Tìm thấy 14+ kết quả cho từ khóa "Principles of Clinical Pharmacology"
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Principles of Clinical Pharmacology. Principles of Pharmacokinetics. collectively termed drug disposition—determine the concentration of drug delivered to target effector molecules.. When a drug is administered orally, subcutaneously, intramuscularly, rectally, sublingually, or directly into desired sites of action, the amount of drug actually entering the systemic circulation may be less than with the intravenous route (Fig.
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Principles of Clinical Pharmacology. 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..
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Principles of Clinical Pharmacology. 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..
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Principles of Clinical Pharmacology. While elimination half-life determines the time required to achieve steady- state plasma concentrations (C ss. the magnitude of that steady state is determined by clearance (Cl) and dose alone. When drug is administered orally, the average plasma concentration within a dosing interval (C avg,ss ) replaces C ss , and bioavailability (F) must be included:.
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Principles of Clinical Pharmacology. Principles of Genetic Variation and Human Traits. 62 and 64) Variants in the human genome resulting in variation in level of expression or function of molecules important for pharmacokinetics and pharmacodynamics are increasingly recognized. These may be mutations (very rare variants, often associated with disease) or polymorphisms, variants that are much more common in a population.
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Potential approaches range from an increased understanding of the molecular and genetic basis of variability in drug actions to expanded postmarketing surveillance mechanisms. Many of the principles in clinical pharmacology and examples outlined below, which can be applied broadly to therapeutics, have been developed in these arenas.
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An important approach to quantifying this reduction is to consider that drug concentration at the beginning and end of a time period are unchanged, and that a specific volume of the body has been "cleared". of the drug. during that time period. Clinical Implications of Altered Clearance
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For example, a set of polymorphisms in the gene encoding 5- lipoxygenase activating protein (FLAP) has been identified as a risk factor for myocardial infarction in an Icelandic population, and an initial clinical trial of a FLAP inhibitor was conducted only in subjects with the high risk allele.
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Multiple Variants Modulating Drug Effects. 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.
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Clinical consequences of fluoxetine's interaction with CYP2D6 substrates may not be apparent for weeks after the drug is started, because of its very long half-life and slow generation of a CYP2D6-inhibiting metabolite.. 6-Mercaptopurine, the active metabolite of azathioprine, is metabolized not only by TPMT but also by xanthine oxidase.
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Because of the relatively small number of patients studied in clinical trials and the selected nature of these patients, rare adverse effects are generally not detected prior to a drug's approval, and physicians therefore need to be cautious in the prescription of new drugs and alert for the appearance of previously unrecognized adverse events..
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The hepatic necrosis produced by the ingestion of acetaminophen can be prevented or attenuated by the administration of substances such as N-acetylcysteine that reduce the binding of electrophilic metabolites to hepatic proteins. The risk of acetaminophen-related hepatic necrosis is increased in patients receiving drugs such as phenobarbital or phenytoin that increase the rate of drug metabolism or ethanol that exhaust.
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Recognition of the role of a drug or drugs in an illness depends on appreciation of the possible adverse reactions to drugs in any disease, on identification of the temporal relationship between drug administration and development of the illness, and on familiarity with the common manifestations of the drugs.
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Aging also results in a decrease in the size of, and blood flow to, the liver and possibly in the activity of hepatic drug-metabolizing enzymes. clearance of some drugs is impaired in the elderly. Adverse drug reactions are especially common in the elderly because of altered pharmacokinetics and pharmacodynamics, the frequent use of multidrug regimens, and concomitant disease.
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pharmacology but also with knowledge of clinical medicine. clinical pharmacology.. Brater D C, Daly W J 2000 Clinical pharmacology in the middle ages: principles that presage the 21st century. Clinical Pharmacology and Therapeutics . Breckenridge A1995 Science, medicine and clinical pharmacology. British Journal of Clinical Pharmacology 40:1-9. Breckenridge A1999 Clinical pharmacology and drug regulation. British Journal of Clinical.
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The ability to handle new developments depends, now more than ever, on comprehension of the principles of pharma- cology. The principles of pharmacology and drug therapy will be found in chapters 1-8 and they are applied in the subsequent specialist chapters which are offered as a reasonably brief solution to the problem of combining practical clinical utility with some account of the principles on which clinical practice rests.. Use of the book.
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Surveillance studies and the reporting of spontaneous adverse reactions respectively determine the clinical profile of the drug and detect rare adverse events. There are four main reasons why doctors should have a grounding in the knowledge and application of the principles of experimental therapeutics:. Modern medicine is sometimes accused of callous application of science to human problems and of subordinating the interest of the individual to those of the group (society).
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It is claimed that death has not occurred.. 39 When a chronic user discontinues, cannabinoids remain detectable in the urine for an average of 4 weeks and it can be as long as 11 weeks before 10 consecutive daily tests are negative (Ellis G M et al 1986 Clinical Pharmacology and Therapeutics 38: 572).. It is difficult to assess, when personal traits and intellectual rejection of techno- logical civilisation are also taken into account.
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Anderson IM, Nutt D J et al 2000 Evidence-based guidelines for treating depressive disorders with antidepressants: a revision of the 1993 British Association for Psychopharmacology guidelines.. American Journal of Medicine . Fink M 2001 Convulsive therapy: a review of the first 55 years. Kuperberg G R, Murray R 1996 Advances in the treatment of schizophrenia. British Journal of Clinical Practice . New insights into the role of the GABA-A benzodiazepine receptor. British Journal of Psychiatry .
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OECD PRINCIPLES OF CORPORATE GOVERNANCE – 37. and how they will assess the effectiveness of the strategy. 38 – OECD PRINCIPLES OF CORPORATE GOVERNANCE. OECD PRINCIPLES OF CORPORATE GOVERNANCE – 39. OECD PRINCIPLES OF CORPORATE GOVERNANCE – 41. The optimal capital structure of the firm is best decided by the management and the board, subject to the approval of the shareholders.. 42 – OECD PRINCIPLES OF CORPORATE GOVERNANCE. OECD PRINCIPLES OF CORPORATE GOVERNANCE – 43.