Pharm 100 - Lesson A.1
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“All substances are poisons.There is none which is not a poison.The right dose differentiates a poison and a remedy.”
West and Central Africa: Poisons used in ordeal trials
- The purpose of ordeal trials was to identify sorcerers.
- the drug physostigmine (used in the treatment of glaucoma) which is derivedfrom the Calabar bean.
Amazon: Arrow poisons.
- The natives of the Amazon dipped their arrows in a poison known as Curare
- Curarecombines with the receptors in the muscle normally reserved for acetylcholine. By doing so, it preventsacetylcholine combining with the muscle and therefore prevents muscle contraction
- a valuable drug in the hands of the skilled anaesthetist a small dose of curare to the patient, muscle relaxation isachieved, thereby greatly facilitating the surgeon’s work.
Ergot: Fungus on rye.
- a fungus which grows upon the ears of rye
- terrible epidemics occurred when ground into bread
- Burning in the limbs: (St. Anthony’s Fire)
- Constriction of blood vessels: limbs becoming starved of their blood became black and gradually died
- Mental frenzy, hallucinations and convulsions: resemble LSD
- Abortion: Ergot caused violent contractions of the uteru Dr. John Stearns of New York State introduced ergot into modern medicine. He called itPulvis Parturiens
- Ergotamine: Migraine is believed to be caused bypulsation of the blood vessels (arterial) which carry blood to the head. Ergotamine constrictsthese blood vessels and reduces the amplitude of the pulsation of these blood vessels.
- Ergonovine: After the baby hasbeen delivered and the placenta has separated from the wall of the uterus, there can be a large lossof blood. Ergonovine causes the uterus to contract forcibly and arrests the bleeding.
Early Chinese Medicine
emperor Shen Nung tasted all known drugs and classified them according to taste. Thedrug Ma Huang was classified as a medium drug. This drug was widely used in Chinese medicine forcoughs, influenza and fevers. In the modern era, ephedrine has been isolated from it. This drug hasbeen used in asthma and other conditions.
Early Egyptian Medicine
In the 19th century, a great deal of interest was shown in ancientEgyptian history and careful search of Egypt revealed a number of papyri. These papyri or documentscontained a great deal of ancient Egyptian writings. One of these papyri was discovered by Ebers and hence is known as the Ebers Papyrus. It dates from the year 1550 B.C. Careful examination of thispapyrus reveals that it was intended to be a textbook of drug use for medical students. Scholars have shown that this papyrus contained many true observations on the use of drugs, particularly on purgatives. Purgatives are drugs used tocause bowel movements. Some of the drugs that were recommended for use were castor oil, figs and senna.
Early Greek Medicine
- In the year 380 B.C., Theophrastus, a pupil of Aristotle, wrote a textbook on Therapeutics whichincludes opium. Opium is obtained from the Opium poppy (Papaver somniferum). To obtain the opium,the poppy bulb is slashed and the fluid which emerges is dried and constitutes opium
- Seturner, a pharmacist, working in a pharmacy store inPaderborn, Germany in 1803, isolated crystals of morphine from opium and tested the pure substance onhimself and three companions. Opium was found to contain approximately 10% morphine. Seturnercoined the name morphine from Morpheus, God of dreams. Its greatest virtue is that it is able to relievepain of very great intensity. Morphine is also valuable in relieving anxiety and it is given to patients prior to an operation in order to remove their apprehension
- Morphinemay be chemically converted to Heroin. Heroin is not generally available for therapeutic use because ofits liability for abuse. It is only available for use in Canada for treatment of terminal cancer pain inspecial treatment units.
- it has been shown that morphine acts by combining with receptors in the nervoussystem normally utilized by pain-relieving chemicals produced in the nervous system, known as enkephalins and endorphins.
- In addition to morphine, opium contains 0.5% of codeine. Codeine is widely used for pain relief andis a constituent of Tylenol 1, an over-the-counter drug in Canada.
Spain, Persia (Iran) and Mesopotamia (Iraq)
In the 10th and 11th centuries, great medical schools were found in Islamic cities located in Spain,Persia, and Mesopotamia. During this period, the plant Colchicum was introduced for gout. In the modern era the chemical colchicine has been extracted from this plant and is still a very valuable drug inthe treatment of gout.
- Digitalis purpurea (foxglove) was introduced into medicine in 1785 by William Withering, who wasboth a physician and a botanist.
- The digitalis drugs are extremely useful for patients with certain forms of heart disease. When the heart muscle in a healthy individual is stretched by blood entering the heart, it is able tocontract forcefully and eject the blood with great force. In certain forms of heart disease, the heartmuscle becomes weak. The heart muscle cannot then expel the blood with force and as a result, the flowof blood through small blood vessels is decreased. When this medication is given to patients with thistype of heart disease, there is a marked improvement in performance of the heart muscle.
- While thepowdered leaf of digitalis was used in therapeutics for many years, modern physicians now use the majorpure component, namely digoxin (Lanoxin), to treat patients. Digoxin is also used to treat certain typesof disordered rhythms of the heart. It is rumoured that Withering learned about this flower and itstherapeutic effects from an “old Shropshire lady” and this has inspired a painting entitled “Goldensovereigns for the secret of the Wayside flower”
- This explosive material used in the manufacture of dynamite is valuable for treatment of the disease Angina pectoris (Latin: choking in the chest)
- Lauder Brunton (1867)suggested the use of amyl nitrite in the treatment of the disease. This suggestion was based on a reportthat amyl nitrite lowered blood pressure in animals and man. He demonstrated its efficacy on himself in1867 as he was a sufferer from angina. He then used it successfully on other patients. The effect of amylnitrite is short lived and a longer acting agent was desirable
- William Murrell (1879) showed that thechemically related compound, nitroglycerin, exerted a similar effect to that of amyl nitrite but ofconsiderably greater duration. In angina pectoris, the pain in the chest is due to insufficient oxygenavailability to heart muscle. Nitroglycerin dilates blood vessels in the heart and elsewhere inthe body. This action of nitroglycerin increases the supply of oxygen to the heart and decreases the oxygen requirement of the heart, thus relieving pain.
- Quinine is a constituent of the bark of the Cinchona tree which is indigenous to regions of SouthAmerica. In 1639 a monk in Lima, Peru wrote “A tree grows which they call the fever tree – it hasproduced miraculous results in Lima”. For two centuries, powdered bark of the Cinchona tree was used therapeutically.
- The situation changed in 1820 when two French pharmacists, Pelletier and Caventou,isolated the active principle from Cinchona bark and named it quinine. A statue in honour of Pelletierand Caventou has been erected in Paris and a stamp in their honour was issued some years ago. Quinineis an important drug in the treatment of malaria.
- A Dutch sea captain, when taking quinine, noticed that the drug improved his disordered heart rhythm and he reported this finding to an Amsterdam cardiologist. This report led to the introductioninto therapeutics of quinidine, a close relative of quinine, for treatment of certain disorders of heartrhythms. Disorders of heart rhythms are known by the medical name, arrhythmias.
- Extracts of the Rauwolfia plant had long been used in Indian medicine to reduce tension and anxiety and to lower blood pressure. However, outside India, little attention was paid to theserauwolfia extracts. In the 1950’s, a Swiss pharmaceutical company isolated the chemical, reserpine, fromthe rauwolfia plant and studied its action in both animals and patients. When reserpine was given tomonkeys or dogs who were fierce and aggressive, animals became placid within a few days. Patientswho were difficult to manage behaved reasonably after receiving reserpine and this drug enabled manypatients to return home and to live at peace with their families.
- Reserpine remains a valuable drug for the treatment of hypertension (high bloodpressure)
Chlorpromazine was obtained by synthetic procedures. It is a valuable drug and converts the anxious, tense, and hostile person into someone who is placid and tranquil.
Lysergic Acid Diethylamide (LSD)
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 a chemical,LSD, which was similar in chemical structure to ergotamine and ergonovine
Father of chemotherapy; born Germany 1854. He designed complexes of arsenic and organic molecules (organoarsenicals) which selectively bound to parasites. These studies led to a dramatic cure for syphilis in the early 20th century.
Introduced sulfa drugs in 1930’s in Germany. These were the first successful synthetic drugs for the treatment of bacterial disease.
St. Mary’s Hospital, London, 1929. 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 disease caused by grampositive bacteria.
Discovered streptomycin in 1943. This was a turning point in the chemotherapyof tuberculosis and diseases caused by gram-negative bacteria.
- The noted British scientist, Humphrey Davy showed in 1800 that nitrous oxide hadthe ability to prevent pain and suggested that it be tried in surgery. However, this suggestion wentunheeded for 42 years. In the early 1840’s, a chemist-lecturer known as Colton gave publicdemonstrations of nitrous oxide known then as “laughing gas” for a 25 cent admission fee.
- In 1818, Faraday pointed out that ether had similar properties to nitrous oxide.
- Morton, who was associated with Wells in the practice of dentistry, entered Harvard Medical School While still a medical student, he requested permission from the professor of surgery to try ether in a surgical operation. The professor of surgery was extremely skeptical but agreed to give Morton an opportunity. The first operation under ether anaesthesia was carried out at the Massachusetts General Hospital
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