How Medicines Work

The following sections are included:

• Table of contents
• Foreword
• Preface
• Biographical Information
• History
• Acknowledgments

The introductory chapter will describe the two-page format that will be used to illustrate how a selected medicine works. First, the disease, together with symptoms and patient profiles, will be described with the prescribing information and composition of the medicine. The second part is the description of the normal biology of the system, which will combine relevant parts of organic chemistry, organ biochemistry, endocrinology, biochemical pharmacology, and clinical chemistry. The integrated information will be used to gain understanding of the disease perturbations, together with the mechanism of action of the medicine. The medicines selected in this chapter will illustrate the functions of enzymes and protein receptors and how related diseases can be treated with recently approved medicines. Ethnic differences in diseases and medicines will be illustrated with variabilities in lactose tolerance, which is a common excipient in tablets, as well as a common variant of alcohol dehydrogenase, which can reduce the effectiveness of nitroglycerine for the treatment of angina. The final section of the chapter reviews the role of the liver and kidney in detoxification of small molecule medicines and their metabolites.

The ingestion of food provides the building blocks of life, which include the macromolecules, nucleic acids, proteins, polysaccharides, and lipids. This chapter will describe the organ biochemistry of the mouth, stomach, small and large intestine, as well as the pancreas and liver. The biochemistry provides an understanding of the diseases that occur in the digestive systems and the mechanism of action of the medicines used to treat these diseases. Although many of the medicines covered in the book involve recent approvals from the FDA, this chapter will include heavily prescribed medicines such as statins for treatment of elevated cholesterol levels and a drug to stimulate insulin secretion in diabetes. The use of medicines to regulate nucleic acid metabolism in the liver can interfere in the supply of nucleotides required for lymphocyte proliferation and offer therapeutic options for diseases ranging from cancer, viral infections, and autoimmune disorders.

The survival of life in a hostile environment includes the hazards of intaking essential nutrients of oxygen, water, and food. Food provides the building blocks for the essential molecules of the body and energy needed for the required processes of biosynthesis, catabolism, movement, and transport within the body. The organs involved in nutrient intake and their primary defense systems are shown in the introduction. Although the impact of viruses on the lung and the defensive systems are listed here, the biology of viruses as well as related diseases and medicines are described in detail in Chapter 7. However, this chapter does list examples of standard and newly developed medicines to treat the diseases of the eye, lung, skin, and blood cells.

Homeostasis is essential to the healthy functioning of the body and an imbalance in one of these intricate systems is the origin of many diseases. For example, in aging, the control mechanisms of homeostasis can operate at reduced efficiency. Genetic mutations and certain life styles can also result in diseases related to significant disturbances in homeostasis. This chapter will describe drugs that are used to treat prevalent diseases, namely, anemia, hypothyroidism, diabetes, blood pressure, and the disease cluster of inflammation, aging, and cancer. The drugs selected in this book represent both recently approved drugs resulting from medical innovations but are currently used in restricted patient groups and drugs, which have been the mainstay of healthcare for many years and are widely prescribed to the US population. Many of the drugs described in this chapter represent top selling brands for common diseases such as hypothyroidism, diabetes, blood pressure, and inflammation.

Researchers are examining the biology behind disturbances of the brain and connections between distinct psychiatric conditions, such as "anxiety" or "psychosis." The concept of a clear demarcation between such conditions has largely been disproved. We now have the understanding that disorders shade into each other, there are no hard dividing lines and patients can exhibit a mixture of symptoms from different disorders. For example, a clear diagnosis of depression can be accompanied by another disorder such as anxiety.

In this context, the discovery of the biological basis of disorders will allow greater insights into commonalities and differences in brain disturbances. The chapter will describe both commonly prescribed drugs such as vicodin as well drugs recently approved by the FDA to treat a variety of disorders. New discoveries in biology has enabled the development of new therapies. An example is the calcitonin generelated peptide, which is a potent vasodilator and has enabled the development of drugs for the treatment of migraine.

One group of drugs has been developed to treat diseases that result from disturbances of the blood–brain barrier as well as neurodegenerative diseases. Discussion of the treatment of psychiatric and neurological disorders will be organized on the basis of the associated neurotransmitters. Recent FDA approvals include drugs that target both the major excitatory and inhibitory neurotransmitters as well as dopamine, which can play either role depending on the location of a specific receptor in the nervous system.

The development of drugs which may address serious or life-threatening diseases and which lack effective treatments can be facilitated by an accelerated review by the FDA. Treatment of resistant disease such as advanced metastatic or relapsed/refractory disease can be facilitated by the availability of preliminary evidence of a clinically significant endpoint with can expedite the drug review process…

The huge diversity of viruses can be described by properties such as the type of genetic material (DNA or RNA), the presence of a protective envelope, the size of the viral particle and genome, as well as the number of viral proteins expressed. DNA and RNA viruses have important differences in how they replicate in host cells as DNA viruses contain their own polymerase genes, whereas RNA genomes use the host cellular processes. Retrovirus integration into the host genome can occur in infections such as with HIV…

The following sections are included:

• Appendix 1: Diseases (organ involved)
• Appendix 2: Medicines (site of action)
• Target biochemistry for action of medicines