PHAR 100 Module 1: History of Drug Use and Development PDF

MODULE 01 COMPANION GUIDE PHAR 100 SECTION 01: HISTORY OF DRUG USE AND DEVELOPMENT Introduction to the History of Drug Use and Development Humans have used drugs since before recorded history. Early written records from China and E...

MODULE 01 COMPANION GUIDE PHAR 100 SECTION 01: HISTORY OF DRUG USE AND DEVELOPMENT Introduction to the History of Drug Use and Development Humans have used drugs since before recorded history. Early written records from China and Egypt provide a glimpse of the ancient traditions of drug use. Although a few useful drugs (e.g., opium) were identified over 2000 years ago, the majority of clinically useful drugs have been developed over the past 250 years with the advent of the experimental biological sciences, including pharmacology. In this section, you will learn about some of the historical influences that have shaped modern pharmacology. You will also be introduced to different types of drugs that have been discovered over time, including drugs that act on the brain and those that act against infectious disease. Historical Influences and Modern Pharmacology Several key historical influences have shaped modern pharmacology. Some of these influences include: 1. The many discoveries made by ancient civilizations 2. The role of poisons in history 3. The influence of religion You will explore each of these influences in more detail on the next pages. Ancient Civilizations The history of pharmacology might appear to be only a few decades old, however, it dates back to the traditions and cultures of ancient times. Ancient civilizations such as ancient Greece, Egypt, and China have their unique contributions to modern pharmacology and have further shaped its history. Learn about the contributions of three civilizations to the development of drugs. Ancient Greece – see page 7 Ancient Egypt – see page 8 Ancient China – see page 8 PRINCIPLES OF PHARMACOLOGY | PHAR 100 MODULE 01 PAGE 6 MODULE 01 COMPANION GUIDE PHAR 100 Ancient Greece In the year 380 B.C.E, Theophrastus, a pupil of Aristotle, wrote a textbook on therapeutics that included opium. Opium is obtained from the Opium poppy (Papaver somniferum). Serturner, a pharmacist working in Germany in 1803, isolated crystals of morphine from opium and tested the pure substance on himself and three companions, discovering its pain relieving capabilities. Opium was found to contain two important substances: morphine and codeine. Learn about the two substances found in opium. Morphine Opium was found to contain approximately 10% morphine. Serturner coined the name morphine from Morpheus, god of dreams. Morphine is able to relieve pain of very great intensity. By contrast, acetylsalicylic acid (Aspirin®) and acetaminophen (Tylenol®), while valuable medications, will only relieve mild to moderate pain. Codeine Opium contains 0.5% codeine. Codeine is a constituent of Tylenol-3®, a prescription drug in Canada. Ancient Egypt Ancient Egyptian history was recorded on documents called papyri. It was discovered that one of these papyri, the Ebers Papyrus dating from the year 1550 B.C., was intended to be a textbook of drug use for medical students. Scholars have shown that this papyrus contains many true observations on the use of drugs, particularly on purgatives, which are drugs used to cause bowel movements. One of the drugs recommended for use was senna. Products containing senna are still available today. Ancient China The earliest recorded drug experiments are those emanating from China in the year 2700 B.C. It is reported that the emperor Shen Nung classified all drugs according to taste. PRINCIPLES OF PHARMACOLOGY | PHAR 100 MODULE 01 PAGE 7 MODULE 01 COMPANION GUIDE PHAR 100 For example, the drug Ma Huang was classified as a “medium drug”. This drug was widely used in Chinese medicine for coughs, influenza, and fevers. In the modern era, ephedrine has been isolated from Ma Huang. Ephedrine has been used to treat asthma, and a derivative of ephedrine is used as a decongestant. The Influence of Poisons The use of poisons in ancient times resulted in the discovery of drugs still used today. Additionally, many poisons have resulted in the development of drugs. “All substances are poisons. There is none which is not a poison. The right dose differentiates a poison and a remedy.” - Paracelsus, 16th century Swiss physician Learn about two examples of poisons that have led to the development of drugs. Curare – see page 9 Ergot – see page 10 PRINCIPLES OF PHARMACOLOGY | PHAR 100 MODULE 01 PAGE 8 MODULE 01 COMPANION GUIDE PHAR 100 Curare Curare, a plant-derived drug, was historically used by Indigenous Peoples in various regions of the Amazon rainforest in South America. Read the flashcards to learn about the use of curare as a poison and as a drug. Use as a Poison Use as a Drug Indigenous Peoples of the Amazon dipped their Eventually, curare was used by anesthetists arrows in curare to use as a poison. Curare during surgery. By giving a small dose of curare acted upon the voluntary muscles of the animal, to the patient, muscle relaxation was achieved, causing paralysis and eventually death by greatly facilitating the surgeon’s work. The respiratory paralysis. structure of curare has been modified to make the drug safer, and these newer derivatives of curare are used by anesthetists today. Ergot Ergot is a poisonous fungus that grows on the heads of rye, particularly during wet seasons. In the Middle Ages, ergot was ground together with the rye, thereby finding its way into bread. As a result, terrible epidemics occurred, and 250 years ago one of these epidemics killed 20,000 people in one region of Russia. Ergot: Effects of Poisoning The effects of ergot poisoning impact various systems in the body, including the nervous, cardiovascular, and reproductive systems. Nervous System PRINCIPLES OF PHARMACOLOGY | PHAR 100 MODULE 01 PAGE 9 MODULE 01 COMPANION GUIDE PHAR 100 Once it enters the body, ergot targets the nervous system. This results in symptoms such as mental frenzy, hallucinations, and convulsions. Cardiovascular System Ergot poisoning can cause the constriction of blood vessels leading to fingers, toes, and limbs becoming starved of their blood supply, and a resulting burning sensation. Over time, the limbs become black and gradually die, and, in extreme cases, may even fall off. Reproductive System Ergot poisoning can cause violent contractions of the uterus, which is part of the female reproductive system. As early as the 16th century, some midwives recognized that small amounts of ergot could be useful in hastening labour. In the 1800s, physicians used ergot to expedite lingering labour. However, if not used appropriately, it could result in death. Ergot: Use as a Drug Besides acting as a poison, ergot has been found to be useful as a drug. Ergotamine and ergonovine are two compounds derived from ergot that have pharmacological uses. Learn about the two active principles of ergot used in modern medicine. Ergotamine Ergotamine is useful in the treatment of migraines. One theory suggests that migraines are caused by pulsation of the arterial blood vessels that carry blood to the head. Ergotamine constricts these blood vessels, reducing the amplitude of the pulsation. Ergonovine Ergonovine was once used to hasten birth, however, it is no longer used for this purpose, as the force of uterine contractions may be too strong and the mother may be injured by too rapid delivery of the child. It can be used to arrest uterine bleeding after childbirth. The Influence of Religion In ancient societies, medicine men acted as both physicians and priests, resulting in therapy being heavily influenced by both religion and magic. In most parts of the world, plants containing intoxicating substances were used by medicine men in order to alter the state of consciousness and facilitate communication with their gods. The following is an example of the role of religion in the use of drugs. Peyote In Mexico, the peyote cactus was widely used to achieve a mystical state. The Peyote cactus contains the potent substance mescaline, which causes hallucinations, a feeling of well-being, and distortion of perception similar to that experienced with L S D. PRINCIPLES OF PHARMACOLOGY | PHAR 100 MODULE 01 PAGE 10 MODULE 01 COMPANION GUIDE PHAR 100 For Your Interest: Ancient Roman Medicine In ancient times, zinc oxide was considered of great importance in therapies. A Roman shipping vessel sunk off the coast of Tuscany around 120 B.C.E. In the 1980s and 90s, the ruins of the shipwreck were excavated, uncovering ancient Roman medical tablets sealed in tin containers. Analysis of the medical tablets revealed a number of zinc compounds, as well as iron oxide, starch, beeswax, pine resin, and other plant-derived materials. Interestingly, zinc oxide is found in a number of topical creams today, including diaper rash creams and calamine lotion. If you’re interested, read an article that describes the shipwreck excavation and tablet analysis and highlights how ancient civilizations were influential to drug development. What’s Inside a 2,000-year-old, Shipwreck-Preserved Roman Pill? Drug Discovery A drug is any substance received by a biological system that is not received for nutritive purposes, and which influences the biological function of the organism. This broad definition means that chemicals, biological agents, and herbal products are all considered drugs. Many modern sources of drugs exist. About 25% of the drugs used today are derived from plant sources, with the active substances being purified and then potentially modified to be either more effective or less toxic. The 19th century heralded the era of chemical synthesis and most drugs discovered or introduced into therapy were small molecules obtained by chemical synthesis in the laboratory. Two majors categories of drugs discovered throughout history include drugs that act on the brain and drugs that act against infectious disease. Learn about two major categories of drugs discovered throughout history. Drugs Acting on the Brain Drugs that act on the brain alter the normal chemical signalling in the brain. One example of a drug that acts on the brain is L S D, or lysergic acid diethylamide. L S D is one of the most potent hallucinogenic drugs. Discovery Albert Hofmann, who worked for a Swiss pharmaceutical firm, was involved in trying to synthesize improved pharmaceutical products based on components of ergot. In 1943, he synthesized L S D, which was similar in chemical structure to ergotamine and ergonovine. Contribution to Pharmacology The discovery of the psychedelic effects of L S D supported the idea that certain mental illnesses might be due to the production of potent substances in the brain that could produce psychic disturbance. Research into potential therapeutic effects of L S D stopped around the 1970's as it was classified as a controlled substance. Recently, however, some evidence indicates that derivatives of psychedelic PRINCIPLES OF PHARMACOLOGY | PHAR 100 MODULE 01 PAGE 11 MODULE 01 COMPANION GUIDE PHAR 100 compounds like L S D might be effective in treating certain mental illnesses such as depression, anxiety, and addiction. Drugs Acting Against Infectious Diseases An infectious disease is any disease caused by an organism, such as bacteria, viruses, fungi, or parasites. The introduction of drugs to combat infectious diseases was a major milestone in drug development. Review a brief history of drugs that target infectious disease. 1900s Organoarsenicals: Paul Ehrlich designed complexes of arsenic and organic molecules (called organoarsenicals), which selectively bound to parasites. This idea was applied to other infectious diseases and led to a dramatic cure for syphilis in the early 20th century. 1930s Sulfa Drugs: Gerhard Domagk introduced sulfa drugs in the 1930s in Germany. These were the first successful synthetic drugs for the treatment of bacterial disease, and hence nowadays they are are termed antibacterial compounds (the term antibiotic refers specifically to chemical substances produced by microorganisms, and not synthetic compounds). 1940s Penicillin: Alexander Fleming discovered the first antibiotic, penicillin. Its introduction into modern medicine occurred during the Second World War (1939-1945). Its major use was in the therapy of Gram-positive bacterial disease (e.g., diphtheria, staphylococcus). 1950s Streptomycin: Selman Waksman discovered a different kind of antibiotic, streptomycin. This was a turning point in the treatment of tuberculosis and Gram-negative bacterial diseases (e.g., cholera, E. coli). Drugs that act against infectious diseases will be discussed in greater detail in Module 04. Answer the questions based on what you have learned in this section. 1 of 2: How has historical use of chemicals contributed to the advancement of pharmacology? a) Weaponized poisons at higher doses were found to have therapeutic effects. b) Use of sulfa drugs lead to the development of the first synthetic antibacterial compounds. c) Historical use of natural compounds at ultra low doses resulted in therapeutic effects. d) Extraction of chemical compounds from man-made poisons that resulted in large-scale human epidemics led to the discovery of drugs still used today. Feedback: PRINCIPLES OF PHARMACOLOGY | PHAR 100 MODULE 01 PAGE 12 MODULE 01 COMPANION GUIDE PHAR 100 Correct response: b). Sulfa drugs were the first synthetic drugs used to treat bacterial disease and lead to the development of antibacterial compounds. 2 of 2: Which one of the historical drugs listed is still used clinically today? a) Ma Huang b) LSD c) Morphine d) Curare Feedback: Correct response: c). Morphine is the only drug listed that is still commonly used therapeutically. Ma Huang is no longer used in its own form in North America, but ephedrine has been isolated from it and is used to treat asthma. Curare is no longer used as a therapeutic agent due to safety concerns. LSD use is most often recreational; although some studies have shown it may have some therapeutic indications, it is not currently used as a therapeutic agent. Section 01 Summary In this section, you learned about some of the historical influences on modern pharmacology. You explored the role of ancient civilizations such as Greece, Egypt, and China, as well as the role poisons and religion had in influencing pharmacology. Finally, you explored two main categories of drugs that have been discovered throughout history: drugs that act directly on the brain and drugs that act again infectious diseases. In the next section, you will learn about the drug development process. Definitions: Drugs: Any substance received by a biological system that is not received for nutritive purposes, and which influences the biological function of the organism. This broad definition means that chemicals, biological agents, and herbal products are all considered drugs. Pharmacology: The science of drugs, including their uses, effects, and mechanisms of action. B.C.E: Before Common Era L S D: Lysergic acid diethylamide. A potent hallucinogenic drug that acts on the brain. Syphilis: A bacterial infection transmitted sexually through direct contact with a syphilis sore. Syphilis is easy to cure when diagnosed and treated in its earlier stages. Gram-positive: Bacteria with thick cells walls and no outer membrane. Gram-negative: Bacteria with thin cells walls and an outer membrane. Page Links: http://www.smithsonianmag.com/science-nature/whats-inside-a-2000-year-old-shipwreck-preserved- roman-pill-403649/?no-ist PRINCIPLES OF PHARMACOLOGY | PHAR 100 MODULE 01 PAGE 13