DOCSLIB.ORG

Treatment of Opioid-Induced Gut Dysfunction

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Treatment of Opioid-Induced Gut Dysfunction Review Central & Peripheral Nervous Systems Treatment of opioid-induced gut dysfunction Peter Holzer 1. Introduction Research Unit of Translational Neurogastroenterology, Institute of Experimental and Clinical 2. Opioid peptides and opioid Pharmacology, Medical University of Graz, Universitätsplatz 4, A-8010 Graz, Austria receptors in the gastrointestinal Opioid analgesics are the mainstay in the treatment of moderate-to-severe tract pain, yet their use is frequently associated with adverse effects, the most 3. Opioid actions in the common and debilitating being constipation. Opioid-induced motor stasis gastrointestinal tract results from blockade of gastrointestinal peristalsis and fluid secretion, and 4. Significance of endogenous reflects the action of the endogenous opioid system in the gut. Methyl- opioid peptides in naltrexone and alvimopan are new investigational drugs that selectively tar- gastointestinal physiology get peripheral µ-opioid receptors because they are poorly absorbed in the 5. Homeostatic roles of intestine and do not enter the brain. Clinical studies have proved the concept endogenous opioids in gut that these drugs prevent opioid-induced bowel dysfunction without inter- dysfunction fering with analgesia. As reviewed in this article, opioid receptor antagonists 6. Beneficial effects of opioid with a peripherally restricted site of action also hold therapeutic promise in receptor stimulants under postoperative ileus and chronic constipation due to the fact that they have conditions of gut dysfunction been found to stimulate intestinal transit. 7. Adverse effects of opioid receptor agonists on gut Keywords: alvimopan, constipation, enteric nervous system, intestinal peristalsis, naloxone, N-methylnaltrexone, opioid peptides, opioid-induced bowel dysfunction, peripherally restricted function: opioid-induced bowel opioid receptor antagonists, prokinetic effects dysfunction and prolongation of postoperative ileus Expert Opin. Investig. Drugs (2007) 16(2):181-194 8. Treatment of opioid-induced Printing and distribution strictly prohibited disturbances of bowel function 1. Introduction with laxatives and non-opioid prokinetic drugs Morphine and related substances contained in the unripe seed capsules of 9. Management of opioid-induced Papaver somniferum have been used to treat pain and diarrhoea for thousands of bowel dysfunction by opioid years. At present, opioid analgesics are the mainstay of therapy in many patients receptor antagonists with a with moderate-to-severe pain. Unfortunately, adverse effects can severely com- peripherally restricted site of promise the therapeutic benefit offered by these drugs [1]. The gastrointestinal (GI) action tract is one of the main targets of their unwanted actions and, in this property, opioid analgesics are similar to other neuroactive drugs, notably adrenoceptor ago- 10. Opioid receptor antagonists nists [2-4]. This pharmacological profile reflects the significant role that neurons play with a peripherally Informa restricted UK Ltd. in GI function and the fact that many of the transmitters and transmitter receptors site of action as possible present in the brain have also been localised to the gut. This is particularly true for prokinetic drugs opioid receptors and adrenoceptors whose activation by opiates and catecholamines, 11. Expert opinion respectively, interferes with pathways of the enteric nervous system that regulate motility and secretion [1-9]. To comprehend the adverse actions of opioid analgesics and other neuroactive drugs on the gut, it needs to be considered that the alimentary canal is equipped Copyright of with the largest collection of neurons outside the CNS. Enteric neurons originating from the myenteric and submucosal plexuses supply all of the layers of the alimentary canal and, therefore, are in a position to regulate virtually every aspect of digestion [10-12]. These neurons not only synthesise and release acetylcholine, sub- stance P, NO, ATP, vasoactive intestinal polypeptide and 5-HT but also opioid pep- tides as their transmitters. The enteric nervous system is arranged in polarised circuits that are typically composed of intrinsic primary afferent neurons, a variable number of interneurons and excitatory or inhibitory output (motor, secretomotor and vasodilator) neurons to the effector tissues [10-12]. With this organisation, the 10.1517/13543784.16.2.181 © 2007 Informa UK Ltd ISSN 1354-3784 181 Treatment of opioid-induced gut dysfunction enteric nervous system is capable of regulating GI peristalsis, animals; however, analysis of the cellular mechanisms of opi- ion and fluid secretion, circulation, endocrine and immune ate action has shown that opioid receptor agonists can inter- activity independently of the brain [10-12]. rupt both excitatory and inhibitory neural inputs to the GI muscle in both human and animal models [21]. 2. Opioid peptides and opioid receptors in the Inhibition of excitatory neural inputs is associated with gastrointestinal tract inhibition of the release of excitatory transmitters such as acetylcholine and blockade of distension-induced peri- The adverse influence of opioid analgesics on GI function staltic contractions, whereas blockade of inhibitory neural remained an enigma to scientists until it was realised that both inputs results in depression of NO release from inhibitory opioid peptides and opioid receptors are expressed in the motor neurons, disinhibition of GI muscle activity, eleva- digestive tract; therefore, it is important to briefly consider the tion of resting muscle tone and non-propulsive motility endogenous opioid system in the gut and its physiological and patterns [6,8,13,21,23,24]. A direct activation of the interstitial pathophysiological implications (Figure 1) to understand the cell–muscle network has also been envisaged [25,26]. In the basis of opioid-induced bowel dysfunction (OBD). canine gut, µ-opioid receptor agonists have a biphasic exci- Met-enkephalin, leu-enkephalin, β-endorphin and dynorphin tatory and inhibitory influence on the migrating myo- are among the endogenous opioids that are present in the GI electrical complex [27], and transit in the human colon is tract where they have been localised to both neurons and retarded by activation of µ-opioid (but not κ-opioid) endocrine cells of the mucosa [1,5,13]. Neuroanatomical tracing receptors [28,29]. Other studies have shown that activation of studies have revealed that opioid peptides are present in dis- µ-opioid receptors in the human gut can increase pyloric tinct classes of enteric neurons in the guinea-pig, notably in tone, induce pyloric (as well as duodenojejunal phasic) myenteric neurons projecting to the circular muscle and in pressure activity and elevate the resting anal sphincter pres- neurons of descending enteric pathways [13-15]. sure [30,31]. The relative contribution of these multiple The presence of endogenous opioids in the alimentary effects to opioid-induced constipation is not clear [7]. canal is matched by the expression of opioid receptors that Apart from affecting GI motor activity, opioids also influ- mediate the effect of both endogenous and exogenous opioid ence GI ion and fluid transport (Figure 1). Blunted peristalsis receptor ligands on bowel function. By using mRNA quantifi- delays GI transit and, thereby, prolongs the contact of the cation and immunocytochemistry, opioid receptors of the µ-, intestinal contents with the mucosa [1]. As a result, absorption κ- and δ-subtype have been localised to the GI tract of rats, of fluid is increased, whereas the secretion of electrolytes and guinea-pigs and humans [13,16-18]. In the rat and guinea-pig, Printingwater is decreased and distributionin the small and large strictlyintestines [6,21,32,33] prohibited. all three subtypes of opioid receptors are found on neurons of The antisecretory effect of opiates is mediated by opioid the myenteric and submucosal plexuses and on nerve fibres receptors on enteric neurons, whose activation results in the supplying muscularis and mucosa; however, their relative dis- interruption of prosecretory enteric reflexes [6,21]. tribution varies with GI layer, GI region and species [13]. In The actions of endogenous opioids on the GI tract are the human gut, µ-opioid receptors are present on myenteric mediated by multiple opioid receptors. Studies with isolated and submucosal neurons and on immune cells of the lamina tissues from the human intestine suggest that δ-, κ- and propria [13]. µ-opioid receptors contribute to opiate-induced inhibition of muscle activity [34,35]. Propulsion in the rat intestine is 3. Opioid actions in the gastrointestinal tract blocked by δ- and µ- (but not κ-) opioid receptor agonists [6], whereas peristalsis in the guinea-pig intestine is suppressed by When released from Informa enteric neurons, UK it is Ltd. likely that opioid activation of κ- and µ- (but not δ-) opioid receptors [20]. Opi- peptides play a mediator role in the regulation of propulsion ate-induced inhibition of cholinergic transmission in the and secretion [2,5,6,8,9,19-21]. This conjecture is reflected by the guinea-pig gut is similarly mediated by µ- and κ-opioid actions of exogenous opioid receptor agonists and antagonists receptors [36]. on GI function (Figure 1). The inhibitory effect of opioid Opioid receptors belong to the family of metabotropic receptor agonists on peristalsis in the guinea-pig small intes- membrane receptors that couple via the Gi/Go subtypes of Copyrighttine is thought of to arise primarily from
Load more

Recommended publications
  • Vol 3:3 Properties of Proteins Relate to Their Contribution to the 168 Physiochemicalf and Sensory Properties of Foods
    Popular Article Journal Home: www.bioticainternational.com Article: RT520 How to cite this article? Biotica Vinoth et al., 2021. Food Derived Peptides – Role in Research [Human Health. Biotica Research Today 3(3): 165-168. [ Today Abstract ood proteins have long been recognized for their nutritional 165 and functional properties. On the other hand, the functional Vol 3:3 properties of proteins relate to their contribution to the 168 physiochemicalF and sensory properties of foods. Nowadays, a 2021 considerable amount of research has also focused on bioactive peptides which are present in foods, and researchers are trying Food Derived Peptides – to utilize such peptides as functional food ingredients aimed at health maintenance. Several bioactive peptides such as antioxidant, Role in Human Health antihypertensive, antiproliferative, antimicrobial, neuroactive, * hormonal and mineral binding were isolated from the fishes Vinoth Kumar L. , Manivannan M. and and shellfishes. The process flow of bioactive peptides includes Vignaesh D. purification and filtration methods and the peptide sequence was identified. The commercial application were also reported and Paraprofessional Institute of Fisheries Technology, Tamil Nadu discussed by many researches. Although the efficacies of these Dr. J. Jayalalithaa Fisheries University, Madhavaram, Chennai, peptides were wide range, the safety and conditions of usage are Tamil Nadu (600 051), India yet to be proven. Introduction t has been defined as specific protein fragments that have a Open Access positive impact on body functions and conditions and may Corresponding Author Iultimately influence health. Bioactive peptides have been defined as peptides with hormone- or drug like activity that Vinoth Kumar L. e-mail: [email protected] eventually modulate physiological function through binding interactions to specific receptors on target cells leading to induction of physiological responses (Murray and Fitzgerald, 2007).
    [Show full text]
  • Literature Review of Prescription Analgesics in the Causal Path to Pain
    Literature Review: Opioids and Death compiled by Bill Stockdale ([email protected]) This review is the result of searches for the terms opioid/opioid-related-disorders and death/ADE done in the PubMed database. This bibliography includes selected articles from the 1,075 found by searching during May, 2008, which represent key findings in the study of opioids. Articles for which there is no abstract are excluded. Also case reports and initial clinical trial reports are excluded. This is a compendium of all articles and do not lead to a specific target. There are three major topics developed in the literature as shown in this table of contents; • Topic One: Opioids in Causal Path to Death (page 1) o Prescription Drug Deaths (page 1) o Illicit Drug Deaths (page 30) o Neonatal Deaths (page 49) • Topic Two: Deaths in Palliative Care and Pain Treatment (page 57) • Topic Three: Pharmacology, Psychology, Origins of Abuse Relating to Death (page 72) • Bibliography (page 77) The three topics are presented below; each is followed in chronological order. Topic One: Opioids in Causal Path to Death Prescription Drug Deaths Karlson et al. describe differences in treatment of acute myocardial infarction, including different opioid use among men and women. The question whether women and men with acute myocardial infarction (AMI) are treated differently is currently debated. In this analysis we compared pharmacological treatments and revascularization procedures during hospitalization and during 1 year of follow-up in 300 women and 621 men who suffered an AMI in 1986 or 1987 at our hospital. During hospitalization, the mean dose of morphine (+/- SD) during the first 3 days was higher in men compared to women (14.5 +/- 15.7 vs.
    [Show full text]
  • A Qualitative Assessment of Eating Behaviors in Adults with Autism
    Illinois State University ISU ReD: Research and eData Theses and Dissertations 2-21-2015 A Qualitative Assessment Of Eating Behaviors In Adults With Autism Samantha Barbier Illinois State University, [email protected] Follow this and additional works at: https://ir.library.illinoisstate.edu/etd Part of the Human and Clinical Nutrition Commons Recommended Citation Barbier, Samantha, "A Qualitative Assessment Of Eating Behaviors In Adults With Autism" (2015). Theses and Dissertations. 317. https://ir.library.illinoisstate.edu/etd/317 This Thesis is brought to you for free and open access by ISU ReD: Research and eData. It has been accepted for inclusion in Theses and Dissertations by an authorized administrator of ISU ReD: Research and eData. For more information, please contact [email protected]. A QUALITATIVE ASSESSMENT OF EATING BEHAVIORS IN ADULTS WITH AUTISM Samantha J. Barbier 45 Pages May 2015 Diagnosis of autism has increased ten-fold in the last 40 years, and adults with autism remain an underrepresented population in research. The purpose of this study was to qualitatively explore the relationship between eating behaviors and autism using a questionnaire and interviews with adults diagnosed with autism spectrum disorder. Four males aged 22-27 were interviewed with their mothers present and completed the Swedish Eating Assessment for Autism Spectrum Disorders (SWEAA). Interviews were analyzed through the process of open coding, and the questionnaires were analyzed to determine consistent findings between the interview and the SWEAA questionnaire. Participants generally recognized hunger and satiety and were consuming a high carbohydrate, high fat diet low in vegetables. Variety in food choices was highly dependent upon encouragement from family members.
    [Show full text]
  • Peripherally Acting Mu-Opioid Receptor Antagonists and Postoperative Ileus: Mechanisms of Action and Clinical Applicability
    Review Article Peripherally Acting Mu-Opioid Receptor Antagonists and Postoperative Ileus: Mechanisms of Action and Clinical Applicability Eugene R. Viscusi, MD* Postoperative ileus (POI), a transient cessation of coordinated bowel function after surgery, is an important health care problem. The etiology of POI is multifactorial Tong J. Gan, MD† and related to both the surgical and anesthetic pathways chosen. Opioids used to manage surgical pain can exacerbate POI, delaying gastrointestinal (GI) recovery. John B. Leslie, MD, MBA‡ Peripherally acting mu-opioid receptor (PAM-OR) antagonists are designed to mitigate the deleterious effects of opioids on GI motility. This new class is investigational for POI management with the goal of accelerating the recovery of Joseph F. Foss, MD§ upper and lower GI tract function after bowel resection. In this review, we summarize the mechanisms by which POI occurs and the role of opioids and opioid Mark D. Talon, CRNA࿣ receptors in the enteric nervous system, discuss the mechanism of action of PAM-OR antagonists, and review clinical pharmacology and Phase II/III POI trial Wei Du, PhD¶ results of methylnaltrexone and alvimopan. Finally, the role of anesthesiologists in managing POI in the context of a multimodal approach is discussed. Gay Owens, PharmD¶ (Anesth Analg 2009;108:1811–22) Postoperative ileus (POI) is a transient cessation of (BR), often not resolving for 4 days or longer.3 Clini- coordinated bowel motility that prevents effective cally, POI is characterized by delayed passage of flatus transit of intestinal contents or tolerance of oral in- and stool, bloating, abdominal distension, abdominal take.1,2 POI occurs universally after bowel resection pain, nausea, and vomiting and is associated with an increase in postoperative morbidity and length of 4,5 From the *Department of Anesthesiology, Jefferson Medical hospital stay (LOS).
    [Show full text]
  • Bioactive Compounds and Milk Peptides Forhuman Health-A Review
    Novel Techniques in CRIMSON PUBLISHERS C Wings to the Research Nutrition and Food Science ISSN: 2640-9208 Review Article Bioactive Compounds and Milk Peptides for Human Health-A Review K Jayathilakan*, Rajkumar Ahirwar and MC Pandey Freeze Drying and Animal Products Technology Division, Defence Food Research Laboratory, India *Corresponding author: K Jayathilakan, Freeze Drying and Animal Product Technology Division, Defence Food Research Laboratory, Siddarthanagar, Mysore -570011, India Submission: March, 26, 2018; Published: May 08, 2018 Abstract portion of milk contains a variety of substances including lactose (milk sugar), protein (casein and whey), minerals and certain vitamins. It is a good Milk is a complex mixture and highly nutritious food for human being. It is an emulsion of fat globules in an aqueous environment. The aqueous a good source of nutrients for any neonate of mammalian species and nourishment of adult humans. Recent studies have shown that milk furnishes a broadsource range of bio ofpeptides biologically and otheractive bioactive compounds components that guard which neonates are necessary and adults for against body maintenance pathogens and and illnesses to fight againstsuch as severalimmunoglobulin, disease conditions. antibacterial It is peptides, antimicrobial proteins, oligosaccharides and lipids. Bioactive compounds are distinguished from essential nutrients which can have an Manyinfluence phenolic on health. compounds These are have extra antioxidant nutritional properties constituents and that some typically studies occur have indemonstrated small quantities favourable in foods. effects Phenolic on compounds,thrombosis andincluding tumorigenesis. their sub Conjugatedcategory, flavonoids linoleic acid,are present pre biotic, in all probiotic, plants and bio have peptides been andstudied bioactive extensively components in cereals, along legumes, with amino nuts, oliveacids oil,and vegetables, proteins molecules fruits, tea areand present red wine.
    [Show full text]
  • Volume C, Module 2 Leader's Guide Opioids: Basics of Addiction
    Volume C, Module 2 Leader’s Guide Opioids: Basics of Addiction; Treatment with Agonists, Partial Agonists, and Antagonists Treatnet Training Volume C: Module 2 – Updated 21 February 2008 1 1 Module 2: Training goals To describe the: z Key components of opiate addiction and its medical / psychiatric consequences z Benefits and limitations of methadone as a pharmacotherapy for opiate dependence z Benefits and limitations of buprenorphine as a pharmacotherapy for opiate dependence z Benefits and limitations of narcotic antagonists for overdose (naloxone) and relapse prevention (naltrexone) for opiate dependence 2 2 Module 2: Workshops Workshop 1: Opiates: What they are, problems associated with their use, and medical treatment implications Workshop 2: Opiate addiction treatment with methadone Workshop 3: Opiate addiction treatment with buprenorphine Workshop 4: Opiate Antagonist Treatment: Naloxone for overdose, Naltrexone for relapse prevention 3 3 Icebreaker: Opiate medication in my country Does your country use opiate medications, and if so, what type of medication? What are the main problems in your country regarding the use of these medications? 15 minutes 4 4 Workshop 1: Opiates What they are, problems associated with their use, and medical treatment implications 5 5 Pre-assessment Please respond to the pre-assessment questions in your workbook. (Your responses are strictly confidential.) 10 minutes 6 6 Training objectives At the end of this training you will understand the: 1. Epidemiology of opiate addiction worldwide and its relationship to infectious diseases 2. Basic neurobiology of opiate addiction 3. Medical / psychiatric co-morbidities and treatment strategies for these disorders used with opiate addicts 4. Key issues in engaging opiate addicts into treatment with low threshold approaches 7 7 Opioids Definition Opioids are natural derivatives of opium or synthetic psychoactive substances that have effects similar to morphine or are capable of converting into a drug having such effects.
    [Show full text]
  • Neurotransmitters: Their Role Within the Body
    Neurotransmitters: Their Role in the Body WWW.RN.ORG® Reviewed October, 2019, Expires October, 2021 Provider Information and Specifics available on our Website Unauthorized Distribution Prohibited ©2019 RN.ORG®, S.A., RN.ORG®, LLC Developed by Melissa K Slate, RN, CRN Objectives By the end of this educational encounter, the clinician will be able to: 1. Understand how nerve impulses travel along neural pathways 2. Identify common neurotransmitters and their effect in the body 3. Explain the effect of altered concentrations of specific neurotransmitters upon the system. The purpose of this course is to give an overview of the neurotransmitter system of the human body and increase understanding about how altered neurotransmitter concentrations affect various body organs. Definition of a Neurotransmitter Neurotransmitters are types of hormones in the brain that transmit information from one neuron to another. They are made by amino acids. Neurotransmitters control major body functions including movement, emotional response, and the physical ability to experience pleasure and pain. The most familiar neurotransmitters, which are thought to play a role in mood regulation, are serotonin, norepinephrine, dopamine, acetylcholine, and GABA. In order to adequately understand the effect of neurotransmitters, we must first understand what occurs in the process of neurotransmission. We will start with an oversimplified version for better understanding and then follow up with a more detailed explaination. A nerve impulse, which is an electrical signal, travels along the neural pathway until it reaches the end. Here the electrical signal is converted to a chemical signal. This area of conversion is called a synapse. The chemical signal is called a neurotransmitter.
    [Show full text]
  • Drug/Substance Trade Name(S)
    A B C D E F G H I J K 1 Drug/Substance Trade Name(s) Drug Class Existing Penalty Class Special Notation T1:Doping/Endangerment Level T2: Mismanagement Level Comments Methylenedioxypyrovalerone is a stimulant of the cathinone class which acts as a 3,4-methylenedioxypyprovaleroneMDPV, “bath salts” norepinephrine-dopamine reuptake inhibitor. It was first developed in the 1960s by a team at 1 A Yes A A 2 Boehringer Ingelheim. No 3 Alfentanil Alfenta Narcotic used to control pain and keep patients asleep during surgery. 1 A Yes A No A Aminoxafen, Aminorex is a weight loss stimulant drug. It was withdrawn from the market after it was found Aminorex Aminoxaphen, Apiquel, to cause pulmonary hypertension. 1 A Yes A A 4 McN-742, Menocil No Amphetamine is a potent central nervous system stimulant that is used in the treatment of Amphetamine Speed, Upper 1 A Yes A A 5 attention deficit hyperactivity disorder, narcolepsy, and obesity. No Anileridine is a synthetic analgesic drug and is a member of the piperidine class of analgesic Anileridine Leritine 1 A Yes A A 6 agents developed by Merck & Co. in the 1950s. No Dopamine promoter used to treat loss of muscle movement control caused by Parkinson's Apomorphine Apokyn, Ixense 1 A Yes A A 7 disease. No Recreational drug with euphoriant and stimulant properties. The effects produced by BZP are comparable to those produced by amphetamine. It is often claimed that BZP was originally Benzylpiperazine BZP 1 A Yes A A synthesized as a potential antihelminthic (anti-parasitic) agent for use in farm animals.
    [Show full text]
  • Opium HEROIN BARBITURATES Hallucinogens
    OPIUM OPIUM • Opium poppy, Papaver somniferum var. album, is the species of plant from which opium and poppy seeds are extracted. • The Latin botanical name means, loosely, the "sleep‐bringing poppy, white form", referring to the sedative properties of some of these opiates • The plant itself is also valuable for ornamental purposes, and has been known as the "common garden poppy", • Poppy seeds of Papaver somniferum are an important food item and the source of poppyseed oil, a healthy edible oil that has many uses. Poppy seeds are called Khuskhus in Hindi, Gasagasalu in Telugu, Gasagasa in Kannada, Posto dana in Bengali. • The opium poppy is the principal source of all natural opiates. • Opium (raw opium) is the latex harvested by making incisions on the green capsules (seed pods). Poppy straw is the dried mature plant except the seeds, harvested by mowing. • Morphine is the predominant alkaloid found in the varieties of opium poppy plant cultivated in most producing countries • Poppies as medicine: Australia, Turkey and India are the major producers of poppy for medicinal purposes and poppy‐based drugs, such as morphine or codeine • In medicine, the term opiate describes any of the narcotic opioid alkaloids found as natural products in the opium poppy plant, as well as many semisynthetic chemical derivatives of such alkaloids • There are a number of broad classes of opioids: • Natural opiates: alkaloids contained in the resin of the opium poppy, primarily morphine, codeine, and thebaine, papaverine and noscapine • Semi‐synthetic opioids: created from the natural opiates, such as hydromorphone, hydrocodone, oxycodone, oxymorphone, desomorphine, diacetylmorphine (heroin), nicomorphine, dipropanoylmorphine, benzylmorphine and ethylmorphine; • Fully synthetic opioids: such as fentanyl, pethidine, methadone, tramadol and dextropropoxyphene; • Endogenous opioid peptides, produced naturally in the body, such as endorphins, enkephalins, dynorphins, and endomorphins.
    [Show full text]
  • Opioid Analgesics – a 2018 Update
    REVIEW Opioid analgesics – a 2018 update Schellack G, BCur, Adv Univ Dipl Nurs Sc (HSM), Hons BSc (Pharmacology), Clinical research specialist in the pharmaceutical industry Schellack N, BCur, BPharm, PhD (Pharmacy), Associate Professor* Meyer JC, BPharm, MSc (Med) Pharmacy, PhD (Pharmacy), Associate Professor* *School of Pharmacy, Sefako Makgatho Health Sciences University (SMU) Correspondence to: Prof Natalie Schellack, e-mail: [email protected] Keywords: pain, opioid, morphine, codeine, oxycodone, hydromorphone, buprenorphine, pain ladder, tapentadol Abstract The opioid analgesic drugs constitute one of the most important groups of pharmacotherapeutic agents in the clinical practice setting. They are vital to pain management, especially moderate to severe cancer and visceral pain, in a myriad of healthcare settings. The key to optimal pain management is the ability to effectively manage patients to ensure optimal pain relief, whilst also minimising or managing the side-effects of their pain medication. This necessitates effective collaboration between all the healthcare professionals managing the patient. This article provides an updated overview of the opioid analgesics, and their usefulness in clinical practice. © Medpharm S Afr Pharm J 2018;85(1):43-49 Introduction true opioid peptide receptors, but they do explain many of the unwanted effects of some opioid analgesics, such as As a class, the opioid analgesics are arguably one of the most pentazocine). important groups of pharmacotherapeutic agents in the clinical • Nociceptin opioid peptide (NOP) receptors have also been practice setting. These drugs are either related to morphine identified; these are G-protein-coupled receptors for the in structure and action, or they are synthetic derivatives with endogenous opioid-like ligand known as nociceptin or orphanin different chemical structures.
    [Show full text]
  • What Do We Know About Opioids and the Kidney?
    International Journal of Molecular Sciences Review What Do We Know about Opioids and the Kidney? Mary Mallappallil *, Jacob Sabu, Eli A. Friedman and Moro Salifu Department of Internal Medicine, State University of New York at Downstate, Brooklyn, New York, NY 11203, USA; [email protected] (J.S.); [email protected] (E.A.F.); [email protected] (M.S.) * Correspondence: [email protected]; Tel.: +1-917-301-9860 Academic Editor: Monica Valentovic Received: 21 November 2016; Accepted: 17 January 2017; Published: 22 January 2017 Abstract: Evidence suggests a link between opioid use and kidney disease. This review summarizes the known renal manifestations of opioid use including its role in acute and chronic kidney injury. Both the direct and indirect effects of the drug, and the context which leads to the development of renal failure, are explored. While commonly used safely for pain control and anesthesia in those with kidney disease, the concerns with respect to side effects and toxicity of opioids are addressed. This is especially relevant with the worldwide increase in the use of opioids for medical and recreational use. Keywords: opioids; renal failure; pharmacokinetics 1. Introduction The universal increase in opioid use requires practitioners to be comfortable with the use of these medications, especially in those with organ dysfunction such as kidney disease to avoid complications. This article targets to highlight the safe use of opioids in those with kidney disease. Pain occurs when a signal from a noxious stimulus is transmitted via peripheral nerve fibers to the spino-thalamic tract, and finally relayed to the somatosensory cortex.
    [Show full text]
  • Methylnaltrexone for the Management of Unwanted Peripheral Opioid Effects
    DRUG EVALUATION Methylnaltrexone for the management of unwanted peripheral opioid effects Peter Holzer For many a patient suffering from moderate to severe pain, opioid analgesics offer the Medical University of Graz, Research Unit of anxiously sought-after relief, but at a high price. While the pain is wearing off, distressful Translational constipation, abdominal discomfort, nausea and urinary retention ensue. These unwanted Neurogastroenterology, effects have been difficult to deal with, and the laxatives that are usually prescribed Institute of Experimental and Clinical Pharmacology, ameliorate constipation in no more than 50% of the patients receiving opiates. A new Universitätsplatz 4, treatment concept emerged from the development of opioid receptor antagonists with a A-8010 Graz, Austria peripherally restricted site of action. One of these treatments is methylnaltrexone, which Tel.: +43 316 380 4500 Fax: +43 316 380 9645 clinical trials have shown to be of benefit in opioid-induced constipation, postoperative [email protected] ileus and urinary retention, while analgesia remains unabated. The drug is well tolerated and holds great promise in freeing opioid therapy of some of its most-feared adverse aspects. In 2008, methylnaltrexone (RelistorTM) was approved in the USA, Canada and Europe for the treatment of opioid-induced constipation in patients with advanced illness. Opioids denominate exogenous and endogenous the bowel, anorexia, nausea and vomiting, as well compounds that activate the principal µ-, κ- and as interference with oral drug administration and δ-opioid receptors. The term opioid has been absorption [1,2]. The symptoms associated with derived from opium, which refers to the dried OBD can profoundly impair the quality of life, latex collected from the unripe seed capsules of and in some patients can be so severe that they Papaver somniferum.
    [Show full text]