Clinical pharmacology

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  • Clinical pharmacology comprises all aspects of the scientific study of drugs in man. Its objective is to optimise drug therapy and it is justified in so far as it is of practical use. Over recent years pharmacology has undergone great expansion resulting from technology that allows the understanding of molecular action and the capacity to exploit this. The potential consequences for therapeutics are enormous. All cellular mechanisms (normal and pathological), in their immense complexity are, in principle, identifiable.

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  • Five years have passed since the first edition of Principles of Clinical Pharmacology was published. The second edition remains focused on the principles underlying the clinical use and contemporary development of pharmaceuticals. However, recent advances in the areas of pharmacogenetics, membrane transport, and biotechnology and in our understanding of the pathways of drug metabolism, mechanisms of enzyme induction, and adverse drug reactions have warranted the preparation of this new edition.

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  • Harrison's Internal Medicine Chapter 5. Principles of Clinical Pharmacology Principles of Clinical Pharmacology: Introduction Drugs are the cornerstone of modern therapeutics. Nevertheless, it is well recognized among physicians and among the lay community that the outcome of drug therapy varies widely among individuals. While this variability has been perceived as an unpredictable, and therefore inevitable, accompaniment of drug therapy, this is not the case.

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  • Professor D. R. Laurence was either author or coauthor of this textbook from its 1st edition in 1960 to its 8th in 1997. This is a long life for any textbook. Its achievement bears testimony to a style of presentation that strives to be clear and readable, and to retain the reader's interest whilst imparting information about a subject that can be at times both complex and confusing.

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  • PRESCRIBING, CONSUMPTION AND ECONOMICS Prescribing, consumption and economics The reasons for taking a drug history from patients are: • Drugs are a cause of disease. Withdrawal of drugs, if abrupt, can cause disease, e.g. benzodiazepines, antiepilepsy drugs. • Drugs can conceal disease, e.g. adrenal steroid. • Drugs can interact causing positive adverse effect, or negative adverse effect, i.e. therapeutic failure. • Drugs can give diagnostic clues, e.g. ampicillin and amoxicillin causing rash in infectious mononucleosis — a diagnostic adverse effect, not a diagnostic test.

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  • We must be daring and search after Truth; even if we do not succeed in finding her, we shall at least come closer than we are at present (Galen AD 130-200) SYNOPSIS (CONTINUED) Surveillance studies and the reporting of spontaneous adverse reactions respectively determine the clinical profile of the drug and detect rare adverse events. Further trials to compare new medicines with existing medicines are also required.These form the basis of cost-effectiveness comparisons.

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  • The nonmedical use of drugs presents social problems with important pharmacological aspects. Social aspects Rewards for the individual Decriminalisation and legalisation Dependence Drugs and sport Tobacco Dependence Nicotine pharmacology Effects of chronic smoking Starting and stopping use Passive smoking Ethyl alcohol Pharmacology Car driving and alcohol Chronic consumption Withdrawal Pregnancy Pharmacological deterrence Psychodysleptics • Experiences with psychodysleptics • Individual substances, especially cannabis Stimulants • cocaine, • amfetamines.

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  • The principally pharmacological aspects of vitamins are described here.The nutritional aspects, physiological function, sources, daily requirements and deficiency syndromes (primary and secondary) are to be found in any textbook of medicine. • • • • Vitamin A: retinol Vitamin B: complex Vitamin C: ascorbic acid Vitamin D, calcium, parathyroid hormone, calcitonin, bisphosphonates, bone • Treatment of calcium and bone disorders • Vitamin E:tocopherol that subclinical vitamin deficiencies are a cause of much chronic ill-health and liability to infections.

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  • The eleventh edition of Basic & Clinical Pharmacology is a new book in two important ways. First, the addition of new Associate Editors to the editorial group has increased currency, depth, and breadth of coverage; second, conversion to fullcolor style has increased the clarity of presentation and total information content. At the same time, the overall organization has been improved and the educational content of previous editions has been expanded.

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  • The administration of general anaesthetics and neuromuscular blocking drugs is generally confined to trained specialists. Nevertheless, nonspecialists are involved in perioperative care and will benefit from an understanding of how these drugs act. Doctors from a variety of specialties use local anaesthetics and the pharmacology of these drugs is discussed in detail.

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  • Hypertension and coronary heart disease (CHD) are of great importance. Hypertension affects above 20% of the total population of the USA with its major impact on those over age 50. CHD is the cause of death in 30% of males and 22% of females in England and Wales. Management requires attention to detail, both clinical and pharmacological. The way drugs act in these diseases is outlined and the drugs are described according to class.

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  • Tham khảo sách 'clinical pharmacology - part 1', y tế - sức khoẻ, y học thường thức phục vụ nhu cầu học tập, nghiên cứu và làm việc hiệu quả

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  • Tham khảo sách 'clinical pharmacology - part 2 (end)', y tế - sức khoẻ, y học thường thức phục vụ nhu cầu học tập, nghiên cứu và làm việc hiệu quả

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  • Clinical Implications of Altered Bioavailability Some drugs undergo near-complete presystemic metabolism and thus cannot be administered orally. Nitroglycerin cannot be used orally because it is completely extracted prior to reaching the systemic circulation. The drug is therefore used by the sublingual or transdermal routes, which bypass presystemic metabolism. Some drugs with very extensive presystemic metabolism can still be administered by the oral route, using much higher doses than those required intravenously.

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  • Clinical Implications of Drug Distribution Digoxin accesses its cardiac site of action slowly, over a distribution phase of several hours. Thus, after an intravenous dose, plasma levels fall, but those at the site of action increase over hours. Only when distribution is near-complete does the concentration of digoxin in plasma reflect pharmacologic effect. For this reason, there should be a 6–8 h wait after administration before plasma levels of digoxin are measured as a guide to therapy.

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  • From the emergence of clinical sleep medicine marked by the establishment of the harbinger Stanford Sleep Disorders Clinic in the mid 1970s, offspring sleep disorders clinics and centers have grown exponentially with the recognition of the unmet diagnostic and treatment needs of the reservoir of patients suffering from symptoms of what are now recognized and classified as the nosology of human sleep disorders.

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  • Principles of Dose Selection The desired goal of therapy with any drug is to maximize the likelihood of a beneficial effect while minimizing the risk of adverse effects. Previous experience with the drug, in controlled clinical trials or in postmarketing use, defines the relationships between dose (or plasma concentration) and these dual effects and provides a starting point for initiation of drug therapy. Figure 5-1 illustrates the relationships among dose, plasma concentrations, efficacy, and adverse effects and carries with it several important implications: 1.

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  • Multiple Variants Modulating Drug Effects As this discussion makes clear, for each drug with a defined mechanism of action and disposition pathways, a set of "candidate genes," in which polymorphisms may mediate variable clinical responses, can be identified. Indeed, polymorphisms in multiple genes have been associated with variability in the effect of a single drug. CYP2C9 loss-of-function variants are associated with a requirement for lower maintenance doses of the vitamin K antagonist anticoagulant warfarin. In rarer (...

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  • Appendix hTheWorld Health Organization model list of essential drugs' We reprint the current list (by permission). Whilst the WHO programme (revised 1999) was instituted particularly to help less developed countries, the list has interest and lessons for all societies facing, as they now are, the problems of delivering economically affordable health care to all. We commend a study of the list to our readers (see also p. 18). The list of essential drugs may be considered against the background of the available marketed medicines worldwide.

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  • How drugs act and interact, how they enter the body, what happens to them inside the body, how they are eliminated from it; the effects of genetics, age, and disease on drug action — these topics are important for, although they will generally not be in the front of the conscious mind of the prescriber, an understanding of them will enhance rational decision taking. Knowledge of the requirements for success and the explanations for failure and for adverse events will enable the doctor to maximise the benefits and minimise the risks of drug therapy. Pharmacodynamics.

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