View the rest of my pharmacology videos in order be. In other words, the metabolites are pharmacologically inactive. Conjugation reactions phase ii biotransformations attach a hydrophilic moiety onto drugmetabolite. As most small molecule drugs are lipophilic in nature, drug metabolism converts these hydrophobic compounds into more water soluble compounds that can be excreted. The metabolism phase is absent for the few drugs that are not transformed. Drug metabolism can be divided into the phase i reactions functionalisation and the phase ii reactions conjugation. Allied organic compounds williams, 1949 helped to establish the study of drug and. 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. Concluding, culturing heparg cells in the amcbal yields substantial phase 1 and phase 2 drug metabolism, while maintaining high viability, rendering dmso addition superfluous for the.
Phase 1 metabolism involves chemical reactions such as oxidation most common, reduction and hydrolysis. Phase ii reactions involve conjugation of the drug with endogenous charged. This results in activation or inactivation of the parent drug. 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. Phase i reactions include oxidation especially by the cytochrome p450 group of enzymes, also called mixedfunction oxidases, reduction, deamination, and hydrolysis. Phase 1 drug metabolism functional conversion to polar metabolites in preparation for conjugation. Phase 1 reactions function to convert lipophilic drug molecules into more polar molecules by introducing or unmasking a polar functional group, such as oh or nh2. Drug metabolizing enzymes and biotransformation reactions 1 nalia at penner, caoline r woodward and, chandra prakash a.
Drug metabolism is the phase of biochemical transformation of the drug. Biopharmaceutics and pharmacokinetics by brahmankar pg no 9190 2. The primary objective of drug metabolism is to facilitate a drugs excretion by increasing its water solubility hydrophilicity. Phase i and phase ii biotransformation reactions catalyzed by xenobiotic biotransforming enzymes are generally divided into two groups. Phase i biotransformations include oxidation, reduction, and hydrolysis. As most small molecule drugs are lipophilic in nature, drug metabolism converts these hydrophobic. There are three possible results of phase 1 metabolism. The whole range of biochemical processes that occur within an organism, metabolism consists both of anabolism and catabolism the buildup and breakdown of substances.
Abnormal metabolism of fats lipids leading to abnormalities in the level of fats in the blood. Metabolism, or the biotransformation of a drug, is the process whereby living. More generally, xenobiotic metabolism from the greek xenos stranger and biotic. The terms in the table below are a collection of items from the lectures that you should be able to. What phase 1 reaction is mainly performed by the cytochrome p450 enzymes also called mixedfunction enzymes. Pharmacokinetics for pharmacokinetics describes the action. 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. Typically, oxidation is the most common phase i reaction. The following are multiple choice questions in a style similar to those included in the usmle step 1. The hydroxylated product produced from phase 1 reactions can also be conjugated by conjugation enzymes to more. 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. This form of metabolism involves oxidation with the cyp450 enzymatic family. Similar mean maximum thc concentrations were reported in specimens collected immediately after cannabis smoking was completed. Drug metabolism is the metabolic breakdown of drugs by living organisms, usually through.
It is convenient to divide drug metabolism into two phases i and ii. Definition drug metabolism is the process by which the body breaks down and converts medication into active chemical substances. Pdf on feb 1, 2005, p david josephy and others published phase i and phase ii drug metabolism. The involved chemical modifications incidentally decrease or increase a. Xenobiotic metabolism, which includes drug metabolism, has become a major pharmacolo. Phase i metabolism of drug candidates can be simulated in the laboratory using nonenzyme. The chemical modification of drugs with the overall goal of getting rid of the drug. Human cytochromes p450 associated with the phase 1.
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. As explained in great detail in other chapters see 5. Human cytochromes p450 associated with the phase 1 metabolism of drugs and other xenobiotics. Introduction to phase i and ii metabolisms phase i. The drug metabolism happening in the liver is termed as hepatic metabolism. It is highly variable among drugs and depends on biological conditions. Drug metabolism is the metabolic breakdown of drugs by living organisms, usually through specialized enzymatic systems.
One of them is gst or glutathione stransferases, which are a family of ubiquitously expressed polymorphic enzymes that are involved in the. Drug metabolizing enzymes dmes play central roles in the metabolism, elimination and detoxification of xenobiotics and drugs introduced into the human body. Phase i reactions include oxidation, reduction, and hydrolysis that are catalyzed by several enzymes including cytochrome p450. 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. Induction of phase i, ii and iii drug metabolismtransport. Phase i reactions are broadly grouped into three categories, oxidation, reduction, and hydrolysis. In addition to the liver, every biological tissue of the body has the ability to metabolize drugs. Jianda lu, jun xue, in critical care nephrology third edition, 2019. Drug metabolism is the chemical alteration of a drug by the body. Metabolism or biotransformation the conversion from one chemical form of a substance to another. The content has been concisely summarized to help understand various steps involved in the phase 1 and pase 2 metabolism processes of. The liver is the principal, but not the sole, site of most. The primary objective of drug metabolism is to facilitate a drug s excretion by increasing its water solubility hydrophilicity. Many drugs undergo a number of these reactions main function of phase i metabolism is to.
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