BIMM118!“One of the features which is thought to distinguish man from other animals is his desire to take medicines” (Sir William Osler, 1849-1919) 2011 UpdatedBIMM118!Questions whose answers are based on pharmacology as a discipline Why is low dose aspirin better than high dose aspirin in preventing heart attacks? Aspirin and tylenol both reduce inflammation (NSAID) and both lower fever (antipyretic) but tylenol does not prevent heart attacks, why? Why is racial profiling acceptable in deciding what drug to use for the treatment of high blood pressure – beta blockers versus angiotensin receptor blockers or ACE inhibitors? Why is it so difficult to find a drug which can be used in treating different metastatic tumors (cancer)?BIMM118!Definitions!• Pharmacology is the science of the interaction of chemicals with living ! !systems at all levels!• Pharmacokinetics investigates the effects of the biological system on drugs ! !(absorption, distribution, elimination…)!• Pharmacodynamics describes the fundamental action of a drug on a ! !physiological, biochemical or molecular level !• Pharmacogenetics examines the effects of genetic factors to variations in the !drug response (“Asian Flush”, Codeine “resistance”)!• Toxicology studies the undesirable effects of chemicals on living systems !(includes poisons, antidotes and unwanted side effects of drugs)!• Pharmacy classically is the art of preparing, compounding and dispensing chemicals for !medicinal use, new functions are advising on specific therapies to prevent drug-drug interactions, monitoring drug usage, clinical informatics!BIMM118!Definitions!• Prophylactic refers to a drug or procedure aimed to prevent disease!• Palliative refers to a drug or procedure aimed to relieve symptoms!• Therapeutic refers to a drug or procedure aimed to cure disease or condition!• Tolerance is the increased resistance to the usual effects of an established ! !!dose of a particular drug!• Effective dose (ED50) is the concentration at which 50% of the subject show !!a predefined response!• Efficacy refers to the inherent capability of a drug to produce a desired effect or response!!• Potency compares the relative effectiveness of drugs to produce a desired effect!!e.g. Drug A requires fewer milligrams than Drug B to achieve the same pharmacological response !!--> Drug A has the higher potency, yet, both drugs have the same efficacy.!BIMM118!History of Pharmacology!• For 1000s of years most medicines were of botanical or zoological origin – it was the Era of drug “magic”: shamans, self-appointed priests, midwifes.!• 1500-1600 BC Chinese herbal medicines; 1550 – the Ebers Papryus codified diseases and medicinals!• 500 BC Sashruta, Dhanwantari – smallpox vaccination!• Hippocrates (460-370 BC); Aristotle (384-322 BC)!• Theophratus (372-287 BC) philosopher, successor to Aristotle, “Father of Pharmacognosy”!• Pedanius Dioscorides (57 CE) “Father of Materia Medica”!• Galen (131-201 CE) Anatomy, proposed a theory of “humors”, galenicals!• 800-1500 the Era of religion – Mediterranean medicines: Rhazes (844-926), Avincenna (980-1037) “Father of Clinical Pharmacology”; Maimonides (1135-1204)!BIMM118!History of Pharmacology!• Paracelsus (1493-1541) marks the rise of European pharmacology – discarded Galenʼs theory of humors, mercurials for syphilis; “All things are poisons, nothing is without poisonous qualities, it is only the dose which makes a thing a poison!”!• 19th & 20th Centuries saw rise of European pharmacology, the scientific method, chemical synthesis, etc. Drug discovery and development shifted to Europe and North America.!• Since 1950ʼs, large increase in synthetic organic chemicals!• Recent introduction of recombinant DNA technology has extended synthesis to molecules of human origin!BIMM118!History of Pharmacology!• Early agents were naturally occurring inorganic salts and plant alkaloids!– Opium !– Foxglove!– Mercury, arsenic or lead compounds!• Most ineffective or actually dangerous!• Standardization of dose very difficult!– Narrow therapeutic index with foxglove!BIMM118!Therapeutic Index!Luellmann 2011 TI ~ Safety MarginBIMM118!History of Pharmacology: Homeopathy!• 1790-96: Dr. Samuel Hahnemann:!!To discover the true mode of action by which cinchona bark cured !!malaria, he ingested cinchona juice twice daily for a few days. To his !!great astonishment, he very soon developed symptoms very similar !!to malarial fever.!– Postulated a new principle of treatment: “Likes cure likes”!– Drug is called the remedy, obtained through serial dilutions of the chemical !!The remedy is mainly extracted from the plants, animals and minerals. The medicinal extract is diluted and potentiated to such an extent that not even an atom of the mother material can be detected in the remedy by the time it reaches the 12th potency. Dilutions are done in steps. For example: In the centi scale, one drop of mother tincture is mixed with 99 drops of alcohol and shaken rigorously using pre-determined strokes. This is termed as 1c. From this, one drop is mixed with 99 drops of alcohol and is termed as 2c and so on. The higher the dilution, the more powerful the remedy. It was proposed recently that the magnetic aura of the remedy increases with potency (supposedly, this had been proven with Kirlian photography). !!Since the remedies are used after diluting several times, it cannot have chemical effects on the body to create a long standing side effect.!BIMM118!History of Pharmacology!• Major advance in safe use of naturally derived agents was the isolation, purification and chemical characterization of the active compound:!– Allowed administration of a controlled dose!– Allowed administration of the active component of herbal mixtures to be given alone!– Identification and characterization of active component allowed definition of mechanism of action, leading to synthesis of improved agents with greater selectivity, potency, altered duration of action, etc.!BIMM118!History of Pharmacology!• Aspirin® - first synthetic drug!– Hippocrates: pain relief treatments with powder made from the bark and leaves of the willow tree (Salix sp.) – Johann Buchner (1829): isolated Salicin as the $active ingredient in
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