial Drugs. 2 Antimicrobal Chemotherapy Terms

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Antimicrobial Drugs

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Antimicrobal Chemotherapy Terms

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Chemotherapy

• The use of drugs to treat a disease

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 prominenceGerhard 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

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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

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

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The

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x• Selective toxicity: A drug that kills harmful

microbes without damaging the host

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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The

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xTherapeutic Index = Toxic Dose/Therapeutic Dose

Dru

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Small Ratio(dangerous)

ModerateRatio

High Ratio(safe)

Most desirable.

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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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rugs

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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

Agar diffusion = disk-diffusion test Kirby-Bauer Disk Diffusion Test

Sensitive

Intermediate

resistant

(cont’d)

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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

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

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