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History Paul Ehrlich Chemotherapy as a science began with Paul Ehrlich in the first decade of last century. Nobel Prize 1908 Ehrlich received the Nobel Prize for Medicine in 1908. 1906 atoxyl sleeping sickness In 1906 he discovered the structural formula of atoxyl, a chemical compound which had been shown to be able to treat sleeping sickness (trypanosomiasis). 1909Sahachiro Hata Salvarsan In 1909 he and his student Sahachiro Hata developed Salvarsan (arsphenamine), a treatment effective against syphilis.
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Continue Gerhard Domagk (marketed under the brand name Prontosil) Gerhard Domagk was a German pathologist and bacteriologist recognized with the discovery of the first commercially available antibiotic (marketed under the brand name Prontosil). 1939Nobel Prize streptococcal In 1939, he received the Nobel Prize in Medicine for this discovery, the first drug effective against bacterial infections (streptococcal infections ). Prontosil active sulphonamide toxic thiaminobenzene Prontosil decomposes in the living body to give a highly active sulphonamide and the toxic compound thiaminobenzene.
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penicillin The 'golden age' of antimicrobial therapy began with the production of penicillin. Sir Alexander Fleming (1929) staphylococci Penicilian notatum This was discovered by Sir Alexander Fleming (1929) who noticed that the growth of staphylococci was inhibited round a mould of Penicilian notatum which was growing by accident on a culture plate. 1940Florey & Chain From this mould, penicillin was extracted and mass produced in 1940 by the work of Florey & Chain. Continue
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He shared the Nobel Prize in Physiology or Medicine in 1945 with Howard Florey and Ernst Chain.Nobel Prize in Physiology or MedicineHoward FloreyErnst Chain
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Antibiotics = Antibiotics = a natural substance produced by a micro-organism to kill another. Anti-infectives / Anti-microbrial = Anti-infectives / Anti-microbrial = any agent (natural or synthetic) that kills pathogens (microbes). Continue
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Classification of antibiotics antibacterial Classification of antibiotics l antibacterial According to their origin (sources) According to their chemical structure According to the spectrum of their biological action According to their mode of action
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According to their origin (sources) Microorganisms Synthetic antibiotics Semi synthetic antibiotics Bacteria Fungi Streptomyces spp
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Examples of Microbial Sources of Antibiotics
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Streptomyces Streptomyces is the largest genus of Actinobacteria. Over 500 species of Streptomyces bacteria have been described.
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According to their chemical structure a. Beta-lactam antibioticsb. Aminoglycosides c. Aminocyclitolsd. Tetracyclines e. Polyenesf. Macrolides
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β-Lactam antibiotics a β-Lactam nucleus β-Lactam antibiotics are a broad class of antibiotics, consisting of all antibiotic agents that contains a β-Lactam nucleus in its molecular structure. It includes penicillins, cephalosporins, and cephmycins. a. Beta-lactam antibiotics
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An aminoglycoside is a molecule or a portion of a molecule composed of amino-modified sugars. They are glycosidic derivatives of streptamine. Both streptomycin and dihydrostreptomycin contain streptidin and aminosugars in their structure, while other members containing deoxystreptamine and amino sugar in their structure e.g. neomycin, kanamycin, tobramycin, amikacin, and gentamicin. Streptomycesmycin, Micromonospora micin. Aminoglycosides that are derived from bacteria of the Streptomyces genus are named with the suffix -mycin, whereas those that are derived from Micromonospora are named with the suffix –micin. b. Aminoglycosides
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closely related aminoglycosides It is a closely related group to aminoglycosides. no amino sugar These contain no amino sugar in their structure e.g. spectinomycin. c. Aminocyclitols
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four-ringed structure A family of closely related antibiotics with four-ringed structure e.g. tetracycline, chlorotetracycline, oxytetracycline, demeclocycline, methacycline, doxycycline and minocycline. d. Tetracyclines
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a large ring lactone group and a hydrophobic region sequence of 4-7 conjugated double bonds. These are characterized by possessing a large ring containing a lactone group and a hydrophobic region consisting of a sequence of 4-7 conjugated double bonds. nstatin, amphotericin. Polyenes are poly-unsaturated organic compounds that contain one or more sequences of alternating double and single carbon-carbon bonds, e.g. nstatin, amphotericin. e. Polyenes
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macrocyclic lactone These consisting of a macrocyclic lactone ring to which sugars are attached. erythromycinoleandomycin spiramycin They include erythromycin, oleandomycin and spiramycin. f. Macrolides
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According to the spectrum of their biological action a. Antibacterial antibioticsb. Antifungal antibiotics c. Antitumor antibioticsd. Antiprotozoal antibiotics e. Antiviral antibiotics
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a. Antibacterial antibiotics Narrow spectrum Broad spectrum Tuberculostatic Natural penicillins and erythromycin (G +ve) Polymyxin (G –ve). Effective against at least some members of most genera Tetracyclines and chloramphenicol. Streptomycin, kanamycin and cycloserine.
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b. Antifungal antibiotics c. Antitumor antibiotics d. Antiprotozoal antibiotics e. Antiviral antibiotics Nystatin, amphotericin B, griseofulvin, and candicin. Actinomycins, mitomycins. Fumagillin. Helinine.
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According to their mode of action a. Inhibitors of cell wall synthesis. b. Antibiotics acting on cell membranes c. Inhibitors of protein synthesis d. Inhibitors of nucleic acid synthesis e. Inhibitors of folic acid synthesis (antifolates)
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a. Inhibitors of cell wall synthesis
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The steps of biosynthesis involves many essential enzymes: Racemes I. Racemes (catalyze change of L-alanine to D-alanine). Synthetase D-alanyl-D-alanine II. Synthetase (join two D-alanine molecules forming the terminal D-alanyl-D-alanine residue of the penta peptide). Transpeptidases III. Transpeptidases (catalyze transpeptidation or cross-linking reactions). Continue
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Penicillins. Cephalosporins. Bacitracin. Vancomycin. Teicoplanin. Cycloserine. Continue
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