History of Pharmacology

Presented by: Dr.Adithi.S.RaghavanModerated by:Dr.Cuckoo Aiyappa

Why Study History?

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.

.

“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

Vaghbhata

Ashtanga hridayaAshtanga sangraha

Madhava nidana

Unani

Chinese & Egyptian

PAN TSAO-CHINESE MATERIA MEDICA

EBERS PAPYRUS-EGYPTIAN MATERIA MEDICA

2500 BC1500 BC

Babylonian clay tablet

700 bc

300 drugs

HIPPOCRATES

Hippocrates- father of modern medicine

377-460 BC

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.

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.

Arabian Medicine

Avicenna (980-1027) – “Canon of Medicine” (14 vol.) Galenic medicine

(standard text till 18th century).

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.

The Renaissance

Obnoxious remedies as flesh,excreta and

blood of various animals James Gregory(1753-1821) Disastrous results Wrongly applied name to modern scientific

medicine

Allopathy(the other suffering)

Early 19th century “like cures like” Hannemann

Homeopathy(similar suffering)

The Rise Of Experimental Pharmacology

François Magendie (1783 –1855) French physiologist. “Formulary for

preparation and use of many new remedies,.

Paris academy in 1809

19

Friedrich Wilhelm Adam Sertürner (1783-1841) Isolated morphine

1804, The first ever

alkaloid Administered to

himself and three friends.

Cholera -living organism.

20

Claude Bernard (1813-1878) - Magendie’s pupil

Pancreatic juice in digestion, liver glycogen and its importance

Vasomotor nerves.

CO on hemoglobin.

Action of Curare

21

Rudolf Buchheim (1820 –1879)

First pharmacology laboratory in the world (1860, University of Dorpat in Estonia)

Introduced bioassay .

22

Oswald Schmiedeberg (1838 –1921) Father of modern

pharmacology

23

Sir Thomas Lauder Brunton (1844 –1916) Scottish physician “Textbook of

Pharmacology, Therapeutics and Materia Medica (1885)”.

24

John Jacob Abel (1857–1938) Father of American

Pharmacology. Co-founded Journal of

Pharmacology and Experimental Therapeutics in 1909.

25

Arthur Robertson Cushny (1866-1926) Trained by Oswald

Schmiedeberg. “Text-Book of

Pharmacology and Therapeutics”

History of Some Important Alkaloids

Pilocarpine

Chewing of leaves;Salivation

1874-Brazilian physician Coutinhou first experiments

1875-alkaloid isolated

Weber-actions pupil,sweat,salivary glands.

South American genus Pilocarpus

Physostigmine

Also called eserine.

Alkaloid;Calabar bean.

West Africa;”Ordeal poison”

1864;Jobst and Hesse

1877;Laqueur-Tx glaucoma

Belladona

Roman empire;obscure poisoning

Atropos;Linnaeus India-root&leaves-Tx

Asthma Mein 1831 Bezold&Bloebaum(186

7) Heidanhain(1872)

Muscuranic receptor antagonists

Atropine&Scopalamine

Curare

Von Humboldt 1805

Strychnos species

Griffith & Johnson 1942

King 1935

South American arrow poisons

Ergot

Claviceps purpurea

600BC Assyrian tablet

Middle ages-epidemics

Active principles-early 20th century

Castor Oil

Oil(chiefly of triglyceride of ricinoleic acid)

Ricin extremely toxic protein

Active agent-Ricinoleic acid

Ricinus Communis

Vinca alkaloids

Periwinkle plant Cantharanthus roseus(formerly Vinca rosea)

Exracts;hypoglycemic effects in Diabetes.

Vinblastine& Vincristine-regression ALL in mice

Vinorelbine-lung& breast cancer

Foxglove

History of Treatment of

Thyroid Disorders

.

Hypothyroidism

Precursors of Thiocyanate

ions

Antithyroid Drugs

Evolution of Antimicrobials

1. Alkaloids(natural plant products)

2. Synthetic Compounds

3. Antibiotics

The three eras of Chemotherapy

South American discovery-efficacy of

ipecacuanha root in amoebic dysentry -Successful treatment of Malaria with an

extract of Cinchona bark.

Alkaloids

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.

Discovery of Prontosil

GERHARD DOMAGK

PRONTOSIL First effective antibiotic Marketed in 1935

Antibiotics

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

Discovery of Penicillin

Cecil George Paine treated ophthalmia neonatorum - first recorded cure with penicillin (25 Nov 1930).

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.

.

51

Discovery of Streptomycin

Selman Abraham Waksman (1888–1973)

Studied actinomycetes.

1940-1952 isolated 10 antibiotics.

Albert Schatz (1922-2005)

Extracted and tested the new antibiotic.

Purified drug by Merck for clinical trials

History of Important

Cardiovascular drugss

HEPARIN

Canine liver cells;hepar greek “Liver”.

Jay McLean & William Henry Howell

1916,fatsoluble phosphatide anticogulant

Spoiled sweet clover sillage

Campbell &Link 1939-Dicoumarol

1948 Warfarin

Wisconsin Alumni Reseach Foundation

1951-army inductee suicide failed

Warfarin

1929-Dam;reduced prothrobin

Dam&Coworkers(1935,1936);

Unidentified fat soluble

Vitamin K(Koagulation Vitamin

Vitamin K

Aspirin

Willow bark to relieve fever by Hippocrates

Meadowsweet(spiraeaulmaria)

Salicin 1829 Leroux Pina 1836 salicylic

acid Hoffman;Bayer

Nitrates

Nitroglycein 1846 Sobrero

1857 ,T.Lauder Brunton Amyl nitrate

Alfred nobel 1863

William Murell,sublingual nitroglycerine

Statins

Mold,Penicillim citrinum,1976;Endo&colleaguesin

Brown&Goldstein;HMG-CoA Reductase

Compactin;Mevastatin

Alberts&colleagues;Lovastatin

Anesthetics and Hypnotics

62

Ether

William Thomas Green Morton (1819–1868) American dentist 30 September 1846

- painless tooth extraction after administering ether to a patient.

1847 James Simpson

1868 Edmond Andrews

Lundy 1935 Thiopental

CocaineKarl Koller (1857-1944)

Introduced cocaine as a local anaesthetic for eye surgery (1884).

“Coca Koller

Click icon to add picture

History of Histamine

Dale & Laidlaw-endogenous

histamine;immediate hypersensitivity,cellular injury

Best&colleagues(1927),fresh samples liver &lung

Histos-greek word for tissue

Lewiss and colleagues-”H-substance”

Discovery of Corticosteroids

Tadeus Reichstein

(1897-1996)Edward Calvin Kendall

(1886–1972)

Philip Showalter Hench (1896–1965)

Discovery of Prostaglandins

Eicosanoids eikosi

1930;Kurzrok&Lieb

Von Euler in Sweden

Bengt Ingemar

Samuelsson (1934- )Sune Karl Bergström (1916–2004)

PG E1

PGF1

PGE2

History of OCs

Austrian physiologist Haberlandt

1927;temporary sterility,feeding ovarian & placental extracts

1950s Pincus,Gardia& Rock;progesterone&19-norprogetins

1950s;Puerto Rico& Haiti-norethynodrel

Discovery of Insulin

79

80

Chemical Neurotransmission

John Newport Langley (1852-1925)“Receptive substance” concept (1905).

82

Thomas Renton Elliott (1877-1961)

Sir Henry Hallett Dale (1875-1968)

84

85

History of Antimetabolites

Gertrude Elion (1918-1999) and George Hitchings (1905-1998)

87

Indian Scenario

89

Colonel Ram Nath Chopra FATHER OF INDIAN PHARMACOLOGY

1882-1973

90

91

Yellapragada Subbarao (1895-1948)

Phosphocreatine and ATP.

Folic acid. methotrexate and

hetrazan. Benjamin Duggar

he world's first tetracycline antibiotic, aureomycin (in 1945).

FUTURE OF PHARMACOLOGY

GENE THERAPYMONOCLONAL ANTIBODIES

“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

Thank you!

Ipecacuanha Vasaka Adathoda Goodman Gillman James black Chalmoogra oil Concept of Antibiosis First clinical trial?-James Lindt

Questions asked on

Pls read the notes below

Ipecacuanha

Vasaka adathoda

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.

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

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. Gas-liquid 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

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