Chapter 005 Principles of Clinical Pharmacology (Part 11) pps
Chapter 005. Principles of Clinical Pharmacology (Part 11) pps
... cimetidine decreases the renal clearance of dofetilide and of procainamide and its active metabolite NAPA. Chapter 005. Principles of Clinical Pharmacology (Part 11) Pharmacokinetic Interactions ... the risk of cyclosporine toxicity or of rhabdomyolysis with some HMG-CoA reductase inhibitors (lovastatin, simvastatin, atorvastatin), and P-glycoprotein inhibitors increasing risk of digoxin ... Phenytoin, an inducer of many systems, including CYP3A, inhibits CYP2C9. CYP2C9 metabolism of losartan to its active metabolite is inhibited by phenytoin, with potential loss of antihypertensive...
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Chapter 005. Principles of Clinical Pharmacology (Part 1) pps
... Chapter 005. Principles of Clinical Pharmacology (Part 1) Harrison's Internal Medicine > Chapter 5. Principles of Clinical Pharmacology Principles of Clinical Pharmacology: ... accompaniment 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 ... of the target molecule itself or of variability in the broad biologic context in which the drug-target interaction occurs to achieve drug effects. Two important goals of the discipline of clinical...
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Chapter 005. Principles of Clinical Pharmacology (Part 4) ppsx
... orally Chapter 005. Principles of Clinical Pharmacology (Part 4) Clinical Implications of Drug Distribution Digoxin accesses its cardiac site of action slowly, over a distribution phase of ... volume of distribution of lidocaine is reduced. Therefore, lower-than-normal loading regimens are required to achieve equivalent plasma drug concentrations and to avoid toxicity. Rate of Intravenous ... prevent elimination by very rapid (t1/2 of seconds) uptake into erythrocytes and endothelial cells before the drug can reach its clinical site of action, the atrioventricular node. Plasma...
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Chapter 005. Principles of Clinical Pharmacology (Part 9) pps
... 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 phase II polymorphisms ... Deficiency of glucose-6-phosphate dehydrogenase (G6PD), most often in individuals of African or Mediterranean descent, increases risk of hemolytic anemia in response to primaquine and a number of ... therapy and of hepatitis with isoniazid. Induction of CYPs (e.g., by rifampin) also increases the risk of isoniazid-related hepatitis, likely reflecting generation of reactive metabolites of acetylhydrazine,...
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Chapter 005. Principles of Clinical Pharmacology (Part 2) ppt
... P-glycoprotein, the product of the normal expression of the MDR1 gene. P-glycoprotein is expressed on the apical aspect of the enterocyte and on the canalicular aspect of the hepatocyte (Fig. 5-3); ... from the site of administration (Fig. 5-2). The extent of absorption may be reduced because a drug is incompletely released from its dosage form, undergoes destruction at its site of administration, ... aInhibitors affect the molecular pathway, and thus may affect substrate. bClinically important genetics variants described. A listing of CYP substrates, inhibitors, and inducers is maintained at http://medicine.iupui.edu/flockhart/table.htm....
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Chapter 005. Principles of Clinical Pharmacology (Part 3) docx
... intravenous infusion, plasma concentrations at steady Chapter 005. Principles of Clinical Pharmacology (Part 3) Clinical Implications of Altered Bioavailability Some drugs undergo near-complete ... a typical intravenous dose of verapamil is 1–5 mg, compared to the usual single oral dose of 40–120 mg. Administration of low-dose aspirin can result in exposure of cyclooxygenase in platelets ... tissues, the volume of distribution can be far greater than any physiologic space. For example, the volume of distribution of digoxin and tricyclic antidepressants is hundreds of liters, obviously...
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Chapter 005. Principles of Clinical Pharmacology (Part 5) doc
... effect of the drugs, it may produce severe agonist–mediated effects (such as hypertension or tachycardia) if the blocking drug is abruptly withdrawn. Chapter 005. Principles of Clinical Pharmacology ... site of action, it alters the function of that molecular target, with the ultimate result of a drug effect that the patient or physician can perceive. For drugs used in the urgent treatment of ... accumulation of active metabolites. Commonly, the clinical effect develops as a downstream consequence of the initial molecular effect the drug produces. Thus, administration of a proton-pump...
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Chapter 005. Principles of Clinical Pharmacology (Part 6) pdf
... and Response Chapter 005. Principles of Clinical Pharmacology (Part 6) Principles of Dose Selection The desired goal of therapy with any drug is to maximize the likelihood of a beneficial ... an understanding of the relationships between plasma concentration and anticipated effects. For example, measurement of QT interval is used during treatment with sotalol or dofetilide to avoid ... concentration and beneficial or adverse drug effect, measurement of plasma levels can provide a valuable tool to guide selection of an optimal dose. This is particularly true when there is a...
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Chapter 005. Principles of Clinical Pharmacology (Part 7) pptx
... Chapter 005. Principles of Clinical Pharmacology (Part 7) Renal Disease Renal excretion of parent drug and metabolites is generally accomplished ... of lidocaine is reduced by about 50% in heart failure, and therapeutic plasma levels are achieved at infusion rates of 50% or less than those usually required. The volume of distribution of ... linked to the occurrence of hip fractures in elderly patients, perhaps reflecting both a risk of falls from these drugs (due to increased sedation) and the increased incidence of osteoporosis in...
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Chapter 005. Principles of Clinical Pharmacology (Part 8) pot
... drug effects. However, 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 ... advanced at the end of the nineteenth century, and the first examples of familial clustering of unusual drug responses due to this mechanism were noted in the mid-twentieth century. Clinically important ... multiple molecular pathways of drug disposition (Table 5-1). A distinct multimodal distribution of drug disposition (as shown in Fig. 5-6) argues for a predominant effect of variants in a single...
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