Lecture 2 Chemotherapy-2010

Lecture 2 Chemotherapy-2010 - Lecture 2 Chemotherapy of...

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Lecture 2 Chemotherapy of Bacterial Infections
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The Magic Bullet-The birth of Chemotherapy-1909 Paul Ehrlich 1854-1915 -differential staining of cells and bacteria inspired him to look for a compound that would only kill bacteria “Magic Bullet” Started looking for cure of syphilis, screened 605 compounds for 7 years, finally compound 606 was successful (Salvarsan) http://nobelprize.org
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History Paul Ehrlich “Magic Bullet”; Chemotherapy Chemicals with selective toxicity ORIGIN : Selective Stains (histology) DRUG : Arsphenamine (1910) “606” Salvarsan DISEASE : Syphilis ( Trepanoma palladium ) NOBEL : 1908 (related to previous immunological (cont’d)
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History (cont’d) Gerhard Domagk Drugs are changed in the body ORIGIN : Prontosil (Only active in vivo ) DRUG : Sulfonamide (1935) Disease: Streptococcus (but broad spectrum) NOBEL: 1939 (1947)
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Discovery of Antibiotics-1928 A. Fleming (1881-1955) The penicillin mold inhibits bacterial growth
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History Alexander Fleming (Florey and Chain) Microbes make antibiotics ORIGIN : mold Penicillium notatum DRUG : Penicillin (1928) Disease: gram-pos bacteria NOBEL: 1945 (cont’d)
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History (cont’d) Selman Waksman Soil Streptomyces make antibiotics comes up with definition of antibiotic ORIGIN : bacteria, Streptomyces DRUG : Streptomycin (1944) Disease: Tuberculosis NOBEL: 1952
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Discovery of Antibiotics A.Fleming: 1928-first description of Penicillin (accidental discovery) R. Dubos: 1938 –first experimental design to screen for antibiotic ( Gramicidin: toxic but OK for topical application) Chain and Florey: 1938-1940 Purification and application of Penicillin S.Waksman: 1944 Discovery of Streptomycin (Tuberculosis!)
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ANTIBIOTICS Some key concepts Bioactivity bactericidal vs. bacteriostatic broad vs. narrow spectrum distribution in the body Pharmacokinetics degradation
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ANTIBIOTICS Some key concepts
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ANTIBIOTICS Some key concepts LD50=Dose that kills 50% of test animals (LD=Lethal Dose) ED50=Dose that is effective in 50% of the test population (ED=Effective Dose)
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ANTIBIOTICS Some key concepts Side effects Therapeutic index/ratio the ratio between the median lethal dose (LD50) and the median effective dose (ED50) The bigger the value the better the antibiotic (drug) (cont’d)
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ANTIBIOTICS Some key concepts MIC= lowest concentration that inhibits growth of organism (Minimum Inhibitory Concentration)
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Susceptibility Tests 1. Broth dilution - MIC test 2. Agar dilution - MIC test
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Susceptibility Tests 1. Agar diffusion “Kirby-Bauer Disk-plate test” (cont’d)
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Lecture 2 Chemotherapy-2010 - Lecture 2 Chemotherapy of...

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