The general intention is to demonstrate that the metabolism of a drug is a primary concern throughout. Phase ii biotransformations attach a hydrophilic moiety onto drug metabolite. Drug metabolism in the liver university of washington. Handbook of drug metabolism 3rd edition pdf free pdf. On the other hand, these conjugations also play an essential role in the toxicity.
Understanding the cyp system is essential for advanced practitioners aps, as the consequences of drug drug interactions can be profound. Often these reactions involve the introduction of polar functional groups such as oh to drug molecules to make them more hydrophilic. In other words, the metabolites are pharmacologically inactive. Of the drugs metabolized by phase i cytochrome p450s, approximately 75% are metabolized by just two. Phase ii drugmetabolizing enzymes such as glutathione stransferase, aryl sulfatase and. Cytochrome p450 cyp is a hemeprotein that plays a key role in the metabolism of drugs and other xenobiotics estabrook, 2003. Since its inception, the goal of the handbook was to provide a comprehensive text to serve as a graduate course in drug metabolism, a. Drug metabolic process involves two phases, the occurrence of which may vary from compound to compound. Phase i reactions of drug metabolism involve oxidation, reduction, or hydrolysis of the parent drug, resulting in its conversion to a more polar molecule. There are three possible results of phase 1 metabolism. Phases of drug metabolism phase 1 drug metabolism functional conversion to polar metabolites in preparation for conjugation mostly in endoplasmic reticulum of the liver oh, nh2, sh, cooh often results in inactive metabolite, although sometimes metabolite more active prepares drug for phase 2 metabolism.
Drug metabolism is an immense area of study and this is reflected in the range of chemical reactions the substrates can undergo during metabolism, e. Phase ii reactions involve conjugation by coupling the drug or its metabolites to another molecule, such as glucuronidation, acylation, sulfate, or glicine. More generally, xenobiotic metabolism from the greek xenos stranger and biotic related to living beings is the set of metabolic pathways that modify the chemical structure of xenobiotics, which are compounds foreign to an organisms normal biochemistry, such as any drug. During reduction reactions, a chemical can enter futile cycling, in which it gains a free radical electron, then promptly loses it to.
This quiz has been uploaded to scribd by medical student james lamberg. Drugs get metabolize through various types of metabplic reactions, in this video, there is explanation about these reactions with examples. A free online edition of this book is available at. Induction of phase i, ii and iii drug metabolismtransport. Individual drug metabolism rates are influenced by genetic factors, coexisting disorders particularly chronic liver disorders and advanced heart failure, and drug interactions especially those involving induction or inhibition of metabolism. Liver is the principal organ of drug metabolism although every tissue has some ability to metabolize drugs. Cytochrome p450 isozyme system play important role in phase i. Drug metabolism is the metabolic breakdown of drugs by living organisms, usually through specialized enzymatic systems. Current concepts provides a comprehensive understanding of the processes that take place following ingestion of a medicinal agent or xenobiotic, with an emphasis on the crucial role of metabolism biotransformation. Chapters 2 and 3 deal with the chemistry of drug biotransformation. Phase i reactions include oxidation, reduction, and hydrolysis that are catalyzed by several enzymes including cytochrome p450.
The following are multiple choice questions in a style similar to those included in the usmle step 1. This is an advanced course, intended to present and discuss drug metabolism of the major drugs of abuse and its importance in the interpretation of drug test results in the clinical laboratory. Learn vocabulary, terms, and more with flashcards, games, and other study tools. Phase i drug metabolism free download as powerpoint presentation. During reduction reactions, a chemical can enter futile cycling, in which it gains a freeradical electron, then promptly loses it to. Phase i reactions include oxidation especially by the cytochrome p450 group of enzymes, also called mixedfunction oxidases, reduction, deamination, and hydrolysis. Ppt drug metabolism powerpoint presentation free to.
Phase i metabolism includes oxidation, reduction, hydrolysis, and hydration and isomerization plus rarer misc. Handbook of drug metabolism 3rd edition pdf free download. This learnatyourownpace online course is designed to provide scientists and regulatory professionals with a basic understanding of drug metabolism and its. The terms in the table below are a collection of items from the lectures that you should be able to define and relate in a sentence or two to drug metabolism as set out in the notes.
Sult1 and 2 are most important in the metabolism of drugs found in liver, kidney, intestine, in cytosol catalyze the sulfation of alcohols roh phenols main group of substrates, aroh arylamines arnh. The usual classification of drug metabolism enzymes and reactions as phase i or ii is somewhat misleading, as these reactions affect some drugs in a reverse order phase ii followed by phase i, e. Phase i biotransformation reactions introduce or expose functional groups on the drug with the goal of increasing the polarity of the compound. 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. A read is counted each time someone views a publication summary such as the title, abstract, and list of authors, clicks on a figure, or views or downloads the fulltext. Drug metabolism rates vary among patients genetic factors coexisting disorders chronic liver disorders drug interactions especially those involving induction or inhibition of metabolism phase i involve formation of a new or modified functional group through oxidation, reduction, hydrolysis. Since its inception, the goal of the handbook was to provide a comprehensive text to serve as a graduate course in drug metabolism, a useful reference for academic and industrial drug metabolism scientists, but also as an important reference tool for those pursuing a career in drug discovery and development. Importantly, steroid sulfation is reversible and sulfated steroids can be hydrolyzed to free steroids by steroid sulfatase sts, while. Prodrug biochemical or chemical processes drug inactive active the definition of a prodrug is controversial in some circles. Preclinical drug metabolism and pharmacokinetics studies play a key role in lead identification and. Xenobiotic metabolism, which includes drug metabolism.
Drug metabolism phase i almost any drug can undergo modi. These enzymes are found in high concentrations in the smooth endoplasmic reticulum of the liver. These reactions are categorized as phase i and phase. Phase i reactions convert the parent drug into more polar metabolites through introduction or exposing oh, sh, or nh2 functional groups. In phase ii more lipophilic groups are conjugated to the. Phases of metabolism drug biotransformation could be classified into two phases 1. The most common phase i drugmetabolizing enzymes are represented by. This results in activation or inactivation of the parent drug. Drug metabolism is the metabolic breakdown of drugs by living organisms, usually through. Phase i reactions phase i reactions also termed nonsynthetic reactions may occur by oxidation, reduction, hydrolysis, cyclization, and decyclization addition of oxygen or removal of hydrogen, carried out by mixed function oxidases, often in the liver. Pdf drugmetabolizing enzymes are called mixedfunction oxidase or monooxygenase and. Examples of phase i drug substrates are listed in table 41.
Antiepileptic drugs although considered one of the safest drugs, it has sedative effects. Topics include the effects of phase i and phase ii metabolic reactions, the bodys elimination of drugs and drug metabolites, and the various factors. Drug metabolism can be divided into the phase i reactions functionalisation and the phase ii reactions conjugation. Infrastructural part of this project has been supported by cz.
Phasei drug metabolism drug metabolism cytochrome p450. Metabolism is an essential pharmacokinetic process, which converts lipid soluble and nonpolar compounds to water soluble and polar compounds so that they are excreted by various. Introduction to phase i and ii metabolisms phase i. Many drugs undergo a number of these reactions main function of phase i metabolism is to prepare the compound for phase ii metabolism mixed function enzyme system found in microsomes of many cells esp liver, kidney, lung. Product areas highlighted include our portfolio of reagents for drug transport, phase i metabolism, and drug conjugate analysis. In this article, we discuss the basics of drug metabolism, the process, metabolising organs and enzymes especially cyp450 involved, chemistry. Prodrugs are inactive drugs that undergo a chemical or biochemical conversion to the active drug. This issue of biofiles features selected products from sigmaaldrich s drug metabolism platform. Developing effective new drugs requires a thorough understanding of how the drugs will act once they are administered to the patient.
Preclinical drug metabolism and pharmacokinetics studies play a key role. Oral absorption, intestinal metabolism and human oral bioavailability, pharmacogenetics and metabolism, altered drug metabolism and transport in pathophysiological conditions, anticancer drug metabolism. The correct answers can be found in link at the end of this post. Importantly, recent work toward an understanding of the specific targets of apapprotein binding and new developments in the possible clinical use of measurements of. Phase i reactions in microsomes are cata lyzed by a group of enzymes known. Metabolism or biotransformation it is the enzymatic conversion from one chemical form of a substance to another. Phase 1 metabolism involves chemical reactions such as oxidation most common, reduction and hydrolysis. Completely revised and updated throughout, the new edition focuses only on essential chemical detail and includes patient case histories to illustrate the clinical consequences of changes. Human drug metabolism, an introduction, second edition provides an accessible introduction to the subject and will be particularly invaluable to those who already have some understanding of the life sciences.
It is almost a decade since the second edition of the handbook of drug metabolism was published. This selfpaced course consists of approximately 5 hours of recorded lectures and materials. Phase i, ii, and iii metabolism will be included beginning with phase ii, which is first in the timeline for apap. Most of the tissues and organs in our body are well equipped with diverse and various dmes including phase i, phase ii metabolizing enzymes and phase iii transporters, which are present in abundance either at the basal unstimulated level. Sarita sharma assistant professor of pharmacology mumbai 2. It is convenient to divide drug metabolism into two phases i and ii. Burgers medicinal chemistry, drug discovery, and development, seventh. Phase i biotransformations include oxidation, reduction, and hydrolysis reactions. What are the 2 phases a drug needs to go through in order to become polarized.
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