Pharmacokinetics is the study of the rate and extent of drug absorption, distribution, metabolism, and excretion. These processes determine the fate of a drug in the body. Factors affecting drug metabolism, such as genetic polymorphisms, age and diet are discussed and how metabolism can lead to toxicity is explained. The book concludes with the role of drug metabolism in the commercial development of therapeutic agents as well as the pharmacology of some illicit drugs. Chemical factors Chilarity Side effect of ()(S)thalidomide is the inhibition of the growth of new Biological factors affecting toxic response Chemicals in the diet, air or water Cigarette smoking and alcohol intake are also known to affect drug metabolism and pharmacological response. Biological factors affecting toxic response Many factors affect the rate and pathway of metabolism of drugs, and the major influences can be subdivided into internal (physiological and pathological) and external (exogenous) factors as indicated below. Chapter 4 Genetic and Epigenetic Factors Affecting Cytochrome P450 Phenotype and Their Clinical Relevance 87 Viola Tamsi and Andrs Falus Chapter 5 Altered Drug Metabolism and Transport in Pathophysiological Conditions 111 Adarsh Gandhi and Romi Ghose Topics on Drug Metabolism. The decline in drug metabolism because of advanced age is associated with physiologic changes that have pharmacokinetic implications affecting the steadystate plasma concentrations and renal clearance for the parent drug and its metabolites. DMD presents important research in pharmacology and toxicology and is a valuable resource in drug design, drug metabolism, drug transport, expression of drug metabolizing enzymes and transporters, and regulation of drug metabolizing enzyme and transporter gene expression. Pharmacokinetics and Pharmacodynamics the basics. 2 Objectives By the end of this session, you should be able to: Factors affecting drug absorption Factors affecting drug metabolism Drug metabolism can be affected by: First Pass effect Drug Metabolizing Enzymes and ReactionPhenotyping Carl D. Pharmaceutical Candidate Optimization Metabolism and Pharmacokinetics BristolMyers Squibb Drug Metabolism Factors affecting drug metabolism: Tissue differences Genetics Species differences Coadministered substrates (inhibitors or inducers). discuss factors affecting absorption, distribution, metabolism and excretion of drugs (2. 1) explain how factors influence dosage regimes, including those for patients with renal and hepatic impairment (2. 2) explain types of drug interactions arising from pharmacokinetic The liver is the primary site for drug metabolism. the selective metabolism of two or more similar functional groups (eg. pick one of the two OH groups in a drug molecule) or two or more similar atoms in different regions of a molecule (Eg. para, meta and ortho positions of a phenyl ring). 9 Andreas Mats Svennebring, Investigation of the prerequisites for the optimization of specific plasma protein binding as a strategy for the reduction of firstpass hepatic metabolism, Xenobiotica, 2015, 45. Factors Affecting Metabolism of Xenobiotics In: Hodgson E, Smart RC. INTRODUCTION TO BIOCHEMICAL TOXICOLOGY 3rd ed. (2001) Drug Metabolism Not: Detoxication Reactions 2. Phase I and Phase II Reactions: Classification Phase I Reactions: Oxidation, Reduction, Hydrolysis 1 FACTORS AFFECTING DRUG ABSORPTION List of content: I. PHARMACEUTICAL FACTORS A Chemical factors B Physicochemical properties of drug substances 1. drug solubility dissolution rate 5 Factors affecting drug metabolism: external factors In the previous chapter. it has been shown how physiological and pathological factors can affect drug metabolism. The full text of this article hosted at iucr. org is unavailable due to technical difficulties. At the end of this lesson, students will be able to: Define what factors affecting Drug Metabolism. Demonstrate the concept of DrugDrug interactions. Rate of drug metabolism Pharmacokinetics of a drug depends on patientrelated factors as well as on the drugs chemical properties. Some patientrelated factors (eg, renal function, genetic makeup, sex, age) can be used to predict the pharmacokinetic parameters in populations. factors affecting drug action body size pregnancy lactation age peadiatric geriatric genetic factors disease states kidney liver routes of drug administration environmental factors psychological factors tolerance resistance Absorption, distribution, metabolism, and excretion are sometimes referred to collec Distribution, and Excretion of Drugs 29 Knowledge of these processes and the ways that they can vary between individuals is chemical properties of the drug, and physiologic. 4 Factors affecting drug metabolism: internal factors 4. 1 Introduction Many factors affect the rate and pathway of metabolism of drugs, and the major influences can be subdivided into internal (physiological and pathological) and Drug absorption depends on the lipid solubility of the drug, its formulation and the route of administration. A drug needs to be lipid soluble to penetrate membranes unless there is an active transport system or it is so small that it can pass through the aqueous channels in the membrane. Impairment of Drug Metab olism by Liver Disease Viral hepatitis Cirrhosis Pethidine Pethidine Lignocaine Lignocaine Diazepam Diazepam Phenytoin Chlordiazepoxide Hexobarbitone Hexobarbitone Tolbutamide Amylobarbitone Antipyrine Antipyrine Theophyllinc Environmental factors affecting drug metabolism 111. In order to discuss this topic, the factors affecting drug metabolism will be split into internal (i. physiological and pathological) factors (discussed in this chapter) and external factors (i. diet and environment) (discussed in chapter 5). Factors affecting drug metabolism. Many factors affect the rate and pathway of metabolism of drugs, and the major. Recent advances in the characterization of specific isoenzymes of drug metabolism paved the way for preliminary identification of the enzyme system affected by. Enter your email address below. If your address has been previously registered, you will receive an email with instructions on how to reset your password. If Factors Modifying Action of Drugs. range of variability may be marked or limited depending on the pharmacokinetic Pharmacodynamic characteristics of the drug. Drugs mostly disposed by metabolism are most effected (e. propanolol) while those excreted by the kidneys are least effected (e. All factors affecting absorption. blood is influenced by biologic and physicochemical factors (discussed in detail below), and by the dosage form. For most drugs, two to fivefold Since the liver is a major site of drug metabolism, Drug absorption, distribution and elimination. 3 Factors Affecting DRUG ABSORPTION Biopharmaceutic Factors Interactions PHYSIOLOGICAL FACTORS Drug Absorption Passive NonIonic Diffusion: Primary mechanism for most drugs. Drug Absorption Specialized Transport Mechanisms Drug metabolism is the metabolic breakdown of drugs by living organisms, usually through specialized enzymatic systems. More generally, xenobiotic metabolism Pathological factors can also influence drug metabolism, including liver, kidney, or heart diseases. factors affecting drug metabolism Various physiological and pathological factors can increase or decrease the rate of metabolism. Physiological factors include; age, sex, individual variationgenetic polymorphism, enterohepatic Bitten Stripp and James R. Gillette, Role of drug metabolism in drug research and development: Factors affecting metabolism of drugs and their pharmacological and toxicological activity, Journal of Pharmaceutical Sciences, 61, 10, ( ), (2006). Factors Affecting Drug Metabolism O H N NH 2 O H N H N O N N Prof. Factor Affecting Drug Metabolism Age Dose Induction Species Differences Enzyme Inhibition Gender Diet Pregnancy HeredityGenetics Pharmacogenetics Environmental Pharmacogenomics Disease Enzyme Drug May look complex. Overview of factors affecting oral drug absorption NaiNing Song a, b, ShaoY u Zhang b, ChangXiao Liu a a Tianjin State Key Laboratory of Pharmacokinetics and Pharmaco dynamics, Tianjin Inst. The factors affecting absorption of drugs are related both to the drugs and to the body. Lipid water solubility coefficient is the ratio of dissolution of drug in lipid as compared to water. Greater the lipid water solubility coefficient, more is the lipid solubility of the drug and greater is the absorption. Liver Microsomal System Oxidative Reactions: Cytochrome P450 mediated Most of the drug metabolizing enzymes are in CYP 1, 2, 3 families. Factors affecting FMOs (diet, drugs, sex) not as highly studied as CYPs: NonCYP drug oxidations (2) Hydrolysis Ester or Amide Genetic Factors in Drug Metabolism Donna J. Belle, PhD, RPh, and HaRleen SInGH, PharmD, Oregon State University College of Pharmacy, Portland Campus at Oregon Health. FACTORS AFFECTING DRUG METABOLISM James R. Laboratory of Chemical Pharmacology, National Heart and Lung Institute, National Institutes of Health Bethesda, Md. INTRODUCTION The biological fate of a drug depends on a host of factors, including those Drug Metabolism and Pharmacokinetics (DMPK) is an official online journal of the Japanese Society for the Study of Xenobiotics (JSSX), and it replaces the JSSX's former journal, Xenobiotic Metabolism and. Factors affecting drug absorption PPT. Download Let's Connect by such eliminating organs during the passage to systemic circulation is called as firstpass or presystemic metabolism. complete absence of the drug in plasma after oral administration is indicative of the firstpass effects. The four primary systems which. 00: 01 What are the factors that affect drug metabolism. Well you have genetic differences of cytochrome P450. You can have competitive inhibition of Cytochrome P450. You can have direct inhibition. You can inhibit PGlycoprotein and you can alter blood flow. Major process for absorption of more than 90 of drugs Diffusion follows Ficks law: The drug molecules diffuse from a region of higher concentration to a region of lower concentration till equilibrium is attained. Rate of diffusion is directly proportional to the concentration gradient across the membrane. Factors Affecting Metabolism A number of factors may influence the metabolic rate of a drug. Chemical factors a) Enzyme induction b) Enzyme inhibition c) Environmental chemicals 2. In order to discuss this topic, the factors affecting drug metabolism will be split into internal (i. physiological and pathological) factors (discussed in this chapter) and external factors (i. Genetic and environmental factors affecting host response to drugs and other chemical compounds in our environment. Get a printable copy (PDF file) of the complete article (3 Sjqvist F. Effect of environmental factors on drug metabolism: decreased plasma halflife of antipyrine in workers exposed to chlorinated hydrocarbon. Physiological Factors Affecting Oral Absorption In the next few Chapters physiological, physicalchemical, and formulation factors which can inuence the observed rate and extent of oral absorption will be discussed. not only transports drug into the lumen but causes the metabolism of substantial amounts of the drug as well (e. Pharmacotherapy in the Elderly Judy MY Wong drug logos discourse study of the fate and actions of drugs Pharmacokinetics study of time course of drug concentration and the factors affecting it Pharmacodynamics study of the mechanisms of drug action. Drug metabolism changes in the elderly Liver Here are ten factors that affect BMR and metabolism: 1. Muscle mass that is, the amount of muscle tissue on your body. Muscle requires more energy to function than fat. Factors affecting drug stability: 1. Temperature: high temperature accelerate oxidation, reduction and hydrolysis reaction which lead to drug degradation 2. pH: Acidic and alkaline pH influence the rate of decomposition of most drugs. Many drugs are stable between pH 4 and 8. Factors affecting drug metabolism. PMID: [PubMed indexed for MEDLINE Publication Types:.