... basic principles of clinical phar-macology currently are being applied in the process of drugdevelopment.Journals Clinical Pharmacology and TherapeuticsBritish Journal of Clinical Pharmacology Journal ... RudolphBucheim (1820–1879), who has been credited with1 PRINCIPLES OF CLINICAL PHARMACOLOGY, SECOND EDITION20 Principles of Clinical Pharmacology Therefore, just before the second dose,X1(min)= ... measured by the immunoassays11 PRINCIPLES OF CLINICAL PHARMACOLOGY, SECOND EDITIONCHAPTER3Compartmental Analysis of DrugDistribution ARTHUR J. ATKINSON, JR. Clinical Center, National Institutes...
... Chapter 005. Principles of Clinical Pharmacology (Part 1) Harrison's Internal Medicine > Chapter 5. Principles of Clinical Pharmacology Principles of Clinical Pharmacology: Introduction ... of drug therapy, this is not the case. The goal of this chapter is to describe the principles of clinical pharmacology that can be used for the safe and optimal use of available and new drugs. ... agents, such as certain antiarrhythmics, anticonvulsants, and antibiotics. Many of the principles in clinicalpharmacology and examples outlined below, which can be applied broadly to therapeutics,...
... Erythromycin aInhibitors affect the molecular pathway, and thus may affect substrate. bClinically important genetics variants described. A listing of CYP substrates, inhibitors, and...
... continuous intravenous infusion, plasma concentrations at steady Chapter 005. Principles of Clinical Pharmacology (Part 3) Clinical Implications of Altered Bioavailability Some drugs undergo near-complete ... (four to five distribution half-lives), plasma and tissue concentrations decline in parallel. Clinical Implications of Half-Life Measurements The elimination half-life not only determines the...
... result. Rather, drugs are more usually administered orally Chapter 005. Principles of Clinical Pharmacology (Part 4) Clinical Implications of Drug Distribution Digoxin accesses its cardiac ... plasma levels of digoxin are measured as a guide to therapy. Animal models have suggested, and clinical studies are confirming, that limited drug penetration into the brain, the "blood-brain ... (t1/2 of seconds) uptake into erythrocytes and endothelial cells before the drug can reach its clinical site of action, the atrioventricular node. Plasma Protein Binding Many drugs circulate...
... hypertension or tachycardia) if the blocking drug is abruptly withdrawn. Chapter 005. Principles of Clinical Pharmacology (Part 5) Adjusting Drug Dosages While elimination half-life determines ... clinical effect is common. Pharmacokinetic mechanisms that can contribute to such a delay include uptake into peripheral compartments or accumulation of active metabolites. Commonly, the clinical ... amenable than pharmacokinetics to rigorous mathematical analysis. Nevertheless, some clinically important principles can be elucidated. and liver prior to drug entry to the systemic circulation...
... Effects of Disease on Drug Concentration and Response Chapter 005. Principles of Clinical Pharmacology (Part 6) Principles of Dose Selection The desired goal of therapy with any drug ... 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)...
... loss-of-function alleles in these genes have not yet been described. Chapter 005. Principles of Clinical Pharmacology (Part 8) Principles of Genetic Variation and Human Traits (See also Chaps. 62 and ... phenotype); many variants can produce such a loss of function, complicating the use of genotyping in clinical practice. Individuals with one functional allele make up a second (intermediate metabolizers) ... clustering of unusual drug responses due to this mechanism were noted in the mid-twentieth century. Clinically important genetic variants have been described in multiple molecular pathways of drug...
... polymorphisms in ion channel genes that are not themselves the target of QT-Chapter 005. Principles of Clinical Pharmacology (Part 9) Transferase Variants One of the most extensively studied ... Drug-Target Interactions Occur The interaction of a drug with its molecular target is translated into a clinical action in a complex biologic milieu that is itself often perturbed by disease. Thus, polymorphisms ... pointes (Chap. 226), and in some patients this adverse effect represents unmasking of previously subclinical congenital long QT syndrome. Polymorphisms that Modulate the Biologic Context Within Which...
... Chapter 005. Principles of Clinical Pharmacology (Part 10) Multiple Variants Modulating Drug Effects As this discussion ... 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 ... genomic predictors of variable drug effects. Prospects for Incorporating Genetic Information into Clinical Practice sequestrants Proton pump inhibitors H2-receptor blockers Altered gastric...
... of dofetilide and of procainamide and its active metabolite NAPA. Chapter 005. Principles of Clinical Pharmacology (Part 11) Pharmacokinetic Interactions Causing Decreased Drug Effects...
... nuclear material, stimulating the formation of antinuclear antibodies and Chapter 005. Principles of Clinical Pharmacology (Part 13) Epidemiology Patients receive, on average, 10 different...
... response to drug treatment. Molecular pharmacology, pharmacokinetics, genetics, clinical trials, and the educated prescriber all Chapter 005. Principles of Clinical Pharmacology (Part 14) Diagnosis ... related to serum concentration may take a considerable time to disappear. Summary Modern clinicalpharmacology aims to replace empiricism in the use of drugs with therapy based on in-depth ... for a novel association, and any drug should be suspected of causing an adverse effect if the clinical setting is appropriate. overlooked source of additional drug exposure is topical therapy;...