History of pharmacology part 1

Dr. Chandini Rao
PG in dept of pharmacology
FMMC

1. HISTORY OF PHARMACOLOGY - I Dr. Chandini Y Rao Moderator – Dr. Nicole Pereira 1

2. What is Pharmacology? ‘ Study of substances that interact with living systems through chemical processes, especially by binding to regulatory molecules and activating or inhibiting normal body processes. ’ pharmacon = active principle logos = a discourse or treatise Science that deals with drugs 2

3. What is a drug? Synthetic chemicals, chemicals obtained from plants or animals, or products of genetic engineering . Substance must be ‘administered’ (rather than released by physiological mechanisms). What is a medicine? Chemical preparation, which usually but not necessarily contains 1 or more drugs, administered with the intention of producing a therapeutic effect. Usually contains other substances (excipients) besides the active drug, to make them more convenient to use. 3

4. History.. Intro – Born as a science – mid 19 th century. Long before that – use of natural substances eg . plants, animals, minerals.. (some of are still used today) But no scientific basis. Eg . Concoctions of worms, dung, urine & moss from a dead man’s skull. 4

5. Homeopathy (similar suffering) ‘like cures like’ ‘dilution enhances potency of drugs’ Dilutions of 1:10 60 (equivalent to 1 molecule in a sphere the size of orbit of Neptune!) Dr. Samuel Hahnemann 5

6. Allopathy (other suffering) Blood letting, emetics and purgatives – many deaths To introduce ‘other suffering’ to relieve pain/suffering. James Gregory (1735-1821) Treatment of malaria – Cinchona bark Calomel ( mercurous chloride) 6

7. Reason for failure – Poor knowledge of functioning of the body. lack of experimentation and observation. Close relationship between religion and treatment of diseases. (drugs were thought to be magical!) End of 17 th century – observation and experimentation began to replace theorizing. * Materia medica – precursor to pharmacology Lack of methods for testing hypotheses. 7

8. In the late 18 th & early 19 th centuries : Francois Magendie & Claude Bernard - Experimental Physiology & Pharmacology. Simultaneous developments in botany, zoology, chemistry & physiology. New drugs  New challenges  establishment of Pharmacology. 8

9. 9

10. Ancient civilizations and their therapeutics Indian Chinese Roman Greece Persian Egypt 10

11. India Vedas – earliest records. Rig veda (3000 BC) Charaka – Father of Indian medicine - along with Sushruta & Vagbhata described about 300 herbal preparations (50 grps ). Ayurveda (2500 BC) – ‘Science of life’ 11

12. Ayurveda Based on 2 treatises : Charaka Samhita – medical, > 650 drugs (animal, plants and mineral origins) Sushruta Samhita - surgical Lord Dhanvantari (Physician of the Gods) - Father of Ayurveda - natural remedies - antiseptic properties of turmeric - preservative properties of salt 12

13. Disturbances in 4 elements – Wind ( Vayu ), Bile ( Pitta ), Phlegm ( Kapha ) & Blood ( Rakta ), responsible for disease. (4 humors of Greek medicine) Plant-based treatments – roots, leaves, fruits, bark or seeds Animal products – milk, bones & gall stones. (fats) Minerals – sulphur, arsenic, lead, copper sulphate & gold. 13

14. Alcoholic beverages ( Madya ) Purified opium – diarrhoea & dysentery, increasing sexual & muscular abilities. Oils – head massage, applied on affected areas. Still widely practiced today 14

15. 15 Siddha system Tamil Nadu Siddhars – Spiritual adepts with supernatural powers. Agasthya – Father of Siddha medicine. Palm leaf manuscripts A healthy  soul  can only be developed through a healthy body. Herbal products, inorganic substances & animal products.

16. 16 Based on mode of application – Internal medicine – oral route External medicine – nasal/eye/ear drops & leech application Still practiced in Tamil Nadu – jaundice. BSMS – Bachelor in Siddha Medicine & Surgery.

17. Unani Persio -Arabic traditional medicine, created by Arabic physicians by combining Greek medicine with Ayurveda. Mughal India Similar to Ayurveda. India – Egg oil ( Roghan Baiza Murgh ) & Almond oil ( Roghan Badaam Shirin ) for hair care. 17

18. Therapies – Ilaj-Bil-Tadbeer wa Ilaj-Bil-Ghiza ( Regimenal therapy) : Cupping therapy ( Hijamat ) Aroma therapy ( Shamoomat ) Ilaj-Bil-Advia (Pharmacotherapy) Ilaj-Bil-Yad (Surgery) Currently practised in South Asia & modern day Central Asia. 18

19. China ‘ Pan Tsao ’ - Chinese materia medica (~2500 BC) - plant & metallic preparations, few animal products. - 1 st mention of the medical/ euphoriant uses of Cannabis. ‘ Nei Chang’ – Acupuncture. Yin (female) & Yang ( male) Extensive pharmacy - 2000 items, 16000 remedies Pulverized seahorses for goiter Snake meat for eye ailment Octopus ink with vinegar for heart disease Elephant skin for sores 19

20. Traditional Chinese medicine still used today – Ginseng root 5000 yrs ag0 – Northern China (Manchuria) ‘Man root’ Energy drinks or herbal teas (Ginseng coffee) Folk medicine – aphrodisiac or stimulant treatment Snake oil Liniment – joint pain Higher eicosapentanoic acid No scientific basis 20

21. Gingko biloba Symbol of longevity & vitality Seed, root & leaves – asthma, bronchitis & leukorrhoea Seahorse ( Hai Ma ) Originally used for goitre. Asthma, throat infections, insomnia & abdominal pain Powerful aphrodisiac Skin infections & sores. 21

22. Egypt ‘ Ebers Papyrus’ – Egyptian materia medica (1550 BC) - 800 prescriptions. - ‘Recipes’ for treatment of diseases - beer, turpentine, berries , poppy, lead, salt & crushed precious stones etc George Ebers (1872 AD) – 700 herbal prescriptions, including opium. 3 different interacting branches : Physicians – used internal & external remedies for cure (lettuce & onions to hippopotamus fat & human excreta!) Surgeons Sorcerers or exorcists 22

23. Imhotep – ‘God of Medicine’ Introduced simple surgeries Diagnosed over 200 diseases Treated TB, gallstones, appendicitis, gout and arthritis Position of vital organs and circulation of blood 23

24. Atropine extracts - Cleopatra Atropine – species: ‘Belladonna’ (beautiful women) deadly nightshade, to dilate pupils Roman empire & Middle ages – prolonged poisoning Atropa belladonna ( Atropos ) Used by ancient Hindus to treat asthma. Introduced to western medicine in early 1800s 24

25. Babylo -Assyrian civilization 1 of the earliest sources of western medicine . S orcerers ( ashipu ) & Physicians ( asu ). Ritual incantations, herbal remedies & physical therapy 25

26. 26 Clay tablets – lists conditions, remedies & prognoses ‘ Sumerian clay tablet’ (2150 BC) Possibly the 1 st to regulate medicine by law - ‘Hammurabi code’

27. Greece 4 humors – blood, phlegm, yellow bile & black bile. Hippocrates (400BC) – ‘ Father of modern medicine ’ introduced the concept of disease as a pathologic process. Observation, analysis & deduction did not believe in magical remedies Medicatrix naturae – ‘healing power of nature’ recommended judicious use of simple & efficacious drugs. Hippocratic oath Hippocratic corpus – 70 volumes haemorrhoid & polyp removal 27

28. Galen (460-355 BC) C ontributed greatly to Ancient Greek Medicine . Elevated Hippocratic humoral basis of medicine. D rugs possessed certain fundamental effects (warming, cooling, drying, humidifying ) Dogmatic approach  ill health & many deaths hampered scientific growth for a 1000 years. P harmaceutical works - used for reference for centuries 28

29. Temple medicine – Spiritual side of healing. P atients attended 1 of the many temples ( asklepieia ) Asklepios – God of Physicians. ‘dream drug’ or ‘dream surgery’ while asleep. 29

30. Pedanius Dioscorides – Greek physician De Materia Medica (“Regarding medical matters”) preparation, properties & testing of drugs. 1000 plants & minerals basis for the Western pharmacopeia through the 19th century. Mercury, copper, lead topical application . Anaesthesia – ‘absence of sensation’ wine from mandragora 30

31. Persia Avicenna (980-1037) Canon Medicina – medical bible Supplanted Galen’s work – Arab world & then western Europe. Contagious nature of TB D issemination of diseases by water & soil . use of cautery instead of knife in surgeries 31

32. The Middle Ages Roman medical regulations disappeared. Medical care taken over by the Church. Medicine became a matter of faith & prescriptions became prayers . The greek concept of 4 humors - basis of all diagnoses & treatments . Cupping , blood letting, leeches, medications & diet – R oman, with ritual added Most prescriptions - multiple ingredients. 32

33. Black death One of history’s greatest tragedies. ‘God’s punishment for the sinfulness of mankind’ ‘ pestinential atmosphere’. Huge fires of aromatic wood lit, bells rung, guns fired, birds made to fly around rooms. Mass hysteria – persecution of Jews 1894 – plague bacilli identified - disease of black rats, spread by fleas 33

34. The Renaissance & Enlightenment “Re-birth” 15 th & 16 th century. Paracelsus - ‘ Grand father of Pharmacology’ Challenged Galenic medicine Dose-response concept: ‘ Poison is in everything, and no thing is without poison. The dosage makes it either a poison or a remedy. use of chemicals and minerals (zinc) in medicine. 34

35. Coined – ‘Alcohol’ Distilled oils as remedies. Mercury, antimony, sulphur & potassium salts. “Laudanum” (opium dissolved in alcohol) - effective painkiller. 35

36. Jenner’s breakthrough Discovery of small pox vaccine in 1796. Studied dairy workers for 20 yrs. 14 th May 1796 – inoculated an 8 yr old boy with cowpox & 6 wks later with small pox - proved to be immune. By 1801: 100,000 people in Britian – vaccinated Spain, America & rest of the world. Eradicated by 1975. 36

37. 37

38. The story of ASPIRIN (the tree & the flower) 400 BC: Hippocrates – bark & leaves of the Willow tree - reduces pain & fever. 1820s: Johann S. F. (Swiss pharmacist) - extracts from the leaves of Spirea Ulmaria (meadowsweet) - pain reliever 1835: Karl Jacob Lowig (German chemist) - ‘ Spirsaure ’ (acid)  Salicylic acid 38

39. 1853: Karl Friedrich Gerhardt - discovered t he molecular structure. - tried to eliminate ‘painful irritation of the stomach lining’ - time-consuming – abandoned the drug. 1895: Herr Hoffman – arthritis Felix (chemist at the Bayer drug plant) - Acetylsalicylic acid - also reduced fevers & inflammation (along with pain) 1899: Hoffmann & Dreser – Aspirin ( ‘A’ for acetyl, ‘ spir ’ for Spirea & ‘in’ to round it off) 39

40. US – marketed aspirin as ‘Bayer’ 1826: 2 Italians - ‘ Salicin ’ (active ingredient) from willow bark  Salicylic acid. - obtained from both the willow & meadowsweet. (now made from ‘phenol’) 1971: British researchers – mechanism of action ‘ Prostaglandins ’ Aspirin – NSAIDs 1980 – superceded by Paracetamol 40

41. OPIUM ‘The miracle cure that addicted millions’ Sumerian writings (4000 yrs old) – hul gil ‘joy plant’ Ancient Egyptian, Persian, I ndian , Greek and Roman medicine 16 th century – established in Western European medicine. Paracelsus – ‘stone of immortality’ - ‘Laudanum’ Addiction – rare. 41

42. Opium wars - British imported opium from Turkey - British East India company exported to China in exchange for silver - First opium war(1840-42) - Second (1857- 60) Cholera, dysentery, toothache, flatulence, insanity and menopause Friedrich Serturner – Morphine (1805) ( Morpheus = the Greek god of sleep) 42

43. US – Importation of crude opium grew  patent medicines 1900 – 250,000 addicts in the US. 19 th century – Opium concern Hypodermic syringe – exacerbated morphine & codeine abuse 43

44. 1898 – Dionin (semisynthetic morphine derivative) Heroin (diacetylmorphine) – ‘heroic drug’; safer 1860 – Restrictive legislation 1 st passed in Britian 1909 – smoking opium prohibited in the US 44

45. Pioneers in Pharmacology 45

46. Francois Magendie (1783-1855) Early 19 th century French Physiologist. Pioneer of Experimental P harmacology. Studied action of nux vomica (Strychnine) spinal cord – site of action. Introduced morphine, codeine, quinine & strychnine. Foramen of Magendie 46

47. Claud Bernard (1813 – 1878) Magendie’s student. Father of Modern Experimental Medicine 1842 - arrow poison Curare specifically acts at the neuromuscular junction. Pancreatic juice, liver glycogen & its importance. Existence of Vasomotor system – Vasodilatation & Vasoconstriction. 47

48. Oswald Schmiedeberg (1838 – 1921) Father of Modern Pharmacology 1869 – muscarine had similar effect on the heart as electrical stimulation of the vagus nerve. 1878 – classic text: “Outline of Pharmacology”. Discovered glucuronic acid. 1885: urethane - hypnotic 48

49. John Jacob Abel (1857 – 1938) Father of American Pharmacology. Gave the name ‘Pharmacology’ as a subject (earlier – Materia Medica ) 2 nd to isolate Epinephrine from adrenal gland. (1 st - Napolean Cybulski in 1895) Isolated amino acids from the blood (1914) Isolated histamine from pituitary extracts (1919) Prepared pure crystalline Insulin (1926) 49

50. Colonel Ram N ath Chopra (1882 – 1973) Father of Indian Pharmacology. 1921 : Calcutta School of Tropical Medicine. HOD of Pharmacology – Calcutta Medical College 1941 – 1957: Director – Drug Research Lab at Srinagar. 1 st introduced & studied Rauwolfia Serpentina 1 st National Drug Research Institute of India, Lucknow (Central Drug Research Institute, CDRI ) pioneered research on herbal drugs in India sarpagandha 50

51. Louis Lasagna (1923 – 2003) Father of Clinical Pharmacology 1954 - 1 st clinical pharmacology dept – Johns Hopkins University. Conceptualized Controlled clinical trial & placebo effect. Improvement in testing drug effectiveness & regulation of drugs for effectiveness & safety. 1964 – revised the Hippocratic oath “ The incidence of patient availability sharply decreases when a clinical trial begins and returns to its original level as soon as the trial is completed .” - Lasagna’s Law 51

52. Paul Ehrlich (1854 – 1915) Father of Modern Chemotherapy Syphilis & autoimmunity Coined – Chemotherapy & Receptor ‘Magic bullet’ Effective preparation of diphtheria antitoxin 1908 – Nobel Prize in Medicine. 1909 - Salvarsan : most widely prescribed & most effective drug for treating  syphilis until penicillin. 52

53. 53

54. References : A History of Medicine - Nancy Duin & Dr Jenny Sutcliffe The Pharmacological Basis of Therepeutics -Goodman & Gilman, 12 th edition Basic and clinical pharmacology : Katzung , Masters and Trevor, 11 th edition Medical Pharmacology – Dr Padmaja Udaykumar , revised 4 th edition Rang & Dayle’s pharmacology, 7 th edition Pharmacognosy – Dr C.K Kokate , A.P Purohit , S. B Gokhale Pictures from the internet 54