Reductive metabolism is carried out by various enzymes. Examples of phase i drug substrates are listed in table 41. Overview definition consequences types phase iii in detail. This provides a handle for phase 2 conjugating species with which to react with. 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. The letrozole phase 1 metabolite carbinol as a novel probe. Most metabolic products are less pharmacologically active. View the rest of my pharmacology videos in order be.
Learn phase 1 metabolism toxicity with free interactive flashcards. In phase ii more lipophilic groups are conjugated to the. The term drug metabolism in its broadest sense may be considered as the absorption, distribution, biotransformation and excretion of drugs. In the present study, four new metabolites, 5dehydroxyhexahydrodemethoxycurcumina m1, 5dehydroxyhexahydrodemethoxycurcuminb. Phase 1 metabolism involves chemical reactions such as oxidation most common, reduction and hydrolysis.
There are three possible results of phase 1 metabolism. Drug metabolism is the metabolic breakdown of drugs by living organisms, usually through specialized enzymatic systems. To cover all these facets of drug metabolism in a single text is a voluminous task and therefore we have focused primarily on the biotransformation aspects of. Jianda lu, jun xue, in critical care nephrology third edition, 2019. 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. Identification of ugt isoforms was performed using a panel of. Drug metabolism is an immense area of study where drugs undergo a range of enzymemediated chemical reactions, such as oxidation, reduction, hydrolysis, hydration, conjugation, and migration. Many xenobiotics are lipophilic and almost chemically inert e. The content has been concisely summarized to help understand various steps involved in the phase 1 and pase 2 metabolism processes of xenobiotics. We elucidated the contribution of udpglucuronosyltransferase ugt isoforms on the glucuronidation of carbinol.
In other words, the metabolites are pharmacologically inactive. For example, if 500 mg is present in the body at time zero, after metabolism, 250 mg may be present at 1 hour and 125 mg at 2 hours illustrating a half. Conjugation reactions phase ii biotransformations attach a hydrophilic moiety onto drugmetabolite. In such cases, called firstorder elimination or kinetics, the metabolism rate of the drug is a constant fraction of the drug remaining in the body ie, the drug has a specific halflife. Curcuminoids are a safe natural food coloring additive with antiinflammatory, antioxidant, and anticarcinogenic activities.
Cytochrome p450 cyp is a hemeprotein that plays a key role in the metabolism of drugs and other xenobiotics estabrook, 2003. The nats identified to date and involved in human drug metabolism include nat1 and. These enzymes are found in high concentrations in the smooth endoplasmic reticulum of the liver. 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. Pahs so would not necessarily undergo a phase 2 reaction. The whole range of biochemical processes that occur within an organism, metabolism consists both of anabolism and catabolism the buildup and breakdown of substances, respectively.
Phase 1 of metabolism is concerned with functionalization, that is the introduction or exposure of functional groups on the chemical structure of a compound. Phase i biotransformations include oxidation, reduction, and hydrolysis reactions. The enzymecatalyzed reactions of phase i metabolism bind oxygen, hydrogen, water, or amino acids to the lipophilic drug molecule to expose or introduce a hydroxyl oh, amino nh 2, sulfhydryl sh, or carboxyl cooh polar functional group, and thus, result in a modest increase in the parent drugs water solubility. 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. 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.
The content is so presented to allow the reader to compare various processes simultaneously and can easily memorize and learn about the topic. The liver is the principal, but not the sole, site of most drug metabolism in the body. Ppt drug metabolism powerpoint presentation free to. The adobe flash plugin is needed to view this content. Cytochrome p450 enzymes are the most important class of enzymes in phase i metabolism. Other oxidative enzymes in drug metabolism include flavin monooxygenase and monoamine oxidase.
Homework 1 drug metabolism 20 university of washington. This section takes a look at drug metabolism specifically, it provides a short overview of the various common conjugation reactions involved in the metabolism of drugs. Drug metabolism is the chemical alteration of a drug by the body. Choose from 198 different sets of phase 1 metabolism toxicity flashcards on quizlet. Phase i biotransformation reactions introduce or expose functional groups on the drug with the goal of increasing the polarity of the compound. Introduction to drug metabolism gibson and skett lots of metabolism info, cheap. Drug metabolism can be divided into the phase i reactions functionalisation and the phase ii reactions conjugation. In phase 2, the active drug is made inactive and transformed in such a way that it is now suitable. The resulting product is too polar to recross membranes back into tissues and is readily excreted. The biochemical reactions are known as metabolic pathways and involve enzymes that transform one substance into another substance, either. This is done by adding a functional group oh here on to the drug compound. The cytochrome p450 enzyme system is particularly important because many different drugs also can induce or inhibit these enzymes, resulting in changing. Cytochrome p450 isozyme system play important role in phase i. During phase 1, the inactive drug is made active by a set of drug metabolising enzymes.
Often these reactions involve the introduction of polar functional groups such as oh to drug molecules to make them more hydrophilic. These reactions include hydrolysis, reduction, and oxidation. Phasei drug metabolism free download as powerpoint presentation. Isolation and identification of phase 1 metabolites of. How a sound knowledge of these phenomena is incorporated into the. Introduction of magnetic and supermagnetic nanoparticles in new approach of targeting drug delivery and cancer therapy application. Understanding the cyp system is essential for advanced practitioners aps, as the consequences of drugdrug interactions can be profound. Although phase i drug metabolism occurs in most tissues, the primary and first pass site of metabolism occurs during hepatic circulation. 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.
Ppt drug metabolism powerpoint presentation free to download id. Evolution of drug metabolism as a science post wwii pioneers richard tecwyn williams great britain 1942, worked on the metabolism on tnt with regard to toxicity in munitions workers. Liver is the primary site where majority of drug metabolism occurs in two phases. During phase i reactions hydrophobic molecules are transformed into more polar. Although demethoxycurcumin is one of the major bioactive constituents of curcuminoids, knowledge about its metabolic fate is scant.