Pharmacology I PDF

PHARMACOLOGY I INTRODUCTION Roger K. Verbeeck, Ph.D. D.F Chuma School of Pharmacy UNAM [email protected]  CONTENTS  Definitions.  History of pharmacology.  The development of a new drug. 1 ...

PHARMACOLOGY I INTRODUCTION Roger K. Verbeeck, Ph.D. D.F Chuma School of Pharmacy UNAM [email protected]  CONTENTS  Definitions.  History of pharmacology.  The development of a new drug. 1  PHARMACOLOGY  “Thesubject of pharmacology is a broad one and embraces the knowledge of the source, physical and chemical properties, compounding, physiological actions, absorption, fate, and excretion, and therapeutic uses of drugs.” Goodman & Gilman The Pharmacological Basis of Therapeutics, 1st edition, 1941. 2  PHARMACOLOGY The word Pharmacology is derived from two Greek words Pharmacon (an active principle) and logos (a discourse or treatise). It is the science that deals with drugs. 3  PHARMACOLOGY  Pharmacology studies how drugs work (pharmacodynamics) and how they are processed by the body (pharmacokinetics).  Pharmacology is crucial for: - discovering new drugs to help fight diseases, - improving the effectiveness of drugs, - reducing unwanted side effects of drugs, - understanding why patients differ in their response to drugs. 4  PHARMACOLOGY  Pharmacology lies at the heart of biomedical science linking together chemistry, biochemistry, physiology and pathology.  Pharmacologists work together with many other disciplines such as molecular and cell biology, immunology, cancer biology, neuroscience, etc. 5  PHARMACOLOGY  What Is a Drug?  A drug is the active chemical entity that is present in a prescribed medicine, which is used for diagnosis, prevention, treatment or cure of a disease.  The term “drug” is derived from a French word “drogue”, meaning “dried herb”.  In 1966, WHO defined “drug” as “any substance or product that is used or intended to be used to modify or explore physiological systems or pathological states for the benefit of the recipient”. 6  NOMENCLATURE OF DRUGS Every drug has three different names, as follows: 1. Chemical name: Chemical name depicts the drug’s chemical nature. e.g (RS)-2-(4-(−2- methylpropyl) phenyl) propanoic acid (Ibuprofen) 2. Non-proprietary or Generic Name The non-proprietary or generic name is the one that is authoritatively accepted by a scientific body. To avoid ambiguity, all member nations of the WHO signed an agreement to use a single recommended International Non-proprietary Name (rINN) for each drug. (Ibuprofen) 3. Proprietary or Brand Name Proprietary name is the name that is owned and designated by the manufacturer.(ibuprofen is marketed under various brand names like Brufen®,Combiflam®, Unafen®, Advil®, etc. 7  PHARMACOLOGY Pharmacodynamics refers to relationship between the blood concentrations of the drug and both the desired and adverse (toxic) effects produced in the body. Pharmacokinetics studies the time course of the absorption, distribution, metabolism and excretion (ADME) of the drug as a function of time. 8 HISTORY OF PHARMACOLOGY ∼1600 AD ∼1800 ∼1900 ∼1970 Academia Pharmaceutical Industry 9  ASPIRIN  Medicines derived from willow trees and other salicylate-rich plants have been part of pharmacopoeias at least dating back to ancient Sumeria (around 2,000 BC).  Acetylsalicylic acid (ASA) was first synthesized in 1853 and produced and marketed by Bayer as Aspirin in 1899. 10  MORPHINE Morphine is an opiate found in opium, the dried latex from unripe seedpods of Papaver somniferum. The first known cultivations of opium poppies dates back to 3,400 BC. Morphine was discovered as the first active alkaloid extracted from opium by Friedrich Sertürner in 1804 and commercialized as an analgesic in 1817. Morphine was first synthesized in 1952. 11  HISTORY OF PHARMACOLOGY  Pharmacology, as a science, started in the mid-19th century when knowledge of the normal and abnormal functioning of the body was slowly developed.  1847: the first department of pharmacology was set up by Rudolph Buchheim, at the University of Dorpat (Estonia), in recognition of the need to try to understand how therapeutic drugs and poisons produced their effects.  Oswald Schmiedeberg (1838-1921), a student of Buchheim, is generally recognised as the founder of modern pharmacology. 12  HISTORY OF PHARMACOLOGY  The concept of receptors (“receptive substance”) for chemical mediators was proposed in 1905 by John Newport Langley (1852-1925), a Cambridge physiologist receptors remained hypothetical entities until the end of the 1960’s!  In 1907, Paul Ehrlich (1854-1915) revised the concept of “receptive substance” to include the binding of drugs to ‘receptors’; he discovered in 1909 that arsenical compounds (arsphenamine, Salvarsan®) were effective to treat syphilis the first modern chemotherapeutic agent. 13  HISTORY OF PHARMACOLOGY  Penicillin was discovered in 1928 by Alexander Fleming (1881-1955).  Sulfonamides were discovered by Gerhard Domagk (1895- 1964) in 1935.  From the middle of the 20th century on many important drug classes were developed: histamine-1 antagonists (1943), phenothiazine antipsychotics (1953), β-adrenergic blockers (1964), histamine-2 receptor blockers (1976), Selective Serotonin Reuptake Inhibitors (1986), … 14  HISTORY OF PHARMACOLOGY mould Fleming A: On the antibacterial action of cultures of a penicillium, with special reference to their use in the isolation of B. Influenzae. Br J Exp Pathol 10: 226-236, 1929. 15  HISTORY OF PHARMACOLOGY Nobel Prize in Physiology or Medicine, 1945. PENICILLIN AS A CHEMOTHERAPEUTIC AGENT BY E. CHAIN, PH.D. CAMB. M. A. JENNINGS, B.M. OXFD, H. W. FLOREY, M.B. ADELAIDE, J. ORR-EWING, A. D. GARDNER, B.M. OXFD, D.M. OXFD, F.R.C.S. A. G. SANDERS, N. G. HEATLEY, PH.D. CAMB. M.B. LOND. (From the Sir William Dunn School of Pathology, Oxford) The Lancet, Aug 24 1940. 16  Sources of Drugs 1. Natural Sources Plants Animals Microbiota Minerals 2. Semi-synthetics Sources 3. Synthetic Sources 17  Sources of Drugs Introduction to Basics of Pharmacology and Toxicology 2019 18  Sources of Drugs Animals as Drug Sources Whole Animals Hirudin and heparin are obtained from the European medical leech (Hirudo medicinalis) and the Mexican medical leech (Hirudo manillensis), respectively. Organs of Animals Cod liver oil from Gadus spp., insulin from bovine or porcine pancreas (though recombinant insulins are used nowadays), vitamin B12 extracts from liver and various antitoxic sera. Glandular Products or Extracts Vaccines, sera, antitoxins, antidotes and hCG. 19  Sources of Drugs Microbiota as Drug Sources 20  Sources of Drugs Minerals as Drug Sources 21  Sources of Drugs Semi-synthetic Sources When the nucleus of the drugs obtained from natural sources is kept intact while altering the chemical structure, the resultant products are semi-synthetic drugs. Homatropine (from atropine), heroin (from morphine), bromoscopolamine (from scopolamine) and ampicillin (from penicillin) are some of the examples. 22  Sources of Drugs Synthetic Sources Unlike semi-synthetic drugs, synthetic drugs are those in which both the nucleus and the chemical structure are altered or modified. These are exclusively prepared in the laboratory. Synthetic drugs have many advantages over natural and semi-synthetic sources of drugs: Chemical purity High quality, which can be manually controlled Improved safety profile, particularly in terms of less antigenicity Cost-effective preparation methodology 23  DRUG DEVELOPMENT  Historically, drugs were discovered through identifying the active ingredient in traditional remedies, or by serendipitous discovery (e.g. penicillin).  More recently, drug discovery relies on high-throughput screening of a large number of compounds for their ability to interact with specific drug targets (i.e. receptors).  Rational drug design begins with the hypothesis that modulation of a specific biological target (receptor) may have a therapeutic benefit reverse pharmacology or target- based drug discovery. 24  DRUG DEVELOPMENT  Computer-aided drug design: to predict whether a given molecule will bind to a specific drug target.  With the exception of a few naturally occurring hormones (e.g. insulin, MW 5,808 Da), most drugs were small organic molecules, typically