These processes determine the fate of a drug in the body. Metabolism or biotransformation the conversion from one chemical form of a substance to another. Chapters 8 and 11 pharmacokinetics and pharmacodynamics pharmacodynamics is the study of how drugs interact with a molecular target, i. Introduction drug metabolism biotransformation or detoxication is the biochemical changes of the drugs and other. Gastric emptying times vary among patients and contribute significantly to. Apr 12, 2018 drug metabolism as a discipline plays an important role in drug discovery and development and the effects of drug metabolism on pharmacokinetics pk, pharmacodynamics pd, and safety should be carefully considered. Homework 1 drug metabolism 20 university of washington. Preclinical drug metabolism and pharmacokinetics studies play a key role in lead identification and. 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. Drug metabolism often converts lipophilic chemical compounds into more readily excreted polar products. 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. They focus on the biochemical pathways that we find in humans, and they also take into account some physiological and clinical aspects.
Apr 02, 2020 drug metabolism pptpowerpoint presentation, medical notes edurev is made by best teachers of. Drug metabolism biotransformation drug metabolism is the biochemical modification of pharmaceutical substances by living organisms, usually through specialized enzymatic systems. The drug metabolism process occurring in organs other than the figure 1. Ppt drug metabolism powerpoint presentation free to. Find materials for this course in the pages linked along the left. Metabolism is an essential pharmacokinetic process, which renders lipid soluble and nonpolar compounds to water soluble and polar compounds so that. The notes, and the corresponding slides, are also freely available in pdf and powerpoint formats. 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. Food and drug administration declared ibrutinib as a breakthrough therapy in february 20 for the treatment of relapsed refractory mantle cell lymphoma and gave approval for this indication in november 20 wang et al. In addition to the liver, every biological tissue of the body has the ability to metabolize drugs.
Basic principles of drug metabolism is the property of its rightful owner. Metabolism describes the chemical reactions that change drugs into compounds which are easier to eliminate. Drug metabolizing enzymes thermo fisher scientific. Recently, in february 2014 the food and drug administration provided accelerated approval for. Pdf drugs and the liver drug metabolism in liver disease.
Drug metabolism as a discipline plays an important role in drug discovery and development and the effects of drug metabolism on pharmacokinetics pk, pharmacodynamics pd, and safety should be carefully considered. Introduction to drug metabolism ppt download effect of liver disease on drug metabolism liver dysfunction and drugs metabolism dr v sebghatollahi. The drug metabolism happening in the liver is termed as hepatic metabolism. 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 processes.
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. Understand how atp is formed from adp and inorganic phosphate p i, and vice versa. Theprimary site of drug metabolism is the smooth endoplasmic reticulum of the liver cell. The involved chemical modifications incidentally decrease or increase a drug s pharmacological activity andor halflife, the most extreme example being the metabolic activation of inactive prodrugs into active drugs, e. The general intention is to demonstrate that the metabolism of a drug is a primary concern throughout.
Drug metabolism is often considered during drug design. Its a presentation done by me in the given topic at the pharmacology seminar organised at r. Markey laboratory of neurotoxicology nimh, nih nov. However, there is growing evidence that most common drug metabolizing enzymes are expressed in the skin. The primary objective of drug metabolism is to facilitate a drugs excretion by increasing its water solubility hydrophilicity. The chemistry of drug metabolism needs an elaborate understanding it is a fascinatingand a complicatedprocess. The hepatic cytochrome p450s cyp are a multigene family of enzymes that play a critical role in the metabolism of many drugs and xenobiotics with each.
When drugs enter the body, they are subject to attack from a range of metabolic enzymes. Ppt basic principles of drug metabolism powerpoint. Drug metabolism pptpowerpoint presentation, medical. Drug metabolism in drug design and development donglu zhang, ming she zhu, william g. Role of metabolism in drug discovery 36 in drug development it is important to have an information on the enzymes responsible for the metabolism of the candidate drug invitro studies can give information about metabolite stability metabolite profile metabolite identification cyp inductioninhibition drug drug. Drug metabolites can have the same, increased or decreased activity compared to parent compound.
Drug metabolism principles and applications 100% online. Path of a drug after administration by any route, a drug will reach the blood stream as schematically shown in f2. Metabolism is an essential pharmacokinetic process, which renders lipid soluble and nonpolar compounds to water soluble and. We then take a brief look at where metabolism does occur in the body chapt. Drug metabolism university of california, san diego.
Nov 01, 2016 explain scientific and regulatory expectations with respect to drug metabolism and transport studies, and the impact of these studies in accelerating drug development. This biotransformation can be deterred by replacing the hydrogen at the paraposition and using fluorine as a bioisostere. Drug metabolism pptpowerpoint presentation, medical notes. Drug metabolism is the property of its rightful owner. 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. Elimination irreversible removal of the drug from the body metabolism liver and intestine as major sites.
Factors affecting drug metabolism drug metabolism metabolism. Scribd is the worlds largest social reading and publishing site. Phase i and phase ii reactions of drug authorstream presentation. Penicillin changes to penicilloic acid in presence of enzyme penicilase. In part ii we will discuss the kinetics of drug metabolism and the relationship of kinetic data to the pharmacokinetics of a drug. This document is highly rated by students and has been viewed 490 times. 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. The reactions are catalysed by enzymes and happen mostly in the liver, though some changes take place in the gut wall. In some cases, the firstpass effect results in metabolic activation of an inert pro drug. The primary objective of drug metabolism is to facilitate a drug s excretion by increasing its water solubility hydrophilicity. Factors affecting drug metabolism free download as powerpoint presentation. The liver plays a central role in metabolism of nutrients, synthesis of glucose and lipids, and detoxification of drugs and xenobiotics.
Developing effective new drugs requires a thorough understanding of how the drugs will act once they are administered to the patient. Despite the fact that the drug is slowly metabolized, however, the duration of anesthesia is short because of drug redistribution into adipose tissue, which can act as a storage site, or drug reservoir. 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 biochemistry of drug metabolism an introduction. Ppt pharmacokinetics powerpoint presentation free to. Oct 26, 2014 a drug may inhibit one isoenzyme while being itself a substrate of another isoenzyme e. Medicinal chemistry drug metabolism december 3rd, 2014 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. The products of these chemical reactions are called metabolites. This learnatyourownpace online course is designed to provide scientists and regulatory professionals with a basic understanding of drug metabolism and its. The process of metabolism is divided into 3 phases.
Genetic factors in drug metabolism american family physician. The major pathways in the liver are glucose, fatty acids. Since the liver is a major site of drug metabolism, this firstpass effect may reduce the amount of drug reaching the target tissue. This biotransformation can be deterred by replacing the hydrogen at the paraposition and using fluorine as a. For instance, a drug containing a benzene group may undergo phase i reactions e. Drug metabolism is the metabolic breakdown of drugs by living organisms, usually through specialized enzymatic systems.
Introduction to drug metabolism ppt download effect of liver disease on drug metabolism. Jun 01, 2008 pharmacokinetics is the study of the rate and extent of drug absorption, distribution, metabolism, and excretion. Drug metabolism free download as powerpoint presentation. Although it is the largest organ of the human body, skin is often not considered in discussions of drug metabolism. Dmd presents important research in pharmacology and toxicology and is a valuable resource in drug design, drug metabolism. Metabolism biotransformation catalyzed by drug metabolizing enzymes is a main defense mechanism of the body against xenobiotic threats, and regarded as a key determinant of pharmacokinetics and. Absorbed drugs 3 changes metabolic changes by enzymes microsomal, cytoplasmic, mitochondrial spontaneous molecular.
Prodrugs excretion how is the drug eliminated pharmacokinetics is concerned with the variation in drug concentration with time as a result of absorption, metabolism, distribution and excretion. Scientists, technicians and regulatory professionals who desire to learn the essentials of drug metabolism, a key aspect of the drug development process. A free powerpoint ppt presentation displayed as a flash slide show on id. Preclinical drug metabolism and pharmacokinetics studies play a key role in lead identification and optimization. Introduction biotransformation is defined as the conversion from one chemical form to another synonym metabolism detoxification process these chemical changes takes place within our body in presence of some enzymes e. A primer for bioanalytical chemists, part i in the face of advancing technology in combinatorial synthesis and high throughput screening, the drug discovery process continues to evolve. Metabolism or biotransformation it is the enzymatic conversion from one chemical form of a substance to another. First pass metabolism presystemic metabolism first pass effect metabolism of a drug during its passage from the site of absorption into the systemic circulation. The term metabolism is commonly used probably because products of drug transformation are called metabolites. Metabolism is a biotransformation process, where endogenous and exogenous compounds are converted to more polar products to facilitate their elimination from the body. The involved chemical modifications incidentally decrease or increase a drugs pharmacological activity andor halflife, the most extreme example being the metabolic activation of inactive prodrugs into active drugs, e. Drug metabolism drug metabolism medical treatments.
Define the terms metabolism, metabolic pathway, catabolism, and anabolism. Invitrogen corporation 501 charmany drive madison, wi 53719 usa drugdiscovery. Phase i metabolism involves functionalization reactions. Drug metabolism is an immense area of study where drugs undergo a range of enzymemediated chemical reactions, such as oxidation. Drug metabolism phase i almost any drug can undergo modi. Understand how coenzymea is used to transfer acyl groups. Some patients metabolize a drug so rapidly that therapeutically effective blood and tissue concentrations are not reached. The enzymes involved in metabolism are present in many tissues but generally are more concentrated in the liver. It is almost a decade since the second edition of the handbook of drug metabolism was published.
Pdf drugs and the liver drug metabolism in liver disease drug metabolism in the liver benzodiazepine mnemonics memory tools. Handbook of drug metabolism paul gerard pearson, larry c. Apr 04, 2020 the pharmacogenetics of drug metabolizing enzymes is a prominent focus of this field, because genetic makeup is responsible for a significant portion of drug induced toxicity. This is because of the presenceof largeamounts of many varieties of enzymes. Biotransformation of drugs in human skin drug metabolism. Lecture notes principles of pharmacology health sciences. Drugs can be metabolized by oxidation, reduction, hydrolysis, hydration, conjugation, condensation, or isomerization. If so, share your ppt presentation slides online with. Sarita sharma assistant professor of pharmacology mumbai 2. Set 1 powerpoint links collected from the website of. Drug metabolism is one of the most important events a drug faces after administration. Major location of drug metabolizing enzymes dysfunction can lead to impaired drug metabolismdecreased enzyme activity first pass metabolism effected may inc 24 x bioavailiability results in exaggerated pharmacological responses and adverse effects cardiac failure causes decreased blood flow to the liver.
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