For thousands of years, humans have used a variety of sources with which to cure their ills, cast out devils, promote their well-being, relieve their misery, and control their fertility. Until the beginning of the twentieth century, the agents used were all of natural origin, including many derived from plants as well as elements such as antimony, sulfur, mercury, and arsenic. The sixteenth-century alchemist and physician Paracelsus used mercury and arsenic in his treatment of syphilis, worms, and other diseases that were common at that time; his cure rates, however, remain unknown. Many drugs used today have their origins in natural products. Antimony derivatives, for example, are used in the treatment of the nasty tropical disease leish-maniasis. These plant-derived products represent molecules that have been "forged in the crucible of evolution" and continue to supply the scientist with molecular scaffolds for new drug development.
Our story of modern drug discovery may be considered to start with the German physician and scientist Paul Ehrlich, often called the father of chemotherapy. Born in 1854, Ehrlich became interested in the ways in which synthetic dyes, then becoming a major product of the German fine chemical industry, could stain selectively certain tissues and components of cells. He reasoned that such dyes might form the basis for drugs that could interact selectively with diseased or foreign cells and organisms. One of Ehrlich’s early successes was his development of the arsenical "606"-patented under the name Salvarsan-as a treatment for syphilis. Ehrlich’s goal was to create a "magic bullet," a drug that would target only the diseased cell or the invading disease-causing organism and have no effect on healthy cells and tissues. In this he was not successful, but his great research did lay the groundwork for the successes of the twentieth century, including the discovery of the sulfonamides and the antibiotic penicillin. The latter agent saved countless lives during World War II. Ehrlich, like many scientists, was an optimist. On the eve of World War I, he wrote, "Now that the liability to, and danger of, disease are to a large extent circumscribed-the efforts of chemotherapeutics are directed as far as possible to fill up the gaps left in this ring." As we shall see in this volume, it is neither the first nor the last time that science has proclaimed its victory over Nature only to have to see this optimism dashed in the light of some freshly emerging infection.
From these advances, however, has come the vast array of drugs that are available to the modern physician. We are increasingly close to Ehrlich’s magic bullet: Drugs can now target very specific molecular defects in a number of cancers, and doctors today have the ability to investigate the human genome to more effectively match the drug and the patient. In the next one to two decades, it is almost certain that the cost of "reading" an individual genome will be sufficiently cheap that, at least in the developed world, such personalized medicines will become the norm. The development of such drugs, however, is extremely costly and raises significant social issues, including equity in the delivery of medical treatment.
The twenty-first century will continue to produce major advances in medicines and medicine delivery. Nature is, however, a resilient foe. Diseases and organisms develop resistance to existing drugs, and new drugs must constantly be developed. (This is particularly true for anti-infective and anticancer agents.) Additionally, new and more lethal forms of existing infectious diseases can develop rapidly. With the ease of global travel, these illnesses can spread from Timbuktu to Toledo in fewer than 24 hours and become pandemics. Hence the current concerns about avian flu. Also, diseases that have previously been dormant or geographically circumscribed may suddenly break out worldwide. (Imagine, for example, a worldwide pandemic of Ebola disease, and how this event would totally overwhelm public health agencies.) Finally, there are serious concerns regarding the possibility of man-made epidemics occurring through the deliberate or accidental spread of disease agents-including manufactured agents, such as smallpox with enhanced lethality. It is therefore imperative that the search for new medicines continues.
All of us at some time in our life will take a medicine, even if it is only aspirin for a headache. For some individuals, drug use will be constant throughout life. As we age, we will likely be exposed to a variety of medications-from childhood vaccines to drugs to relieve pain caused by a terminal disease. It is not easy to get accurate and understandable information about the drugs that we consume to treat diseases and disorders. There are, of course, highly specialized volumes aimed at medical or scientific professionals. However, such texts require their readers to possess a sophisticated knowledge base and experience. Advertising on television is widely available but provides only fleeting information, usually about only a single drug and designed to market rather than inform. The intent of this series of books, Drugs: The Straight Facts, is to provide the lay reader with intelligent, readable, and accurate descriptions of drugs; an explanation of why and how they are used; and information about their limitations, their side effects, and their future. It is our hope that these books will provide readers with sufficient information to satisfy their immediate needs and to serve as an adequate base for further investigation and for asking intelligent questions of health care providers.
The present volume, Weight-Loss Drugs, discusses a group of drugs that are employed in the control of weight. The twenty-first century presents an ironic picture of a world population expanding simultaneously in both number and size. The ready availability of highly palatable, energy-dense foods has, together with major lifestyle changes, resulted in a population that is increasingly overweight or obese. This epidemic of weight increase is not confined to adults, but is also an increasingly serious problem with children. To be sure, this epidemic is not uniform-the world is still dramatically unequal, and the number of obese individuals is counterbalanced by an even greater number of people for whom the arrival of the next meal is uncertain.
How to tackle this global epidemic of obesity is a major problem. It is both a medical and a public health problem. It is quite clear that public health measures must be a major component of any approach; and that these interventions, involving diet, exercise, and education, must start at an early age. Intervention with drugs will also be a part of an integrated approach, but the complexities of the physiological processes that control feeding behavior make this a very difficult task. The drugs that are available and that are discussed in this volume are far from satisfactory, and some have been associated with extremely serious side effects, including death, and virtually all are subject to abuse. Awareness of these limitations is a vital component of any effort to tackle the problems of overweight and obesity.
David J. Triggle, Ph.D.
University Professor School of Pharmacy and Pharmaceutical Sciences State University of New York at Buffalo
Source: "Drugs The Straight Facts: Weight-Loss Drugs," Chelsea House, 2009
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