Drug metabolism pptpowerpoint presentation, medical. In this phase an existing functional group already presents in the drug molecule or created by phase i metabolism such as alcohol, phenol, amine is masked or inactivated by a process of. Genetic polymorphisms, drug metabolism and drug concentrations. Hydroxylation of an nmethyl group leads to expulsion of a molecule of formaldehyde, while oxidation of the omethyl groups takes place to a lesser extent. Quantitatively, the liver and gastrointestinal tract are the most important organs of drug metabolism. K arthik kumar, 09bu1r0010, mlr institute of pharmacy. The phase 1 oxidation reactions are carried out by cyps, flavincontaining monooxygenases fmo, and epoxide hydrolases eh.
In addition to the liver, every biological tissue of the body has the ability to metabolize drugs. Phase 1 andor phase 2 some drugs undergo either phase 1 or phase 2 metabolism, but most undergo phase 1. Phase 1 drug metabolism ghosal 1 and 2 flashcards quizlet. A free powerpoint ppt presentation displayed as a flash slide show on id. What are the possible metabolism of phase 1 and phase 2 for the drug carbamazepine. This is because of the presenceof largeamounts of many varieties of enzymes.
In part ii we will discuss the kinetics of drug metabolism and the relationship of kinetic data to the pharmacokinetics of a drug. 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. Phase i reactions include oxidation, reduction, and hydrolysis that are catalyzed by several enzymes including cytochrome p450. For example, phase i metabolism converts acetonitrile to hoch 2 cn, which rapidly dissociates into formaldehyde and hydrogen cyanide. Answer to what are the possible metabolism of phase 1 and phase 2 for the drug carbamazepine skip navigation. Drug metabolism can be divided into the phase i reactions functionalisation and the phase ii reactions conjugation. Phase 1 andor phase 2 some drugs undergo either phase 1 or phase 2 metabolism, but most undergo phase 1 metabolism followed by phase 2 metabolism. As drug concentration increases, metabolism shifts from firstorder to zeroorder kinetics. Drug botanical dietary supplement interactions can include inhibition or induction of 1 p450 enzymes involved in drug metabolism, 2 udpglucuronosyl transferases, 3 other phase i and phase ii enzymes, and 4 drug transporters and drug efflux proteins. Drugs undergo either phase i metabolism or phase ii metabolism in addition, a drug can undergo both eg.
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. Phase i reactions involve hydrolysis, reduction and oxidation, exposing or introducing a functional group oh, nh 2, sh or cooh to increase reactivity and slightly increase hydrophilicity. Page 1 drug metabolism page 2 drug metabolism metabolism biotransformation of compounds is essential for survival of the organism. Outline the phase 1 studies conducted to characterize the clinical pharmacology of a drug. Phases i and ii of the metabolism of a lipophilic drug. Phase ii drug metabolism is a conjugation reaction. Most phase 2 reactions inactivate drugs or the active metabolites formed from phase 1 reactions. Modeling of phase 2 metabolism enzymes drug metabolism. Phase i biotransformation reactions introduce or expose functional groups on the drug with the goal of increasing the polarity of the compound. Pandya 9 phases of metabolism phase 1 reaction non synthetic phase phase 2. Although phase i drug metabolism occurs in most tissues, the primary and first pass site of metabolism occurs during hepatic circulation.
Atotw 179 the role of the liver in drug metabolism 17052010 page 3 of 6. 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 2 nhydroxy compounds rnhoh cofactor 3phosphoadenosine5phosphosulfate, paps is in limited supply, drug can overwhelm the system. The content has been concisely summarized to help understand various steps involved in the phase 1 and pase 2 metabolism processes of xenobiotics. When the drug molecule is oxidized, hydrolyzed, or covalently attached to a hydrophilic species, the whole molecule becomes more hydrophilic, and is excreted more easily. Oxidation is catalysed by cytochrome p450 enzymes and results in the loss of electrons from the drug. Ppt drug metabolism powerpoint presentation free to download id. Learn vocabulary, terms, and more with flashcards, games, and other study tools. Phase 2 conjugation of a drug can occur in the absence of phase 1 metabolism. What are the possible metabolism of phase 1 and ph.
This is called conjugation and the product is called a conjugate. Tylenol can be metabolized by phase or phase 2 metabolism however the phase 2 metabolism predominates at lower concentrations of the drug. Pharmacokinetic interactions between drugs and botanical. Liver hepatic metabolism continues to be the most important route of metabolism for foreign ingested chemicals xenobiotics and drugs. Phase 1 metabolism can involve reduction or hydrolysis of the drug, but the most common biochemical process that occurs is oxidation. Intestinal mucosa, kidney, lungs, skin and adrenals intestinal mucosa intestinal wall is rich in esterases and lipases enzymes. 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 on feb 1, 2005, p david josephy and others published phase i and phase ii drug metabolism.
Phase i reactions convert the parent drug into more polar metabolites through introduction or exposing oh, sh, or nh2 functional groups. Introduction to phase i and ii metabolisms phase i metabolism. Introduction to phase i and ii metabolisms phase i. Feb 27, 2019 drug metabolism is the term used to describe the biotransformation of pharmaceutical substances in the body so that they can be eliminated more easily. Phase ii conjugation reactions subsequent reaction in which a covalent linkage is. Overview definition consequences types phase iii in detail enzyme inductioninhibition first pass metabolism. A drug may inhibit one isoenzyme while being itself a substrate of another isoenzyme e. Metabolism is an essential pharmacokinetic process, which renders lipid soluble and nonpolar compounds to water soluble and polar compounds so that they are excreted by various processes. Part 1 of the article covers the basics of drug metabolism. Protein binding attachment of the drug to blood proteins is an important factor influencing drug distribution. Ppt drug metabolism powerpoint presentation free to. Drugs get metabolize through various types of metabplic reactions, in this video, there is explanation about these reactions with examples. Often, phases 1 and 2 pathways work together to help in the removal of the xenobiotic.
Drug metabolism is the metabolic breakdown of drugs by living organisms, usually through specialized enzymatic systems. Metabolic organs the chemistry of drug metabolism needs an elaborate understanding it is a fascinatingand a complicatedprocess. Sep 22, 2017 metabolism is the protective biochemical process by which our bodies alter xenobiotics either enzymatically or nonenzymatically. Phase i and phase ii reactions of drug authorstream presentation. Although there are many types of enzymes capable of biotransformation, cyps are the most. The product for the p1 metabolism pathway is napqi which is toxic to the liver. Some drugs just undergo one or the other but the majority will undergo phase 1 and then phase 2 sequentially. Markey laboratory of neurotoxicology nimh, nih nov. Biotransformation an overview sciencedirect topics. This document is highly rated by students and has been viewed 490 times. Biotransformation is the chemical modification or modifications made by an organism on a chemical compound. Oxidation is the chemical reaction that occurs when apples turn brown when exposed to the oxygen in air. The drug metabolism happening in the liver is termed as hepatic metabolism. Convert parent compound into a more polar hydrophilic metabolite by adding or unmasking functional groups oh, sh, nh2, cooh, etc.
Previous question next question get more help from chegg. The cyps and fmos are composed of superfamilies of enzymes. The term metabolism is commonly used probably because products of drug transformation are called metabolites. Cyp2c8 substrate drugs include amodiaquine, cerivastatin, dasabuvir, enzalutamide, imatinib, loperamide, montelukast, paclitaxel, pioglitazone, repaglinide, and rosiglitazone, and the. 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. Convert parent compound into a more polar hydrophilic metabolite by adding or unmasking.
Metabolism of active drug to an inactive substance typically by the liver, but other organs kidney, lungs also metabolise some substances. It is highly variable among drugs and depends on biological conditions. This is because only watersoluble substances undergo excretion, whereas lipid soluble substances. Excretion of active drug often by the kidneys, but may also be in bile, or exhaled. Role of cytochrome p450 2c8 in drug metabolism and. The nats identified to date and involved in human drug metabolism include nat 1 and nat 2. Cyp2c8 is highly expressed in human liver and is known to metabolize more than 100 drugs. The content is so presented to allow the reader to compare various processes simultaneously and can easily memorize and learn about the topic. Phase ii reactions include glucuronidation, sulfation, acetylation, methylation. Whereas phase 1 metabolism involves hydroxylation, oxidation, and reduction pathways, phase 2 metabolism involves primarily conjugation of the phase 1 metabolites with a variety of groups e. Path of a drug after administration by any route, a drug will reach the blood stream as. Addition of the sulfonate moiety to the molecule of a parent compound or most often to the molecule of its metabolite originating in the oxidative phase of drug metabolism leads to formation of a watersoluble compound which is then easily eliminated from the body.
Drug metabolism principles and applications 100% online. During the last 1015 years, cytochrome p450 cyp 2c8 has emerged as an important drug metabolizing enzyme. Phase 2 metabolism involves reactions that chemically change the drug or phase 1 metabolites into compounds that are soluble enough to be excreted in urine. Table showing examples of anaesthetic drug metabolism by cytochrome p450 system phases of metabolism metabolism of drugs is usually divided into phase 1 and phase 2.
Cyp3 drug metabolism 1 subfamily, 4 genes, 2 pseudogenes. As the drug concentration increases the p1 pathway cyp is used more. Often these reactions involve the introduction of polar functional groups such as oh to drug molecules to make them more hydrophilic. Types of biotransformation phasei or functionalization or non synthetic. Simple hydrolysis in the stomach is normally an innocuous reaction, however there are exceptions. Metabolism is an essential pharmacokinetic process, which renders lipid soluble and nonpolar compounds to water soluble and polar compounds so that. The hydroxylated product produced from phase 1 reactions can also be conjugated by conjugation enzymes to more hydrophilic products, easier to excrete. Phase iii refers to transportermediated elimination of drug and or metabolites from body normally via liver, gut, kidney, or lung. But phase i metabolism converts acetonitrile to hoch 2 cn, which rapidly dissociates into formaldehyde and hydrogen cyanide, both of which are toxic. As a fundamental element in precision medicine, pharmacogenomics, the study of responses of individuals to medication based on their genomic information, enables the evaluation of some specific genetic variants responsible for an individuals.
The metabolism phase is absent for the few drugs that are not transformed. 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. Many drugs are bound to blood proteins such as serum albumin the main blood protein and are not available as active drugs. Difference between phase i and phase ii metabolism compare. Metabolism drug metabolism is the anabolic and catabolic breakdown of drugs by living organisms. Renal excretion mechanisms are low at birth, but mature over a few months. Types of phase 1 and phase 2 metabolism associated enzymes and cofactors learn with flashcards, games, and more for free.
Drug metabolism is basically a process that introduces hydrophilic functionailities onto the drug molecule to facilitate excretion. Limited data are available on the pharmacodynamics of drugs. Phase i metabolism of drug candidates can be simulated in the laboratory using nonenzyme catalysts. In this case, if 500 mg is present in the body at time zero, after metabolism, 450 mg may be present at 1 hour and 400 mg at 2 hours illustrating a maximal clearance of 50 mgh and no specific halflife. Siteorgans of drug metabolism the major site of drug metabolism is the liver.
Phase i and phase ii reactions of drug authorstream. Metabolites formed in phase 2 are unlikely to be pharmacologically active. Drug metabolism enzyme activity is typically reduced in the neonate, but rapidly develops over the first year of life. View the rest of my pharmacology videos in order be. Describe the mechanisms of drug clearance and metabolism. Phase i biotransformations include oxidation, reduction, and hydrolysis reactions. Drug metabolism is the phase of biochemical transformation of the drug. Jan 06, 2019 the key difference between phase i and phase ii metabolism is that the phase i metabolism converts a parent drug to polar active metabolites while phase ii metabolism converts a parent drug to polar inactive metabolites. The interindividual genetic variations in drug metabolizing enzymes and transporters influence the efficacy and toxicity of numerous drugs. The drug metabolism process occurring in organs other than the figure 1.
Apr 02, 2020 drug metabolism pptpowerpoint presentation, medical notes edurev is made by best teachers of. Drug metabolism is conventionally described as consisting of phase 1 oxidation reactions, primarily mediated by cytochrome p450 enzymes in the liver, and phase 2 conjugations such as glucuronidation, sulphation and acetylation. Oct 26, 2014 2 outline introduction history phases of metabolism phase i metabolism cytochrome p family phase ii metabolism first pass metabolism ante drug microsomal enzyme induction role of metabolism in drug discovery dr swaroop hs copyighted 3. Little overlap in substrate specificities of the two isoforms appears to exist. 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. Technology phase i and phase ii reactions of drug metabolism. 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.
The first drug metabolising polymorphism was described over 40 years ago for acetylation. As explained in great detail in other chapters see 5. Phases i and ii of the metabolism of a lipophilic xenobiotic. Theprimary site of drug metabolism is the smooth endoplasmic reticulum of the liver cell.
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