DOCSLIB.ORG

Opioid Metabolism

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Opioid Metabolism REVIEW Opioid Metabolism HOWARD S. SMITH, MD Clinicians undeistand that Individual patients differ In their re- Experienced clinicians are aware that the efficacy and sponse to specific opioid analgesics and that patients may require trials of several opioids tiefbre finding an agent that provides tolerability of specific opioids may vary dramatically effective analgesia with acceptahle tolerahlllty. Reasons fer this among patients and that trials of several opioids may be variability Include factors that are not clearly understood, such as needed before finding one that provides an acceptable bal- allellc variants that dictate the complement of opioid receptors and sutttle differences In the receptor-binding profiles of opioids. ance of analgesia and tolerability for an individual patient,*"' However, aitered opioid metaboiism may aiso infiuence response Pharmacodynamic and pharmacokinetic differences under- In terms of efficacy and toierabllity, and severai fectors contribut- lie this variability of response. Pharmacodynamics refers to ing to this metaboiic variability have been identified. For exampie, the risk of drug Interactions with an opioid is determined iargeiy by how a drug affects the body, whereas pharmacokinetics which enzyme systems metabolize the opioid. The rate and path- describes how the body alters the drug, ways of opioid metaboiism may also be infiuenced by genetic Pharmacokinetics contributes to the factors, race, and medicai conditions (most notabiy iiver or kidney For editorial disease). This review describes the basics of opioid metaboiism variability in response to opioids by af- comment, as weli as the factors Infiuencing it and provides recommenda- fecting the bioavailability of a drug, the see page 572 tions for addressing metaboiic issues that may compromise effec- production of active or inactive metabo- tive pain management. Articies cited in this review were identified lites, and their elimination from the body. Pharmacodynamic via a search of iVIEDUNE, EiVflBASE, and PubMed. Articies se- iected fer Inciusion discussed gênerai physioiogic aspects of factors contributing to variability of response to opioids opioid metaboiism, metaboiic characteristics of specific opioids, include between-patient differences in specific opioid recep- patient-specific factors infiuencing drug metaboiism, drug interac- tors and between-opioid differences in binding to receptor tions, and adverse events. subtypes. The receptor binding of opioids is imperfectly Mayo Clin Proc. 2009;84<7):613-624 understood; hence, matching individual patients with spe- cific opioids to optimize efficacy and tolerability remains a CYP = cytochrome P450; Ml = (Mesmethyttramadol; M3G = morphlne- 3^ucuronlde; M6G = niorphin»€-glucuronide; UGT = uridlne dlphos- trial-and-error procedure,*"' phate glucuronosyltransferase This review primarily considers drug metabolism in the context of pharmacokinetics. It summarizes the basics of opioid metabolism; discusses the potential influences of pioids are a cornerstone of the management of cancer patient-specific factors such as age, genetics, comorbid Opain' and postoperative pain^ and are used increas- conditions, and concomitant medications; and explores the ingly for the management of chronic noncancer pain,'''* differences in metabolism between specific opioids. It aims Understanding the metabolism of opioids is of great practi- to equip physicians with an understanding of opioid me- cal importance to primary care clinicians, Opioid metabo- tabolism that will guide safe and appropriate prescribing, lism is a vital safety consideration in older and medically permit anticipation and avoidance of adverse drug-drug complicated patients, who may be taking multiple medica- interactions, identify and accommodate patient-specific tions and may have inflammation, impaired renal and he- metabolic concerns, rationalize treatment failure, inform patic function, and impaired immunity. Chronic pain, such opioid switching and rotation strategies, and facilitate as lower back pain, also occurs in younger persons and is the therapeutic monitoring. To that end, recommendations for leading cause of disability in Americans younger than 45 tailoring opioid therapy to individual patients and specific years.' In younger patients, physicians may be more con- populations will be included, cerned with opioid metabolism in reference to development of tolerance, impairment of skills and mental function, ad- verse events during pregnancy and lactation, and prevention METHODS of abuse by monitoring drug and metabolite levels. Articles cited in this review were identified via a search of MEDLINE, EMBASE, and PubMed databases for literature published between January 1980 and June 2008, The opioid From the Department of Anesthesiology, Albany Medical Coiiege, Albany, NY. medication search terms used were as follows: codeine, Individual reprints of this articie are not avaiiabie. Address con-espondence to Howard S. Smith, MD, Department of Anesthesiology, Albany Medicai College, fentanyl, hydrocodone, hydromorphone, methadone, mor- 47 New Scotland Ave, MC-131, Albany, NY 12208 (smithh@maii,amc.edu). phine, opioid, opioid analgesic, oxycodone, oxymorphone, © 2009 Mayo Foundation for Medical Education and Research and tramadol. Each medication search term was combined Mayo Clin Proc. July 2W9;84(7):613-624 wwwmayoclinicproceedings.com 613 OPIOID METABOLISM with the following general search terms: metabolism, active glucuronidation, catalyzed by the enzyme uridine diphos- metabolites, pharmacokinetics, lipophilicity, physio- phate glucuronosyltransferase (UGT). Glucuronidation chemical properties, pharmacology, genetics, receptor, re- produces molecules that are highly hydrophilic and there- ceptor binding, receptor genetics or variation, transporter, fore easily excreted. Opioids undergo varying degrees of formulations, AND adverse effects, safety, or toxicity. The phase 1 and 2 metabolism. Phase 1 metabolism usually reference lists of relevant papers were examined for addi- precedes phase 2 metabolism, but this is not always the case. tional articles of interest. Both phase 1 and 2 metabolites can be active or inactive. The process of metabolism ends when the molecules are suffi- ciently hydrophilic to be excreted from the body. BASICS OF OPIOID METABOLISM Metabolism refers to the process of biotransformation by FACTORS INFLUENCING OPIOID METABOLISM which drugs are broken down so that they can be elimi- nated by the body. Some drugs perform their functions and PATHWAYS then are excreted from the body intact, but many require Opioids undergo phase 1 metabolism by the CYP pathway, metabolism to enable them to reach their target site in an phase 2 metabolism by conjugation, or both. Phase 1 me- appropriate amount of time, remain there an adequate time, tabolism of opioids mainly involves the CYP3A4 and and then be eliminated from the body. This review refers to CYP2D6 enzymes. The CYP3A4 enzyme metabolizes opioid metabolism; however, the processes described oc- more than 50% of all drugs; consequently, opioids metabo- cur with many medications. lized by this enzyme have a high risk of drug-drug interac- Altered metabolism in a patient or population can result tions. The CYP2D6 enzyme metabolizes fewer drugs and in an opioid or metabolite leaving the body too rapidly, not therefore is associated with an intermediate risk of drug- reaching its therapeutic target, or staying in the body too drug interactions. Drugs that undergo phase 2 conjugation, long and producing toxic effects. Opioid metabolism re- and therefore have little or no involvement with the CYP sults in the production of both inactive and active metabo- system, have minimal interaction potential. lites. In fact, active metabolites may be more potent than the parent compound. Thus, although metabolism is ulti- PHASE 1 METABOUSM mately a process of detoxification, it produces intermediate The CYP3A4 enzyme is the primary metabolizer of fenta- products that may have clinically useful activity, be associ- nyl'" and oxycodone," although normally a small portion of ated with toxicity, or both. oxycodone undergoes CYP2D6 metabolism to oxymor- Opioids differ with respect to the means by which they phone (Table 1'"-'*). Tramadol undergoes both CYP3A4- are metabolized, and patients differ in their ability to me- and CYP2D6-mediated metabolism.'* Methadone is prima- tabolize individual opioids. However, several general pat- rily metabolized by CYP3A4 and CYP2B6; CYP2C8, terns of metabolism can be discerned. Most opioids un- CYP2C19, CYP2D6, and CYP2C9 also contribute in vary- dergo extensive first-pass metabolism in the liver before ing degrees to its metabolism.""^ The complex interplay of entering the systemic circulation. First-pass metabolism methadone with the CYP system, involving as many as 6 reduces the bioavailability of the opioid. Opioids are typi- different enzymes, is accompanied by considerable interac- cally lipophilic, which allows them to cross cell mem- tion potential. branes to reach target tissues. Drug metabolism is ulti- Each of these opioids has substantial interaction poten- mately intended to make a drug hydrophil ic to facilitate its tial with other commonly used drugs that are substrates, excretion in the urine. Opioid metabolism takes place pri- inducers, or inhibitors of the CYP3A4 enzyme (Table marily in the liver, which produces enzymes for this pur- 2) 2425 Administration of CYP3A4 substrates or inhibitors pose. These enzymes promote 2
Load more

Recommended publications
  • Coffee and Its Effect on Digestion
    Expert report Coffee and its effect on digestion By Dr. Carlo La Vecchia, Professor of Medical Statistics and Epidemiology, Dept. of Clinical Sciences and Community Health, Università degli Studi di Milano, Italy. Contents 1 Overview 2 2 Coffee, a diet staple for millions 3 3 What effect can coffee have on the stomach? 4 4 Can coffee trigger heartburn or GORD? 5 5 Is coffee associated with the development of gastric or duodenal ulcers? 6 6 Can coffee help gallbladder or pancreatic function? 7 7 Does coffee consumption have an impact on the lower digestive tract? 8 8 Coffee and gut microbiota — an emerging area of research 9 9 About ISIC 10 10 References 11 www.coffeeandhealth.org May 2020 1 Expert report Coffee and its effect on digestion Overview There have been a number of studies published on coffee and its effect on different areas of digestion; some reporting favourable effects, while other studies report fewer positive effects. This report provides an overview of this body of research, highlighting a number of interesting findings that have emerged to date. Digestion is the breakdown of food and drink, which occurs through the synchronised function of several organs. It is coordinated by the nervous system and a number of different hormones, and can be impacted by a number of external factors. Coffee has been suggested as a trigger for some common digestive complaints from stomach ache and heartburn, through to bowel problems. Research suggests that coffee consumption can stimulate gastric, bile and pancreatic secretions, all of which play important roles in the overall process of digestion1–6.
    [Show full text]
  • Coffee and Liver Diseases
    Fitoterapia 81 (2010) 297–305 Contents lists available at ScienceDirect Fitoterapia journal homepage: www.elsevier.com/locate/fitote Review Coffee and liver diseases Pablo Muriel ⁎, Jonathan Arauz Departamento de Farmacología, Cinvestav-IPN., Apdo. Postal 14-740, México 07000, D.F., Mexico article info abstract Article history: Coffee consumption is worldwide spread with few side effects. Interestingly, coffee intake has Received 26 August 2009 been inversely related to the serum enzyme activities gamma-glutamyltransferase, and alanine Accepted in revised form 25 September 2009 aminotransferase in studies performed in various countries. In addition, epidemiological Available online 13 October 2009 results, taken together, indicate that coffee consumption is inversely related with hepatic cirrhosis; however, they cannot demonstrate a causative role of coffee with prevention of liver Keywords: injury. Animal models and cell culture studies indicate that kahweol, diterpenes and cafestol Coffee (some coffee compounds) can function as blocking agents by modulating multiple enzymes Hepatic injury involved in carcinogenic detoxification; these molecules also alter the xenotoxic metabolism by Fibrosis Cirrhosis inducing the enzymes glutathione-S-transferase and inhibiting N-acetyltransferase. Drinking Cancer coffee has been associated with reduced risk of hepatic injury and cirrhosis, a major pathogenic step in the process of hepatocarcinogenesis, thus, the benefit that produces coffee consumption on hepatic cancer may be attributed to its inverse relation with cirrhosis, although allowance for clinical history of cirrhosis did not completely account for the inverse association. Therefore, it seems to be a continuum of the beneficial effect of coffee consumption on liver enzymes, cirrhosis and hepatocellular carcinoma. At present, it seems reasonable to propose experiments with animal models of liver damage and to test the effect of coffee, and/or isolated compounds of this beverage, not only to evaluate the possible causative role of coffee but also its action mechanism.
    [Show full text]
  • Phthalates: Toxicology and Food Safety – a Review
    Czech J. Food Sci. Vol. 23, No. 6: 217–223 Phthalates: Toxicology and Food Safety – a Review PŘEMYSL MIKULA1, ZDEŇKA SVOBODOVÁ1 and MIRIAM SMUTNÁ2 1Department of Veterinary Public Health and Toxicology and 2Department of Biochemistry and Biophysics, Faculty of Veterinary Hygiene and Ecology, University of Veterinary and Pharmaceutical Sciences, Brno, Czech Republic Abstract MIKULA P., SVOBODOVÁ Z., SMUTNÁ M. (2005): Phthalates: toxicology and food safety – a review. Czech J. Food Sci., 23: 217–223. Phthalates are organic substances used mainly as plasticisers in the manufacture of plastics. They are ubiquitous in the environment. Although tests in rodents have demonstrated numerous negative effects of phthalates, it is still unclear whether the exposure to phthalates may also damage human health. This paper describes phthalate toxicity and toxicokinetics, explains the mechanisms of phthalate action, and outlines the issues relating to the presence of phthalates in foods. Keywords: di(2-ethylhexyl)phthalate; dibutyl phthalate; peroxisome proliferators; reproductive toxicity Phthalic acid esters, often also called phtha- air, soil, food, etc.). People as well as animals lates, are organic substances frequently used can be exposed to these compounds through in many industries. They are usually colourless ingestion, inhalation or dermal exposure, and or slightly yellowish oily and odourless liquids iatrogenic exposure to phthalates from blood only very slightly soluble in water. Phthalates are bags, injection syringes, intravenous canyllas much more readily soluble in organic solvents, and catheters, and from plastic parts of dialysers and the longer their side chain, the higher their is also a possibility (VELÍŠEK 1999; ČERNÁ 2000; liposolubility and the boiling point. Phthalates LOVEKAMP-SWAN & DAVIS 2003).
    [Show full text]
  • Therapeutic Potential of Nicotinamide Adenine Dinucleotide (NAD) T ∗ Marta Arenas-Jala,B, , J.M
    European Journal of Pharmacology 879 (2020) 173158 Contents lists available at ScienceDirect European Journal of Pharmacology journal homepage: www.elsevier.com/locate/ejphar Therapeutic potential of nicotinamide adenine dinucleotide (NAD) T ∗ Marta Arenas-Jala,b, , J.M. Suñé-Negrea, Encarna García-Montoyaa a Pharmacy and Pharmaceutical Technology Department (Faculty of Pharmacy and Food Sciences), University of Barcelona, Barcelona, Spain b ICN2 – Catalan Institute of Nanoscience and Nanotechnology (Autonomous University of Barcelona), Bellaterra (Barcelona), Spain ARTICLE INFO ABSTRACT Keywords: Nicotinamide adenine nucleotide (NAD) is a small ubiquitous hydrophilic cofactor that participates in several NAD aspects of cellular metabolism. As a coenzyme it has an essential role in the regulation of energetic metabolism, Metabolism but it is also a cosubstrate for enzymes that regulate fundamental biological processes such as transcriptional Therapeutic potential regulation, signaling and DNA repairing among others. The fluctuation and oxidative state of NAD levels reg- Drug discovery ulate the activity of these enzymes, which is translated into marked effects on cellular function. While alterations Supplementation in NAD homeostasis are a common feature of different conditions and age-associated diseases, in general, in- creased NAD levels have been associated with beneficial health effects. Due to its therapeutic potential, the interest in this molecule has been renewed, and the regulation of NAD metabolism has become an attractive target for drug discovery. In fact, different approaches to replenish or increase NAD levels have been tested, including enhancement of biosynthesis and inhibition of NAD breakdown. Despite further research is needed, this review provides an overview and update on NAD metabolism, including the therapeutic potential of its regulation, as well as pharmacokinetics, safety, precautions and formulation challenges of NAD supplementa- tion.
    [Show full text]
  • Metabolic-Hydroxy and Carboxy Functionalization of Alkyl Moieties in Drug Molecules: Prediction of Structure Influence and Pharmacologic Activity
    molecules Review Metabolic-Hydroxy and Carboxy Functionalization of Alkyl Moieties in Drug Molecules: Prediction of Structure Influence and Pharmacologic Activity Babiker M. El-Haj 1,* and Samrein B.M. Ahmed 2 1 Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, University of Science and Technology of Fujairah, Fufairah 00971, UAE 2 College of Medicine, Sharjah Institute for Medical Research, University of Sharjah, Sharjah 00971, UAE; [email protected] * Correspondence: [email protected] Received: 6 February 2020; Accepted: 7 April 2020; Published: 22 April 2020 Abstract: Alkyl moieties—open chain or cyclic, linear, or branched—are common in drug molecules. The hydrophobicity of alkyl moieties in drug molecules is modified by metabolic hydroxy functionalization via free-radical intermediates to give primary, secondary, or tertiary alcohols depending on the class of the substrate carbon. The hydroxymethyl groups resulting from the functionalization of methyl groups are mostly oxidized further to carboxyl groups to give carboxy metabolites. As observed from the surveyed cases in this review, hydroxy functionalization leads to loss, attenuation, or retention of pharmacologic activity with respect to the parent drug. On the other hand, carboxy functionalization leads to a loss of activity with the exception of only a few cases in which activity is retained. The exceptions are those groups in which the carboxy functionalization occurs at a position distant from a well-defined primary pharmacophore. Some hydroxy metabolites, which are equiactive with their parent drugs, have been developed into ester prodrugs while carboxy metabolites, which are equiactive to their parent drugs, have been developed into drugs as per se.
    [Show full text]
  • Medical Review Officer Manual
    Department of Health and Human Services Substance Abuse and Mental Health Services Administration Center for Substance Abuse Prevention Medical Review Officer Manual for Federal Agency Workplace Drug Testing Programs EFFECTIVE OCTOBER 1, 2010 Note: This manual applies to Federal agency drug testing programs that come under Executive Order 12564 dated September 15, 1986, section 503 of Public Law 100-71, 5 U.S.C. section 7301 note dated July 11, 1987, and the Department of Health and Human Services Mandatory Guidelines for Federal Workplace Drug Testing Programs (73 FR 71858) dated November 25, 2008 (effective October 1, 2010). This manual does not apply to specimens submitted for testing under U.S. Department of Transportation (DOT) Procedures for Transportation Workplace Drug and Alcohol Testing Programs (49 CFR Part 40). The current version of this manual and other information including MRO Case Studies are available on the Drug Testing page under Medical Review Officer (MRO) Resources on the SAMHSA website: http://www.workplace.samhsa.gov Previous Versions of this Manual are Obsolete 3 Table of Contents Chapter 1. The Medical Review Officer (MRO)........................................................................... 6 Chapter 2. The Federal Drug Testing Custody and Control Form ................................................ 7 Chapter 3. Urine Drug Testing ...................................................................................................... 9 A. Federal Workplace Drug Testing Overview..................................................................
    [Show full text]
  • The Disposition of Morphine and Its 3- and 6-Glucuronide Metabolites in Humans
    >+'è ,'i5 1. The Disposition of Morphine and its 3- and 6- Glucuronide Metabolites in Humans and Sheep A Thesis submitted in Fulfilment of the Requirements for the Degree of Doctor of Philosophy in Science at the University of Adelaide Robert W. Milne B.Pharm.(Hons), M.Sc. Department of Clinical and Experimental Pharmacology University of Adelaide August 1994 Ar,-,..u i.'..t itttlí I Corrigenda Page 4 The paragraph at the top of the page should be relocated to inimediatèly follow the section heading "1.2 Chemistry" on page 3" Page 42 (lines 2,5 and/) "a1-acid glycoProtein" should read "cr1-acid glycoprotein". Page 90 In the footnote "Amoxicillin" and "Haemacell" should read "Amoxycillin" and "Haemaccel", respectively. Page I 13 (tine -l l) "supernate!' should read "supernatant". ' '(j- Page I 15 (line -9) "supernate" should read "supernatalït1-. Page 135 To the unfinished sentence at the bottom of the page should be added "appears to be responsible for the formation of M3G, but its relative importance remains unknown. It was also proposed that morphine is involved in an enterohepatic cycle." Page 144 Add "Both infusions ceased at 6 hr" to the legend to Figure 6.3. Page 195 (line 2) "was" should fead "were". Page 198 (line l3) "ro re-€xamine" should read "to te-examine". Pages 245 to29l Bibliosraohv: "8r.." should read "Br.". For the reference by Bhargava et aI. (1991), "J. Pharmacol.Exp.Ther." should read "J. Pharmacol. Exp. Ther." For the reference by Chapman et aI. (1984), a full-stop should appear after"Biomed" . For the reference by Murphey et aI.
    [Show full text]
  • Information to Users
    The direct and modulatory antinociceptive actions of endogenous and exogenous opioid delta agonists Item Type text; Dissertation-Reproduction (electronic) Authors Vanderah, Todd William. Publisher The University of Arizona. Rights Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author. Download date 04/10/2021 00:14:57 Link to Item http://hdl.handle.net/10150/187190 INFORMATION TO USERS This ~uscript }las been reproduced from the microfilm master. UMI films the text directly from the original or copy submitted. Thus, some thesis and dissertation copies are in typewriter face, while others may be from any type of computer printer. The quality of this reproduction is dependent upon the quality of the copy submitted. Broken or indistinct print, colored or poor quality illustrations and photographs, print bleedthrough, substandard margins, and improper alignment can adversely affect reproduction. In the unlikely. event that the author did not send UMI a complete mannscript and there are missing pages, these will be noted Also, if unauthorized copyright material had to be removed, a note will indicate the deletion. Oversize materials (e.g., maps, drawings, charts) are reproduced by sectioning the original, beginnjng at the upper left-hand comer and contimJing from left to right in equal sections with small overlaps. Each original is also photographed in one exposure and is included in reduced form at the back of the book. Photographs included in the original manuscript have been reproduced xerographically in this copy.
    [Show full text]
  • Kappa Opioid Receptor Regulation of Erk1/2 Map Kinase Signaling Cascade
    1 KAPPA OPIOID RECEPTOR REGULATION OF ERK1/2 MAP KINASE SIGNALING CASCADE: MOLECULAR MECHANISMS MODULATING COCAINE REWARD A dissertation presented by Khampaseuth Rasakham to The Department of Psychology In partial fulfillment of the requirements for the degree of Doctor of Philosophy in the field of Psychology Northeastern University Boston, Massachusetts August, 2008 2 KAPPA OPIOID RECEPTOR REGULATION OF ERK1/2 MAP KINASE SIGNALING CASCADE: MOLECULAR MECHANISMS MODULATING COCAINE REWARD by Khampaseuth Rasakham ABSTRACT OF DISSERTATION Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Psychology in the Graduate School of Arts and Sciences of Northeastern University, August, 2008 3 ABSTRACT Activation of the Kappa Opioid Receptor (KOR) modulates dopamine (DA) signaling, and Extracellular Regulated Kinase (ERK) Mitogen-Activated Protein (MAP) kinase activity, thereby potentially regulating the rewarding effects of cocaine. The central hypothesis to be tested is that the time-and drug-dependent KOR-mediated regulation of ERK1/2 MAP kinase activity occurs via distinct molecular mechanisms, which in turn may determine the modulation (suppression or potentiation) by KOR effects on cocaine conditioned place preference (CPP). Three studies were performed to test this hypothesis. Study 1 examined the effects of U50,488 and salvinorin A on cocaine reward. In these studies, mice were treated with equianalgesic doses of agonist from 15 to 360 min prior to daily saline or cocaine place conditioning. At time points corresponding with peak biological activity, both agonists produced saline-conditioned place aversion and suppressed cocaine-CPP, effects blocked by the KOR antagonist nor-BNI. However, when mice were place conditioned with cocaine 90 min after agonist pretreatment, U50,488-pretreated mice demonstrated a 2.5-fold potentiation of cocaine-CPP, whereas salvinorin A-pretreated mice demonstrated normal cocaine-CPP responses.
    [Show full text]
  • CONTROLLED SUBSTANCE, DRUG, DEVICE and COSMETIC ACT - SCHEDULE I CONTROLLED SUBSTANCES Act of Jun
    CONTROLLED SUBSTANCE, DRUG, DEVICE AND COSMETIC ACT - SCHEDULE I CONTROLLED SUBSTANCES Act of Jun. 23, 2011, P.L. 36, No. 7 Cl. 35 Session of 2011 No. 2011-7 SB 1006 AN ACT Amending the act of April 14, 1972 (P.L.233, No.64), entitled "An act relating to the manufacture, sale and possession of controlled substances, other drugs, devices and cosmetics; conferring powers on the courts and the secretary and Department of Health, and a newly created Pennsylvania Drug, Device and Cosmetic Board; establishing schedules of controlled substances; providing penalties; requiring registration of persons engaged in the drug trade and for the revocation or suspension of certain licenses and registrations; and repealing an act," further providing for Schedule I controlled substances. The General Assembly of the Commonwealth of Pennsylvania hereby enacts as follows: Section 1. Section 4(1) of the act of April 14, 1972 (P.L.233, No.64), known as The Controlled Substance, Drug, Device and Cosmetic Act, amended November 24, 1999 (P.L.894, No.55), is amended to read: Section 4. Schedules of Controlled Substances.--The following schedules include the controlled substances listed or to be listed by whatever official name, common or usual name, chemical name, or trade name designated. (1) Schedule I--In determining that a substance comes within this schedule, the secretary shall find: a high potential for abuse, no currently accepted medical use in the United States, and a lack of accepted safety for use under medical supervision. The following controlled substances are included in this schedule: (i) Any of the following opiates, including their isomers, esters, ethers, salts, and salts of isomers, esters, and ethers, unless specifically excepted, whenever the existence of such isomers, esters, ethers and salts is possible within the specific chemical designation: 1.
    [Show full text]
  • Evaluation of the Effect of CYP2D6 Genotypes on Tramadol and O
    pharmaceutics Article Evaluation of the Effect of CYP2D6 Genotypes on Tramadol and O-Desmethyltramadol Pharmacokinetic Profiles in a Korean Population Using Physiologically-Based Pharmacokinetic Modeling Hyeon-Cheol Jeong 1, Soo Hyeon Bae 2 , Jung-Woo Bae 3, Sooyeun Lee 3, Anhye Kim 4 , Yoojeong Jang 1 and Kwang-Hee Shin 1,* 1 College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 41566, Korea; [email protected] (H.-C.J.); [email protected] (Y.J.) 2 Korea Institute of Radiological & Medical Sciences, Seoul 01812, Korea; [email protected] 3 College of Pharmacy, Keimyung University, Daegu 42601, Korea; [email protected] (J.-W.B.); [email protected] (S.L.) 4 Department of Clinical Pharmacology and Therapeutics, CHA Bundang Medical Center, CHA University, Seongnam 13496, Korea; [email protected] * Correspondence: [email protected]; Tel.: +82-53-950-8582 Received: 6 October 2019; Accepted: 15 November 2019; Published: 17 November 2019 Abstract: Tramadol is a µ-opioid receptor agonist and a monoamine reuptake inhibitor. O-desmethyltramadol (M1), the major active metabolite of tramadol, is produced by CYP2D6. A physiologically-based pharmacokinetic model was developed to predict changes in time-concentration profiles for tramadol and M1 according to dosage and CYP2D6 genotypes in the Korean population. Parallel artificial membrane permeation assay was performed to determine tramadol permeability, and the metabolic clearance of M1 was determined using human liver microsomes. Clinical study data were used to develop the model. Other physicochemical and pharmacokinetic parameters were obtained from the literature. Simulations for plasma concentrations of tramadol and M1 (after 100 mg tramadol was administered five times at 12-h intervals) were based on a total of 1000 virtual healthy Koreans using SimCYP® simulator.
    [Show full text]
  • Understanding and Challenging the Drugs: Chemistry and Toxicology
    UNDERSTANDING AND CHALLENGING THE DRUGS: CHEMISTRY AND TOXICOLOGY Presenter: • Dr. Jasmine Drake, Graduate Program Director and Assistant Professor, Administration of Justice Department, Barbara Jordan-Mickey Leland School of Public Affairs, Texas Southern University NACDL Training Defending Drug Overdose Homicides in Pennsylvania Penn State Harrisburg, Middletown, PA November 6th, 2019 11:30- 12:45 p.m. Understanding & Challenging the Drugs: Chemistry & Toxicology Dr. Jasmine Drake, Forensic Science Learning Laboratory, Texas Southern University I. Opioid Drug Classifications A. Types of Opioids B. Classic vs. Synthetic C. Toxicology of Opioids 1) How opioids interact with the body 2) Addiction (psychological vs. physiological II. New Classes of Drugs A. Emerging Threats B. Potency III. National Trends in Opioid Overdose Deaths in the U.S. A. Based on State B. Ethnicity C. Drug-Type (prescription vs. fentanyl vs. heroin) IV. Trends of Opioid Overdose Deaths in Philadelphia A. Based on Ethnicity B. Drug Type (prescription vs. fentanyl vs. heroin) V. Legal Considerations to the Opioid Epidemic A. Punitive Measures vs. Rehabilitative Treatment B. Progressive Jurisdictions Nationwide C. New Legal Measures in Philadelphia VI. Toxicology Reports A. What’s in the report? B. Key Aspects of the Tox Report C. Terminology D. Evaluating and Interpreting the data? E. Questions and considerations. VII. Conclusion and Discussion A. Case Specific Examples B. Sample Toxicology Reports The Opioid Epidemic: What labs have to do with it? Ewa King, Ph.D. Associate Director of Health RIDOH State Health Laboratories Analysis. Answers. Action. www.aphl.org Overview • Overdose trends • Opioids and their effects • Analytical testing approaches • Toxicology laboratories Analysis. Answers. Action.
    [Show full text]