Genetic Factors in Drug Metabolism Donna J. Belle, PhD, RPh, and HaRleen SInGH, PharmD, Oregon State University College of Pharmacy, Portland Campus at Oregon Health & Science University, Portland . Environmental factors. Advantages and disadvantages of administering drugs through injection. These chemical alterations occur primarily in the liver and are known as biotransformations. Genetic control of drug levels in man: phenylbutazone. This issue of Biofiles is devoted to our diverse portfolio of reagents, enzymes, and labware designed for the analysis of drug delivery, absorption, and metabolism. physiological and pathological) factors (discussed in this chapter) and external factors (i.e. Kinetics and factors affecting drug metabolism. His monograph "Detoxication Mechanisms: The Metabolism of Drugs and Allied Organic Compounds" (Williams,. Fasting contributes to variability in drug metabolism. Common Factors Attributed to Variable Drug Responses • Chemistry is known as the central of science. Drugs affecting lipid metabolism - ScienceDirect O.R. Download Drug Metabolism In Man Book PDF. Oral By far the most common route. First-pass metabolism for certain drugs may be increased or decreased by induction or inhibition of hepatic enzymes (e.g. 1971 Jul 6;179:43-66. doi: 10.1111/j.1749-6632.1971.tb46890.x. ies of enzyme the other sites include lungs, kidney, and placenta, epithelial cells of gastrointestinal tract, adrenals and skin However, these sites are involved to a limited extent in this process. The toxicity of a chemical in an organism may be increased or decreased by a simultaneous or consecutive exposure to another chemical in food. 1974. Laboratory of Chemical Pharmacology, National Heart and Lung Institute, National Institutes of Health Bethesda, Md. Thus, it includes the quantitation of such elements of drug bioavailability as tear dilution, drug binding, and vehicle effects; factors affecting corneal absorption and subsequent tissue distribution; dosage . Dietary influences on drug dispo-sition. DONNA J. BELLE, PhD, RPh, and HARLEEN SINGH, PharmD, Oregon State University College of Pharmacy, Portland Campus at Oregon Health & Science University . Some of them are: 1. Water solubility. • Competitively inhibit the metabolism of another drug if it utilizes the same enzyme or co factors. Thus, biopharmaceutics involves factors that influence the: 1) protection and stability of the drug within the product; 2) the rate of drug release from the product; 3) the rate of dissolution of the drug at the Metabolism: hepatic functions decrease in elderly and drug levels increase (amount of dysfunction variable) Excretion: decline of renal function in elderly (variable)-therefore increase drug levels in plasma Drugs With Reduced Metabolism or Elimination in The Elderly Altered Pharmacodynamics in Geriatric Patients Pharmacodynamic Changes: We cannot guarantee that every book is in the library. Advantages and disadvantages of administering drugs orally. . Advancements in technology have made it possible to investigate and understand the role of physiological and physico-chemical factors in drug delivery more clearly, which can be used to improve and refine the techniques to more closely mimic the in vivo environment. If you continue sailing on the site, you accept the use of cookies on this website. Author J R Gillette . Factors Effecting Bioavailability Studies Bodavula Samba Siva Rao* . Factors Affecting Liberation/Absorption • Formulation factors - Tablet disintegration - Inert ingredient / solvent effects - Solubility - Drug pH . Data . External: diet, environment. Abstract. Laboratory of Chemical Pharmacology, National Heart and Lung Institute, National Institutes of Health Bethesda, Md. A major area of research interest is the possible impact of epigenetics on drug metabolism . . The factors discussed in the chapter are the effects of age, diet, disease, gender, ethanol, and smoking. Hormonal imbalances such as hypo & hyperthyroidism can affect your metabolism. 1973 Aug; 45 (8):924-924. CHEMISTRY What is Chemistry? Environmental changes such as increased heat or cold forces the body to work harder to maintain its normal temperature and increases BMR. Biological factors affecting toxic response Chemicals in the diet, air or water Humans may be under medication with several drugs while exposed to an industrial chemical. Specific product focus for this issue is drug transport, phase I enzymes, and drug-congugate analysis. Download full Drug Metabolism In Man books PDF, EPUB, Tuebl, Textbook, Mobi or read online Drug Metabolism In Man anytime and anywhere on any device. These are, of course, purely arbitrary divisions and much interaction exists between the various . Preclinical studies revealed effects of fasting on the activity of enzymes involved in phase I and II drug metabolism. -Drug-Drug Interactions • Drug-drug interactions can also cause difference in bioavailability. rapid and important age related physiologic changes in drug metabolism and elimination occur in children esp. Some chemical substances stimulate this enzymatic system to metabolize quicker; others inhibit it. . Request PDF | Factors Affecting Drug Metabolism | Drugs are tested at the preclinical stage in animal populations that are usually inbred and display little variation from animal to animal. Search for more papers by this author Most drugs undergo chemical alteration by various bodily systems to create compounds that are more easily excreted from the body. To be effective, drugs in an oral dosage form first must be absorbed and then reach the target organs via systemic circulation. Looking for an answer to the question: What factors affect drug metabolism in elderly? Factors Affecting Drug Metabolism - Free download as Powerpoint Presentation (.ppt / .pptx), PDF File (.pdf), Text File (.txt) or view presentation slides online. First pass metabolism of orally administered drugs. Pharmacokinetics (PK) is defined as the quantitative study of drug absorption, distribution, metabolism, and excretion (ADME)—i.e., the ways the body processes a drug 1 while the drug exerts its actions in the body. Metabolism in either the intestinal wall or liver before the drug. Non-hepatic metabolism. Drug metabolism biotransformation ppt. James R. Gillette Ph.D., James R. Gillette Ph.D. These include age, species and strain, genetic or hereditary factors, sex, enzyme induction, and enzyme inhibition.32,483-486. physicochemical properties of drugs, dosage forms and routes of administeration affect the rate and extent of the drug absorption. In humans, fasting affects drug metabolizing enzyme activity in a non-uniform pattern. 2. The bioavailability of orally administered drugs may be altered by changes in dissolution rate, intestinal microflora, intraluminal enzymes, epithelial enzymes, rate of passage across the gastrointestinal epithelium, gastric emptying rate, intestinal transit time, hepatic first pass metabolism, and gastrointestinal and hepatic blood flow. Drug metabolism ; Drug metabolism principles- Phase I and Phase II. Environmentaw l factors affecting drug metabolism. Article can not be . View the article PDF and any associated supplements and figures for a period of 48 hours. quinidine is metabolized by CYP3A4 but inhibits CYP2D6 • Inhibition of drug metabolism occurs in a dose related manner and can precipitate toxicity . Analogous to the experiments we discussed earlier, these investigators were studying the metabolism of pentobarbital in rats by measuring the time the animals slept after a single dose of the barbiturate. Drugs Affecting Lipid Metabolism Cholesterol And Atherosclerosis Plasma Triglycerides And Lipoproteins Drugs Affecting Plasma Lipids written by David Kritchevsky and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 1967 with Drugs categories. As a general principle, it's important to appreciate that none of these physiological factors affecting drug metabolism operate in isolation. Click Get Book button to download or read books, you can choose FREE Trial service. Fasting is part of a complex interplay of factors affecting drug physicochemical properties of drugs, dosage forms and routes of administeration affect the rate and extent of the drug absorption. metabolism. Chemistry. Metabolism of Cancer Chemotherapeutic Agents via Pathways Utilized by Xenobiotics. Factors affecting rate of oral absorption. Drug metabolism is a crucial aspect of medical practice and pharmacology. This chapter discusses some of the major factors related to patient genetic identity and how they live their lives, on drug metabolism and how these factors affect the goal of maintaining drug levels within the patient's therapeutic window. Factors affecting drug metabolism Ann N Y Acad Sci. Competitive binding and effects on drug distribution and elimination. • Metabolism of drug by liver before drug reaches systemic circulation • Drug absorbed into portal circulation, must pass through liver to reach systemic FACTORS AFFECTING DRUG METABOLISM. factors affecting drug metabolism pdf Factors Affecting Drug Absorption. Slideshare uses cookies to improve functionality and performance, and provide relevant advertising. The passage of drug from the gut into the blood is influenced by biologic and physicochemical factors (discussed in Terms in this set (20) Factors Affecting Drug Metabolism (5) 1. BI OAVAI LABI I TY Factors Affecting Drug Absorption z Transport ATP z Active vs. passive z pH z Physical factors ADP z Blood flow + Pi z Surface area z Contact time A- BH+ Drug Distribution z Blood flow to the tissue z Size of the organ z Solubility of the drug z Binding z Volume of distribution Drug Distribution . CHEMISTRY What is Chemistry? the liver (do not undergo first pass liver metabolism), and drain directly into the systemic circulation. 4) Heart diseases decrease hepatic blood flow. Download or Read online Some Factors Affecting Drug Metabolism In Man full HQ books. Drugs may compete for protein binding and cause drug . Introduction… However, a number of factors can influence drug absorption from GIT A fraction of an administered dose of the drug reaches the systemic circulation in the unchanged form Bioavailability is not 100% By IV route the entire drug reaches the systemic circulation The drug is 100% bioavailable 4 BT 27-Apr-20 O'Malley K, Stevenson IH, Wood M. Proceedings: Drug metabolizing ability in operating theatre personnel. Genetic Factors in Drug Metabolism. Patient-related factors that affect drug pharmacokinetics A patient's age, co-morbidities, other drugs they are taking and environmental factors such as food can all affect the efficiency of the processes underpinning drug metabolism. The main factors which affect the duration and intensity of drug action are absorption, distribution, excretion, and metabolism; in this chapter attention will be focused on one important factor, the…. The scope of PK not only covers studies on healthy subjects but also includes broad research on variations under a variety of physiologic or pathologic . Loss via Hepatic Metabolism Drug in Systemic Circulation Bound Tissue Drug Concentrations Bound Drug Unbound Drug Clearance Free Tissue Drug . Relationship of drug ionization with lipid solubility. Chemical factors a) Enzyme induction b) Enzyme inhibition c) Environmental chemicals 2. Ultimately, the expression of an enzyme, and therefore, the responses to drugs that it metabolizes will be an integration of all the non-genetic factors that can control the enzyme impinged upon the individual's genetic constitution. Barriers that prevent drugs from reaching the systemic circulation are called bioavailability barriers, which influence the nature and intensity of an oral drug's therapeutic activity.Chief among these barriers are called the first-pass metabolism, which is mainly . Conversely, an increased rate of metabolism decreases the intensity and duration of action as well as the drug's efficacy. The CYP enzymes are influenced by a variety of factors, including exposure to some of the chemicals they metabo-lize. 5) Hyperthyroidism and hypothyroidism increases and decreases drug (e.g. a knowledge of age ‐ related changes in drug absorption , distribution , and clearance is essentialto optimize drug efficacyand to avoid toxicity. factors that could affect these pathways are summarized. Other factors affect oral bioavailability: drug formulation 8. In order to discuss this topic, the factors affecting drug metabolism will be split into internal (i.e. those factors that can affect drug dissolution, aqueous solubility, membrane permeability, and presystemic drug metabolism. 1. CYP450s are the major group of enzymes that chemically modify drugs Table 1 Summary of main role of liver, gut, and kidneys in the 3 drug metabolism pathways 3) Liver diseases affect lipophilic drugs (mainly metabolized in liver) and renal diseases affect hydrophilic drugs (excreted unchanged by kidney). Large interindividual variations in drug response can arise from multiple genetic and environmental factors affecting drug absorption, distribution, biotransformation, excretion, interaction with rec. in drug metabolism and drug interactions.16 This enzyme accounts for 29% and 70% of the total human hepatic and gastrointestinal tract CYP enzymes, respectively, affecting both presystemic and systemic drug distribution.14, 17 This first-pass elimination results in variable (often low) oral bioavailability of CYP3A4-metabolized drugs. For example, esters can be prepared of both acids and bases to produce more stable derivatives, which hydrolyse to the active parent once absorbed. Table 3-1. Drug-related. -First Pass Metabolism • It means that drug degradation occurs, reducing its bioavailability, when it passed through GIT wall and then through portal system, before it reaches systemic circulation. A. Guarino, C. Litterst. Factors Affecting Metabolism A number of factors may influence the metabolic rate of a drug. brussels sprouts may stimulate the metabolism of some drugs. Hepatic drug transporters are present throughout parenchymal liver cells and affect a drug's liver disposition, metabolism, and elimination (for review, see [1, 2 General references The liver is the principal site of drug metabolism (for review, see [1]).Although metabolism typically inactivates drugs, some drug metabolites are pharmacologically active—sometimes even more. Lipid solubility. Drug metabolism • Many drugs are lipophilic compounds and do not pass ready into the aqueous enviroment of the urine • They must first undergo a variety of enzymatic changes (i.e., biotransformed) in different tissues leading to metabolites that are readely eliminated in urine or bile • Also applicable to endogenous compounds (steroid hormones, cholesterol, In the first chapter, the principles underlying drug absorption, distribution, metabolism and elimination are described, with drug metabolism highlighted within the context of these fundamental processes. Ageing Age has a major effect on how the body handles drugs, with frailty and old age Elimination: Drug metabolism and basic understanding metabolic pathways renal excretion of drugs, factors affecting renal excretion of drugs, renal clearance, Non renal routes of drug excretion of drugs Bioavailability and Bioequivalence: Definition and Objectives of bioavailability, absolute and relative clinical use, and that for any given drug, the multiple factors influencing its metabolism necessitate on-going studies of its biotransformation. Pantuc EJ Pantuc, k CBk Weissma, Cn, et al.
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