Chairperson: Dr. S. V.

Hiremath MD Professor & Head, Dept of Pharmacology, JNMC

Guide: Dr. Suneel I. Majagi, MD Asso. Professor, Dept of Pharmacology, JNMC.

Presenter:

Dr. Rohan Kolla PG in Pharmacology

Date : 4th June, 2011

Pharmacology
Can be defined as the study of substances that interact with living systems through chemical processes, especially by binding to regulatory molecules and activating or inhibiting normal body processes.

History of Pharmacology

The Origins
It all began when man first used a plant extract to relieve the symptoms of his ailments Man tried to make use of materials he found around him & it was inevitable that he find substances that had some pharmacological properties. Opium and Alcohol - 7000 yrs ago. Archaeological evidence Attempts to treat diseases with herbs and other substances.

 Remains of flowers with psychoactive properties have been found at many Prehistoric burial sites. tzi the Iceman : ~ 5300 ybp
Contained in his possessions was a fungus that scientists found could kill internal parasites.

 Supernatural Forces, Gods and Evil spirits Diseases & Ailments This reflected in the treatments attempted. Medicine men (also witch-doctors, shamans): health of their tribe by >distributing herbs, >performing minor surgical rocedures, >supernatural treatments such as charms, spells and amulets to ward off evil spirits

Trephination (or trepanation)

Skulls like these have been found at various Neolithic sites and also in the American Civilizations. It was done to relieve a person suffering from mental illness, epilepsy etc.

From Antiquity to Middle Ages

India & China

Rigveda & Ayurveda: 1700
- 1100 BC
> Three humors Vata, Pitta, Kapha. >Remedies from natural products

Pan Tsao

- Its a list herbal remedies for common ailments :

2700BC

Harappan Civilisation (c. 3300 BC): evidence of medical and dentistry knowledge.

Sushruta
~ 800 BC Sushruta Samhita 300 Surgical procedures 120 Surgical Instruments Rhinoplasty Cataract Surgery, Fistulae, Hernia, Ascites Fractures traction Paramedian Forehead Flap Indian Flap.

Charaka
~ 300 BC Charaka Samhita It is one of the oldest texts of Ayurveda. It deals with Internal Medicine & has descriptions of 300 herbs He Revised the work of Atreya Samhita

Vagbhata

Egypt & Babylonia

> Tree resins, Frankincense, Myrrh & Manna > Purgatives Senna, Castor Oil >> Antimony, > Use of Opium Copper werw was also known used as astringents. >Animal EDWIN SMITH products like fat, PAPYRUS & ox spleen, pigs EBERS PAPYRUS brain,etc

Greece and Rome

HIPPOCRATES
~460BC -350BC

GALEN Of Pergamum
(127 -190 AD) > He created a typology of diff temperaments sanguine, choleric, melancholic & phlegmatic

Dioscorides
(40 90 AD) Author of 'De Materia Medica a five volume treatise on Herbal Medicine

- Introduced the
concept of disease as a pathological process - Recommended judicious use of drugs

> Bloodletting, Venesection,

> First Cataract Operation

# Western Medicine was dominated by the teachings of hippocratric corpus till 15th century.

Arabic Medicine
Avicenna (or Ibn Sina, c 980 -1037 AD):
Canon Of Medicine - It was a authoritative textbook on the whole gamut of Medical Knowledge. The first book dealing with experimental medicine, evidence-based medicine, randomized controlled trials, and efficacy tests.

Title Page of Avicennas Canon Of Medicine

Renaissance
Similar voices of dissent began to arise all over Europe during 15th century. Paracelsus(1493 1541 AD): - He denounced the teachings based on Galen & Avicenna He burnt their books!! - He was a keen observer & a great Theorist - He Advised using mercurials, arsenic, iron & lead for various purposes

 But much of the theorizing gave rise to treatments derived from faith, superstition & only partly scientific observation. Blood Letting, Emetics and Strong Purgatives were used to cleanse the body and restore balance among the humors. Irrational remedies dominated the scene till the very end of 19th century

Blood Letting : It was said that it was to be done till the patient faints when he gets gets up he will be purified of his ailments.!!

Etymology
Pharmaks : Ancient Greek religion - a human scapegoat (a slave, a cripple or a criminal) "pharmakos" "pharmakeus" which means a drug, spell-giving potion, druggist, poisoner, by extension a magician or a sorcerer. A variation of this term is "pharmakon : a complex term meaning sacrament, remedy, poison, talisman, cosmetic, perfume or intoxicant. From this, the modern term "pharmacology" emerged

Modern Pharmacology

First Scientific Underpinnings

Jean Fernel (1497-1554): Father of physiology; he wrote a book called 'Physiologia' in 1554 in which he denounced the use of magic & faith. He also wrote a treatise on pharmacy 'Pharmacology' was added to the lexicon in 1693 when Samuel Dale wrote 'Pharmacologia seu Manuductio ad Materium medicum'

 James Lind, a British Naval surgeon conducted the first ever clinical trials for the treatment of Scurvy using lime juice in the year 1747. Frederick Sertuner discovered Morphine in 1804 Ist alkaloid to be extracted. Francois Magendie(1783 1855) : Experimental Physiology studied the effect of Strychnine on dogs Claude Bernard: Curare acts at the Neuro muscular Junction > He also discovered the vasomotor system.

 The first laboratory of pharmacology: Rudolf Buchheim in the Dorpat University in Estonia in 1849. He introduced the Bioassay. Carl Binz established a pharmacology lab in Bonn, Switzerland in 1969.

Oswald Schmeideberg - Professor of Pharmacology at Strasbourg, Germany.

> Muscarine = Stimulation of Vagus > Glucuronic acid > Effectiveness of Narcotics.

Father of Pharmacology
1838 -1932 JJ Abel, J Langley, T Frazer, P Ehrlich, AJ Clark, AR Cushny, Reid Hunt German Pharmaceutical Industry during the Interwar period.

Pharmacology in Britain & America

Robert Christison & Richard Fraser Experimental Pharmacologists in Edinburgh Physostigmine from calabar bean Sir Thomas Brunton (1844 -1916) A lab in St. Bartholomew Hospital in 1873. He also published Textbook of Pharmacology, Therapeutics & Materia Medica.

Pharmacology In Britain & America (contd)

Sydney Ringer: >Author of Ringers Handbook of Therapeutics, >Ringers solution around 1882 -1885 John Jacob Abel(1857 1931): Epinephrine, Aminoacids from blood, Arthur Robert Cushny : Ist experimantal analysis of action of digitalis. Alfred J. Clark - pharmacokinetics Reid Hunt discovered Ach in 1904 adrenal extracts

 Sir Henry Dale (1875 1968): called the Doyen of British Pharmaccology sfound out the actions of Ach in heart Otto Loewi (1873 1961): demonstrated the importance of Ach and called it vagustoff . Both of them shared the Nobel for Medicine in 1936.

Birth of Chemotherapy
Pasteur, Koch, von Behring Medical Microbiology Paul Ehrlich : cure for Syphilis in 1910Salvarsan, an arsenical he considered it to be the Magic Bullet. Sulfonamides were introduced by Gerhardt Domagk in 1936 and Penicillins by Alexander Fleming in the 1923.

Hormones
George Murray fed a patient of Myxoedema extracts from sheep thyroid in 1891. By 1927, Thyroid Hormone was synthesized. In 1921, Frederick G. Banting & Charles H. Best isolated Insulin. Frederick Sanger determined the structure of Insulin.

Anesthetics
Inca Shamans Chewed Coca leaves while operating. Karl Koller: Used Cocaine for eye surgery in 1884 Crawford Long: 1842 Diethyl Ether W. T. G. Morton: Ether Dome Horace Wells: 1844 Nitrous Oxide

Modern Indian Pharmacology

Sir Ramnath Chopra
Books Indigenious Plants Of India, Poisonous Plants Of India & Drug Addiction In India. Calcutta School Of Tropical Medicine & Dept of Pharmacology in Calcutta Medical College Central Drug Research Institute Of India. Lucknow

Indian Pharmacology
Yellapragada Subbarao: - Phosphocreatinine & ATP in Muscle, - Methotrexate - Folic Acid - Aureomycin H R. Bawaskar : blockers for scorpion bite Rustom Jal Vakil: Reserpine

Definitions

Pharmacokinetics
is the study of Absorption, Distribution, Metabolism and Excretion of drugs and their relationship to the pharmacological response. In short what the body does to the drug!!

Pharmacodynamics
the Quantitative study of Biochemical and Physiological effects of drugs and the Mechanism with which they bring about their that effect. In short What the drug does to the body!!

Pharmacotherapeutics
Therapeutics : means to care for or to tend to or to nurse Pharmacotherapeutics is a branch of medicine which deals with the cure of disease or relief of symptoms with the use of drugs.

Pharmacogenomics & Pharmacogenetics

The science which studies the inherent variations in genes that dictate the drug response of humans, microbes and tumors and explores ways these variations can be used to predict the response. Pharmacogenomics employs tools for surveying the entire genome to assess multigenic determinants of drug responses.

Examples of variations!
G6PD deficiency an X linked trait that results in severe hemolytic anemia after ingestion of various drugs like antimalarials. In some pts having NSCLC, the tumors have activating mutations of TK domain of EGFR those having the mutation can be given GEFTINIB an inhibitor of EGFR receptor.

Chemotherapy
Chemotherapy of Microbial diseases: concerned with the effect of drugs on microorganisms & parasites, living and multiplying in a living organism. Cancer Chemotherapy: concerned with the effect of drugs on tumors and their use in the treatment.

Pharmacy

Science of identification, selection, presentation, standardization, compounding and dispensing of medicinal substances.

Toxicology
The science of poisons which includes detection and measurement of poisons as well as treatment of poisoning Poisons are substances that cause harmful, dangerous &fatal symptoms in living organisms.

Pharmacoeconomics
Its a branch of Health Economics which aims to quantify in economic terms, the cost & benefit of drugs used therapeutically. what therapeutic measures represent the best value for money.

Pharmacoepidemiology
It is the study of variability of the effects of drugs between individuals of a population and among different populations. it studies the effects of drugs at the population level

Pharmacovigilance
The process of identifying and responding to the issues of drug safety through the monitoring and detection of adverse drug effects. National Pharmacovigilance Center has been established in AIIMS. There are 7 regional Pharmacovigilance centres & also many peripheral centres.

DRUGS
A drug is any substance or product that is used to modify or explore physiological or pathological states for the benefit of the recepient.

Naming of Drugs
Chemical Name: It describes the substances chemically. Generic Name (Non-proprietary name, Official name, Approved Name): It is approved by a competant scientific body: rINN (recommended International Nonproprietary Name) Brand Name(Proprietary name): Its the intellectual property of the company.

Examples:
3-910,11-dihydro-5H-debenz[b.f]-azepam-5-yl propyldimethylamine Imipramine Antidep

Chlorodihydromethylphenylbenzodiazepine-2one Diazepam Valium, Calmpose

Essential Drugs WHO those that satisfy the priority healthcare needs of the population Public health relevance, evidence of efficacy and safety and cost effectiveness 1977 Model List of Essential Drugs 1996 National Essential Drugs List 2003 National List of Essential Medicines

Orphan Drugs Drugs or biological products used for diagnosis/ treatment/ prevention of a rare disease or condition fro which there is no reasonable expectation that the cost of developing and marketing it will be recovered ! Fomepizole, Rifabutin, digoxin immune Fab, liothryonine, etc

Sources of Drugs
1. Mineral: Liquid Paraffin, Magnesium Sulphate, Kaolin 2. Animal: Insulin, thyroid extract, heparin, gonadotrophic hormones 3. Plant : a. Glycosides digitoxin, ouabain
b. Alkaloids atropine, quinine, morphine, c. Oils clove oil, castor oil, d. Gums e. Tannins f. Resins

4. Microbiological Source: Penicillin, Streptomycin, Aminoglycosides 5. Synthetic : Aspirin was prepared and manufactured and sold commercially by a German company called Bayer 6. Hybridoma technique Monoclonal Antibodies, 7. Genetic Engineering: Recombinant Dna technique Insulin, Growth Hormone, Erythropoetin

Clinical Trials
Its a special type of Bioassay done to compare the clinical efficacy of a new drug or procedure with that of a known drug or procedure (or a placebo)

References
1. Essentials of Medical Pharmacological, K D. Tripathi, 6th ed 2. Pharmacology and Pharmacotherapeutics, R S. Satoskar, S D. Bhandarkar, Nirmala N. Rege, 21st ed. 3. Goodman & Gilmans The Pharmacological Basis of Therapeutics, 12th ed 4. Lewiss Pharmacology, James Crossland, 5th ed. 5. Rang & Dales Pharmacology 6th ed, 6. Basic & Clinical Pharmacology, Katzungs, 11th ed. 7. The Cambridge Illustrated History of Medicine, Roy Porter, 1st ed

References(contd)
Clinical Pharmacology, Bennet & Brown, 10th ed.

Thank you