History of pharmacology
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It was my first pg seminar.I have added notes on which speaker can speak.A few slides that were added after the thank u slide were just for reference and not fit for presenting to audience.
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History of pharmacology
- 1. Presented by: Dr.Adithi.S.Raghavan Moderated by:Dr.Cuckoo Aiyappa
- 3. Historical knowledge is no more and no less than carefully and critically constructed collective memory. Without individual memory, a person literally loses his or her identity, and would not know how to act in encounters with others. .
- 6. “Whatever act is done by one who is deranged of understanding ,will or memory is to be regarded as a volitional transgression(prajnaparadha).It is the inducer of all pathological conditions.” -Charaka
- 8. Vaghbhata Ashtanga hridaya Ashtanga sangraha Madhava nidana
- 9. Unani
- 10. Chinese & Egyptian 1500 BC 2500 BC PAN TSAO-CHINESE MATERIA MEDICA EBERS PAPYRUS-EGYPTIAN MATERIA MEDICA
- 11. Babylonian clay tablet 700 bc 300 drugs
- 12. HIPPOCRATES Hippocrates- father of modern medicine 377-460 BC
- 13. Celsus - “Cicero of Medicine” (25-35 AD). Use of poppy extract and mandrake to induce sleep. Pedanius Dioscorides (40-90 AD) - De Materia Medica > 900 drugs, was in use until 1600 AD. Mercury, copper, lead topical application. Blood and excrements still used. Style of presentation followed by many later authors, even today's Physicians' Desk Reference.
- 14. Galen (129-217) - Roman physician Followed Hippocrates’ (460-355 BC) humoral basis of medicine. He taught that drugs possessed certain fundamental effects (warming, cooling, drying, humidifying) which might be combined in different ways and also some specific actions (e.g. emetic, diuretic, etc.). Dogmatic approach hampered scientific growth for a 1000 years.
- 15. Arabian Medicine Avicenna (980-1027) – “Canon of Medicine” (14 vol.) Galenic medicine (standard text till 18th century).
- 16. The Renaissance Paracelsus (1493 – 1541) Travelled all over the known world in search of knowledge. Challenged Galenic medicine (burnt his books) Dose-response concept - “All things are poison and nothing is without poison, only the dose permits something not to be poisonous”. Used distilled oils as remedies. Used ether on animals. Mercury for syphilis.
- 17. Allopathy(the other suffering) Obnoxious remedies as flesh,excreta and blood of various animals James Gregory(1753-1821) Disastrous results Wrongly applied name to modern scientific medicine
- 18. Homeopathy(similar suffering) Early 19th century “like cures like” Hannemann
- 19. François Magendie (1783 –1855) French physiologist. “Formulary for preparation and use of many new remedies,. Paris academy in 1809 The Rise Of Experimental Pharmacology 19
- 20. Friedrich Wilhelm Adam Sertürner (1783-1841) Isolated morphine 1804, The first ever alkaloid Administered to himself and three friends. Cholera -living organism. 20
- 21. Claude Bernard (18131878) - Magendie’s pupil Pancreatic juice in digestion, liver glycogen and its importance Vasomotor nerves. CO on hemoglobin. Action of Curare 21
- 22. Rudolf Buchheim (1820 – 1879) First pharmacology laboratory in the world (1860, University of Dorpat in Estonia) Introduced bioassay . 22
- 23. Oswald Schmiedeberg (1838 –1921) Father of modern pharmacology 23
- 24. Sir Thomas Lauder Brunton (1844 –1916) Scottish physician “Textbook of Pharmacology, Therapeutics and Materia Medica (1885)”. 24
- 25. John Jacob Abel (1857– 1938) Father of American Pharmacology. Co-founded Journal of Pharmacology and Experimental Therapeutics in 1909. 25
- 26. Arthur Robertson Cushny (1866-1926) Trained by Oswald Schmiedeberg. “Text-Book of Pharmacology and Therapeutics”
- 28. Pilocarpine Chewing of leaves;Salivation 1874-Brazilian physician Coutinhou first experiments 1875-alkaloid isolated Weber-actions pupil,sweat,salivary glands. South American genus Pilocarpus
- 29. Physostigmine Also called eserine. Alkaloid;Calabar bean. West Africa;”Ordeal poison” 1864;Jobst and Hesse 1877;Laqueur-Tx glaucoma
- 30. Roman empire;obscure poisoning Atropos;Linnaeus India-root&leaves-Tx Asthma Mein 1831 Bezold&Bloebaum(1867) Heidanhain(1872) Atropine&Scopalamine Belladona Muscuranic receptor antagonists
- 31. Von Humboldt 1805 Strychnos species Griffith & Johnson 1942 King 1935 Curare South American arrow poisons
- 32. Claviceps purpurea 600BC Assyrian tablet Middle ages-epidemics Active principles-early 20th century Ergot
- 33. Castor Oil Ricinus Communis Oil(chiefly of triglyceride of ricinoleic acid) Ricin extremely toxic protein Active agent-Ricinoleic acid
- 34. Vinca alkaloids Periwinkle plant Cantharanthus roseus(formerly Vinca rosea) Exracts;hypoglycemic effects in Diabetes. Vinblastine& Vincristine-regression ALL in mice Vinorelbine-lung& breast cancer
- 35. Foxglove
- 40. The three eras of Chemotherapy 1. Alkaloids(natural plant products) 2. Synthetic Compounds 3. Antibiotics
- 41. Alkaloids South American discovery-efficacy of ipecacuanha root in amoebic dysentry -Successful treatment of Malaria with an extract of Cinchona bark.
- 42. Quinine
- 43. Synthetic Compounds Paul Ehrlich (1854– 1915) “Receptor” concept (1907) With Sahachiro Hata, Salvarsan (compound 606, arsphenamine) for syphilis (1909). Nobel Prize in 1908. 43
- 44. Discovery of Prontosil PRONTOSIL First effective antibiotic Marketed in 1935 GERHARD DOMAGK
- 46. Antibiotics
- 47. Discovery of Penicillin Sir Alexander Fleming (1881–1955) Lysozyme – 1923 Penicillin – 28 September 1928. Described its basic properties but never performed an animal experiment with iatrogenic infection. Couldn’t purify - stopped studying it in 1931. 47
- 48. Cecil George Paine treated ophthalmia neonatorum - first recorded cure with penicillin (25 Nov 1930).
- 49. Howard Walter Florey (1898–1968) Australian pharmacologist and pathologist.
- 50. Sir Ernst Boris Chain (1906–1979) In 1939, he joined Howard Florey to investigate natural antibacterial agents produced by microorganisms – revisited Fleming’s work. . 50
- 51. Discovery of Streptomycin Selman Abraham Waksman (1888–1973) Studied actinomycetes. 1940-1952 isolated 10 antibiotics. 51
- 52. Albert Schatz (19222005) Extracted and tested the new antibiotic. Purified drug by Merck for clinical trials
- 54. HEPARIN Canine liver cells;hepar greek “Liver”. Jay McLean & William Henry Howell 1916,fatsoluble phosphatide anticogulant
- 55. Warfarin Spoiled sweet clover sillage Campbell &Link 1939-Dicoumarol 1948 Warfarin Wisconsin Alumni Reseach Foundation 1951-army inductee suicide failed
- 56. Vitamin K 1929-Dam;reduced prothrobin Dam&Coworkers(1935,1936); Unidentified fat soluble Vitamin K(Koagulation Vitamin
- 57. Aspirin Willow bark to relieve fever by Hippocrates Meadowsweet(spiraeaul maria) Salicin 1829 Leroux Pina 1836 salicylic acid Hoffman;Bayer
- 58. Nitrates Nitroglycein 1846 Sobrero 1857 ,T.Lauder Brunton Amyl nitrate Alfred nobel 1863 William Murell,sublingual nitroglycerine
- 59. Statins Mold,Penicillim citrinum,1976;Endo&colle aguesin Brown&Goldstein; HMG-CoA Reductase Compactin;Mevastatin Alberts&colleagues;Lovas tatin
- 61. Ether William Thomas Green Morton (1819– 1868) American dentist 30 September 1846 painless tooth extraction after administering ether to a patient. 62
- 62. 1847 James Simpson 1868 Edmond Andrews
- 64. Cocaine Karl Koller (1857-1944) Introduced cocaine as a local anaesthetic for eye surgery (1884). “Coca Koller
- 66. Dale & Laidlaw-endogenous histamine;immediate hypersensitivity,cellular injury Best&colleagues(1927),fresh samples liver &lung Histos-greek word for tissue
- 69. Tadeus Reichstein (1897-1996) Edward Calvin Kendall (1886–1972)
- 70. Philip Showalter Hench (1896–1965)
- 73. Von Euler in Sweden
- 74. Bengt Ingemar Samuelsson (1934- ) Sune Karl Bergström (1916–2004)
- 75. History of OCs Austrian physiologist Haberlandt 1927;temporary sterility,feeding ovarian & placental extracts 1950s Pincus,Gardia& Rock;progesterone&19norprogetins 1950s;Puerto Rico& Haiti-norethynodrel
- 77. 79
- 78. 80
- 80. John Newport Langley (1852-1925) “Receptive substance” concept (1905). 82
- 81. Thomas Renton Elliott (1877-1961)
- 82. Sir Henry Hallett Dale (1875-1968) 84
- 83. 85
- 85. Gertrude Elion (1918-1999) and George Hitchings (19051998) 87
- 87. Colonel Ram Nath Chopra FATHER OF INDIAN PHARMACOLOGY 1882-1973 89
- 88. 90
- 89. Yellapragada Subbarao (1895-1948) Phosphocreatine and ATP. Folic acid. methotrexate and hetrazan. Benjamin Duggar he world's first tetracycline antibiotic, aureomycin (in 1945). 91
- 91. Thank you! “History, if it has taught us anything at all, has taught us that the strange ideas we deride today will one day be our celebrated truths.” ― Dan Brown, The Lost Symbol
- 92. Questions asked on Ipecacuanha Vasaka Adathoda Goodman Gillman James black Chalmoogra oil Concept of Antibiosis First clinical trial?-James Lindt
- 93. Ipecacuanha Pls read the notes below
- 95. Alfred Goodman Gilman (born July 1, 1941) is an American pharmacologist and biochemist. He shared the 1994 Nobel Prize in Physiology or Medicine with Martin Rodbell for their discoveries regarding G-proteins. G-proteins are a vital intermediary between the extracellular activation of receptors (GPCR) on the cell membrane and actions within the cell. Rodbell had shown in the 1960s that GTP was involved in cell signaling. It was Gilman who actually discovered the proteins that interacted with the GTP to initiate signalling cascades within the cell.
- 96. Sir James Whyte Black OM FRS FRSE FRCP (14 June 1924 – 22 March 2010[1]) was a Scottish doctor and pharmacologist. He spent his career both as researcher and as an academic at several universities. Black established the physiology department at the University of Glasgow, where he became interested in the effects of adrenaline on the human heart. He went to work for ICI Pharmaceuticals in 1958 and, while there, developed propranolol, a beta blocker used for the treatment of heart disease.[2] Black was also responsible for the development of cimetidine, a drug used in a similar manner to treat stomach ulcers. He was awarded the Nobel Prize for Medicine in 1988 for work leading to the development of propranolol and cimetidine.[3] Contents
- 97. Hydnocarpus wightiana or Chaulmoogra is a tree in the Achariaceae family. The oil from its seeds has been widely used in Indian medicine and Chinese traditional medicine for the treatment of leprosy. It entered early Western medicine in the nineteenth century before the era of sulfones and antibiotics for the treatment of several skin diseases and leprosy.[2] The oil was prescribed for leprosy as a mixture suspended in gum or as an emulsion.[3][4] Physical characteristics and composition The oil is semi-solid at room temperature and does not have a strong odour. Gasliquid chromatography analysis has shown the oil to contain the following fatty acids hydnocarpic acid, chaulmoogric acid, gorlic acid, lower cyclic homologues, myristic acid, palmitic acid, stearic acid, palmitoleic acid, oleic acid, linoleic acid and linolenic acid.[5] Med
- 98. Antibiosis was coined by Vuillemin in1889 to denote antagonism between living creature in general Antibiotic was first used by Waksman in 1942 which confined it to substances produced by microorganisms antagonistic to the growth of life of others in high dilution
Editor's Notes
- Imagine waking up one morning unable to tell total strangers from family and friends! Collective memory is similar.But ignorance of history-deprive us of the best available guide for public action, especially in encounters with outsiders
- Illness has been man’s heritage from the beginning of his existence.Ravages of bacterial infection 40 years agoLobar pneumonia was a common cause of death even in young and vigorous patients.Acute streptococcal infections had a high mortality
- And the search for remedies to combat it is perhaps equally old.The World’s oldest known therapeutic writings come from India and China.The earliest Indian records are the vedas.,oldest being Rig Veda(about 3000 BC).Ayurveda was upaveda of Atharva Veda.
- Charaka attributed crimes against wisdom i.eprajnaparadha as the cause of all disease.Charaka described about 300 herbal drugs and classified them according to their effects ,mostly on symptoms into 50 groups.At the turn of the first milleniumBC,the treatise now known as CharakaSamhita which is the most important Ayurvedic text appeared.SushruthaSamhitha was also compiled during this period ,the development of surgery being spurred by the need to treat injuries sustained in warfare.
- India had entered golden age during this period with universities like Takshashila,Nalanda.
- During this period of intellectual flowering ,3 more famous ayurvedic texts appeared.AshtangaSangraha and AshtangaHridaya composed by Vagbhata and MadhavaNidhana
- Unani(the word means ‘greek’) was created by arabic physicians by combining Greek Medicine with Ayurveda,which they learned from texta translated into persian in the early years of modern era when the Sassanian dynasty controlled part of northern India.Akbar,a remarkably enlightened ruler personally ordered the compilation of all Indian medical knowledge,a project that was directed by his personal finance minister Raja todar Mal during the sixteenth century.
- The Chinese materiamedica’PanTsao’ was probably written in 2500(2735)B.C and contained many plant and metallic preparations and a few animal products.The earliest sources of Western Medicine come from egypt and the 2 kingdoms of assyria & babylonia.Th papyri were the first written account of medical experiences from egypt and date back to 1900 b.c.Discovered by George ebers in 1872 a d mentions about 700 herbal remedies including opium.
- Babylonian clay tablet(700 b c) mentions about 300 drugs.
- Modern medicine is considered to date from hippocrates ,a greek physician (450 bc) who introduced the concept of disease as a pathologic process and tried to organise the science of medicine on the basis of observation,analysis and deduction.He recommended judicious use of simple and efficacious drugs.
- PedaniusDioscorides(40-90 AD) - De MateriaMedica> 900 drugs, was in use until 1600 AD.Mercury, copper, lead topical application.Blood and excrements still used.Style of presentation followed by many later authors, even today's Physicians' Desk Reference
- Followed Hippocrates’ (460-355 BC) humoral basis of medicine.Advised against the use of human and animal excrements for therapy.He taught that drugs possessed certain fundamental effects (warming, cooling, drying, humidifying) which might be combined in different ways and also some specific actions (e.g. emetic, diuretic, etc.).Dogmatic approach hampered scientific growth for a 1000 years.
- Discovery of contagious and sexually transmitted diseases, neuropsychiatry, the idea of a syndrome in the diagnosis of diseases and hypothesized the existence of microrganisms.Principles for testing the effectiveness of new drugs which form the basis of modern clinical trials.
- Paracelsus(1493 – 1541)Travelled all over the known world in search of knowledge.Challenged Galenic medicine (burnt his books)Dose-response concept - “All things are poison and nothing is without poison, only the dose permits something not to be poisonous”.Used distilled oils as remedies. Used ether on animals.Mercury for syphilis.
- Till beginning of 19th century, the treatment of diseases withObnoxious remedies as flesh,excreta and blood of various animals James Gregory(1753-1821) heroic tx like blood letting ,drastic purgatives,lage dose of emetics.Disastrous resultsTx without ratoinal basis.Wrongly applied name to modern scientific medicine
- Outlines therapy of various ailments with drugs in very high dilutions
- His book “Formulary for preparation and use of many new remedies, such as nux vomica, morphine, prussic acid, strychnine, veratrine, quinine, emetine, iodine, etc” based on personal experience. His work was presented to the paris academy in 1809In the early 19thcentury,there was a rise of experimental pharmacology.physiologists performed pharmacological studies.Francois magendie studied the action of nux vomica(a strychnine containing plant drug) and showed that spinal cord was the site of its anticonvulsant action..{Foramen of Magendie, Magendie sign, Bell-Magendie law.Notorious vivisector. Firm believer in experiments.}}
- The alkaloid was named morphine,formorpheusgreek god of sleep. Friedrich Wilhelm Adam Sertürner(1783-1841)Isolated morphine from opium in 1804, the first ever alkaloid to be isolated from any plant.Investigated the effects of morphine by administering a high dose (100 mg) to himself and three friends. All experienced the symptoms of severe opium poisoning for several days.Suggested that cholera was caused by a living organism that could be killed by disinfectants or by boiling the water.
- Claude Bernard (1813-1878) - Magendie’s pupilDiscovered role of pancreatic juice in digestion, liver glycogen and its importance, and experiments on the vasomotor nerves.Effect of carbon monoxide gas on hemoglobin.Action of curare – nerves become inexcitable after curarization but muscles still react on direct stimulation.
- Lacking outside finding,he built up a lab at his own expense in the basement of his home.{Rudolf Buchheim(1820 –1879) Set up the first pharmacology laboratory in the world (1860, University of Dorpat in Estonia)Introduced the bioassay to pharmacology.As a student, he translated and edited Jonathan Pereira's Handbook of Pharmacology from English into German. Added his own chapter called Art der Wirkung (The Pharmacological Action).
- Son of a lativian forester.Obtained medical doctorate in 1866 with a thesis on measurement of chloroform in blood.Worked in Dorpat under Bucheim.He became a professor of pharmacology at university of Strassburg receiving government support. In 1872.In 1869, demonstrated that muscarine had a similar effect on the heart as electrical stimulation of the vagus nerve.In 46 years,he trained 120 pupils from 20 countries.In 1878,Classic textbook "Outline of Pharmacology" (1878).Discovered glucuronic acid.In 1885,Hypnotic properties of urethane.Was a major factor in the success of the German pharmaceutical industry upto WWII.
- Used amyl nitrite to treat angina pectoris - pain and discomfort of angina could be reduced by dilating the coronary arteries of patients.
- Extensively studied pituitary gland secretions.Isolated adrenaline (1897).Isolated crystalline insulin in 1926.
- Described urine formation in the kidneys (1917).1st experimental analysis of digitalis (1925).
- Pilocarpine is the chief alkaloid obtained from the leaflets of South American shrubs of the genus Pilocarpus. Although it was long known by the natives that the chewing of leaves of Pilocarpus plants caused salivation, the first experiments were apparently performed in 1874 by the Brazilian physician Coutinhou. Tthe alkaloid was isolated in 1875, and shortly thereafter the actions of pilocarpine on the pupil and on the sweat and salivary glands were described by Weber
- Physostigmine, also called eserine, is an alkaloid obtained from the Calabar or ordeal bean, the dried, ripe seed of Physostigmavenenosum, a perennial plant found in tropical West Africa. The Calabar bean once was used by native tribes of West Africa as an "ordeal poison" in trials for witchcraft, in which guilt was judged by death from the poison, innocence by survival after ingestion of a bean. A pure alkaloid was isolated by Jobst and Hesse in 1864 and named physostigmine. The first therapeutic use of the drug was in 1877 by Laqueur, in the treatment of glaucoma, one of its clinical uses today. {Accounts of the history of physostigmine have been presented by Karczmar (1970) and Holmstedt (2000)}
- The naturally occurring muscarinic receptor antagonists atropine and scopolamine are alkaloids of the belladonna (Solanaceae) plantsobscure and often prolonged poisoning, prompting Linnaeus to name the shrub Atropa belladonna, after Atropos, the oldest of the three Fates, who cuts the thread of life. The name belladonna derives from the alleged use of this preparation by Italian women to dilate their pupils; modern-day fashion models are known to use this same device for visual appeal. Atropine (d,l-hyoscyamine) also is found in Daturastramonium (Jamestown or jimson weed). Scopolamine (l-hyoscine) is found chiefly in Hyoscyamusniger(henbane). In India, the root and leaves of jimson weed were burned and the smoke inhaled to treat asthma. British colonists observed this ritual and introduced the belladonna alkaloids into western medicine in the early 1800s.Accurate study of the actions of belladonna dates from the isolation of atropine in pure form by Mein in 1831.Bezold and Bloebaum (1867) showed that atropine blocked the cardiac effects of vagal stimulation, and Heidenhain (1872) found that it prevented salivary secretion produced by stimulation of the chorda tympani.
- Curare is a generic term for various South American arrow poisonsparalyzing wild animals used for food; death results from paralysis of skeletal muscles. Following the pioneering work of the scientist/explorer von Humboldt in 1805, the botanical sources of curare became the object of much field research. The curares from eastern Amazonia come from Strychnos speciesGriffith and Johnson reported the first trial of curare for promoting muscular relaxation in general anesthesia in 1942King established the essential structure of tubocurarine in 1935
- Ergot is the product of a fungus (Clavicepspurpurea) that grows on rye and other grainsas 600 B.C., an Assyrian tablet alluded to a "noxious pustule in the ear of grain.Middle Ages, describing strange epidemics in which the characteristic symptom was gangrene of the feet, legs, hands, and arms. In severe cases, extremities became dry and black, and mummified limbs separated off without loss of blood. Limbs were said to be consumed by the holy fire, blackened like charcoal with agonizing burning sensations, the disease was called holy fire or St. Anthony's fire in honor of the saint at whose shrine relief was said to be obtained. The relief that followed migration to the shrine of St. Anthony was probably real, for the sufferers received a diet free of contaminated grain during their sojourn at the shrine.dramatic abortive effect of ergot ingested during pregnancy. The active principles of ergot were isolated and chemically identified in the early 20th century
- A bane of childhood since the time of the ancient Egyptians, castor oil (PURGE, NEOLOID, others) is derived from the bean of the castor plant, Ricinuscommunis. The castor bean is the source of an extremely toxic protein, ricin, as well as the oil (chiefly of the triglyceride of ricinoleic acid). The triglyceride is hydrolyzed in the small bowel by the action of lipases into glycerol and the active agent, ricinoleic acid, which acts primarily in the small intestine to stimulate secretion of fluid and electrolytes and speed intestinal transit. When taken on an empty stomach, as little as 4 mL of castor oil may produce a laxative effect within 1-3 hours; however, the usual dose for a cathartic effect is 15-60 mL for adults. Because of its unpleasant taste and its potential toxic effects on intestinal epithelium and enteric neurons, castor oil is seldom recommended
- HistoryThe beneficial properties of the Madagascar periwinkle plant, Catharanthusroseus (formerly called Vincarosea), Periwinkle extracts attracted interest because of their hypoglycemic effects in diabetes. Purified alkaloids, including vinblastine and vincristine, caused regression of an acute lymphocytic leukemia in mice and were among the earliest clinical agents for treatment of leukemias, lymphomas, and testicular cancer. A closely related derivative, vinorelbine, has important activity against lung and breast cancer
- William withering (1785)He explained the therapeutic effect of digitalis in relieving edema on cardiac decompensationHis report was titled The foxglove and an account of its medicinal properties with practical remarks and dropsy
- 1891-Murray first treated with extact of sheep throid glandParry saw his first patient in 1786 but did not publish his findings until 1825. Graves reported the disorder in 1835 and Basedow in 1840. , Murray first treated a case of hypothyroidism by injecting an extract of sheep thyroid gland, later shown to be fully effective when given by mouth. The successful treatment of thyroid deficiency by administering thyroid extract was an important step toward modern endocrinology
- Studies on the mechanism of the development of goiter began with the observation that rabbits fed a diet composed largely of cabbage often developed goiters. Later, two pure compounds were shown to produce goiter: sulfaguanidine, a sulfanilamide antimicrobial used to treat enteric infections, and phenylthiourea.Investigation of the effects of thiourea derivatives revealed that rats became hypothyroid despite hyperplastic changes in their thyroid glands that were characteristic of intense thyrotropic stimulation.The therapeutic possibilities of such agents in hyperthyroidism were evident, and the substances so used became known as anti-thyroid drugs
- 3 distinct periods1.Great antiquity;only substances capable of curing infection were natural plant products2.Era of synthesis3.Return to natural plant products,plants of lower order i.e bacteria ndmoulds forming antibiotics
- {}Quinine nd emetine till early yrs of this century. 1619-Successful treatment of Malaria with an extract of Cinchona bark.Pt being wife of spanish governor of peru1633-augustininan monk in peru wrote about the power of cinchona bark as a beverage that could cure feversIn 1679The jesuits brought this peruvian bark to europeRobert talbor who was an english apothecary’s assistant used his ‘malaria cure’ to treat king charlesISOLATION OF QUININE -1820
- 1619-Successful treatment of Malaria with an extract of Cinchona bark.Pt being wife of spanish governor of peru1633-augustininan monk in peru wrote about the power of cinchona bark as a beverage that could cure feversIn 1679The jesuits brought this peruvian bark to europeRobert talbor who was an english apothecary’s assistant used his ‘malaria cure’ to treat king charlesISOLATION OF QUININE -1820
- drug invention became more allied with synthetic organic chemistry Study of dyeinteractions stimulated Paul Ehrlich to postulate the existence of chemical receptors in tissues that interacted with and "fixed" the dyes. Ehrlich thought that unique receptors on microorganisms or parasites might react specifically with certain dyes and that such selectivity could spare normal tissue. Ehrlich's work culminated in the invention of arsphenamine in 1907, which was patented as "salvarsan," suggestive of the hope that the chemical would be the salvation of humankind. This arsenic-containing compound and other organic arsenicals were invaluable for the chemotherapy of syphilis until the discovery of penicillin{Almost entirely due to research in germany.successors produced germanin for trypanosomiasis.Common view then- protozoa were susceptible chemotherapeutic attack but not bacteria.treponemata class apart as susceptible to organic arsenicals.}
- Gerhard Johannes Paul Domagk(1895– 1964). During that period and thanks to the work of Gerhard Domagk, another dye, prontosil (the first clinically useful sulfonamide) was shown to be dramatically effective in treating streptococcal infections.Screen to test the survival of mice inoculated with Streptococcus pyogenes.Fritz Mietzsch, Josef Klarer produced Prontosilrubrum (1932).Nobel Prize in 1939.
- 1935 – 100% success rate; treated his own daughter.Sulfanilamide was the sole active moiety.ELIXIR SULFONILAMIDE DISASTER70 deaths from ethylene glycol – Food and Drug Act.Heinrich Hoerlein – patented sulfanilamide (1909).Jacob and Heidelberger (1915).
- Sir Alexander Fleming (1881–1955)Lysozyme – 1923Penicillin – 28 September 1928.Described its basic properties but never performed an animal experiment with iatrogenic infection.Couldn’t purify - stopped studying it in 1
- It was florey who demonstrated it was a chemotherapeutic agent of unexampled potency
- In 1939, he joined Howard Florey to investigate natural antibacterial agents produced by microorganisms – revisited Fleming’s work..Fleming, Florey and Chain were awarded the Nobel Prize in 1945{Norman Heatley(1911–2004).Albert Alexander – first patient.Fleming took a sample and successfully treated streptococcal meningitis – famous overnight.Merck & Co (1942).Deep-tank fermentation by Margaret Hutchinson.}
- Had studied actinomycetes for many years.1940-1952 isolated 10 antibiotics,).3 had practical applications: actinomycin (1940), streptomycin (1944) and neomycin (1949
- Effective in miliary tuberculosis, tubercular meningitis, pneumonic plague, brucellosis, typhoid fever, and tularemia (1946).His work led to the discovery of >20 antibiotics (a word which he coined). Proceeds earned from the licensing of his patents used to establish Waksman Institute of Microbiology.Nobel Prize for Waksman in 1952.Albert Schatz brought litigation against Waksman, requesting recognition as streptomycin's co-discoverer and a portion of streptomycin royalties.Discovery of Artemisinin (Qinghaosu)Artemisia annua – Chinese materiamedica (200 BC).Artemisinin (1972) – TuYouyou (Project 523).
- It was originally isolated from canine liver cells, hence its name (hepar or "ήπαρ" is Greek for "liver"). Heparin's discovery can be attributed to the research activities of Jay McLean and William Henry Howell.In 1916, McLean, a second-year medical student at Johns Hopkins University, was working under the guidance of Howell investigating procoagulant preparations, when he isolated a fat-soluble phosphatide anticoagulant in canine liver tissue. In 1918, Howell coined the term 'heparin' for this type of fat-soluble anticoagulant..A posthumous attempt to nominate McLean for a Nobel Prize failed.[citation needed]
- hemorrhagic disorder in cattle ingestion of spoiled sweet clover silage, Campbell and Link, in 1939, identified the hemorrhagic agent as bishydroxycoumarin (dicoumarol). In 1948, a more potent synthetic congener was introduced as an extremely effective rodenticide; the compound was named warfarin as an acronym derived from the name of the patent holder, Wisconsin Alumni Research Foundation (WARF). Warfarin's potential as a therapeutic anticoagulant was recognized butnot widely accepted, partly due to fear of unacceptable toxicity.1951, an army inductee uneventfully survived an attempted suicide with massive doses of a preparation of warfarin intended for rodent control. Since then, these anticoagulants have become a mainstay for prevention of thromboembolic disease
- In 1929, Dam observed that chickens fed inadequate diets developed a deficiency disease characterized by spontaneous bleeding and reduced prothrombin in the blood. Subsequently, Dam and coworkers (1935, 1936) found that the condition could be alleviated rapidly by feeding an unidentified fat-soluble substance, named vitamin K (Koagulation vitamin) by Dam. {.}
- Derived from the chemical ASAAcetylspirsaure in germanThough pure aspirin was manufactured and marketed in 19thcentury,its use stretches back to antiquityWillow bark extract-used to treat fever,inflammation1853-charles gerhardt reacted acetyl chloride with sodium salicylate. Similar properties were attributed to potions from meadowsweet (Spiraeaulmaria), from which the name aspirin is derived. Salicin was crystallized in 1829 by Leroux, and Pina isolated salicylic acid in 1836. In 1859, Kolbe synthesized salicylic acid, and by 1874, it was being produced industrially. It soon was being used for rheumatic fever, gout, and as a general antipyretic. However, its unpleasant taste and adverse GI effects made it difficult to tolerate for more than short periods. In 1899, Hoffmann, a chemist at Bayer Laboratories, sought to improve the adverse-effect profile of salicylic acid (which his father was taking with difficulty for arthritis). Hoffmann came across the earlier work of the French chemist, Gerhardt, who had acetylated salicylic acid in 1853, apparently ameliorating its adverse-effect profile, but without improving its efficacy, and therefore abandoned the project. Hoffmann resumed the quest, and Bayer began testing acetylsalicylic acid (ASA) in animals by 1899—the first time that a drug was tested on animals in an industrial setting—and proceeded soon thereafter to human studies and the marketing of aspirin.
- Nitroglycerin was first synthesized in 1846 by Sobrero, who observed that a small quantity placed on the tongue elicited a severe headacheuntil Alfred Nobel devised a process to stabilize the nitroglycerin and patented a specialized detonator in 1863In 1857, T. Lauder Brunton of Edinburgh administered amyl nitrite, a known vasodepressor, by inhalation and noted that anginal pain was relieved within 30- 60 seconds, William Murrell surmised that the action of nitroglycerin mimicked that of amyl nitrite and established the use of sublingual nitroglycerin for relief of the acute anginal attack and as a prophylactic agent to be taken prior to exertion. , Alfred Nobel himself was prescribed nitroglycerin by his physicians when he developed angina in 1890The importance of NO as a signaling molecule in the cardiovascular system and elsewhere was recognized by the awarding of the 1998 Nobel Prize in medicine/physiology to the pharmacologists Robert Furchgott, Louis Ignarro, and FeridMurad
- Statins were isolated from a mold, Penicilliumcitrinum, and identified as inhibitors of cholesterol biosynthesis in 1976 by Endo and colleaguesBrown and Goldstein established that statins act by inhibiting HMG-CoA reductase. The first statin studied in humans was compactin, renamed mevastatin, which demonstrated the therapeutic potential of this class of drugs. Alberts and colleagues at Merck developed the first statin approved for use in humans, lovastatin (formerly known as mevinolin), which was isolated from Aspergillusterreus.
- He , administered a very large dose (100 mg) to himself and three friends /All experienced the symptoms of severe opium poisoning for several days. Although humans are no longer used as laboratory animals, they are essential in clinical pharmacology
- Crawford Long, a physician in rural Georgia, first used ether anesthesia in 1842. William T.G. Morton, a Boston dentist and medical student, performed the first public demonstration of general anesthesia using diethyl ether in 1846 when Gilbert Abbott underwent surgical excision of a neck tumor at the Massachusetts General Hospital in the operating room now known as "the ether dome." Ether was the ideal "first" anesthetic.
- The Scottish obstetrician James Simpson introduced chloroform in 1847. Chloroform had a more pleasant odor than ether and was nonflammable. It was, however, a hepatotoxin and a severe cardiovascular depressant, which limited its ultimate utiIn 1868, Edmond Andrews, a Chicago surgeon, described the co-administration of nitrous oxide and oxygen, a practice that continues to this day.
- In 1935, Lundy demonstrated the clinical usefulness of thiopental, a rapidly acting agent that could be administered intravenously; however, anesthetic doses of thiopental resulted in serious depression of the circulatory, respiratory, and nervous systems.
- In 1956 came the introduction of halothane, a nonflammable volatile halogenated alkane that quickly became the dominant anesthetic.
- Cocaine occurs in abundance in the leaves of the coca shrub (Erythroxylon coca). For centuries, Andean natives have chewed an alkali extract of these leavesfor its stimulatory and euphoric actions. Cocaine was first local anaesthetic isolated in 1860 by Albert Niemann.Carl Koller introduced cocaine into clinical practice in 1884 as a topical anesthetic for ophthalmological surgery.
- Dale and Laidlaw subjected histamine to intensive pharmacological study (Dale, 1953), discovering that it stimulated a host of smooth muscles and had an intense vasodepressor action. Importantly, they observed that when a sensitized animal was injected with a normally inert protein, the immediate responses closely resembled those of poisoning by histamine. These observations anticipated by many years the finding that endogenous histamine contributes to immediate hypersensitivity reactions and to responses to cellular injury. Best and colleagues (1927) isolated histamine from fresh samples of liver and lung, thereby establishing it as a natural constituent of mammalian tissues, hence the name histamine after the Greek word for tissue, histos.{ The presence of histamine in tissue extracts delayed the acceptance of the discovery of some peptide and protein hormones (e.g., gastrin) until the technology for separating the naturally occurring substances was sufficiently advanced (Grossman, 1966).}
- Lewis and colleagues (Lewis, 1927) proposed that a substance with the properties of histamine ("H substance") was liberated from the cells of the skin by injurious stimuli, including the reaction of antigen with antibodyReceptorsH1(Ash&Schild,1966)H2(Black et al,1972)H3(Arrang et al 1987)H4(Hough 2001)
- The isolation and identification of the adrenal steroids by Reichstein and Kendall and the effects of these compounds on carbohydrate metabolism (hence the term glucocorticoids) culminated with the synthesis of cortisone, the first pharmacologically effective glucocorticoid to become readily available.
- Shortly after synthetic cortisone became available, Hench and colleagues demonstrated its dramatic effect in the treatment of rheumatoid arthritisHench, Kendall and Reichstein received Nobel Prize in 1950
- .PGs, LTs, and related compounds are called eicosanoids, from the Greek eikosi ("twenty") Precursor essential fatty acids contain 20 carbons and three, four, or five double bonds: 8,11,14-eicosatrienoic acid (dihomo- -linolenic acid), 5,8,11,14-eicosatetraenoic acid [AA; Figure 33–1], and 5,8,11,14,17-eicosapentaenoic acid (EPAIn 1930, Kurzrok and Lieb, two American gynecologists, observed that strips of uterine myometrium relax or contract when exposed to semen.
- Subsequently, Goldblatt in England and von Euler in Sweden reported independently on smooth muscle-contracting and vasodepressor activities in seminal fluid and accessory reproductive glands. In 1935, von Euler identified the active material as a lipid-soluble acid, which he named prostaglandin, inferring its origin in the prostatic gland.
- Samuelsson, Bergström, and their colleagues elucidated the structures of prostaglandin E1 (PGE1) and prostaglandin F1 (PGF1 ) in 1962. In 1964, Bergström and coworkers, and van Dorp and associates, independently achieved biosynthesis of PGE2 from arachidonic acid (AA).Discovery of TxA2, PGI2, and the LTs followed. Vane, Smith, and Willis reported that aspirin and NSAIDs act by inhibiting prostaglandin biosynthesis (Vane, 1971). This remarkable period of discovery linked the Nobel Prize of von Euler in 1970 to that of Bergström, Samuelsson, and Vane in 1982
- . The Austrian physiologist Haberlandt then produced temporary sterility in rodents in 1927 by feeding ovarian and placental extracts—a clear example of an oral contraceptive!In the 1950s, Pincus, Garcia, and Rock found that progesterone and 19-norprogestins prevented ovulation in women. Ironically, this finding grew out of their attempts to treat infertility with progestins or estrogen-progestin combinationsClinical studies in the 1950s in Puerto Rico and Haiti established the virtually complete contraceptive success of the norethynodrel/mestranol combination.
- Sir Frederick Grant Banting, (1891 –1941) was a Canadian medical scientist & doctor Charles Best February (1899 – 1978)was his assistant Known for the discovery of the e insulin—one of the most significant advances in medicine, enabling an effective treatment for diabetes. In 1921, Banting traveled to Toronto to visit J.J.R. Macleod at University of Toronto, where he used his lab for this discovery.
- J.J.R McCleod also supplied Banting with ten dogs to experiment on, and two medical students, Best and Clark Noble, to use as lab assistants.Since Bantingonly required one lab assistant, Best and Noble flipped a coin & Best won the coin toss, and took the first shift as Banting's assistant. Loss of the coin toss was very unfortunate for Noble as Best worked with Banting for the entire summer (and eventually shared half his Nobel Prize money and a large part of the credit for the discovery of insulin with the winner of the toss) In 1923, the Nobel Banting and J.J.R. Macleod won the Nobel Prize in Medicine for the discovery of insulin, & Nobel prize committee ignored Best. This incensed Banting, who voluntarily shared half of his award money with Best
- . Lewandowsky and Langley independently noted the similarity between the effects of injection of extracts of the adrenal gland and stimulation of sympathetic nerves. Langley suggested that effector cells have excitatory and inhibitory "receptive substances" and that the response to epinephrine depended on which type of substance was present.
- In 1905, T. R. Elliott, while a student with Langley at Cambridge, postulated that sympathetic nerve impulses release minute amounts of an epinephrine-like substance in immediate contact with effector cells. He considered this substance to be the chemical step in the process of transmission. He also noted that long after sympathetic nerves had degenerated, the effector organs still responded characteristically to the hormone of the adrenal medulla.
- In 1914, Dale investigated the pharmacological properties of ACh and other choline esters and distinguished its nicotine-like and muscarine-like actions. this drug reproduced the responses to stimulation of parasympathetic nerves, he introduced the term parasympathomimetic to characterize its effects. Dale proposed that an esterase in the tissues rapidly splits ACh to acetic acid and choline, thereby terminating its action.{from ergot – provided support to Elliot’s theory (1910).
- The studies of Loewi, begun in 1921, provided the first direct evidence for the chemical mediation of nerve impulses by the release of specific chemical agents.The legend tells that he had the idea of the experiment in a dream and that he ran to the lab in the middle of the night Loewi stimulated the vagus nerve of a perfused (donor) frog heart and allowed the perfusion fluid to come in contact with a second (recipient) frog heart used as a test object. The recipient frog heart was found to respond, after a short lag, in the same way as the donor heart. It thus was evident that a substance was liberated from the first organ that slowed the rate of the second. Loewi referred to this chemical substance as Vagusstoff ("vagus substance," "parasympathin"); subsequently, Loewi and Navratil presented evidence to identify it as ACh. Loewi also discovered that an accelerator substance similar to epinephrine and called Acceleranstoff was liberated into the perfusion fluid in summer, when the action of the sympathetic fibers in the frog's vagus, a mixed nerve, predominated over that of the inhibitory fibers.{ Feldberg and Krayer demonstrated in 1933 that the cardiac "vagus substance" also is ACh in mammals
- Antimetabolite theory of mechanism of action of sulfa drugs to inhibit neoplastic cells.1951, 6-mercaptopurine and 6-thioguanine.Azathioprine.Developed methotrexate, pyrimethamine and trimethoprim. Promoted combination therapy.Developed the first antiviral drug acyclovir in 1970.Allopurinol for gout.James Black, Gertrude Elion (no doctoral degree) and George Hitchings shared the Nobel Prize in 1988.
- Obtained MD degree from Cambridge University in 1908 In 1921 : Appointed as the first professor of pharmacology in newly established Calcutta School of Tropical Medicine and parallely headed the Department of pharmacology at he Calcutta medical college From 1941 to 1957: he was Director of the Drug Research Lab at Srinagar
- OBTAINED FROM THE ROOT OF RAUWOLFIA SERPENTINAPURIFIED ALKALOID EXTRACTED IN 1952USED TO TREAT HYPERTENSION,SNAKEBITE,CHOLERA CONTRIBUTIONS :He 1st introduced and done systematic study of RauwolfiaserpentinaHad a major contribution in establishing the 1st National Drug Research Institute of India, Lucknow ( presently known as Central Drug Research Institute, CDRI) He pioneered research on herbal drugs in India Indian Posts & Telegraph department has issued a commemorative stamp in his honor.
- Discovered the role of phosphocreatine and ATP.He developed a method to synthesize folic acid.Developed methotrexate and hetrazan.Under him, Benjamin Duggar discovered the world's first tetracycline antibiotic, aureomycin (in 1945).He never marketed his work or gave interviews or went on lecture tours.George Hitchings - "Some of the nucleotides isolated by Subbarao had to be rediscovered years later by other workers because Fiske, apparently out of jealousy, did not let Subbarao's contributions see the light of the day."
- The story of ipecacuanha, derived from the plant Cephaelis, is a fascinating one. It was discovered in Brazil in the 1600s and then transported to Paris in the latter part of the same century. It was used there by the physician Helvetius on various members of the French royal court to treat the flux (dysentery) with some success. Later, in the eighteenth century, it was taken up by the physician and privateer Thomas Dover and became, with opium, a fundamental constituent of his celebrated powder, which was used widely to treat fevers and agues for the next 200 years. Progress was then delayed until the early 1800s when the School of Chemistry at Paris established that the dried root of ipecac contained two powerful alkaloids, emetine and cephaeline, that consistently caused vomiting and diarrhoea. The discovery of the pathogenic amoeba, Entamoebahistolytica, in the latter part of the nineteenth century, allowed a distinction to be made between the two main forms of dysentery (amoebic and bacillary). Emetine was shown to be active against the amoebic form of dysentery but ineffective against that caused by bacteria. Ipecacuanha, its root and the pure alkaloid emetine have now been abandoned on the grounds of toxicity. They have been replaced by safer, more effective compounds. Nevertheless, they deserve an honoured place in the history of medicine, especially in the search for an effective treatment for amoebic dysentery.
- PharmacologyThis shrub has a number of traditional medicinal uses.[citation needed]Vasicine, the active compound, has been compared to theophylline both in vitro and in vivo. Another, vasicinone, showed bronchodilatory activity in vitro but bronchoconstrictory activity in vivo.[citation needed] It is probably biotransformed in vivo, causing bronchoconstriction.[citation needed] Both the alkaloids in combination (1:1) showed pronounced bronchodilatory activity in vivo and in vitro.[citation needed] Vasicine also exhibited strong respiratory stimulant activity, moderate hypotensive activity and cardiac-depressant effect;[citation needed] vasicinone was devoid of these activities. The cardiac-depressant effect was significantly reduced when a mixture of vasicine and vasicinone was used. Vasicinone (dl-form) showed no effect on the isolated heart, but probably the l-form is a weak cardiac stimulant. Clinical trials of a commercial drug containing vasicinone and vasicinone have not revealed any side effects while treating bronchial asthma.[1][verification needed]Cultural referenceIt is the Unofficial provincial flower of the Punjab province of Pakistan
- http://en.wikipedia.org/wiki/Hydnocarpus_wightiana