The History, Use And Effectiveness Of Medicinal Drugs The science and the art of treating, diagnosing, and preventing disease is known as the field of Medicine. It is a science because it is based on knowledge, gained through careful study and experimentation. It is an art because it depends on how skillfully doctors and other medical workers apply this knowledge when dealing with patients. In prehistoric times, Medicine was a vague field, mostly incorporated with magic and superstition. The first physicians were the tribal priests who tried to pacify the gods or drive out the evil spirits. In ancient times, the Egyptian civilization was the first group of people to make important medical progress. The world's first physician known by name was the Egyptian Imhotep, who lived about 2700 B.C. During the Middle Ages, the Moslems made enormous contributions to medicine in their use of drugs. The first truly scientific studies of the human body began during the Renaissance. The scientific study of disease developed during the 1800's and was led by Rudolf Virchow, a German physician and scientist. The study of the effects that chemicals have on living things is called pharmacology. It is a recent science, but it is linked with one of the oldest -- the giving of remedies to relieve disease. Pharmacology began during the 1900's with the rise of chemistry. For the first time, the crude plants and mineral materials that act on living tissues could be analyzed, separated and used as a drug or medicine. Many early treatments didn't actually heal the patient, but just gave him a slight euphoria from the pain. In today's culture, some of the drugs of our ancestors are considered to be harmful and are classified as illegal. Examples of such are marijuana and opium which were key in the Chinese, and Native American medical system. The origin of drugs vary from common plants, (Aspirin, Digitalis, Ergot, Opium, Quinine, Reserpine) to minerals, (Boric Acid, Epsom Salts, Iodine) or synthetic compounds. The difference in a drug from being helpful to being deadly is in the dosage that is administered. This process is known as Serum Monitoring. In addition to determining the dosage of the medication, the "risk-to-benefit" ratio of the drug must be considered as well. A drug might heal one ailment but in turn cause another problem. An example of this is the drug niridazole, which helps schistosomaisis but is known to cause cancer. The national government has some control in the area of drug use and has issues certain regulations. For example drugs have been classified into two categories; Proprietary and Ethical. Proprietary drugs are sold over the counter and promote less addiction that Ethical drugs which can only be obtained legally with a written prescription from a registered doctor. Jurisdiction of illegal drugs which produce a strong addiction is given to the Drug Enforcement Administration of the U.S. Department of Justice. The most important factor about doctor prescribed drugs is that the doctor is aware of any other drugs which the patient might be taking, and therefore prevent adverse reactions between medications. ASPIRIN Acetylsalicylic acid, commonly known as aspirin is one of the most widely used analgesics in the world". Used by Ancient Greeks and Native Americans it was used to reduce fever and pain and could also be used as an anti-inflammatory agent. It interferes with tissue contractions of the prostaglandin which are chemicals involved in the production of inflammation and pain. It modifies the temperature-regulating portion of the brain, dilating blood vessels in the skin and increases perspiration which in turn cools the body reducing fever. _ _ Aspirin also prevents the production of thromboxane which plays a key role in coagulation cascade, which slows blood clotting and is helpful in preventing heart attacks and strokes. It is derived from the bark of the willow tree, and its activity is produced from chemicals called salicylates. _ Charles Gerhardt a French chemist first synthesized the acetyl derivative from the salicylic acid in 1853 developing the first type of aspirin, but Felix Hoffman a German chemist was the first to realize its medical value in 1893. Over a long period of constant use aspirin can cause iron deficiency, gastric ulcers, kidney damage and if given to children having chicken pox or influenza could cause the risk of contracting the fatal brain disease known as Reye's syndrome. Usage of Aspirin varies. Short term use of about 3"6-10 days" is recommended without physician supervision but long term use requires periodic evaluations and dosage restrictions. Side effects also vary with the individual. They could include mild drowsiness, allergic reactions, skin rash, hives, nasal discharge, stomach irritation, heart burn, nausea, vomiting, constipation and in extreme cases erosion of the stomach lining, activation of a peptic ulcer, bone marrow depression, hepatitis, and kidney damage. Overdosing on this drug produces side effects such as stomach distress, nausea, vomiting, ringing in the ears, sweating, stupor, deep and rapid breathing, twitching, and convolutions. Aspirin was the first non-steroidal anti-inflammatory drug (NASID) but by far not the last. One and a half million Americans suffer from heart attacks each year and about 200,000 suffer from heart related deaths. Aspirin helps millions of people each year because it prevents premature blood clotting. No other NSAID can compare with the price or efficacy of aspirin but ibuprofen can come very close. Where aspirin might take up to 12 doses to relieve pain over a long period a strong dosage of ibuprofen could help the patient in one dose. Even though Ibuprofen works as well as aspirin, care must be taken with its usage. It does not irritate the stomach as much as aspirin, however, it could damage the kidneys. Another factor to consider between aspirin and ibuprofen is price. A thirty day supply of aspirin could cost $3.95 whereas a thirty day supply of ibuprofen could cost $22.95. New studies prove that aspirin also has been prescribed to counteract migraine headaches, cataracts, gallstones, diabetic eye problems, insomnia, weight loss for women, wheat intolerance, leprosy and even hip replacement complications. SULFA DRUGS Sulfonamides, the chemical name for sulfa drugs were the first chemical compounds to provide safe and effective treatment for most common bacterial infections. Before the use of penicillin after the mid 1940's, Sulfa drugs played a major role in antibacterial treatment. This resulted in a sharp decrease in deaths from bacterial infections. In today's modern medical system, sulfa drugs are used to treat patients of urinary tract infections. Sulfa Sulfa in its natural form is a tasteless, odorless, light yellow solid, once forcefully fed to children in the belief that it was good for their health. Sulfa compounds, found in dairy products and eggs, are an essential dietary ingredient. Instead of killing bacteria, sulfa drugs prevent them from multiplying, making it easier for the bodies' natural defenses to overcome and destroy them. Bacteria require certain chemicals known as 6"para-aminobenzoic acids" to multiply, sulfa drugs resemble the chemical structure of the acids and can be absorbed by the bacteria. The sulfa drugs combine with the outer shells of the bacteria, therefore not allowing the real acids to penetrate. All bacteria are not reactant to sulfonamides and have to be screened by the physician to see if it is necessary to take a more serious action. Sulfa drugs can be taken orally which is most common, or by an injection just beneath the skin. In former medical history they were used to treat pneumonia, dysentery, blood poising, cellulitis, bubonic plague, and conjunctivitis. Since the recognition of penicillin as an effective bacterial assailant and some bacteria becoming resistant to sulfonamides physicians have been less likely to prescribe them since the late 1940's. The combination of sulfamethoxazole and trimethoprim have given a new usage for sulfa drugs, now they can be used for such ailments as middle ear infections, shigellosis and recurring urinary tract infections. Paul Gelmo, in 1908, discovered the first sulfa drug accidentally while looking for dyes to better color woolen clothing. In 1953, a German pathologist named Gerhard Domagk reported that this dye killed streptococcal bacteria in mice. In the beginning, doctors encountered major problems when administering the drug sulfanilamide because it crystallized in the urine of the patient causing kidney damage. Later development of water soluble sulfa drugs solved the problem of crystallization in the urine and gave the hope of a longer life span to people. ANTIBIOTICS In the ancient language of Greek the term antibiotic meant "against life". They are chemical substances produced by one organism that in turn is destructive to another. This process traditionally has been called antibiosis and is the opposite of symbiosis. An antibiotic is a type of chemotherapeutic agent which has a toxic effect on certain types of disease-producing microorganisms without acting dangerously on the patient. Some chemotherapeutic agents differ from antibiotics in that they are not secreted by microorganisms, as are antibiotics, but rather are made synthetically in a chemical laboratory. Examples of these are quinine, used against malaria; arsphenamine, used against syphilis; the sulfa drugs, used against a wide variety of diseases, notably pneumonia; and the quinolones, used against hospital-derived infections (zoonoses). A few antibiotics, among them penicillin and chloramphenicol, have now been produced synthetically also. The first observation of what would now be called an antibiotic effect was made in the 19th century by the French chemist Louis Pasteur, who discovered that certain saprophytic bacteria can kill anthrax germs. Around the year 1900, the German bacteriologist Rudolf von Emmerich isolated a substance called pyocyanase, which can kill the germs of cholera and diphtheria in the test tube. It was not useful, however, in curing disease. In the 1920's, the British bacteriologist Sir Alexander Fleming, who later discovered penicillin, found a substance called lysozyme. He found it in many of the secretions of the body such as tears and sweat, and in certain other plant and animal substances. Lysozyme has a strong antimicrobial activity, but mainly against harmless bacteria. (Sir Alexander Fleming) Discovery of Penicillin The research of Alexander Fleming in 1928 led to the discovery of penicillin, an important antibiotic derived from the mold Penicillin notatum. Penicillin is effective against a wide range of disease-causing bacteria. It acts by killing bacteria directly or by inhibiting their growth. Penicillin, the archetype of antibiotics was discovered by accident in 1928 by Fleming. He showed its effectiveness in laboratory cultures against many disease-producing bacteria, such as those that cause gonorrhea and certain types of meningitis and bacteria (blood poisoning); however, he performed no experiments on animals or humans. Penicillin was first used on humans by the British scientists Sir Howard Florey and Earnest Chain during the 1940-41 winter. The first antibiotic to be used in the treatment of human diseases was tyrothricin (one of the purified forms of which was called gramicidin), which was isolated from certain soil bacteria by the American bacteriologist, Rene Jules Dubos in 1939. This substance was too toxic for general use, but it is employed in the external treatment of certain infections. Other antibiotics produced by actinomycetes, filamentous and branching bacteria, occurring in soil have proved more successful. One of these is streptomycin, discovered in 1944 by the American microbiologist Selman Waksman and his associates. It is effective against many diseases, including several in which penicillin is useless, especially tuberculosis. Since then, such antibiotics as chloramphenicol, the tetracyclines, erythromycin, neomycin, nystatin, amphotericin, cephalosporins, and kanamycin have been developed and may be used in the treatment of infections caused by some bacteria, fungi, viruses, rickettsia, and other microorganisms. In clinical treatment of infections, the causative organism must be identified and the antibiotics to which it is sensitive must be determined in order to select an antibiotic with the greatest probability of killing the infecting organism. Recently, strains of bacteria have arisen that are resistant to commonly used antibiotics; for example, gonorrhea-causing bacteria that high doses of penicillin are not able to destroy may transfer this resistance to other bacteria by exchange of genetic structures called plasmids. Some bacteria have become simultaneously resistant to two or more antibiotics by this mechanism. New antibiotics that circumvent this problem, such as the quinolones, are being developed. The cephalosporins, for instance, kill many of the same organisms that penicillin does, but they also kill strains of those bacteria that have become resistant to penicillin. Often the resistant organisms arise in hospitals, where antibiotics are used most often, especially to prevent infections from surgery. Another problem in hospitals is that many old and very ill patients develop infections from organisms that are not pathogenic in healthy persons, such as the common intestinal bacterium Escherichia coli. New antibiotics have been synthesized to combat these organisms. Fungus infections have also become more common with the increasing use of chemotherapeutic agents to fight cancer, and more effective antifungal drugs are being sought. The search for new antibiotics continues in general, as researchers examine soil molds for possible agents. Among those found in the 1980s, for example, are the monobactams", which may also prove useful against hospital infections. Antibiotics are found in other sources as well, such as the family of magainins discovered in the late 1980s in frogs; although untested in humans as yet, they hold broad possibilities". Antibiotics have also been used effectively to foster growth in animals. Concern has arisen, however, that this widespread use of antibiotics in animal feed can foster the emergence of antibiotic-resistant organisms that may then be transmitted to human beings. ANTIHISTAMINES Antihistamines are drugs that block the action of histamine. Histamine, also known as histamine phosphate, an amine (beta-imidazolyl-ethylamine, ergamine, or ergotidime) that is a normal constituent of almost all animal body cells. Histamine is also found in small quantities in ergot and purified meat products and is produced synthetically for medicinal purposes. In the body, it is synthesized in a type of leukocyte called a basophil or mast cell. In response to certain stimuli, these cells release histamine which immediately cause a dilation of the blood vessels. This dilation is accompanied by a lowering of blood pressure and an increased permeability of the vessel walls, so that fluids escape into the surrounding tissues. Such reaction may result in a general depletion of vascular fluids, causing a condition known as histamine poisoning or histamine shock. Allergic reactions in which histamine is released, resulting in the swelling of body tissue, show similarities to histamine poisoning; the two may be basically similar, and the two conditions are treated similarly. The release of histamine might also be partly responsible for difficult breathing during an asthma attack. In the 1930s the Italian pharmacologist Daniel Bovet, who live in 1907-1972, working at the Pasteur Institute in Paris, discovered that certain chemicals counteracted the effects of histamine in guinea pigs. The first antihistamines were too toxic for use on humans, but by 1942 they had been modified for use in the treatment of allergies". More than 25 antihistamine drugs are now available. Histamine also causes contraction of involuntary muscles, especially of the genital tract and gastrointestinal canal, with an accompanying secretion by associated glands. Because histamine stimulates the flow of gastric juices, it is used diagnostically in patients with gastric disturbances. One drug effective in treating gastric ulcers acts by antagonizing the action of histamine. The ability of the body to localize infections may be due to the secretion of histamine and the subsequent increased local blood supply and increased permeability of the blood vessels. Antihistamines are used primarily to control symptoms of allergic conditions such as hay fever. They alleviate runny nose and sneezing and to a lesser extent, minimize conjunctivitis and breathing difficulties. Antihistamines can also alleviate itching and rashes caused by food allergy. Chemically, antihistamines comprise several classes and a person who does not obtain relief from one type may benefit from another. Side effects of these drugs can include drowsiness, loss of concentration, and dizziness. People taking antihistamines should not drink alcoholic beverages or perform tasks requiring mental alertness, such as driving. A few antihistamines, such as terfenadine and astemizole, are nonsedating. Although antihistamines are included in many over-the-counter cold remedies, their usefulness in such preparations is questionable. Antihistamines may relieve symptoms of allergy accompanying a cold, or they may have an anticholinergic effect that dries cold secretions, but they do not have any influence on viral infections, which are the cause of colds . Moreover, the drying effect may be undesirable, especially for persons with bronchial infection, glaucoma, or urinary tract difficulties. Although there are not many alternate drugs that have the same properties as antihistamines some non-drug treatments are also effective against allergies. The use of High-Efficiency-Particulate-Arresting (HEPA) filters, eliminate microscopic particles which cause allergies. The use of mattress covers decrease the reaction to dust mites in the mattress itself. These treatments are not equivalent to drug use but could decrease the amount of allergenic agents in the household air. Vitamin C also plays a role in the elimination of allergic reactions. Researchers at the University of California have found that patients that suffer from atopic dermatitis benefited from large dosages of vitamin C. THE HISTORY, USE AND EFFECTIVENESS OF VITAMINS AND NUTRIENT SUPPLEMENTS A Vitamin is any organic compound required by the body in small amounts for metabolism, to protect health, and for proper growth in children. Vitamins also assist in the formation of hormones, blood cells, the chemicals of the nervous-system, and genetic material. The various vitamins are not chemically related, and most differ in their physiological actions. They generally act as catalysts, combining with proteins to create metabolically active enzymes that in turn produce hundreds of important chemical reactions throughout the body. Without vitamins, many of these reactions would slow down or stop. The intricate ways in which vitamins act on the body, however, are still far from clear. The 13 well-identified vitamins are classified according to their ability to be absorbed in fat or water. The fat-soluble vitamins A, D, E, and K are generally consumed along with fat-containing foods, and because they can be stored in the body's fat, they do not have to be consumed every day. The water-soluble vitamins, the eight B vitamins and vitamin C, cannot be stored and must be consumed frequently, preferably every day. The body can manufacture only vitamin D, and all others must be derived from the diet. Lack of them causes a wide range of metabolic and other dysfunctions. In the U.S., since 1940, the Food and Nutrition Board of the National Research Council has published recommended dietary allowances for vitamins, minerals, and other nutrients. Expressed in milligrams or international units for adults and children of normal health, these recommendations are useful guidelines not only for professionals in nutrition but also for the growing number of families and individuals who eat irregular meals and rely on prepared foods, many of which are now required to carry nutritional labeling. A well-balanced diet contains all the necessary vitamins, and most individuals who follow such a diet can correct any previous vitamin deficiencies. However, persons who are on special diets, who are suffering from intestinal disorders that prevent normal absorption of nutrients, or who are pregnant or lactating may need particular vitamin supplements to bolster their metabolism. Beyond such real needs, vitamin supplements are also often believed to offer "cures" for many diseases, from colds to cancer; but in fact the body quickly eliminates most of these preparations without absorbing them. In addition, the fat-soluble vitamins can block the effect of other vitamins and even cause severe poisoning when taken in excess. Vitamin A is a pale yellow primary substance derived from carotene. It affects the formation and maintenance of skin, mucous membranes, bones, and teeth, vision, and reproduction. An early deficiency symptom is night blindness which is the difficulty in adapting to darkness. Other symptoms are excessive skin dryness and lack of mucous membrane secretion. This allows bacterial invasion, and dryness of the eyes due to a malfunctioning of the tear glands, a major cause of blindness in children in developing countries. The body obtains vitamin A in two ways. One is by manufacturing it from carotene, a vitamin precursor found in such vegetables as carrots, broccoli, squash, spinach, kale, and sweet potatoes. The other is by absorbing ready-made vitamin A from plant-eating organisms. In animal form, vitamin A is found in milk, butter, cheese, egg yolk, liver, and fish-liver oil. Although one-third of American children are believed to consume less than the recommended allowance of vitamin A, sufficient amounts can be obtained in a normally balanced diet rather than through supplements. Excess vitamin A can interfere with growth, stop menstruation, damage red blood corpuscles, and cause skin rashes, headaches, nausea, and jaundice. Known also as vitamin B complex, these are fragile, water-soluble substances, several of which are particularly important to carbohydrate metabolism. Thiamine, or vitamin B1, a colorless, crystalline substance, acts as a catalyst in carbohydrate metabolism, enabling pyruvic acid to be absorbed and carbohydrates to release their energy. Thiamine also plays a role in the synthesis of nerve-regulating substances. Deficiency in thiamine causes beriberi, which is characterized by muscular weakness, swelling of the heart, and leg cramps and may, in severe cases, lead to heart failure and death. Many foods contain thiamine, but few supply it in concentrated amounts. Foods richest in thiamine are pork, organ meats such as liver, heart, and kidney, brewer's yeast, lean meats, eggs, leafy green vegetables, whole or enriched cereals, wheat germ, berries, nuts, and legumes. Milling of cereal removes those portions of the grain richest in thiamine; consequently, white flour and polished white rice may be lacking in the vitamin. Widespread enrichment of flour and cereal products has largely eliminated the risk of thiamine deficiency, although it still occurs today in nutritionally deficient alcoholics. Riboflavin, or vitamin B2, like thiamine, serves as a coenzyme, one that must combine with a portion of another enzyme to be effective, in the metabolism of carbohydrates, fats, and, especially, respiratory proteins. It also serves in the maintenance of mucous membranes. Riboflavin deficiency may be complicated by a deficiency of other B vitamins; its symptoms, which are not as definite as those of a lack of thiamine, are skin lesions, especially around the nose and lips, and sensitivity to light. The best sources of riboflavin are liver, milk, meat, dark green vegetables, whole grain and enriched cereals, pasta, bread, and mushrooms. Niacin, or vitamin B3, also works as a coenzyme in the release of energy from nutrients. A deficiency of niacin causes pellagra, the first symptom of which is a sunburnlike eruption that breaks out where the skin is exposed to sunlight. Later symptoms are a red and swollen tongue, diarrhea, mental confusion, irritability, and, when the central nervous system is affected, depression and mental disturbances. The best sources of niacin are liver, poultry, meat, canned tuna and salmon, whole grain and enriched cereals, dried beans and peas, and nuts. The body also makes niacin from the amino acid tryptophan. Megadoses of niacin have been used experimentally in the treatment of schizophrenia, although no experimental proof has been produced to show its efficacy. In large amounts it reduces levels of cholesterol in the blood, and it has been used extensively in preventing and treating arteriosclerosis. Large doses over long periods cause liver damage. Pyridoxine, or vitamin B6, is necessary for the absorption and metabolism of amino acids. It also plays roles in the use of fats in the body and in the formation of red blood cells. Pyridoxine deficiency is characterized by skin disorders, cracks at the mouth corners, smooth tongue, convulsions, dizziness, nausea, anemia, and kidney stones. The best sources of pyridoxine are whole (but not enriched) grains, cereals, bread, liver, avocados, spinach, green beans, and bananas. Pyridoxine is needed in proportion to the amount of protein that is consumed. Cobalamin, or vitamin B12, one of the most recently isolated vitamins, is necessary in minute amounts for the formation of nucleoproteins, proteins, and red blood cells, and for the functioning of the nervous system. Cobalamin deficiency is often due to the inability of the stomach to produce glycoprotein, which aids in the absorption of this vitamin. Pernicious anemia results, with its characteristic symptoms of ineffective production of red blood cells, faulty myelin (nerve sheath) synthesis, and loss of epithelium the membrane lining of the intestinal tract. Cobalamin is obtained only from animal sources such as liver, kidneys, meat, fish, eggs, and milk. Vegetarians are advised to take vitamin B12 supplements. Folic acid, or folacin, is a coenzyme needed for forming body protein and hemoglobin; its deficiency in humans is rare. Folic acid is effective in the treatment of certain anemias and sprue. Dietary sources are organ meats, leafy green vegetables, legumes, nuts, whole grains, and brewer's yeast. Folic acid is lost in foods stored at room temperature and during cooking. Unlike other water-soluble vitamins, folic acid is stored in the liver and need not be consumed daily. Pantothenic acid, another B vitamin, plays a still-undefined role in the metabolism of proteins, carbohydrates, and fats. It is abundant in many foods and is manufactured by intestinal bacteria as well. Biotin, a B vitamin that is also synthesized by intestinal bacteria and widespread in foods, plays a role in the formation of fatty acids and the release of energy from carbohydrates. Its deficiency in humans is unknown. This well-known vitamin is important in the formation and maintenance of collagen, the protein that supports many body structures and plays a major role in the formation of bones and teeth. It also enhances the absorption of iron from foods of vegetable origin. Scurvy is the classic manifestation of severe ascorbic acid deficiency. Its symptoms are due to loss of the cementing action of collagen and include hemorrhages, loosening of teeth, and cellular changes in the long bones of children. Assertions that massive doses of ascorbic acid prevent colds and influenza have not been borne out by carefully controlled experiments. In other experiments, however, ascorbic acid has been shown to prevent the formation of nitrosamines which are compounds found to produce tumors in laboratory animals and possibly also in humans. Although unused ascorbic acid is quickly excreted in the urine, large and prolonged doses can result in the formation of bladder and kidney stones, interference with the effects of blood-thinning drugs, destruction of B12, and the loss of calcium from bones. Sources of vitamin C include citrus fruits, fresh strawberries, cantaloupe, pineapple, and guava. Good vegetable sources are broccoli, Brussels sprouts, tomatoes, spinach, kale, green peppers, cabbage, and turnips. This vitamin is necessary for normal bone formation and for retention of calcium and phosphorus in the body. It also protects the teeth and bones against the effects of low calcium intake by making more effective use of calcium and phosphorus. Also called the sunshine vitamin, vitamin D is obtained from egg yolk, liver, tuna, and vitamin-D fortified milk. It is also manufactured in the body when sterols, which are commonly found in many foods, migrate to the skin and become irradiated. Vitamin D deficiency, or rickets, occurs.