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Antimicrobials, classification of antimicrobials, drug resistance

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  2. 2. Antimicrobial Chemotherapy <ul><li>Chemotherapy –Ehrlich; chemical used to kill pathogens with no harm to host </li></ul><ul><li>Chemotherapeutic Agents – any chemical used in medicine = drugs </li></ul><ul><li>Antimicrobial Agent – special group of drugs used against microbial diseases </li></ul><ul><li>Antibiotic – Waksman – chemical produced by microbes to kill or inhibit other microbes ; Synthetic ( lab made) or Semisynthetic ( part lab, part microbe) </li></ul><ul><li>DO NOT WORK ON VIRUSES </li></ul>
  3. 3. Chemotherapy – History <ul><li>Egyptians – moldy bread – wounds </li></ul><ul><li>Willow Bark – aspirin - alleviate pain </li></ul><ul><li>Foxglove – digitalis - heart disease </li></ul><ul><li>Paul Ehrlich – 1 st – salvarsan 606 ( arsenic compound) – syphilis – 1910 </li></ul><ul><li>Domagk – sulfa drugs or sulfonamides – prontosil </li></ul><ul><li>Fleming – penicillium ( mold) – contaminant on petri plates; saw usefulness if mass produced (Chain & Florey); used WWII </li></ul>
  4. 4. <ul><li>Treatment of disease by Chemical compounds has been practiced for centuries. </li></ul><ul><li>In 1630 Europeans – natural Quinine from the bark of the Chinchona tree – malaria. </li></ul><ul><li>Even used by South American Indians – used to chew the bark of the Chinchona tree. </li></ul>
  5. 5. <ul><li>As early as 1495, Mercury – Syphilis. </li></ul><ul><li>In Twentieth century new developments in Chemotherapy revolutionized the practice of medicine. </li></ul><ul><li>Mercury – toxic to human and animal. </li></ul><ul><li>Moderan era of Chemotherapy – Paul Ehrlich, Gerhard Domagk and Alexander Fleming. </li></ul>
  6. 6. Paul Ehrlich 1854 - 1915 <ul><li>Paul Ehrlich was born on March 14, 1854 in Upper Silesia, Germany. </li></ul><ul><li>Ehrlich was educated at the Universities of Breslau, Strasburg, Freiburg-im-Breisgau and Leipzig. In 1878 he obtained his doctorate of medicine. </li></ul>
  7. 7. <ul><li>Ehrlich created a method of dying different animal tissues. The dyes that he used could be classified as either acidic, basic, or neutral. Ehrlich published his method in 1878 which laid down the foundations of hematology and also the Gram method of staining bacteria which is still used today. </li></ul><ul><li>He worked on Hematology, Immunology and Chemotherapy. </li></ul><ul><li>He predicted autoimmunity calling it “HORROR AUTOTOXICUS”. </li></ul><ul><li>He coined the term “chemotherapy” and popularized the concept of “magic bullet”. </li></ul>
  8. 8. <ul><li>As a schoolboy and student of medicine he was interested in staining microscopic tissue substances. </li></ul><ul><li>He married Hedwig Pinkus (then aged 19) in 1883. </li></ul><ul><li>The couple had two daughters named Stephanie and Marianne. </li></ul><ul><li>After his clinical education and habilitation at the Charite in Berlin in 1886 he received a call from Robert Koch to join the Institute for Infectious Diseases in Berlin (1891). </li></ul>
  9. 9. <ul><li>Ehrlich spent two years in Egypt, (recovering from tuberculosis). </li></ul><ul><li>He worked with his friend Emil Adolf von Behring – Diphtheria Serum. </li></ul><ul><li>Side-chain theory </li></ul><ul><li>1896 – became the Director of Institute of Serum Research and Examination ( Istititute f Ü r Serumforschung und Serumpr Ü fung) in Steglitiz (Berlin). </li></ul>
  10. 10. <ul><li>In 1899 the Institute was moved to Frankfurt and extended to the Royal Institute of Experimental Therapy (Institut f Ü r experimentelle Therapie) . </li></ul><ul><li>Researched chemotherapy and infectious diseases. </li></ul><ul><li>In 1904 Ehrlich became honorary Professor of the University of G Ö ttingen. </li></ul>
  11. 11. <ul><li>He received the Nobel Prize for Medicine together with Ilya Ilyich Mechnikov in 1908. </li></ul><ul><li>1906 – Discovered the structural formula of atoxyl – treat sleeping sickness. </li></ul><ul><li>1909 – along with his student Sahachiro Hata – developed Salvarsan. </li></ul><ul><li>Stimuated research – sulfa drugs, penicillin and other antibiotics. </li></ul>
  12. 12. <ul><li>In 1890, Ehrlich was appointed as an assistant to Robert Koch, Director of the Institute for Infectious Diseases, and Ehrlich began his immunological studies. He showed that chemical reactions are accelerated by heat and slowed down by cold. His name is most associated with these studies. </li></ul>
  13. 13. <ul><li>The first major discovery was made in the early 1900s by Paul Ehrlich. (Chemist) </li></ul><ul><li>Made a chemical coumpount - for syphilis without harming the patient. </li></ul><ul><li>Arsenic for Syphilis? </li></ul><ul><li>Arsenic + organic compound – nontoxic . </li></ul><ul><li>He was the first persons to search for such compound. </li></ul><ul><li>Ehrlich’s compound no. 606. which was eventually named SALVARSAN (first laboratory-synthesized chemical) </li></ul><ul><li>Nobel Prize in 1908. </li></ul>
  14. 14. 200 Deutsche Mark Bank Note from Germany of 1996.
  15. 15. <ul><li>Paul Ehrlich died on August 20 in Germany after having a sever stroke. </li></ul>
  16. 16. <ul><li>His Life is depicted in the movie “ THE MAGIC BULLET”- (ARSPHENAMINE, Compound 606”). </li></ul><ul><li>The concept of a “Magic Bullet” was fully realized with the invention of monoclonal antibodies. </li></ul>
  17. 17. Gerhard Domagk (30 October 1895 – 24 April 1964) <ul><li>After 30 Years of Ehrlich’s discovery of Salvarsan. </li></ul><ul><li>1935 – Gerhard Domagk – Bayer Chemical Company in Germany – more than 1000 synthetic dyes – streptococcal infections in mice – without poisoning the animals. </li></ul>
  18. 18. <ul><li>He discovered that a particular red dye called “Prontosil”. </li></ul><ul><li>Nobel Prize in 1939. </li></ul><ul><li>But dye failed to hihibit bacterial cultures in Laboratory media. </li></ul><ul><li>Effective only in animal body. </li></ul>
  19. 19. Jacques Trefouel <ul><li>Contradiction was resolved . </li></ul><ul><li>Discovered – colorless compound called Sulfanilamide in animal when Prontosil broken. </li></ul><ul><li>1945 Scientists made several derivatives. And collectively called Sulfonamides or Sulfa drugs. </li></ul>
  20. 20. Sir Alexander Fleming (6 August 1881 – 11 March 1955) <ul><li>The Discovery of the Antibiotic Penicillin </li></ul><ul><li>Second category of Chemotherapeutic agent. </li></ul><ul><li>These are natural chemotherapeutic agents, more commonly called antibiotics. </li></ul>
  21. 21. <ul><li>Antibiotics </li></ul><ul><li>These natural substances were known for their curative effects long before they were called antibiotics. </li></ul><ul><li>Chinese used moldy soybean curd to treat boils. </li></ul><ul><li>1881 John Tyndall. </li></ul>
  22. 22. <ul><li>Pasteur and Joubert. </li></ul><ul><li>Emmerich 1901. </li></ul><ul><li>1920 Gratia and Dath </li></ul><ul><li>1945 Fleming, Ernest Chain and Howard W. Florey won a Nobel Prize for their work with Penicillin. (Miracle Drug). </li></ul>
  23. 23. <ul><li>1939 –– Bacillus brevis – Gramicidin and Tyrocidine </li></ul>Rene Dubos
  24. 24. Selman Waksman <ul><li>streptomycin. ( Streptomyces griseus ). </li></ul>
  25. 25. <ul><li>THANK YOU </li></ul>MAJID MOHIUDDIN