Excretion of drugs

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  • In a certain sense, the field of drug metabolism (DM) is standing still. More specifically, the basic experiment of drug metabolism (i.e., administering a new drug to an animal or human and determining the structures, amounts, and disposition of the metabolites) has changed very little over a period of decades. Remarkably, the experimental design and resulting data set from a typical absorption, distribution, metabolism, and excretion (ADME) study conducted today would be instantly recognized and understood by DM scientists from 50 years ago.

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  • Pharmacokinetics (t1/2) and the apparent volume of distribution Vapp (p. 28) by the equation: Vapp t1/2 = In 2 x –––– Cltot The smaller the volume of distribution or the larger the total clearance, the shorter is the half-life. In the case of drugs renally eliminated in unchanged form, the half-life of elimination can be calculated from the cumulative excretion in urine; the final total amount eliminated corresponds to the amount absorbed.

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  • Principles of Pharmacokinetics The processes of absorption, distribution, metabolism, and excretion— collectively termed drug disposition—determine the concentration of drug delivered to target effector molecules. Absorption Bioavailability 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. 5-2A ).

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  • Renal Disease Renal excretion of parent drug and metabolites is generally accomplished by glomerular filtration and by specific drug transporters, only now being identified. If a drug or its metabolites are primarily excreted through the kidneys and increased drug levels are associated with adverse effects, drug dosages must be reduced in patients with renal dysfunction to avoid toxicity. The antiarrhythmics dofetilide and sotalol undergo predominant renal excretion and carry a risk of QT prolongation and arrhythmias if doses are not reduced in renal disease.

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  • The need for a book such as this one has arisen as a result of recent changes in legislation and expansion in the numbers of health care professionals involved in administration and/or prescription of medicines. The book is an introduction to pharmacology for health care professionals. Although anyone involved in the care of patients is a health care professional, this book has been specifically written for physiotherapists, podiatrists and radiographers (otherwise known as allied health professionals). However, the book may be of interest to other health care professionals....

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  • Chapter 16 - Pharmacology and drug calculations. In this chapter, you will: Gain understanding of what is meant by the terms pharmacology, pharmacodynamics and pharmacokinetics; learn about the stages of absorption, distribution, metabolism and excretion of medication; understand the importance of careful prescribing for older patients; understand the importance of patient education and concordance in provision of medications;....

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  • Great efficiencies have been achieved in the drug discovery process as a result of technological advances in target identification, high-throughput screening, high-throughput organic synthesis, just-in-time in vitro ADME (absorption, distribution, metabolism, and excretion), and early pharmacokinetic screening of drug leads. These advances, spanning target selection all the way through to clinical candidate selection, have placed greater and greater demands on the analytical community to develop robust high-throughput methods.

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  • Introduction: There are a number of compounds, such as morphine and codeine, which are classified into the opium alkaloids (opiates). They are being used as ethical drugs of narcotic analgesics and antitussives; 1 % powder of codeine or dihydrocodeine is commonly included in over-the-counter drugs of antitussives. Figure 3.1 shows metabolic pathways of morphine, heroin and codeine. Since morphine and codeine are finally excreted into urine in the conjugated forms with glucuronic acid [1–3], it is necessary to hydrolyze the conjugated forms of these compounds before GC/MS analysis.

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  • (BQ) Part 1 book "Medical pharmacology at a glance" presents the following contents: Principles of drug action, drug absorption, distribution and excretion, drug metabolism, local anaesthetics, autonomic nervous system, autonomic drugs acting at cholinergic synapses, drugs acting on the sympathetic system, ocular pharmacology,... and other contents.

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  • The absorption, distribution, metabolism, and excretion of a drug all involve its passage across cell membranes. Mechanisms by which drugs cross membranes and the physicochemical properties of molecules and membranes that influence this transfer are, therefore, important. The determining characteristics of a drug are its molecular size and shape, degree of ionization, relative lipid solubility of its ionized and nonionized forms, and its binding to tissue proteins.

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  • Diuretics increase the rate of urine flow and sodium excretion and are used to adjust the volume and/or composition of body fluids in a variety of clinical situations, including hypertension, heart failure, renal failure, nephrotic syndrome, and cirrhosis. The objective of this chapter is to provide the reader with unifying concepts as to how the kidney operates and how diuretics modify renal function. The chapter begins with a description of renal anatomy and physiology, as this information is prerequisite to a discussion of diuretic pharmacology....

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  • Hypothermia: Treatment When a patient is hypothermic, target organs and the cardiovascular system respond minimally to most medications. Moreover, cumulative doses can cause toxicity during rewarming because of increased binding of drugs to proteins, and impaired metabolism and excretion. As an example, the administration of repeated doses of digoxin or insulin would be ineffective while the patient is hypothermic, and the residual drugs are potentially toxic during rewarming. Achieving a mean arterial pressure of at least 60 mmHg should be an early objective.

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  • Several years ago we noted a paucity of textbooks that dealt with the principles of pharmacology as a science rather than pharmacology as a therapeutic entity. In an attempt to remedy this we organized a textbook designed to meet the needs of students interested in pharmacology at the advanced undergraduate and early graduate level. This text addresses the many facets that form the foundation of pharmacology. Students will find extensive discussions by leaders in the field are written in clear and straightforward manner.

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  • This book is written for the practicing pharmaceutical scientist involved in absorption–distribution–metabolism–excretion (ADME) measurements who needs to communicate with medicinal chemists persuasively, so that newly synthesized molecules will be more ‘‘drug-like.’’ ADME is all about ‘‘a day in the life of a drug molecule’’ (absorption, distribution, metabolism, and excretion).

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  • The following mechanisms are involved. Glomerular filtration. The rate at which a drug enters the glomerular filtrate depends on the concentration of free drug in plasma water and on its molecular weight. Substances that have a molecular weight in excess of 50 000 are excluded from the glomerular filtrate while those of molecular weight less than 10 000 (which includes almost all drugs)21 pass easily through the pores of the glomerular membrane. Renal tubular excretion. Cells of the proximal renal tubule actively transfer strongly charged molecules from the plasma to the tubular fluid.

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  • Assessment of Glomerular Filtration Rate Monitoring the GFR is important in both the hospital and outpatient settings, and several different methodologies are available (discussed below). In most acute clinical circumstances a measured GFR is not available, and the serum creatinine level is used to estimate the GFR in order to supply appropriate doses of renally excreted drugs and to follow short-term changes in GFR. Serum creatinine is the most widely used marker for GFR, and the GFR is related directly to the urine creatinine excretion and inversely to the serum creatinine (U Cr/PCr).

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  • Algorithm depicting clinical approach to hyperkalemia. NSAID, nonsteroidal anti-inflammatory drug; ACE, angiotensin-converting enzyme; RTA, renal tubular acidosis; TTKG, transtubular K+ concentration gradient. The appropriate renal response to hyperkalemia is to excrete at least 200 mmol of K+ daily. In most cases, diminished renal K+ loss is due to impaired K+ secretion, which can be assessed by measuring the transtubular K + concentration gradient (TTKG).

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