General and Molecular Pharmacology
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General and Molecular Pharmacology

Principles of Drug Action

Francesco Clementi, Guido Fumagalli, Francesco Clementi, Guido Fumagalli

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eBook - ePub

General and Molecular Pharmacology

Principles of Drug Action

Francesco Clementi, Guido Fumagalli, Francesco Clementi, Guido Fumagalli

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About This Book


With a focus on functional relationships between drugs and their targets, this book covers basic and general pharmacology, from a cellular and molecular perspective, with particular attention to the mechanisms of drug action – the fundamental basis for proper clinical use- without neglecting clinical application, toxicology and pharmacokinetics. • Covers cell and molecular pharmacology, bringing together current research on regulation of drug targets, at a level appropriate for advanced undergrad and graduate students
• Discusses the relevance of pharmacokinetics and drug development for the clinical application of drugs
• Presents material from the perspective of drug targets and interaction, the theoretical basis of drug action analysis, and drug properties
• Focuses on structure-function relationships of drug targets – informing about their biochemical and physiologic functions and experimental and clinical pathways for drug discovery and development
• Has a companion website that offers a host of resources: short additional chapters about methodology, topics at the forefront of research, and all figures and tables from the book

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Information

Publisher
Wiley
Year
2015
ISBN
9781118768686
Edition
1

SECTION 1
INTRODUCTION TO PHARMACOLOGY

1
ESSENTIAL LEXICON OF PHARMACOLOGY

FRANCESCO CLEMENTI AND GUIDO FUMAGALLI

By reading this chapter, you will:

  • Become familiar with the pharmacological vocabulary
Pharmacology studies drugs and their interactions with living organisms. In a broad sense, a drug is any substance that induces functional changes in an organism through a chemical or physical action, regardless of whether the resulting effect is beneficial or detrimental to the health of the receiving organism. In a more strict medical sense, a drug is a substance used in the diagnosis, treatment, or prevention of diseases or as a component of a medication.
Thus, the fields of interest in pharmacology are multiple, including chemistry, molecular and cellular biology, pathology, clinic, and toxicology. Studying a drug may mean investigating the chemical properties underlying its biological activity, or the way to synthesize or extract it, or its effects on cells, tissues, and organs or on healthy and diseased human subjects. Pharmacology bridges basic and clinical research, as it provides tools for a rational therapy of known pathologies as well as empirical approaches for diagnosis and cure of obscure diseases (cure ex adjuvantibus).
As Leonardo da Vinci said, “The medical doctor will use drugs in an appropriate way when he knows what a human being is, what life and complexion are and what health is.” In this sense, a pharmacologist is a physiologist, as she/he deals with substances and methods that modify physiological functions. However, she/he is also a pathologist capable of understanding chemical and molecular causes of pathologies, a biochemist and a molecular and cellular biologist using tools and methods of these disciplines to test drugs or vice versa employing drugs to investigate cellular and molecular processes, and a clinician using drugs to cure patients.

THE SOCIAL IMPACT OF PHARMACOLOGY

Using drugs to treat diseases and conditions has changed the life of humanity (see Chapter 2). Several factors have contributed to the remarkable improvements in population health that have occurred over the last century in developed countries: improved hygienic conditions, more widespread culture of prevention and health, richer and more balanced diet, and less physically wearing working conditions. However, such effects on life quality and duration would not have been so significant without the development of drugs and evidence-based approaches to human health care.
Drugs have contributed to the disappearance of many serious diseases. As an example, consider the number of daily deaths from bacterial pneumonia during winter months in general hospitals before World War II as compared to the almost total absence of this disease in current death records. Drugs have also reduced hospitalization, lowered incidence and gravity of several disease-induced permanent damages, and allowed to manage many serious and degenerative diseases. The most striking example of the role played by drugs in the control of serious diseases is the case of acquired immune deficiency syndrome (AIDS): in just a few years, specific antiviral drugs have turned the disease from “plague of the century” to a chronic illness compatible with an almost normal life. Pharmacology has also had an impact on surgery, as, for example, H2 histamine receptor antagonists and proton pump inhibitors have almost eliminated gastric and duodenal ulcers and the need for surgical gastrectomy and antibiotics have significantly reduced the number of appendectomies.
Drug success has been so impressive to induce part of the lay public to believe that there could be a “pill” for every disease or any uncomfortable symptom, causing an excessive “medicalization” of society and often the inability of people to accept that not all diseases are treatable and not all patients can be cured. Unfortunately, when such huge expectation on medicine collides with a failure, it may lead to a general distrust and irrational refusal of medical treatments pushing people toward the so-called alternative medicines. Based on the ethical principle that drug usage must be supported by scientific demonstrations of its effectiveness in patients, pharmacology has created strict rules that preclinical and clinical drug investigations (see Chapters 54, 55, and 56) have to comply with before drugs can be approved for clinical use. These rules are rigorously applied in drug development and use but are often ignored by producers and supporters of “alternative medicines.” This lack of severe preclinical and clinical experimentations implies that “alternative” products and procedures often have not undergone a careful evaluation of benefits (if any) and risks. In the best cases, the evidence supporting these practices is anecdotal, reported by minor scientific journals often lacking serious review procedures (see Supplement E 1.1, “Alternative or Nonconventional Therapies”).
Pharmacology has also a social impact. Consider, for example, drugs controlling fertility, emotions, and mental and physical performances or drugs affecting the individual’s perception of the external world or the social plague of drug addiction.
Pharmacological treatment of diseases is a duty for social health systems; it must be guaranteed to the population but it also has costs. This has important implications, both positive and negative, for the relationships between drug companies and public health systems. All these scientific, economic, ethical aspects make pharmacology a discipline with very broad and loosen borders in which technical aspects are associated with equally important ethical issues.

ESSENTIAL LEXICON

For some of the readers, this book will be the first contact with pharmacology. For this reason, we include here a list of the terms that are typical of this discipline and frequently found in the text. For a more extended definition of each term, the reader should refer to individual chapters of the volume.

Active Substances

Drugs

A drug is any substance that induces functional changes in an organism by chemical or physical action. In a biomedical context, a drug is a substance used in the diagnosis, treatment, or prevention of a disease or as a component of a medication. From a regulatory point of view, drug is any substance recognized in the Official National Pharmacopoeia or formulary. Nutrients or food constituents are not considered drugs.
From a historical point of view, the terms used to indicate drugs have undergone numerous conceptual and lexical changes. In the Middle Ages, the term semplici (simple, from the Latin medicina simplex) was used to indicate medicinal herbs (cultivated in horto dei semplici, the first one built in Salerno, Italy), minerals, and substances of animal origin with supposed therapeutic activity; the term “drug” was introduced in the eighteenth century to indicate a mixture of biologically active substances present in vegetal or animal organisms or parts of these organisms containing these substances (e.g., digitalis was a preparation made from foxglove Digitalis lanata leaves). The term derives probably from the Dutch word droog that indicated the barrels containing plants and dried spices imported from India, from which drugs were extracted.

Drug Name

Drugs may be indicated by (i) the chemical name, which identifies the chemical and molecular composition; (ii) the generic or official name, meaning the name under which the drug is licensed by the manufacturer and internationally identified, with the initial in lower case; and (iii) the trade name or proprietary/brand name (patented) indicating the medicine containing the drug, with the initial in large upper case. Two examples:
  1. Chemical name, 1-(1-methylethylamino)-3-(1-naphthyloxy) propan-2-ol HCl; generic name, propranolol; proprietary name, Bedranol, Inderal, InnoPran, Tesnol, Syprol, and so on
  2. Chemical name, acetylsalicylic acid; generic name, aspirin; proprietary name, Aspirin, Ascriptin, Aspro, Disprin, and so on

Medicinal Preparation

Specialty indicates the formulation labeled with the trade name under which an active ingredient is sold. Active ingredients can be prepared in different formulations: tablet, syrup, ointment, and so on. The active ingredient is generally associated with inert components called excipient. The excipient should not alter the pharmacological properties of the active ingredient, but may modify its pharmacokinetics. The preparation can be carried out on an industrial scale, according to the Official National Pharmacopoeias or in accordance with standards approved by the competent authorities. In this latter case, it is named “medicinal preparation” or “pharmac...

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