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Marín-Medina A, Dávalos-Rodríguez IP, Peña-Durán E, Torre-Castellanos LEDL, González-Vargas LF, Gómez-Ramos JJ. Genetic Factors Related to the Development or Progression of Mesoamerican Endemic Nephropathy. Int J Mol Sci 2025; 26:4486. [PMID: 40429630 DOI: 10.3390/ijms26104486] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2025] [Revised: 05/05/2025] [Accepted: 05/06/2025] [Indexed: 05/29/2025] Open
Abstract
Over the past two decades, Mesoamerican endemic nephropathy (MeN) has become a major public health problem in certain regions of Mexico and Central American countries. The etiology of this disease is multifactorial, and important environmental factors have been described, such as chronic heat stress, recurrent episodes of dehydration, infections, and exposure to toxins of chemical and biological origin. Genetic and epigenetic factors have been proposed to play significant roles in MeN. Recent studies have analyzed the role of these factors in MeN. In some cases, these factors appear to be associated with accelerated deterioration of established kidney disease due to preexisting endothelial dysfunction and tubulopathy. In other cases, they appear to be associated with early kidney damage, even before occupational exposure, suggesting that they may play a relevant role in the genesis of the disease. Other factors appear to act as risk reducers for developing MeN in areas with a high prevalence of the disease. Therefore, this disease has a rather complex multifactorial etiology, with possible polygenic contributions, possible epigenetic phenomena, and multiple environmental factors.
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Affiliation(s)
- Alejandro Marín-Medina
- Departamento de Biología Molecular y Genómicas, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara, Guadalajara 44340, Jalisco, Mexico
| | - Ingrid Patricia Dávalos-Rodríguez
- Departamento de Biología Molecular y Genómicas, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara, Guadalajara 44340, Jalisco, Mexico
- Centro de Investigación Biomédica de Occidente (CIBO), Instituto Mexicano del Seguro Social (IMSS), Guadalajara 44340, Jalisco, Mexico
| | - Emiliano Peña-Durán
- Licenciatura en Médico Cirujano y Partero, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara, Guadalajara 44340, Jalisco, Mexico
| | - Luis Eduardo de la Torre-Castellanos
- Licenciatura en Médico Cirujano y Partero, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara, Guadalajara 44340, Jalisco, Mexico
| | - Luis Felipe González-Vargas
- Licenciatura en Médico Cirujano y Partero, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara, Guadalajara 44340, Jalisco, Mexico
| | - José Juan Gómez-Ramos
- Especialidad de Medicina de Urgencias Adscrita al Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara, Guadalajara 44340, Jalisco, Mexico
- Departamento de Urgencias, Hospital General de Zona 89, Instituto Mexicano del Seguro Social (IMSS), Guadalajara 44100, Jalisco, Mexico
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Shawqi M, Mohamed SAB, Sharkawy E, Hetta D. Dosage of epidural morphine analgesia after lower abdominal cancer surgery: a randomized clinical trial among the older adults. Perioper Med (Lond) 2025; 14:52. [PMID: 40329346 PMCID: PMC12057010 DOI: 10.1186/s13741-025-00521-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2024] [Accepted: 03/29/2025] [Indexed: 05/08/2025] Open
Abstract
BACKGROUND Epidural morphine is considered one of the most potent drugs used for postoperative analgesia; however, its side effects are dose-related and exaggerated in elderly people. In this study, we aimed to determine which of three doses within that range (1.5 mg, 3 mg, or 4.5 mg) can provide adequate pain relief. METHODS A total of 102 patients were assessed for allocation into one of four groups to receive either placebo (group Morphine 0, N = 22), 1.5 mg of epidural morphine (Morphine 1.5, N = 22), 3 mg of epidural morphine (Morphine 3, N = 22), or 4.5 mg of epidural morphine (Morphine 4.5, N = 22) before skin incision, 24 h after surgery and 48 h after surgery. Cumulative intravenous IV-PCA morphine consumption, VAS pain scores, modified Ramsay Sedation Scores, nausea, vomiting, and pruritus were evaluated. RESULTS The VAS pain scores at activity of patients who received epidural morphine at doses of 3 mg and 4.5 mg were significantly lower than the placebo and 1.5 mg groups, VAS Score at 72 h was (2 ± 0.8) and (1.7 ± 1) vs (4.3 ± 1.1) and (4 ± 1) respectively, p value = 0.000. The mean total IV-PCA morphine consumption (mg) was significantly higher in patients who received received epidural 0.9% sodium chloride alone compared to 1.5 mg, 3 mg and 4.5 mg epidural morphine groups (38.1 ± 4.8 mg vs 27.2 ± 5.6 mg, 9.2 ± 3.5 mg, and 6.3 ± 3.3 mg respectively), p value = 0.000). However, the difference between the 3 mg and the 4.5 mg groups was not statistically significant in both of VAS scores and IV-PCA morphine consumption (P value > 0.05 for 3 mg vs. 4.5 mg). Patients who received 4.5 mg of epidural morphine experienced a significant increase in the level of sedation, measured by the Ramsay sedation scale, in comparison with 1.5 mg, 3 mg and placebo epidural morphine groups in the first 24 h, the Scale for this group was (2.5 ± 0.5) vs (2.1 ± 0.2, 2.1 ± 0.2, and 2.2 ± 0.5 respectively); p value = 0.000. No relationship between postoperative nausea and the dosage of epidural morphine was found. CONCLUSION Epidural morphine 3 mg as a bolus every 24 h with add on IV patient control analgesia (PCA) morphine, set to deliver 1.5 mg boluses on demand without background infusion with a lockout period of 45 min, could achieve effective and adequate analgesia lasting up to 72 h postoperatively without increasing in the level of sedation or other side effects in older adults after a lower abdominal cancer surgery.
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Affiliation(s)
- Muhammad Shawqi
- Department of Anaesthesiology, South Egypt Cancer Institute, Assiut University, Assiut, Egypt.
| | | | - Essam Sharkawy
- Department of Anaesthesiology, Faculty of Medicine, Assiut University, Assiut, Egypt
| | - Diab Hetta
- Department of Anaesthesiology, South Egypt Cancer Institute, Assiut University, Assiut, Egypt
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Ornello R, Caponnetto V, Ahmed F, Al-Khazali HM, Ambrosini A, Ashina S, Baraldi C, Bellotti A, Brighina F, Calabresi P, Casillo F, Cevoli S, Cheng S, Chiang CC, Chiarugi A, Christensen RH, Chu MK, Coppola G, Corbelli I, Crema S, De Icco R, de Tommaso M, Di Lorenzo C, Di Stefano V, Diener HC, Ekizoğlu E, Fallacara A, Favoni V, Garces KN, Geppetti P, Goicochea MT, Granato A, Granella F, Guerzoni S, Ha WS, Hassan A, Hirata K, Hoffmann J, Hüssler EM, Hussein M, Iannone LF, Jenkins B, Labastida-Ramirez A, Laporta A, Levin M, Lupica A, Mampreso E, Martinelli D, Monteith TS, Orologio I, Özge A, Pan LLH, Panneerchelvam LL, Peres MFP, Souza MNP, Pozo-Rosich P, Prudenzano MP, Quattrocchi S, Rainero I, Romanenko V, Romozzi M, Russo A, Sances G, Sarchielli P, Schwedt TJ, Silvestro M, Swerts DB, Tassorelli C, Tessitore A, Togha M, Vaghi G, Wang SJ, Ashina M, Sacco S. Evidence-based guidelines for the pharmacological treatment of migraine. Cephalalgia 2025; 45:3331024241305381. [PMID: 40277319 DOI: 10.1177/03331024241305381] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/26/2025]
Abstract
We here present evidence-based guidelines for the pharmacological treatment of migraine. These guidelines, created by the Italian Society for the Study of Headache and the International Headache Society, aim to offer clear, actionable recommendations to healthcare professionals. They incorporate evidence-based recommendations from randomized controlled trials and expert-based opinions. The guidelines follow the Grading of Recommendations, Assessment, Development and Evaluation approach for assessing the quality of evidence. The guideline development involved a systematic review of literature across multiple databases, adherence to Cochrane review methods, and a structured framework for data extraction and interpretation. Although the guidelines provide a robust foundation for migraine treatment, they also highlight gaps in current research, such as the paucity of head-to-head drug comparisons and the need for long-term outcome studies. These guidelines serve as a resource to standardize migraine treatment and promote high-quality care across different healthcare settings.
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Affiliation(s)
- Raffaele Ornello
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy
| | - Valeria Caponnetto
- Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy
| | - Fayyaz Ahmed
- Hull University Teaching Hospitals NHS Trust., Hull, UK
| | - Haidar M Al-Khazali
- Department of Neurology, Danish Headache Center, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
| | | | - Sait Ashina
- Department of Neurology and Department of Anesthesia, Critical Care and Pain Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA, USA
- Department of Clinical Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Carlo Baraldi
- Digital and Predictive Medicine, Pharmacology and Clinical Metabolic Toxicology -Headache Center and Drug Abuse - Laboratory of Clinical Pharmacology and Pharmacogenomics, AOU of Modena, Modena, Italy
| | - Alessia Bellotti
- Department of Medicine and Surgery, University of Perugia, Perugia, Italy
| | - Filippo Brighina
- Department of Biomedicine, Neuroscience and Advanced Diagnostics (BIND), University of Palermo, Palermo Italy
| | - Paolo Calabresi
- Dipartimento di Neuroscienze, Organi di Senso e Torace, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Dipartimento di Neuroscienze, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Francesco Casillo
- Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome Polo Pontino - ICOT - Latina, Italy
| | - Sabina Cevoli
- IRCCS Istituto delle Scienze Neurologiche di Bologna, Programma Cefalee e Algie Facciali, Bologna, Italy
| | - Shuli Cheng
- Department of Neurology, Alfred Health, Melbourne, Victoria, Australia
| | | | - Alberto Chiarugi
- Department of Health Sciences - Section of Clinical Pharmacology and Oncology - Headache Center, Careggi University Hospital - University of Florence, Italy
| | - Rune Häckert Christensen
- Department of Neurology, Danish Headache Center, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
- Department of Clinical Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Min Kyung Chu
- Department of Neurology, Severance Hospital, Yonsei University, Republic of Korea
| | - Gianluca Coppola
- Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome Polo Pontino - ICOT - Latina, Italy
| | - Ilenia Corbelli
- Department of Medicine and Surgery, University of Perugia, Perugia, Italy
| | - Santiago Crema
- Headache Clinic, Neurology Department, Fleni, Buenos Aires, Argentina
| | - Roberto De Icco
- Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy
- Headache Science and Neurorehabilitation Unit, IRCSS Mondino Foundation, Pavia, Italy
| | - Marina de Tommaso
- DiBrain Department, Neurophysiopathology Unit, Bari Aldo Moro University, Bari, Italy
| | - Cherubino Di Lorenzo
- Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome Polo Pontino - ICOT - Latina, Italy
| | - Vincenzo Di Stefano
- Department of Biomedicine, Neuroscience and Advanced Diagnostics (BIND), University of Palermo, Palermo Italy
| | - Hans-Christoph Diener
- Department of Neuroepidemiology, Institute for Medical Informatics, Biometry and Epidemiology (IMIBE), Faculty of Medicine, University Duisburg-Essen, Essen, Germany
| | - Esme Ekizoğlu
- Istanbul Faculty of Medicine, Department of Neurology, Istanbul University, Istanbul, Turkey
| | - Adriana Fallacara
- Headache Center, Amaducci Neurological Clinic, Polyclinic Hospital-University Consortium Bari, Italy
| | - Valentina Favoni
- IRCCS Istituto delle Scienze Neurologiche di Bologna, Programma Cefalee e Algie Facciali, Bologna, Italy
| | - Kimberly N Garces
- Department of Neurology-Headache Division, University of Miami, Miller School of Medicine, Miami, USA
| | - Pierangelo Geppetti
- Department of Health Sciences - Section of Clinical Pharmacology and Oncology - Headache Center, Careggi University Hospital - University of Florence, Italy
- Department of Molecular Pathobiology and Pain Research Center, College of Dentistry, New York University, New York, USA
| | | | - Antonio Granato
- Clinical Unit of Neurology, Headache Center, Department of Medical, Surgical and Health Sciences, University Hospital and Health Services of Trieste, ASUGI, University of Trieste, Trieste, Italy
| | - Franco Granella
- Unit of Neurosciences, Department of Medicine and Surgery, University of Parma, Parma, Italy
| | - Simona Guerzoni
- Digital and Predictive Medicine, Pharmacology and Clinical Metabolic Toxicology -Headache Center and Drug Abuse - Laboratory of Clinical Pharmacology and Pharmacogenomics, AOU of Modena, Modena, Italy
| | - Woo-Seok Ha
- Department of Neurology, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Amr Hassan
- Department of Neurology, Kasr Al Ainy Hospitals, Faculty of Medicine, Cairo University, Egypt
| | | | - Jan Hoffmann
- Wolfson Sensory, Pain and Regeneration Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK
| | - Eva-Maria Hüssler
- Institute for Medical Informatics, Biometry and Epidemiology, University Hospital Essen, Essen, Germany
| | - Mona Hussein
- Department of Neurology, Beni-Suef University, Beni-Suef, Egypt
| | - Luigi Francesco Iannone
- Department of Health Sciences - Section of Clinical Pharmacology and Oncology - Headache Center, Careggi University Hospital - University of Florence, Italy
| | | | - Alejandro Labastida-Ramirez
- Division of Neuroscience, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester; Geoffrey Jefferson Brain Research Centre, Manchester Academic Health Science Centre, Northern Care Alliance NHS Foundation Trust, University of Manchester, Manchester, UK
| | - Anna Laporta
- DiBrain Department, Neurophysiopathology Unit, Bari Aldo Moro University, Bari, Italy
| | - Morris Levin
- Headache Center, University of California, San Francisco, CA, USA
| | - Antonino Lupica
- Department of Biomedicine, Neuroscience and Advanced Diagnostics (BIND), University of Palermo, Palermo Italy
| | | | - Daniele Martinelli
- Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy
| | - Teshamae S Monteith
- Headache Center, Amaducci Neurological Clinic, Polyclinic Hospital-University Consortium Bari, Italy
| | - Ilaria Orologio
- Headache Centre of Department of Advanced Medical and Surgical Sciences University of Campania "Luigi Vanvitelli" Naples, Italy
| | - Aynur Özge
- Department of Neurology, Mersin University Medical School, Mersin, Turkey
| | | | | | - Mario F P Peres
- Department of Neurology, Hospital Israelita Albert Einstein, Sao Paulo, Brazil
| | | | - Patricia Pozo-Rosich
- Headache Clinic, Neurology Department, Vall d'Hebron Hospital, Barcelona, Spain; Headache and Neurological Pain Research Group, VHIR, Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Maria Pia Prudenzano
- Headache Center, Amaducci Neurological Clinic, Polyclinic Hospital-University Consortium Bari, Italy
| | - Silvia Quattrocchi
- IRCCS Istituto delle Scienze Neurologiche di Bologna, Programma Cefalee e Algie Facciali, Bologna, Italy
| | - Innocenzo Rainero
- Headache Center, Department of Neuroscience "Rita Levi Montalcini", University of Torino, Torino, Italy
| | | | - Marina Romozzi
- Dipartimento di Neuroscienze, Organi di Senso e Torace, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Dipartimento di Neuroscienze, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Antonio Russo
- Headache Centre of Department of Advanced Medical and Surgical Sciences University of Campania "Luigi Vanvitelli" Naples, Italy
| | - Grazia Sances
- Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy
| | - Paola Sarchielli
- Department of Medicine and Surgery, University of Perugia, Perugia, Italy
| | - Todd J Schwedt
- Department of Neurology, Mayo Clinic, Phoenix, Arizona, USA
| | - Marcello Silvestro
- Headache Centre of Department of Advanced Medical and Surgical Sciences University of Campania "Luigi Vanvitelli" Naples, Italy
| | | | - Cristina Tassorelli
- Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy
- Headache Science and Neurorehabilitation Unit, IRCSS Mondino Foundation, Pavia, Italy
| | - Alessandro Tessitore
- Headache Centre of Department of Advanced Medical and Surgical Sciences University of Campania "Luigi Vanvitelli" Naples, Italy
| | - Mansoureh Togha
- Headache Department, Iranian Center of Neurological Research, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran
- Headache Department, Neurology Ward, Sina Hospital, Medical School, Tehran University of Medical Sciences, Tehran, Iran
| | - Gloria Vaghi
- Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy
- Headache Science and Neurorehabilitation Unit, IRCSS Mondino Foundation, Pavia, Italy
| | - Shuu-Jiun Wang
- Department of Neurology, Taipei Veterans General Hospital, Taipei
- College of Medicine, National Yang Ming Chiao Tung University, Taipei
| | - Messoud Ashina
- Department of Neurology, Danish Headache Center, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
- Department of Neurology, Severance Hospital, Yonsei University, Republic of Korea
| | - Simona Sacco
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy
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Yaxley J. Anaesthesia in chronic dialysis patients: A narrative review. World J Crit Care Med 2025; 14:100503. [DOI: 10.5492/wjccm.v14.i1.100503] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2024] [Revised: 10/27/2024] [Accepted: 11/12/2024] [Indexed: 12/11/2024] Open
Abstract
The provision of anaesthesia for individuals receiving chronic dialysis can be challenging. Sedation and anaesthesia are frequently managed by critical care clinicians in the intensive care unit or operating room. This narrative review summarizes the important principles of sedation and anaesthesia for individuals on long-term dialysis, with reference to the best available evidence. Topics covered include the pharmacology of anaesthetic agents, the impacts of patient characteristics upon the pre-anaesthetic assessment and critical illness, and the fundamentals of dialysis access procedures.
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Affiliation(s)
- Julian Yaxley
- Department of Medicine, Queensland Health, Meadowbrook 4131, Qld, Australia
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5
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Friedman DJ, Leone DA, Amador JJ, Kupferman J, Francey LJ, Lopez-Pilarte D, Lau J, Delgado I, Yih WK, Salinas A, Wang M, Genovese G, Shah S, Kelly J, Tattersfield CF, Raines NH, Amador M, Dias L, Pitsillides A, Ramirez-Rubio O, Amador AG, Cortopassi M, Applebaum KM, Alper SL, Banks AS, McClean MD, Leibler JH, Scammell MK, Dupuis J, Brooks DR. Genetic risk factors for Mesoamerican nephropathy. Proc Natl Acad Sci U S A 2024; 121:e2404848121. [PMID: 39585978 PMCID: PMC11626114 DOI: 10.1073/pnas.2404848121] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2024] [Accepted: 09/14/2024] [Indexed: 11/27/2024] Open
Abstract
Mesoamerican nephropathy (MeN) is a progressive kidney disease found on the Pacific coast of Central America primarily in young male agricultural workers without typical kidney disease risk factors. While it is generally accepted that environmental exposures contribute to MeN, we hypothesized that there was also an important genetic component. We performed a genome-wide association study comparing individuals with MeN versus individuals with normal kidney function. We found that Native American ancestry was strongly associated with increased risk of MeN. We also identified candidate variants in the OPCML gene, which encodes a protein that binds opioid receptors, that were associated with ~sixfold reduced odds of MeN (allele frequency 0.029 in controls and 0.005 in cases, OR = 0.16; P = 4 × 10-8). Sugarcane workers with the protective OPCML variants had markedly increased urine osmolality suggesting greater ability to defend against hypovolemia. Experiments with Opcml knock-out mice revealed roles for OPCML in fluid balance and temperature regulation consistent with our findings in humans. Our data suggest that heritable differential sensitivity to heat stress and dehydration contributes to high rates of kidney disease in Central America.
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Affiliation(s)
- David J. Friedman
- Division of Nephrology, Beth Israel Deaconess Medical Center, Boston, MA02215
- Harvard Medical School, Boston, MA02215
- Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA02142
| | - Dominick A. Leone
- Department of Epidemiology, Boston University School of Public Health, Boston, MA02118
| | - Juan José Amador
- Department of Epidemiology, Boston University School of Public Health, Boston, MA02118
- Centro Medico del Pacifico, Masaya, Nicaragua 41000
| | - Joseph Kupferman
- Division of Nephrology, Beth Israel Deaconess Medical Center, Boston, MA02215
- Harvard Medical School, Boston, MA02215
| | - Lauren J. Francey
- Division of Nephrology, Beth Israel Deaconess Medical Center, Boston, MA02215
| | | | - Jorge Lau
- Especialistas en Medicina Interna, Chichigalpa, Nicaragua 26100
| | - Iris Delgado
- Department of Epidemiology, Boston University School of Public Health, Boston, MA02118
| | - W. Katherine Yih
- Harvard Medical School, Boston, MA02215
- Department of Population Medicine, Harvard Medical School, Boston, MA02215
- Harvard Pilgrim Healthcare Institute, Boston, MA02215
| | | | - Minxian Wang
- Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA02142
| | - Giulio Genovese
- Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA02142
| | - Shrijal Shah
- Division of Nephrology, Beth Israel Deaconess Medical Center, Boston, MA02215
| | - Jessica Kelly
- Division of Nephrology, Beth Israel Deaconess Medical Center, Boston, MA02215
| | | | - Nathan H. Raines
- Division of Nephrology, Beth Israel Deaconess Medical Center, Boston, MA02215
- Harvard Medical School, Boston, MA02215
| | | | - Leny Dias
- Division of Nephrology, Beth Israel Deaconess Medical Center, Boston, MA02215
| | - Achilleas Pitsillides
- Department of Biostatistics, Boston University School of Public Health, Boston, MA02118
| | - Oriana Ramirez-Rubio
- Department of Epidemiology, Boston University School of Public Health, Boston, MA02118
- Barcelona Institute for Global Health, Barcelona08036, Spain
| | | | - Marissa Cortopassi
- Endocrinology Division, Beth Israel Deaconess Medical Center, Boston, MA02215
| | - Katie M. Applebaum
- Department of Environmental and Occupational Health, Milken Institute School of Public Health, George Washington University, Washington, DC20052
| | - Seth L. Alper
- Division of Nephrology, Beth Israel Deaconess Medical Center, Boston, MA02215
- Harvard Medical School, Boston, MA02215
- Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA02142
| | - Alex S. Banks
- Harvard Medical School, Boston, MA02215
- Endocrinology Division, Beth Israel Deaconess Medical Center, Boston, MA02215
| | - Michael D. McClean
- Department of Environmental Health, Boston University School of Public Health, Boston, MA02118
| | - Jessica H. Leibler
- Department of Environmental Health, Boston University School of Public Health, Boston, MA02118
| | - Madeleine K. Scammell
- Department of Environmental Health, Boston University School of Public Health, Boston, MA02118
| | - Josée Dupuis
- Department of Biostatistics, Boston University School of Public Health, Boston, MA02118
- Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, QCH3A 1G1, Canada
| | - Daniel R. Brooks
- Department of Epidemiology, Boston University School of Public Health, Boston, MA02118
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Mercadante S. Influence of aging on opioid dosing for perioperative pain management: a focus on pharmacokinetics. JOURNAL OF ANESTHESIA, ANALGESIA AND CRITICAL CARE 2024; 4:51. [PMID: 39085914 PMCID: PMC11292879 DOI: 10.1186/s44158-024-00182-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/01/2024] [Accepted: 07/10/2024] [Indexed: 08/02/2024]
Abstract
The older population continues to grow in all countries, and surgeons are encountering older patients more frequently. The management of postoperative pain in older patients can be a difficult task. Opioids are the mainstay of perioperative pain control. This paper assesses some pharmacokinetic age-related aspects and their relationship with the use of opioids in the perioperative period. Changes in body composition and organ function, and pharmacokinetics in older patients, as well as characteristics of opioids commonly used in the perioperative period are described. Specific problems, dose titration, and patient-controlled analgesia in the elderly are also reviewed. Opioids can be safety used in perioperative period, even in the elderly. The choice of drugs and doses can be individualized according to the surgery, opioid pharmacokinetics, comorbidities, and routes of administration.
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Affiliation(s)
- Sebastiano Mercadante
- Main Regional Center for Pain Relief and Supportive/Palliative Care, La Maddalena Cancer Center, Palermo, 90146, Italy.
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7
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Gao S, He Q. Opioids and the kidney: two sides of the same coin. Front Pharmacol 2024; 15:1421248. [PMID: 39135801 PMCID: PMC11317763 DOI: 10.3389/fphar.2024.1421248] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2024] [Accepted: 07/03/2024] [Indexed: 08/15/2024] Open
Abstract
Renal dysfunction, including acute renal failure (ARF) and chronic kidney disease (CKD), continues to present significant health challenges, with renal ischemia-reperfusion injury (IRI) being a pivotal factor in their development and progression. This condition, notably impacting kidney transplantation outcomes, underscores the urgent need for innovative therapeutic interventions. The role of opioid agonists in this context, however, remains a subject of considerable debate. Current reviews tend to offer limited perspectives, focusing predominantly on either the protective or detrimental effects of opioids in isolation. Our review addresses this gap through a thorough and comprehensive evaluation of the existing literature, providing a balanced examination of the dualistic nature of opioids' influence on renal health. We delve into both the nephroprotective and nephrotoxic aspects of opioids, dissecting the complex interactions and paradoxical effects that embody the "two sides of the same coin" phenomenon. This comprehensive analysis is vital for understanding the intricate roles of opioids in renal pathophysiology, potentially informing the development of novel therapeutic strategies for preventing or treating hypoxic kidney injury.
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Affiliation(s)
- Shaowei Gao
- Department of Anesthesiology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
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Sah D, Shoffel-Havakuk H, Tsur N, Uhelski ML, Gottumukkala V, Cata JP. Opioids and Cancer: Current Understanding and Clinical Considerations. Curr Oncol 2024; 31:3086-3098. [PMID: 38920719 PMCID: PMC11203256 DOI: 10.3390/curroncol31060235] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2024] [Revised: 05/23/2024] [Accepted: 05/29/2024] [Indexed: 06/27/2024] Open
Abstract
Pain is one of the most common symptoms in patients with cancer. Pain not only negatively affects the quality of life of patients with cancer, but it has also been associated with reduced survival. Pain management is therefore a critical component of cancer care. Prescription opioids remain the first-line approach for the management of moderate-to-severe pain associated with cancer. However, there has been increasing interest in understanding whether these analgesics could impact cancer progression. Furthermore, epidemiological data link a possible association between prescription opioid usage and cancer development. Until more robust evidence is available, patients with cancer with moderate-to-severe pain may receive opioids to decrease suffering. However, future studies should be conducted to evaluate the role of opioids and opioid receptors in specific cancers.
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Affiliation(s)
- Dhananjay Sah
- Department of Anesthesiology and Perioperative Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; (D.S.); (V.G.)
- Anesthesiology and Surgical Oncology Research Group (ASORG), Houston, TX 77030, USA
| | - Hagit Shoffel-Havakuk
- Department of Otolaryngology-Head and Neck Surgery, Rabin Medical Center, Petach Tiqva 4941492, Israel; (H.S.-H.); (N.T.)
- Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel
| | - Nir Tsur
- Department of Otolaryngology-Head and Neck Surgery, Rabin Medical Center, Petach Tiqva 4941492, Israel; (H.S.-H.); (N.T.)
- Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel
| | - Megan L. Uhelski
- Department of Pain Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA;
| | - Vijaya Gottumukkala
- Department of Anesthesiology and Perioperative Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; (D.S.); (V.G.)
| | - Juan P. Cata
- Department of Anesthesiology and Perioperative Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; (D.S.); (V.G.)
- Anesthesiology and Surgical Oncology Research Group (ASORG), Houston, TX 77030, USA
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9
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Mercadante S. Opioid-induced Neurotoxicity in Patients with Cancer Pain. Curr Treat Options Oncol 2023; 24:1367-1377. [PMID: 37688712 DOI: 10.1007/s11864-023-01117-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/06/2023] [Indexed: 09/11/2023]
Abstract
OPINION STATEMENT Opioid-induced neurotoxicity (OINT) is a neuropsychiatric syndrome observed with opioid therapy. The mechanism of OINT is thought to be multifactorial, and many risk factors may facilitate its development. If symptoms of OINT are seen, the prescriber should consider hydration, discontinuation of the offending opioid drug, or switching of opioid medication, or the use of some adjuvants. Multiple factors like inter- and intraindividual differences in opioid pharmacology may influence the accuracy of dose calculations for opioid switching. Experience and clinical judgment in a specialistic palliative care setting should be used and individual patient characteristics considered when applying any conversion table.
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Affiliation(s)
- Sebastiano Mercadante
- Main Regional Center for Pain Relief & Supportive/Palliative Care, La Maddalena Cancer Center, Via San Lorenzo 312, 90146, Palermo, Italy.
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10
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Stedman M, Heald A, Robinson A, Davies M, Harnett P. Associations and mitigations: an analysis of the changing risk factor landscape for chronic kidney disease in primary care using national general practice level data. BMJ Open 2022; 12:e064723. [PMID: 36549719 PMCID: PMC9791436 DOI: 10.1136/bmjopen-2022-064723] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
OBJECTIVES Early recognition of chronic kidney disease (CKD) should be achieved by every modern healthcare system. The objective of this study was to investigate CKD risk factor trends in England using general practice level data. DESIGN Observational analysis of data at practice level for all general practices in England. Practice characteristics identified as potential CKD risk factors included comorbidities and local demography. Data were analysed using both univariate and multivariate analysis to identify significant factors that were associated with CKD diagnosis for the period 1 April 2019 to 31 March 2020. SETTING Publicly available data from UK primary care sources including Primary Care Quality and Outcomes Framework database, practice-level prescribing data from the British National Formulary and Public Health England health outcome data. PARTICIPANTS All data submitted from 6471 medium to large practices in England were included (over 46 million patients). RISK FACTOR ANALYSIS Potential risk factors were grouped into four classes based on existing literature: demographic factors, comorbidities, service and practice outcome factors, and prescribing data effects. RESULTS The original model's prediction of CKD improved from r2 0.38 to an r2 of 0.66 when updated factors were included. Positive associations included known risk factors with higher relative risk such as hypertension and diabetes, along with less recognised factors such as depression and use of opiates. Negative associations included NSAIDs which are traditionally associated with increased CKD risk, and prescribing of antibiotics, along with more northerly locations. CONCLUSIONS CKD is a preventable disease with high costs and consequences. These data and novel analysis give clearer relative risk values for different patient characteristics with some unexpected findings such as potential harmful association between CKD and opiates, and a more benign association with NSAIDs. A deeper understanding of CKD risk factors is important to update and implement local and national management strategies. Further research is required to establish the causal nature of these associations and to refine location appropriate actions to minimise harm from CKD on regional and local levels.
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Affiliation(s)
| | - Adrian Heald
- University of Manchester, Manchester, UK
- Department of Diabetes and Endocrinology, Salford Royal Hospital, Salford, UK
| | | | | | - Patrick Harnett
- Department of Renal Medicine, Princess Elizabeth Hospital, Saint Andrews, Guernsey
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11
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Perioperative renal protection. Curr Opin Crit Care 2021; 27:676-685. [PMID: 34534999 DOI: 10.1097/mcc.0000000000000881] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
PURPOSE OF REVIEW Acute kidney injury (AKI) is a common but underestimated syndrome in the perioperative setting. AKI can be induced by different causes and is associated with increased morbidity and mortality. Unfortunately, no specific treatment options are available at the moment. RECENT FINDINGS AKI is now understood as being a continuum ranging from normal kidney function over AKI and acute kidney disease to ultimately chronic kidney disease. The KDIGO organization recommend in 2012 implementation of preventive bundles in patients at high risk for AKI. In the perioperative setting, relevant measures include hemodynamic optimization, with careful consideration of blood pressure targets, adequate fluid therapy to maintain organ perfusion and avoidance of hyperglycaemia. These measures are most effective if patients at risk are identified as soon as possible and measures are implemented accordingly. Although current point of care functional biomarkers can detect patients at risk earlier than the established damage biomarkers, some components of the preventive bundle are still under investigation. SUMMARY Good evidence exists for the use of biomarkers to identify individual patients at risk for AKI and for the implementation of haemodynamic optimization, abdication of nephrotoxins, adequate fluid administration using balanced crystalloid solutions and glycaemic control. The data for using colloids or the degree of nephrotoxicity of contrast media still remain inconclusive.
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12
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Keet K, Henry BM, Tubbs RS. Prune-belly syndrome in Africa: An analysis and systematic review of cases, etiology, treatment, and outcomes. JOURNAL OF CLINICAL UROLOGY 2021. [DOI: 10.1177/2051415820903196] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Background: Prune-belly syndrome is a rare congenital disorder characterized by a spectrum of three anomalies: bilateral undescended testes, dilated urinary tract, and anterior abdominal muscle deficiency. Objectives: In developing countries, inadequate access to health care may affect treatment and outcomes of prune-belly syndrome. This study’s goal was to review the anatomical features, etiology, genetics, management, and outcomes of cases in Africa. Methods: PubMed was searched to identify case reports and case studies describing prune-belly syndrome in Africa. Data collected from each study included the number of cases, age at diagnosis, sex, description of the abdominal muscles, testes, and urinary tract, as well as associated anomalies, management, and long-term outcomes. Results: A total of 16 publications that reported 58 cases in African countries were included. The prevalence of female patients (15.5%) was higher than in developed countries (3%). The abdominal muscles were deficient in all cases, and bilateral cryptorchidism was present in nearly all males (96%). Distension of the bladder was common, with normal anatomy reported in only one case. Bilateral hydroureters and hydronephrosis also were present in the majority of cases. Only six cases (10.3%) had no associated anomalies, such as musculoskeletal or cardiovascular. Karyotyping was performed in only three cases (5.2%) because of limited hospital facilities. Six parents (10.3%) declined treatment for their children, 12 cases (20.7%) were managed conservatively, and 25 (43.1%) received surgical intervention. Patients’ mortality rate was higher than in developed countries. Conclusion: Diagnosis and treatment of prune-belly syndrome remains a challenge in Africa, in which multiple factors, such as access to health care and cultural beliefs, affect mortality rates and outcomes. Patient education and support groups may improve compliance with treatment. Level of evidence: Not applicable for this multicenter audit.
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Affiliation(s)
- Kerri Keet
- Division of Clinical Anatomy, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, South Africa
| | - Brandon Michael Henry
- Cardiac Intensive Care Unit, The Heart Institute, Cincinnati Children’s Hospital Medical Center, USA
| | - R Shane Tubbs
- Departments of Neurosurgery and Structural and Cellular Biology, Tulane University School of Medicine, USA
- Department of Anatomical Sciences, St. George’s University, Grenada
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13
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Saadat-Gilani K, Zarbock A. How new biomarkers aid the anesthetist to detect and prevent perioperative acute kidney injury. Curr Opin Anaesthesiol 2021; 34:364-372. [PMID: 33935186 DOI: 10.1097/aco.0000000000000980] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
PURPOSE OF REVIEW Acute kidney injury (AKI) is underestimated but common in the perioperative setting. Although the association of this syndrome with an increased morbidity and mortality has been well established, little progress has been made in the diagnosis or prevention of AKI in recent years. This is partly due to the late detection of AKI by conventional criteria based of functional biomarkers, serum creatinine, and urine output. In addition, conceptually AKI is now recognized as being part of a continuum, in which preventive intervention is time critical. This review will summarize the current best available evidence and explain why timely perioperative management does have impact on the development of AKI and overall outcomes for patients. RECENT FINDINGS Damage biomarkers can reliably identify AKI earlier than conventional functional biomarkers, facilitating more timely preventive intervention. Although the interventions published in the Kidney Disease: Improving Global Outcomes guideline are all important, the most relevant preventive options perioperatively include maintenance of adequate volume status and perfusion pressure, and the focus on balanced crystalloid solutions as maintenance fluid. SUMMARY AKI is a time critical syndrome that requires timely detection and damage biomarkers can help to adjust the perioperative management to prevent further injury.
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Affiliation(s)
- Khaschayar Saadat-Gilani
- Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Münster, Germany
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14
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Davani AB, Snyder SH, Oh ES, Mears SC, Crews DC, Wang NY, Sieber FE. Kidney Function Modifies the Effect of Intraoperative Opioid Dosage on Postoperative Delirium. J Am Geriatr Soc 2021; 69:191-196. [PMID: 33043446 PMCID: PMC11460320 DOI: 10.1111/jgs.16870] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2020] [Revised: 08/31/2020] [Accepted: 09/14/2020] [Indexed: 11/30/2022]
Abstract
BACKGROUND There are few studies demonstrating how kidney function affects the risk of developing delirium in older adult surgical patients administered opioids. This study determined whether baseline kidney function influences the relationship between morphine equivalent dose and the development of delirium on postoperative day (POD) 2 in patients with hip fracture. METHODS This retrospective study analyzed emergency department (ED) estimated glomerular filtration rate (eGFR), perioperative serum creatinine, intravenous morphine equivalents, and POD2 delirium assessment by the Confusion Assessment Method in 652 patients aged 65 years or older without preoperative delirium. ED eGFR was used to divide subjects into groups by presence or absence of chronic kidney disease (CKD), and associations of opioid dose with POD2 delirium were compared using multivariable logistic regression. RESULTS POD2 delirium incidence was 29.8% (N = 194). Intraoperative and postanesthesia care unit (PACU) morphine equivalent dosage as well as ED eGFR were similar comparing patients with and without POD2 delirium. Age, American Society of Anesthesiologists status, and dementia were associated with delirium on POD2. The odds of POD2 delirium increased significantly with increase of intraoperative opioid in patients with CKD (odds ratio = 1.6; 95% confidence interval = 1.2-2.2), but not in patients without CKD (P-interaction = .04). PACU or POD1 opioid doses were not associated with POD2 delirium after covariate adjustment. CONCLUSION This study suggests that incremental increases in intraoperative opioids combined with CKD increase odds of POD2 delirium after hip fracture repair, compared with patients without CKD.
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Affiliation(s)
- Arman B. Davani
- Department of Anesthesiology and Critical Care Medicine, Johns Hopkins Bayview Medical Center, Baltimore, MD, USA
| | - Scott H. Snyder
- Division of Geriatric and Palliative Medicine, Walter Reed National Military Medical Center, Bethesda, MD, USA
| | - Esther S. Oh
- Division of Geriatric Medicine and Gerontology, Psychiatry and Behavioral Sciences and Neuropathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Simon C. Mears
- Department of Orthopedics, University of Arkansas for Medical Sciences College of Medicine, Little Rock, AR, USA
| | - Deidra C. Crews
- Division of Nephrology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Nae-Yuh Wang
- Department of Medicine, Johns Hopkins University School of Medicine; and Departments of Biostatistics and Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
| | - Frederick E. Sieber
- Department of Anesthesiology and Critical Care Medicine, Johns Hopkins Bayview Medical Center, Baltimore, MD, USA
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15
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Dolati S, Tarighat F, Pashazadeh F, Shahsavarinia K, Gholipouri S, Soleimanpour H. The Role of Opioids in Pain Management in Elderly Patients with Chronic Kidney Disease: A Review Article. Anesth Pain Med 2020; 10:e105754. [PMID: 34150565 PMCID: PMC8207885 DOI: 10.5812/aapm.105754] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2020] [Revised: 07/19/2020] [Accepted: 08/20/2020] [Indexed: 12/13/2022] Open
Abstract
Chronic kidney disease (CKD) is a global public health problem. Pain is one of the most generally experienced symptoms by CKD patients. Pain management is a key clinical activity; nonetheless, insufficient pain management by health professionals keeps it up. Opioids as pain relievers are a class of naturally-derived and synthetic medications. They act through interactions with receptors in peripheral nerves. Numerous pharmacokinetic alterations happen with aging that influence drug disposition, metabolism, and quality of life. Acetaminophen alone, or combined with low-potency opioid dose is regarded as the safest pain-relieving choice for CKD. Morphine and codeine are probably eluded in renal impairment patients and used with excessive carefulness. Tramadol, oxycodone, and hydromorphone can be used by patient monitoring, while methadone, transdermal fentanyl, and buprenorphine seem to be safe to use in older non-dialysis patients with renal impairment. Consistent with the available literature, the main aim of this review was to explore the occurrence of chronic pain and its opioid treatment in CKD patients. According to this review, more and well-made randomized controlled trials are necessary to find appropriate opioid doses and explore the occurrence of side effects.
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Affiliation(s)
- Sanam Dolati
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
- Physical Medicine and Rehabilitation Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Faezeh Tarighat
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Fariba Pashazadeh
- Research Center for Evidence-Based Medicine, Health Management and Safety Promotion Research Institute, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Kavous Shahsavarinia
- Emergency Medicine Research Team, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Saina Gholipouri
- Department of Medical Sciences, University of Western Ontario, Ontario, Canada
| | - Hassan Soleimanpour
- Aging Research Institute, Tabriz University of Medical Sciences, Tabriz, Iran
- Corresponding Author: Aging Research Institute, Tabriz University of Medical Sciences, Tabriz, Iran. ,
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16
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Golosova D, Palygin O, Bohovyk R, Klemens CA, Levchenko V, Spires DR, Isaeva E, El-Meanawy A, Staruschenko A. Role of opioid signaling in kidney damage during the development of salt-induced hypertension. Life Sci Alliance 2020; 3:3/12/e202000853. [PMID: 33046522 PMCID: PMC7556751 DOI: 10.26508/lsa.202000853] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2020] [Revised: 10/01/2020] [Accepted: 10/02/2020] [Indexed: 02/06/2023] Open
Abstract
Stimulation of kappa opioid receptors modulates calcium influx via TRPC6 channels in podocytes, which ultimately compromises the integrity of the glomerular filtration barrier and promotes a marked worsening of blood pressure control and renal damage. Opioid use is associated with predictors of poor cardiorenal outcomes. However, little is known about the direct impact of opioids on podocytes and renal function, especially in the context of hypertension and CKD. We hypothesize that stimulation of opioid receptors (ORs) contributes to dysregulation of intracellular calcium ([Ca2+]i) homeostasis in podocytes, thus aggravating the development of renal damage in hypertensive conditions. Herein, freshly isolated glomeruli from Dahl salt-sensitive (SS) rats and human kidneys, as well as immortalized human podocytes, were used to elucidate the contribution of specific ORs to calcium influx. Stimulation of κ-ORs, but not μ-ORs or δ-ORs, evoked a [Ca2+]i transient in podocytes, potentially through the activation of TRPC6 channels. κ-OR agonist BRL52537 was used to assess the long-term effect in SS rats fed a high-salt diet. Hypertensive rats chronically treated with BRL52537 exhibited [Ca2+]i overload in podocytes, nephrinuria, albuminuria, changes in electrolyte balance, and augmented blood pressure. These data demonstrate that the κ-OR/TRPC6 signaling directly influences podocyte calcium handling, provoking the development of kidney injury in the opioid-treated hypertensive cohort.
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Affiliation(s)
- Daria Golosova
- Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Oleg Palygin
- Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, USA.,Cardiovascular Center, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Ruslan Bohovyk
- Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, USA
| | | | | | - Denisha R Spires
- Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Elena Isaeva
- Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Ashraf El-Meanawy
- Cardiovascular Center, Medical College of Wisconsin, Milwaukee, WI, USA.,Division of Nephrology, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Alexander Staruschenko
- Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, USA .,Cardiovascular Center, Medical College of Wisconsin, Milwaukee, WI, USA.,Clement J. Zablocki VA Medical Center, Milwaukee, WI, USA
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17
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Coluzzi F, Caputi FF, Billeci D, Pastore AL, Candeletti S, Rocco M, Romualdi P. Safe Use of Opioids in Chronic Kidney Disease and Hemodialysis Patients: Tips and Tricks for Non-Pain Specialists. Ther Clin Risk Manag 2020; 16:821-837. [PMID: 32982255 PMCID: PMC7490082 DOI: 10.2147/tcrm.s262843] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2020] [Accepted: 07/10/2020] [Indexed: 12/11/2022] Open
Abstract
In patients suffering from moderate-to-severe chronic kidney disease (CKD) or end-stage renal disease (ESRD), subjected to hemodialysis (HD), pain is very common, but often underestimated. Opioids are still the mainstay of severe chronic pain management; however, their prescription in CKD and HD patients is still significantly low and pain is often under-treated. Altered pharmacokinetics and the lack of clinical trials on the use of opioids in patients with renal impairment increase physicians' concerns in this specific population. This narrative review focused on the correct and safe use of opioids in patients with CKD and HD. Morphine and codeine are not recommended, because the accumulation of their metabolites may cause neurotoxic symptoms. Oxycodone and hydromorphone can be safely used, but adequate dosage adjustments are required in CKD. In dialyzed patients, these opioids should be considered as second-line agents and patients should be carefully monitored. According to different studies, buprenorphine and fentanyl could be considered first-line opioids in the management of pain in CKD; however, fentanyl is not appropriate in patients undergoing HD. Tapentadol does not need dosage adjustment in mild-to-moderate renal impairment conditions; however, no data are available on its use in ESRD. Opioid-related side effects may be exacerbated by common comorbidities in CKD patients. Opioid-induced constipation can be managed with peripherally-acting-μ-opioid-receptor-antagonists (PAMORA). Unlike the other PAMORA, naldemedine does not require any dose adjustment in CKD and HD patients. Accurate pain diagnosis, opioid titration and tailoring are mandatory to minimize the risks and to improve the outcome of the analgesic therapy.
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Affiliation(s)
- Flaminia Coluzzi
- Department of Medical and Surgical Sciences and Biotechnologies, Sapienza University of Rome, Polo Pontino, Latina, Italy
- Unit of Anesthesia, Intensive Care and Pain Medicine, Sant’Andrea University Hospital, Rome, Italy
| | | | - Domenico Billeci
- Division of Neurosurgery, Ca’Foncello Hospital, ASL Marca Trevigiana, University of Padova, Treviso, Italy
| | - Antonio Luigi Pastore
- Department of Medical and Surgical Sciences and Biotechnologies, Sapienza University of Rome, Polo Pontino, Latina, Italy
- Unit of Urology, Sapienza c/o I.C.O.T, Polo Pontino, Latina, Italy
| | - Sanzio Candeletti
- Department of Pharmacy and Biotechnology, Alma Mater Studiorum University, Bologna, Italy
| | - Monica Rocco
- Unit of Anesthesia, Intensive Care and Pain Medicine, Sant’Andrea University Hospital, Rome, Italy
- Department of Clinical and Surgical Translational Medicine, Sapienza University of Rome, Rome, Italy
| | - Patrizia Romualdi
- Department of Pharmacy and Biotechnology, Alma Mater Studiorum University, Bologna, Italy
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18
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Barbosa J, Faria J, Garcez F, Leal S, Afonso LP, Nascimento AV, Moreira R, Queirós O, Carvalho F, Dinis-Oliveira RJ. Repeated Administration of Clinical Doses of Tramadol and Tapentadol Causes Hepato- and Nephrotoxic Effects in Wistar Rats. Pharmaceuticals (Basel) 2020; 13:149. [PMID: 32664348 PMCID: PMC7407499 DOI: 10.3390/ph13070149] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2020] [Revised: 07/07/2020] [Accepted: 07/08/2020] [Indexed: 12/18/2022] Open
Abstract
Tramadol and tapentadol are fully synthetic and extensively used analgesic opioids, presenting enhanced therapeutic and safety profiles as compared with their peers. However, reports of adverse reactions, intoxications and fatalities have been increasing. Information regarding the molecular, biochemical, and histological alterations underlying their toxicological potential is missing, particularly for tapentadol, owing to its more recent market authorization. Considering the paramount importance of liver and kidney for the metabolism and excretion of both opioids, these organs are especially susceptible to toxicological damage. In the present study, we aimed to characterize the putative hepatic and renal deleterious effects of repeated exposure to therapeutic doses of tramadol and tapentadol, using an in vivo animal model. Male Wistar rats were randomly divided into six experimental groups, composed of six animals each, which received daily single intraperitoneal injections of 10, 25 or 50 mg/kg tramadol or tapentadol (a low, standard analgesic dose, an intermediate dose and the maximum recommended daily dose, respectively). An additional control group was injected with normal saline. Following 14 consecutive days of administration, serum, urine and liver and kidney tissue samples were processed for biochemical, metabolic and histological analysis. Repeated administration of therapeutic doses of both opioids led to: (i) increased lipid and protein oxidation in liver and kidney, as well as to decreased total liver antioxidant capacity; (ii) decreased serum albumin, urea, butyrylcholinesterase and complement C3 and C4 levels, denoting liver synthesis impairment; (iii) elevated serum activity of liver enzymes, such as alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and γ-glutamyl transpeptidase, as well as lipid profile alterations, also reflecting hepatobiliary commitment; (iv) derangement of iron metabolism, as shown through increases in serum iron, ferritin, haptoglobin and heme oxygenase-1 levels. In turn, elevated serum cystatin C, decreased urine creatinine output and increased urine microalbumin levels were detected upon exposure to tapentadol only, while increased serum amylase and urine N-acetyl-β-D-glucosaminidase activities were observed for both opioids. Collectively, these results are compatible with kidney injury. Changes were also found in the expression levels of liver- and kidney-specific toxicity biomarker genes, upon exposure to tramadol and tapentadol, correlating well with alterations in lipid profile, iron metabolism and glomerular and tubular function. Histopathological analysis evidenced sinusoidal dilatation, microsteatosis, mononuclear cell infiltrates, glomerular and tubular disorganization, and increased Bowman's spaces. Although some findings are more pronounced upon tapentadol exposure, our study shows that, when compared with acute exposure, prolonged administration of both opioids smooths the differences between their toxicological effects, and that these occur at lower doses within the therapeutic range.
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Affiliation(s)
- Joana Barbosa
- IINFACTS—Institute of Research and Advanced Training in Health Sciences and Technologies, Department of Sciences, University Institute of Health Sciences (IUCS), CESPU, CRL, 4585-116 Gandra, Portugal; (J.F.); (F.G.); (S.L.); (A.V.N.); (R.M.); (O.Q.)
- UCIBIO, REQUIMTE—Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal;
- Department of Public Health and Forensic Sciences, and Medical Education, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal
| | - Juliana Faria
- IINFACTS—Institute of Research and Advanced Training in Health Sciences and Technologies, Department of Sciences, University Institute of Health Sciences (IUCS), CESPU, CRL, 4585-116 Gandra, Portugal; (J.F.); (F.G.); (S.L.); (A.V.N.); (R.M.); (O.Q.)
- UCIBIO, REQUIMTE—Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal;
| | - Fernanda Garcez
- IINFACTS—Institute of Research and Advanced Training in Health Sciences and Technologies, Department of Sciences, University Institute of Health Sciences (IUCS), CESPU, CRL, 4585-116 Gandra, Portugal; (J.F.); (F.G.); (S.L.); (A.V.N.); (R.M.); (O.Q.)
| | - Sandra Leal
- IINFACTS—Institute of Research and Advanced Training in Health Sciences and Technologies, Department of Sciences, University Institute of Health Sciences (IUCS), CESPU, CRL, 4585-116 Gandra, Portugal; (J.F.); (F.G.); (S.L.); (A.V.N.); (R.M.); (O.Q.)
- Department of Biomedicine, Unit of Anatomy, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal
- CINTESIS—Center for Health Technology and Services Research, Faculty of Medicine, University of Porto, 4200-450 Porto, Portugal
| | - Luís Pedro Afonso
- Department of Pathology, Portuguese Institute of Oncology of Porto, 4200-072 Porto, Portugal;
| | - Ana Vanessa Nascimento
- IINFACTS—Institute of Research and Advanced Training in Health Sciences and Technologies, Department of Sciences, University Institute of Health Sciences (IUCS), CESPU, CRL, 4585-116 Gandra, Portugal; (J.F.); (F.G.); (S.L.); (A.V.N.); (R.M.); (O.Q.)
| | - Roxana Moreira
- IINFACTS—Institute of Research and Advanced Training in Health Sciences and Technologies, Department of Sciences, University Institute of Health Sciences (IUCS), CESPU, CRL, 4585-116 Gandra, Portugal; (J.F.); (F.G.); (S.L.); (A.V.N.); (R.M.); (O.Q.)
| | - Odília Queirós
- IINFACTS—Institute of Research and Advanced Training in Health Sciences and Technologies, Department of Sciences, University Institute of Health Sciences (IUCS), CESPU, CRL, 4585-116 Gandra, Portugal; (J.F.); (F.G.); (S.L.); (A.V.N.); (R.M.); (O.Q.)
| | - Félix Carvalho
- UCIBIO, REQUIMTE—Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal;
| | - Ricardo Jorge Dinis-Oliveira
- IINFACTS—Institute of Research and Advanced Training in Health Sciences and Technologies, Department of Sciences, University Institute of Health Sciences (IUCS), CESPU, CRL, 4585-116 Gandra, Portugal; (J.F.); (F.G.); (S.L.); (A.V.N.); (R.M.); (O.Q.)
- UCIBIO, REQUIMTE—Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal;
- Department of Public Health and Forensic Sciences, and Medical Education, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal
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Salahshoor MR, Jalili C, Rashidi I, Roshankhah S, Jalili F. Protective Effect of Genistein on the Morphine-Induced Kidney Disorders in Male Mice. ELECTRONIC JOURNAL OF GENERAL MEDICINE 2020. [DOI: 10.29333/ejgm/7874] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
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20
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Brust TF. Biased Ligands at the Kappa Opioid Receptor: Fine-Tuning Receptor Pharmacology. Handb Exp Pharmacol 2020; 271:115-135. [PMID: 33140224 DOI: 10.1007/164_2020_395] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
The kappa opioid receptor (KOR) is a G protein-coupled receptor (GPCR) that can signal through multiple signaling pathways. KOR agonists are known to relieve pain and itch, as well as induce dysphoria, sedation, hallucinations, and diuresis. As is the case with many other GPCRs, specific signaling pathways downstream of the KOR have been linked to certain physiological responses induced by the receptor. Those studies motivated the search and discovery of a number of KOR ligands that preferentially activate one signaling pathway over another. Such compounds are termed functionally selective or biased ligands, and may present a way of inducing desired receptor effects with reduced adverse reactions. In this chapter, I review the molecular intricacies of KOR signaling and discuss the studies that have used biased signaling through the KOR as a way to selectively modulate in vivo physiology.
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Affiliation(s)
- Tarsis F Brust
- Department of Pharmaceutical Sciences, Lloyd L. Gregory School of Pharmacy, Palm Beach Atlantic University, West Palm Beach, FL, USA.
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21
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Ramanjulu R, Thota RS, Ahmed A, Jain P, Bhatnagar S, Salins N, Chatterjee A, Bhattacharya D. Indian Society for Study of Pain, Cancer Pain Special Interest Group Guidelines on Pharmacological Management of Cancer Pain (Part III). Indian J Palliat Care 2020; 26:191-197. [PMID: 32874032 PMCID: PMC7444570 DOI: 10.4103/0973-1075.285694] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
The Indian Society for Study of Pain (ISSP), Cancer Pain Special Interest Group, guidelines on pharmacological management of cancer pain in adults provide a structured, step-wise approach which will help to improve the management of cancer pain and to provide patients with a minimally acceptable quality of life. The guidelines have been developed based on the available literature and evidence, to suit the needs, patient population, and situations in India. A questionnaire based on the key elements of each sub draft addressing certain inconclusive areas where evidence was lacking, was made available on the ISSP website and circulated by E-mail to all the ISSP and Indian Association of Palliative Care members. Antidepressants and/or anticonvulsants should be used to treat neuropathic cancer pain and the dose should be titrated according to the clinical response and side effects. External beam radiotherapy should be offered to all patients with painful metastatic bone pain. There is evidence on the use of ketamine in cancer neuropathic pain, but with no beneficial effect, thus it is not recommended.
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Affiliation(s)
- Raghavendra Ramanjulu
- Department of Pain and Palliative Care, Cytecare Hospital, Bengaluru, Karnataka, India
| | - Raghu S Thota
- Department of Anaesthesiology, Critical Care and Pain, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Arif Ahmed
- Department of Anaesthesia, Critical Care and Pain Management, CK Birla Hospital for Women, Gurugram, Haryana, India
| | - Parmanand Jain
- Department of Anaesthesiology, Critical Care and Pain, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Sushma Bhatnagar
- Department of Onco-Anaesthesia and Palliative Medicine, Dr. B. R. A. Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India
| | - Naveen Salins
- Department of Palliative Medicine and Supportive Care, Manipal Comprehensive Cancer Care Centre, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, Karnataka, India
| | - Aparna Chatterjee
- Department of Anaesthesiology, Critical Care and Pain, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Dipasri Bhattacharya
- Department of Anaesthesiology, Critical Care and Pain, R. G. Kar Medical College, Kolkata, West Bengal, India
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22
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Evidence for nonlinear accumulation of the ultrapotent fentanyl analog, carfentanil, after systemic administration to male rats. Neuropharmacology 2019; 158:107596. [PMID: 30965021 DOI: 10.1016/j.neuropharm.2019.04.002] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2019] [Revised: 04/03/2019] [Accepted: 04/03/2019] [Indexed: 11/21/2022]
Abstract
The current opioid overdose crisis is being exacerbated by illicitly manufactured fentanyl and its analogs. Carfentanil is a fentanyl analog that is 10,000-times more potent than morphine, but limited information is available about its pharmacology. The present study had two aims: 1) to validate a method for quantifying carfentanil and its metabolite norcarfentanil in small-volume samples, and 2) to use the method for examining pharmacodynamic-pharmacokinetic relationships in rats. The analytical method involved liquid-liquid extraction of plasma samples followed by quantitation of carfentanil and norcarfentanil using ultra-high-performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS). The method was validated following SWGTOX guidelines, and both analytes displayed limits of detection and quantification at 7.5 and 15 pg/mL, respectively. Male Sprague-Dawley rats fitted with jugular catheters and temperature transponders received subcutaneous carfentanil (1, 3 and 10 μg/kg) or saline. Repeated blood specimens were obtained over 8 h, along with pharmacodynamic measures including core temperature and catalepsy scores. Carfentanil produced dose-related hypothermia and catalepsy that lasted up to 8 h. Carfentanil Cmax occurred at 15 min whereas metabolite Cmax was at 1-2 h. Concentrations of both analytes increased in a dose-related fashion, but area-under-the-curve values were much greater than predicted after 10 μg/kg. Plasma half-life for carfentanil increased at higher doses. Our findings reveal that carfentanil produces marked hypothermia and catalepsy, which is accompanied by nonlinear accumulation of the drug at high doses. We hypothesize that impaired clearance of carfentanil in humans could contribute to life-threatening effects of this ultrapotent opioid agonist. This article is part of the Special Issue entitled 'New Vistas in Opioid Pharmacology'.
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23
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Sukcharoen K, Jeffery Z, Ratcliffe L, Miller J, Mulgrew C. Prescribing analgesia for patients with impaired renal function. Br J Hosp Med (Lond) 2018; 79:C74-C77. [PMID: 29727243 DOI: 10.12968/hmed.2018.79.5.c74] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Affiliation(s)
- Kittiya Sukcharoen
- Academic Clinical Fellow and Specialty Training Registrar in Renal Medicine, Department of Renal Medicine, Royal Devon and Exeter NHS Foundation Trust, Exeter EX2 5DW
| | - Zachary Jeffery
- ST3 in Anaesthetics, Department of Anaesthetics, Musgrove Park Hospital, Taunton
| | - Laura Ratcliffe
- Specialty Registrar, Department of Renal Medicine, Royal Devon and Exeter NHS Foundation Trust, Exeter
| | - Jessica Miller
- Renal Pharmacist, Department of Renal Medicine, Royal Devon and Exeter NHS Foundation Trust, Exeter
| | - Christopher Mulgrew
- Consultant, Department of Renal Medicine, Royal Devon and Exeter NHS Foundation Trust, Exeter
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24
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Assessing the Impact of Renal Function on Trajectory of Intravenous Patient-controlled Analgesic Demands Over Time After Open and Laparoscopic Colorectal Surgery Using Latent Curve Analysis. Clin J Pain 2017; 32:695-701. [PMID: 26626292 DOI: 10.1097/ajp.0000000000000321] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
OBJECTIVES Intravenous patient-controlled analgesia (IVPCA) is often used to relieve pain after colorectal surgery. This study aimed to model the trajectory of analgesic demand over time after colorectal cancer surgery and explore potentially relevant influential factors using latent curve analysis, focusing on laparoscopic-assisted surgery and renal function. MATERIALS AND METHODS Patients receiving colorectal surgery with postoperative IVPCA were randomly divided into 2 equal parts to enable model construction and cross validation. Archived data were retrieved from the IVPCA pump. Latent curve modeling with 2 latent variables that reflected the baseline and slope of IVPCA demand trajectory over time was used and the effects of potentially influential factors on the 2 latent variables were evaluated. Goodness-of-fit indices were used to assess the model fit to both the model construction and validation data sets. RESULTS Data were collected from 834 patients, of whom 112 had laparoscopic-assisted surgery. Latent curve analysis revealed that body weight increased the baseline analgesic demand over time, whereas increasing age, female sex, poor renal function, and laparoscopic-assisted surgery decrease it. By contrast, only age and weight exerted significant effects on the slope parameter to modify the trajectory of IVPCA demand. Patients with higher age or less weight tended to have a smoother decreasing trajectory of analgesic demands over time. There was good cross validation, as the parameter estimates derived from the model construction data set fitted well to the validation data set (root mean square error of approximation: 0.05). CONCLUSION Laparoscopic-assisted surgery and renal function affected the baseline trajectory of IVPCA demand over time, but had no significant effect on its shape.
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25
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Raina R, Krishnappa V, Gupta M. Management of pain in end-stage renal disease patients: Short review. Hemodial Int 2017; 22:290-296. [DOI: 10.1111/hdi.12622] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2017] [Revised: 10/02/2017] [Indexed: 11/28/2022]
Affiliation(s)
- Rupesh Raina
- Department of Nephrology; Cleveland Clinic Akron General/Akron Nephrology Associates; Akron Ohio USA
| | - Vinod Krishnappa
- Department of Nephrology; Cleveland Clinic Akron General/Akron Nephrology Associates; Akron Ohio USA
| | - Mona Gupta
- Department of Hospice and Palliative Medicine; University Hospitals Cleveland Medical Center; Cleveland Ohio USA
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26
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Ahn JS, Lin J, Ogawa S, Yuan C, O'Brien T, Le BH, Bothwell AM, Moon H, Hadjiat Y, Ganapathi A. Transdermal buprenorphine and fentanyl patches in cancer pain: a network systematic review. J Pain Res 2017; 10:1963-1972. [PMID: 28860851 PMCID: PMC5571859 DOI: 10.2147/jpr.s140320] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Treatment of cancer pain is generally based on the three-step World Health Organization (WHO) pain relief ladder, which utilizes a sequential approach with drugs of increasing potency. Goals of pain management include optimization of analgesia, optimization of activities of daily living, minimization of adverse effects, and avoidance of aberrant drug taking. In addition, it is recommended that analgesic regimens are individualized and simplified to help ensure patient compliance and should provide the least invasive, easiest, and safest route of opioid administration to ensure adequate analgesia. Buprenorphine and fentanyl are two opioids available for the relief of moderate-to-severe cancer pain. Available clinical data regarding the transdermal (TD) formulations of these opioids and the extent to which they fulfill the recommendations mentioned earlier are systematically reviewed, with the aim of providing additional information for oncologists and pain specialists regarding their comparative use. Due to lack of studies directly comparing TD buprenorphine with TD fentanyl, data comparing these with other step-3 opioids are also evaluated in a network fashion.
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Affiliation(s)
- Jin Seok Ahn
- Division of Hematology and Oncology, Samsung Medical Center, Sungkyunkwan University, Seoul, South Korea
| | - Johnson Lin
- Division of Hematology and Oncology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan, Republic of China
| | - Setsuro Ogawa
- Department of Anesthesiology, Nihon University School of Medicine, Tokyo, Japan
| | - Chen Yuan
- Department of Oncology, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, People's Republic of China
| | - Tony O'Brien
- Marymount University Hospital and Hospice.,Cork University Hospital, College of Medicine and Health, University College Cork, Cork, Ireland
| | - Brian Hc Le
- Department of Palliative Care, Royal Melbourne Hospital, Parkville, VIC, Australia
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27
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Barbosa J, Faria J, Leal S, Afonso LP, Lobo J, Queirós O, Moreira R, Carvalho F, Dinis-Oliveira RJ. Acute administration of tramadol and tapentadol at effective analgesic and maximum tolerated doses causes hepato- and nephrotoxic effects in Wistar rats. Toxicology 2017; 389:118-129. [PMID: 28689766 DOI: 10.1016/j.tox.2017.07.001] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2017] [Revised: 06/21/2017] [Accepted: 07/04/2017] [Indexed: 01/12/2023]
Abstract
Tramadol and tapentadol are two atypical synthetic opioid analgesics, with monoamine reuptake inhibition properties. Mainly aimed at the treatment of moderate to severe pain, these drugs are extensively prescribed for multiple clinical applications. Along with the increase in their use, there has been an increment in their abuse, and consequently in the reported number of adverse reactions and intoxications. However, little is known about their mechanisms of toxicity. In this study, we have analyzed the in vivo toxicological effects in liver and kidney resulting from an acute exposure of a rodent animal model to both opioids. Male Wistar rats were intraperitoneally administered with 10, 25 and 50mg/kg tramadol and tapentadol, corresponding to a low, effective analgesic dose, an intermediate dose and the maximum recommended daily dose, respectively, for 24h. Toxicological effects were assessed in terms of oxidative stress, biochemical and metabolic parameters and histopathology, using serum and urine samples, liver and kidney homogenates and tissue specimens. The acute exposure to tapentadol caused a dose-dependent increase in protein oxidation in liver and kidney. Additionally, exposure to both opioids led to hepatic commitment, as shown by increased serum lipid levels, decreased urea concentration, increased alanine aminotransferase and decreased butyrylcholinesterase activities. It also led to renal impairment, as reflected by proteinuria and decreased glomerular filtration rate. Histopathological findings included sinusoidal dilatation, microsteatosis, vacuolization, cell infiltrates and cell degeneration, indicating metabolic changes, inflammation and cell damage. In conclusion, a single effective analgesic dose or the maximum recommended daily dose of both opioids leads to hepatotoxicity and nephrotoxicity, with tapentadol inducing comparatively more toxicity. Whether these effects reflect risks during the therapeutic use or human overdoses requires focused attention by the medical community.
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Affiliation(s)
- Joana Barbosa
- IINFACTS - Institute of Research and Advanced Training in Health Sciences and Technologies, Department of Sciences, University Institute of Health Sciences (IUCS), CESPU, CRL, Gandra, Portugal; UCIBIO, REQUIMTE - Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal; Department of Public Health and Forensic Sciences, and Medical Education, Faculty of Medicine, University of Porto, Porto, Portugal.
| | - Juliana Faria
- IINFACTS - Institute of Research and Advanced Training in Health Sciences and Technologies, Department of Sciences, University Institute of Health Sciences (IUCS), CESPU, CRL, Gandra, Portugal; UCIBIO, REQUIMTE - Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal; Department of Public Health and Forensic Sciences, and Medical Education, Faculty of Medicine, University of Porto, Porto, Portugal
| | - Sandra Leal
- IINFACTS - Institute of Research and Advanced Training in Health Sciences and Technologies, Department of Sciences, University Institute of Health Sciences (IUCS), CESPU, CRL, Gandra, Portugal; Department of Biomedicine, Unit of Anatomy, Faculty of Medicine, University of Porto, Porto, Portugal; CINTESIS - Center for Health Technology and Services Research, Faculty of Medicine, University of Porto, Porto, Portugal
| | - Luís Pedro Afonso
- Department of Pathology, Portuguese Institute of Oncology of Porto, Porto, Portugal
| | - João Lobo
- Department of Pathology, Portuguese Institute of Oncology of Porto, Porto, Portugal
| | - Odília Queirós
- IINFACTS - Institute of Research and Advanced Training in Health Sciences and Technologies, Department of Sciences, University Institute of Health Sciences (IUCS), CESPU, CRL, Gandra, Portugal; CBMA - Center for Molecular Biology and Environment, Department of Biology, University of Minho, Braga, Portugal
| | - Roxana Moreira
- IINFACTS - Institute of Research and Advanced Training in Health Sciences and Technologies, Department of Sciences, University Institute of Health Sciences (IUCS), CESPU, CRL, Gandra, Portugal; CBMA - Center for Molecular Biology and Environment, Department of Biology, University of Minho, Braga, Portugal
| | - Félix Carvalho
- UCIBIO, REQUIMTE - Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal
| | - Ricardo Jorge Dinis-Oliveira
- IINFACTS - Institute of Research and Advanced Training in Health Sciences and Technologies, Department of Sciences, University Institute of Health Sciences (IUCS), CESPU, CRL, Gandra, Portugal; UCIBIO, REQUIMTE - Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal; Department of Public Health and Forensic Sciences, and Medical Education, Faculty of Medicine, University of Porto, Porto, Portugal.
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Abstract
Patients with chronic pain often develop dysphagia during the course of an advanced disease such as cancer. Opioids are the cornerstone of the management of cancer pain and are commonly administered orally. However, the oral route does not suit patients with dysphagia, who require alternative methods to administer analgesic drugs. Opioids given by parenteral or transdermal routes provide adequate pain control, being at least as efficacious as the oral route, but knowledge and experience in conversion ratios are mandatory when using these routes of administration. For breakthrough pain, transmucosal fentanyl preparations should be the preferred option and these can be given as needed due to the route of absorption. In addition, a new class of opioid formulations has been developed for use in dysphagic patients that are administered via nasogastric or enteral tubes while maintaining their sustained-release properties.
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Affiliation(s)
- Sebastiano Mercadante
- Pain Relief and Supportive/Palliative Care, La Maddalena Cancer Center, Via San Lorenzo 312, 90146, Palermo, Italy.
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Alinejad S, Ghaemi K, Abdollahi M, Mehrpour O. Nephrotoxicity of methadone: a systematic review. SPRINGERPLUS 2016; 5:2087. [PMID: 28018795 PMCID: PMC5148752 DOI: 10.1186/s40064-016-3757-1] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/17/2016] [Accepted: 11/29/2016] [Indexed: 12/18/2022]
Abstract
Background Methadone is commonly administered for chronic pain relief and treatment of opioid dependence. Concurrent with its increased consumption, toxicities and fatalities have increased. One of the adverse effects of opioid analgesics, including methadone, is that of nephrotoxicity. Opioids can have an effect on renal function through several different mechanisms. Methods We searched common bibliographical databases for the terms methadone, toxicity, poisoning, kidney, renal, and nephrotoxicity and summarize our findings in this review. Results Methadone can have both direct and indirect effects on the kidney. These effects include rhabdomyolysis (leading to acute kidney injury), volumetric changes, renal lipidosis and amyloidosis, kidney growth during pregnancy, and kidney transplant rejection. Conclusion Improved understanding of the effects of methadone on kidney function can promote safer and more confident use of the drug.
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Affiliation(s)
- Samira Alinejad
- Medical Toxicology and Drug Abuse Research Center (MTDRC), Birjand University of Medical Sciences, Moallem Avenue, Birjand, 9713643138 Iran
| | - Kazem Ghaemi
- Atherosclerosis and Coronary Artery Research Centre, Birjand University of Medical Sciences, Birjand, Iran ; Department of Neurosurgery, Birjand University of Medical Science, Birjand, Iran
| | - Mohammad Abdollahi
- Toxicology and Diseases Group, Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Omid Mehrpour
- Medical Toxicology and Drug Abuse Research Center (MTDRC), Birjand University of Medical Sciences, Moallem Avenue, Birjand, 9713643138 Iran
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30
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Samolsky Dekel BG, Donati G, Vasarri A, Croci Chiocchini AL, Gori A, Cavallari G, Di Nino G, Mercolini L, Protti M, Mandrioli R, Melotti RM, La Manna G. Dialyzability of Oxycodone and Its Metabolites in Chronic Noncancer Pain Patients with End-Stage Renal Disease. Pain Pract 2016; 17:604-615. [PMID: 27589376 DOI: 10.1111/papr.12483] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2016] [Revised: 05/21/2016] [Accepted: 06/03/2016] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Opioids are the preferred analgesic drugs to treat severe chronic pain conditions among dialysis patients; however, knowledge about their dialyzability features is limited. Oxycodone is increasingly used for the treatment of chronic pain conditions as oral controlled release (CR) tablets; however, evidence about this drug and its metabolites' dialyzability is lacking. METHODS We assessed, during 4-hour dialysis sessions, the effect of standard hemodialysis (HD) and online hemodiafiltration (HDF) methods on the plasma concentration of oxycodone and its metabolites in n = 20 chronic pain patients with end-stage renal disease who were stably treated with oral CR oxycodone. Chromatographic techniques were used to evaluate the studied compounds' plasma concentrations at three different time points during dialysis. RESULTS Mean plasma concentrations of oxycodone and noroxycodone in the sample showed an overall reduction trend over time, but it was less enhanced for noroxycodone. Mean reduction in oxycodone and noroxycodone arterial concentrations was significant and higher with HDF (54% and 27%, respectively) than with HD (22% and 17%, respectively). Analysis of the regression of these compounds' clearance on their increasing arterial concentration showed a more stable and linear clearance prediction with HDF (roughly 85 mL/min); with HD, for increasing arterial concentration, clearance of oxycodone decreased while noroxycodone clearance increased. DISCUSSION While no oxymorphone or noroxymorphone metabolites were detected, limited dialyzability of oxycodone and noroxycodone was documented along with insignificant postdialysis pain increment. This evidence will contribute toward considerations as to the safety of the use of oxycodone in dialysis patients in the future.
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Affiliation(s)
- Boaz Gedaliahu Samolsky Dekel
- Department of Medicine and Surgery Sciences, University of Bologna, Bologna, Italy.,Anesthesiology and Intensive Care Unit, University of Bologna's Teaching Hospital, Azienda Ospedaliera-Universitaria di Bologna Policlinico S. Orsola-Malpighi, Bologna, Italy.,Post Graduate School of Anaesthesia and Intensive Care, University of Bologna, Bologna, Italy
| | - Gabriele Donati
- Nephrology, Dialysis and Renal Transplant Unit, University of Bologna's Teaching Hospital, Azienda Ospedaliera-Universitaria di Bologna Policlinico S. Orsola-Malpighi, Bologna, Italy.,Post Graduate School of Nephrology, University of Bologna, Bologna, Italy
| | - Alessio Vasarri
- Anesthesiology and Intensive Care Unit, University of Bologna's Teaching Hospital, Azienda Ospedaliera-Universitaria di Bologna Policlinico S. Orsola-Malpighi, Bologna, Italy.,Post Graduate School of Anaesthesia and Intensive Care, University of Bologna, Bologna, Italy
| | - Anna Laura Croci Chiocchini
- Nephrology, Dialysis and Renal Transplant Unit, University of Bologna's Teaching Hospital, Azienda Ospedaliera-Universitaria di Bologna Policlinico S. Orsola-Malpighi, Bologna, Italy.,Post Graduate School of Nephrology, University of Bologna, Bologna, Italy
| | - Alberto Gori
- Anesthesiology and Intensive Care Unit, University of Bologna's Teaching Hospital, Azienda Ospedaliera-Universitaria di Bologna Policlinico S. Orsola-Malpighi, Bologna, Italy.,Post Graduate School of Anaesthesia and Intensive Care, University of Bologna, Bologna, Italy
| | - Giuseppe Cavallari
- Nephrology, Dialysis and Renal Transplant Unit, University of Bologna's Teaching Hospital, Azienda Ospedaliera-Universitaria di Bologna Policlinico S. Orsola-Malpighi, Bologna, Italy.,Post Graduate School of Nephrology, University of Bologna, Bologna, Italy
| | - Gianfranco Di Nino
- Department of Medicine and Surgery Sciences, University of Bologna, Bologna, Italy.,Anesthesiology and Intensive Care Unit, University of Bologna's Teaching Hospital, Azienda Ospedaliera-Universitaria di Bologna Policlinico S. Orsola-Malpighi, Bologna, Italy.,Post Graduate School of Anaesthesia and Intensive Care, University of Bologna, Bologna, Italy
| | - Laura Mercolini
- Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy
| | - Michele Protti
- Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy
| | - Roberto Mandrioli
- Department for Life Quality Studies, University of Bologna, Rimini, Italy
| | - Rita Maria Melotti
- Department of Medicine and Surgery Sciences, University of Bologna, Bologna, Italy.,Anesthesiology and Intensive Care Unit, University of Bologna's Teaching Hospital, Azienda Ospedaliera-Universitaria di Bologna Policlinico S. Orsola-Malpighi, Bologna, Italy.,Post Graduate School of Anaesthesia and Intensive Care, University of Bologna, Bologna, Italy
| | - Gaetano La Manna
- Department of Medicine and Surgery Sciences, University of Bologna, Bologna, Italy.,Nephrology, Dialysis and Renal Transplant Unit, University of Bologna's Teaching Hospital, Azienda Ospedaliera-Universitaria di Bologna Policlinico S. Orsola-Malpighi, Bologna, Italy.,Post Graduate School of Nephrology, University of Bologna, Bologna, Italy
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31
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Abstract
OBJECTIVE To characterize fentanyl population pharmacokinetics in patients with critical illness and identify patient characteristics associated with altered fentanyl concentrations. DESIGN Prospective cohort study. SETTING Medical and surgical ICUs in a large tertiary care hospital in the United States. PATIENTS Patients with acute respiratory failure and/or shock who received fentanyl during the first 5 days of their ICU stay. MEASUREMENTS AND MAIN RESULTS We collected clinical and hourly drug administration data and measured fentanyl concentrations in plasma collected once daily for up to 5 days after enrollment. Among 337 patients, the mean duration of infusion was 58 hours at a median rate of 100 μg/hr. Using a nonlinear mixed-effects model implemented by NONMEM, we found that fentanyl pharmacokinetics were best described by a two-compartment model in which weight, severe liver disease, and congestive heart failure most affected fentanyl concentrations. For a patient population with a mean weight of 92 kg and no history of severe liver disease or congestive heart failure, the final model, which performed well in repeated 10-fold cross-validation, estimated total clearance, intercompartmental clearance (Q), and volumes of distribution for the central (V1) and peripheral compartments (V2) to be 35 L/hr (95% CI, 32-39 L/hr), 55 L/hr (95% CI, 42-68 L/hr), 203 L (95% CI, 140-266 L), and 523 L (95% CI, 428-618 L), respectively. Severity of illness was marginally associated with fentanyl pharmacokinetics but did not improve the model fit after liver and heart diseases were included. CONCLUSIONS In this study, fentanyl pharmacokinetics during critical illness were strongly influenced by severe liver disease, congestive heart failure, and weight, factors that should be considered when dosing fentanyl in the ICU. Future studies are needed to determine if data-driven fentanyl dosing algorithms can improve outcomes for ICU patients.
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Affiliation(s)
- Nora D Volkow
- From the National Institute on Drug Abuse, National Institutes of Health, Bethesda, MD (N.D.V.); and the Treatment Research Institute, Philadelphia (A.T.M.)
| | - A Thomas McLellan
- From the National Institute on Drug Abuse, National Institutes of Health, Bethesda, MD (N.D.V.); and the Treatment Research Institute, Philadelphia (A.T.M.)
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Mercadante S, Bruera E. Opioid switching in cancer pain: From the beginning to nowadays. Crit Rev Oncol Hematol 2016; 99:241-8. [DOI: 10.1016/j.critrevonc.2015.12.011] [Citation(s) in RCA: 54] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2015] [Revised: 11/02/2015] [Accepted: 12/22/2015] [Indexed: 11/15/2022] Open
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Mercadante S. Opioid metabolism and clinical aspects. Eur J Pharmacol 2015; 769:71-8. [DOI: 10.1016/j.ejphar.2015.10.049] [Citation(s) in RCA: 47] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2015] [Revised: 10/14/2015] [Accepted: 10/27/2015] [Indexed: 12/16/2022]
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Hawi A, Alcorn H, Berg J, Hines C, Hait H, Sciascia T. Pharmacokinetics of nalbuphine hydrochloride extended release tablets in hemodialysis patients with exploratory effect on pruritus. BMC Nephrol 2015; 16:47. [PMID: 25885112 PMCID: PMC4392787 DOI: 10.1186/s12882-015-0043-3] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2014] [Accepted: 03/31/2015] [Indexed: 11/23/2022] Open
Abstract
BACKGROUND Uremic pruritus is a common and deleterious condition among hemodialysis (HD) patients. Central gating of μ/κ opiate circuitry plays an important role in mediating and countering pruritogenic sensation. The objective of this study was to assess the safety and pharmacokinetics (PK) of the mixed μ-antagonist/κ-agonist nalbuphine, administered orally as nalbuphine HCl extended release (ER) tablets in HD patients, and explore its effect on pruritus. METHODS In this open-label multiple escalating dose study, 15 HD patients with pruritus and 9 matched healthy subjects were enrolled. Nalbuphine HCl ER dose was escalated from 30 mg QD to 240 mg BID over 15 days. A full PK profile was obtained under dialysis and non-dialysis conditions as a function of dose. Clearance during dialysis was determined by sampling dialysate and arterial/venous blood during dialysis. Pruritus severity was assessed twice daily using a Visual Analog Scale (VAS). Safety monitoring included extensive monitoring of EKG, blood pressure, and pulse oximetry. RESULTS In HD patients, nalbuphine concentration peaked within 4-9 hours and attained steady state within 2-3 days, with no significant accumulation. Mean half-life was 14.2 hours, mean Cmax and AUCtau ranged between 13 and 83 ng/mL and 118 and 761 ng∙h/mL, respectively, with exposure increasing in a nearly dose-proportional fashion. Exposure in HD patients was about 2-fold higher than in healthy subjects. There was no meaningful difference between exposure on dialysis and non-dialysis days with 1% or less of the dose removed by dialysis. Nalbuphine suppressed itch in a dose-dependent manner, reducing mean VAS score from 4.0 to 1.2 at 180 mg and 0.4 at 240 mg. CONCLUSIONS Nalbuphine HCl ER tablets can be safely administered to HD patients without dose adjustment up to 240 mg BID and may hold promise in treating uremic pruritus.
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Affiliation(s)
| | | | - Jolene Berg
- DaVita Clinical Research, Minneapolis, MN, USA.
| | | | - Howard Hait
- Edenridge Associates LLC, Wilmington, DE, USA.
| | - Thomas Sciascia
- Trevi Therapeutics, 195 Church Street, 14th Floor, New Haven, CT, 06510, USA.
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Pain Characteristics and Analgesic Treatment in an Aged Adult Population: A 4-Week Retrospective Analysis of Advanced Cancer Patients Followed at Home. Drugs Aging 2015; 32:315-20. [DOI: 10.1007/s40266-015-0253-1] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
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Abstract
INTRODUCTION Pain is commonly experienced by patients with cancer, particularly those with advanced disease. Alleviating pain is an important goal of cancer treatment. Opioids are the cornerstone of the analgesic treatment. AREAS COVERED Pharmacology, characteristics, and use of opioids in clinical practice are presented. EXPERT OPINION Although the use of opioids is largely accepted as a fundamental step for controlling cancer pain, existing data supporting this statement are poor. All opioids provide analgesia and are effective in controlling cancer pain. New drugs have been developed and experience is accumulating among clinicians. Despite these drugs having different pharmacokinetic and chemical properties, there is no proof that one opioid is better than another one. Thus, the optimum benefit depends on the experience of the users. Clinicians should weight evidence, clinical experience, patient preferences, and treatment costs when choosing the optimal treatment for an individual patient with cancer pain. New opioids with specific receptor activities are under investigation.
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Affiliation(s)
- Sebastiano Mercadante
- La Maddalena Cancer Center - Pain Relief and Palliative Care Unit , Via san lorenzo 312, Palermo 90145 , Italy
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Marino R, Struck J, Hartmann O, Maisel AS, Rehfeldt M, Magrini L, Melander O, Bergmann A, Di Somma S. Diagnostic and short-term prognostic utility of plasma pro-enkephalin (pro-ENK) for acute kidney injury in patients admitted with sepsis in the emergency department. J Nephrol 2014; 28:717-24. [PMID: 25486879 DOI: 10.1007/s40620-014-0163-z] [Citation(s) in RCA: 56] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2014] [Accepted: 11/18/2014] [Indexed: 11/24/2022]
Abstract
BACKGROUND Acute kidney injury (AKI) aggravates the prognosis of patients with sepsis. Reliable biomarkers for early detection of AKI in this setting are lacking. Enkephalins influence kidney function, and may have a role in AKI from sepsis. We utilized a novel immunoassay for plasma proenkephalin (pro-ENK), a stable surrogate marker for endogenous enkephalins, in patients hospitalized with sepsis, in order to assess its clinical utility. METHODS In an observational retrospective study we enrolled 101 consecutive patients admitted to the emergency department (ED) with suspected sepsis. Plasma levels of pro-ENK and neutrophil gelatinase-associated lipocalin (NGAL) were evaluated at ED arrival for their association with presence and severity of AKI and 7-day mortality. RESULTS pro-ENK was inversely correlated to creatinine clearance (r = -0.72) and increased with severity of AKI as determined by RIFLE (risk, injury, failure, loss of function, end-stage renal disease) stages (p < 0.0001; pro-ENK median [interquartile range, IQR]) pmol/l: no AKI: 71 [41-97]; risk: 72 [51-120]; injury: 200 [104-259]; failure: 230 [104-670]; loss of function: 947 [273-811]. The majority of septic patients without AKI or at risk had pro-ENK concentrations within the normal range. While NGAL was similarly associated with AKI severity, it was strongly elevated already in septic patients without AKI. pro-ENK added predictive information to NGAL for detecting kidney dysfunction (added χ (2) 10.0, p = 0.0016). Admission pro-ENK outperformed creatinine clearance in predicting 7-day mortality (pro-ENK: χ (2) 13.4, p < 0.001, area under curve, AUC 0.69; creatinine clearance: χ (2) 4, p = 0.045, AUC: 0.61), and serial measurement improved prediction. CONCLUSIONS Use of pro-ENK in septic patients can detect the presence and severity of AKI. Moreover, pro-ENK is highly predictive of short-term mortality and could enable early identification of patients at risk of death.
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Affiliation(s)
- Rossella Marino
- Department of Medical Sciences and Translational Medicine, University of Rome Sapienza, Emergency Department Sant'Andrea Hospital, Via di Grottarossa 1035/1039, 00189, Rome, Italy
| | | | | | - Alan S Maisel
- Veterans Affairs San Diego Healthcare System, San Diego, CA, USA
| | | | - Laura Magrini
- Department of Medical Sciences and Translational Medicine, University of Rome Sapienza, Emergency Department Sant'Andrea Hospital, Via di Grottarossa 1035/1039, 00189, Rome, Italy
| | - Olle Melander
- Department of Clinical Sciences, Lund University, Malmö, Sweden
| | | | - Salvatore Di Somma
- Department of Medical Sciences and Translational Medicine, University of Rome Sapienza, Emergency Department Sant'Andrea Hospital, Via di Grottarossa 1035/1039, 00189, Rome, Italy.
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Mercadante S. Fentanyl buccal tablet for the treatment of cancer-related breakthrough pain. Expert Rev Clin Pharmacol 2014; 8:9-13. [DOI: 10.1586/17512433.2015.977254] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
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40
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Linares OA, Schiesser WE, Linares AD, Stefanovski D, Boston RC. A Transit Compartment Model Unmasks OxyContin's Reflective Pharmacokinetics From Urine Measurements in Humans. J Pain Palliat Care Pharmacother 2014; 28:96-108. [DOI: 10.3109/15360288.2014.908991] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
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Linares OA, Daly D, Linares AD, Stefanovski D, Boston RC. Personalized Oxycodone Dosing: Using Pharmacogenetic Testing and Clinical Pharmacokinetics to Reduce Toxicity Risk and Increase Effectiveness. PAIN MEDICINE 2014; 15:791-806. [DOI: 10.1111/pme.12380] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
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Bucher C, Tapernoux D, Diethelm M, Büscher C, Noser A, Fehr T, Henz S. Influence of weather conditions, drugs and comorbidities on serum Na and Cl in 13000 hospital admissions: evidence for a subpopulation susceptible for SIADH. Clin Biochem 2014; 47:618-24. [PMID: 24389078 DOI: 10.1016/j.clinbiochem.2013.12.021] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2013] [Revised: 12/06/2013] [Accepted: 12/17/2013] [Indexed: 01/21/2023]
Abstract
OBJECTIVES Considerable variation in serum sodium (Na) and chloride (Cl) is found in patients at hospital admission. Our goal was to quantify the respective impact of drugs, comorbidities, demographic factors and weather conditions on serum Na and Cl. DESIGN AND METHODS For 13277 consecutive patients without terminal kidney disease admitted to the Department of Internal Medicine of the Kantonsspital St. Gallen drug history on admission, age, sex, body weight, ICD-10 diagnoses, and laboratory data were extracted from electronic medical records. Weather parameters prior to hospital admission were also integrated in a multivariate regression analysis. RESULTS Both serum Na and Cl showed an asymmetric left-tailed distribution. Median (interquartile range) Na was 138 (136/140) and Cl 104 (101/106). The distribution of sodium in patients with one or more risk factors for SIADH was best explained by the presence of two populations: one population with a similar distribution as the unexposed patients and a smaller population (about 25%) shifted to lower sodium levels. Lower weight, lower blood pressure, kidney dysfunction, fever, and diabetes were associated with both lower Na and Cl. Higher ambient temperature and higher air humidity preceding admission were associated with both higher Na and Cl values. CONCLUSIONS Na and Cl at hospital admission are highly influenced by ambient weather conditions, comorbidities and medication. The bimodal distribution of Na and Cl in persons exposed to risk factors for SIADH suggests that SIADH may only affect a genetically distinct vulnerable subpopulation.
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Affiliation(s)
- Christian Bucher
- Department of Internal Medicine, Kantonsspital, St. Gallen, Switzerland
| | - Daniel Tapernoux
- Department of Internal Medicine, Kantonsspital, St. Gallen, Switzerland
| | - Markus Diethelm
- Department of Internal Medicine, Kantonsspital, St. Gallen, Switzerland
| | - Christine Büscher
- Department of Internal Medicine, Kantonsspital, St. Gallen, Switzerland
| | - Anja Noser
- University of Applied Sciences, St. Gallen, Switzerland
| | - Thomas Fehr
- Division of Nephrology, University Hospital, Zürich, Switzerland
| | - Samuel Henz
- Department of Internal Medicine, Kantonsspital, St. Gallen, Switzerland.
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Davison R, Sheerin NS. Prognosis and management of chronic kidney disease (CKD) at the end of life. Postgrad Med J 2013; 90:98-105. [PMID: 24319094 DOI: 10.1136/postgradmedj-2013-132195] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
The prevalence of chronic kidney disease (CKD) increases with age. As people are living longer, nephrologists are responsible for a progressively older cohort of patients with substantial comorbidities. Patients with CKD have a significant symptom burden and can benefit from intervention and symptom control from an early stage in the illness. It is also increasingly recognised that renal replacement therapy may not always offer an improvement in symptoms or a survival advantage to older patients with high levels of comorbidity. For these reasons, non-dialytic (conservative) management and end-of-life care is becoming part of routine nephrology practice. Such patients will also frequently be encountered in other specialities, requiring generalists to have some renal-specific skills and knowledge. Although there have been significant advances in this field in recent years, the optimum model of care and some of the care preferences of patients remain challenges that need to be addressed.
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Affiliation(s)
- Rachel Davison
- Renal Services, Freeman Hospital, , Newcastle upon Tyne, UK
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Perioperative care of the elderly oncology patient: A report from the SIOG task force on the perioperative care of older patients with cancer. J Geriatr Oncol 2012. [DOI: 10.1016/j.jgo.2012.01.003] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
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Ripamonti CI, Bandieri E, Roila F. Management of cancer pain: ESMO Clinical Practice Guidelines. Ann Oncol 2011; 22 Suppl 6:vi69-77. [PMID: 21908508 DOI: 10.1093/annonc/mdr390] [Citation(s) in RCA: 94] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Affiliation(s)
- C I Ripamonti
- Supportive Care in Cancer Unit, IRCCS Foundation, National Cancer Institute of Milano, Milan, Italy
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King S, Forbes K, Hanks GW, Ferro CJ, Chambers EJ. A systematic review of the use of opioid medication for those with moderate to severe cancer pain and renal impairment: a European Palliative Care Research Collaborative opioid guidelines project. Palliat Med 2011; 25:525-52. [PMID: 21708859 DOI: 10.1177/0269216311406313] [Citation(s) in RCA: 100] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
Abstract
BACKGROUND Opioid use in patients with renal impairment can lead to increased adverse effects. Opioids differ in their effect in renal impairment in both efficacy and tolerability. This systematic literature review forms the basis of guidelines for opioid use in renal impairment and cancer pain as part of the European Palliative Care Research Collaborative's opioid guidelines project. OBJECTIVE The objective of this study was to identify and assess the quality of evidence for the safe and effective use of opioids for the relief of cancer pain in patients with renal impairment and to produce guidelines. SEARCH STRATEGY The Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, MedLine, EMBASE and CINAHL were systematically searched in addition to hand searching of relevant journals. SELECTION CRITERIA Studies were included if they reported a clinical outcome relevant to the use of selected opioids in cancer-related pain and renal impairment. The selected opioids were morphine, diamorphine, codeine, dextropropoxyphene, dihydrocodeine, oxycodone, hydromorphone, buprenorphine, tramadol, alfentanil, fentanyl, sufentanil, remifentanil, pethidine and methadone. No direct comparator was required for inclusion. Studies assessing the long-term efficacy of opioids during dialysis were excluded. DATA COLLECTION AND ANALYSIS This is a narrative systematic review and no meta-analysis was performed. The Grading of RECOMMENDATIONS Assessment, Development and Evaluation (GRADE) approach was used to assess the quality of the studies and to formulate guidelines. MAIN RESULTS Fifteen original articles were identified. Eight prospective and seven retrospective clinical studies were identified but no randomized controlled trials. No results were found for diamorphine, codeine, dihydrocodeine, buprenorphine, tramadol, dextropropoxyphene, methadone or remifentanil. CONCLUSIONS All of the studies identified have a significant risk of bias inherent in the study methodology and there is additional significant risk of publication bias. Overall evidence is of very low quality. The direct clinical evidence in cancer-related pain and renal impairment is insufficient to allow formulation of guidelines but is suggestive of significant differences in risk between opioids. RECOMMENDATIONS RECOMMENDATIONS regarding opioid use in renal impairment and cancer pain are made on the basis of pharmacokinetic data, extrapolation from non-cancer pain studies and from clinical experience. The risk of opioid use in renal impairment is stratified according to the activity of opioid metabolites, potential for accumulation and reports of successful or harmful use. Fentanyl, alfentanil and methadone are identified, with caveats, as the least likely to cause harm when used appropriately. Morphine may be associated with toxicity in patients with renal impairment. Unwanted side effects with morphine may be satisfactorily dealt with by either increasing the dosing interval or reducing the 24 hour dose or by switching to an alternative opioid.
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Affiliation(s)
- S King
- Department of Palliative Medicine, University of Bristol, Bristol Oncology and Haematology Centre, Bristol BS2 8ED, UK.
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Sauriyal DS, Jaggi AS, Singh N, Muthuraman A. Investigating the role of endogenous opioids and KATP channels in glycerol-induced acute renal failure. Fundam Clin Pharmacol 2011; 26:347-55. [PMID: 21392099 DOI: 10.1111/j.1472-8206.2011.00936.x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
The present study was designed to investigate the possible role of endogenous opioids and K(ATP) channels in glycerol-induced acute renal failure (ARF) in rats. The rats were subjected to rhabdomyolytic ARF by single intramuscular injection of hypertonic glycerol (50% v/v; 8 mL/kg), and the animals were sacrificed after 24 h of glycerol injection. The plasma creatinine, blood urea nitrogen, creatinine clearance, and histopathological studies were performed to assess the degree of renal injury. Naltrexone (2.5, 5.0 and 10.0 mg/kg s.c.), glibenclamide (5.0 and 10.0 mg/kg i.p.), and minoxidil (25 and 50 mg/kg) were employed to explore the role of endogenous opioids and K(ATP) channels in rhabdomyolysis-induced ARF. Pretreatment with naltrexone and glibenclamide attenuated hypertonic glycerol-induced renal dysfunction in a dose-dependent manner, suggesting the role of endogenous opioids and K(ATP) channels in the pathogenesis of myoglobuniric renal failure. However, the simultaneous pretreatment with naltrexone (10 mg/kg s.c.) and glibenclamide (10 mg/kg i.p.) did not enhance the reno-protective effects of individual drugs, suggesting that release of endogenous opioids and opening of K(ATP) channels constitute a single pathway in acute renal injury triggered by hypertonic glycerol-induced rhabdomyolysis. Furthermore, administration of minoxidil abolished the attenuating effects of naltrexone in glycerol-induced renal failure, suggesting that opening of K(ATP) channels is downstream to opioid receptor activation. It is concluded that hypertonic glycerol-induced rhabdomyolysis may involve release of endogenous opioids that in turn modulate K(ATP) channels to contribute in the pathogenesis of ARF.
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Affiliation(s)
- Dharmraj Singh Sauriyal
- Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala 147002, Punjab, India
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Rurup ML, Rhodius CA, Borgsteede SD, Boddaert MS, Keijser AG, Pasman HRW, Onwuteaka-Philipsen BD. The use of opioids at the end of life: the knowledge level of Dutch physicians as a potential barrier to effective pain management. BMC Palliat Care 2010; 9:23. [PMID: 21073709 PMCID: PMC3000381 DOI: 10.1186/1472-684x-9-23] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2010] [Accepted: 11/12/2010] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Pain is still one of the most frequently occurring symptoms at the end of life, although it can be treated satisfactorily in most cases if the physician has adequate knowledge. In the Netherlands, almost 60% of the patients with non-acute illnesses die at home where end of life care is coordinated by the general practitioner (GP); about 30% die in hospitals (cared for by clinical specialists), and about 10% in nursing homes (cared for by elderly care physicians).The research question of this study is: what is the level of knowledge of Dutch physicians concerning pain management and the use of opioids at the end of life? METHODS A written questionnaire was sent to a random sample of physicians of specialties most often involved in end of life care in the Netherlands. The questionnaire was completed by 406 physicians, response rate 41%. RESULTS Almost all physicians were aware of the most basal knowledge about opioids, e.g. that it is important for treatment purposes to distinguish nociceptive from neuropathic pain (97%). Approximately half of the physicians (46%) did not know that decreased renal function raises plasma concentration of morphine(-metabolites) and 34% of the clinical specialists erroneously thought opioids are the favoured drug for palliative sedation.Although 91% knew that opioids titrated against pain do not shorten life, 10% sometimes or often gave higher dosages than needed with the explicit aim to hasten death. About half felt sometimes or often pressured by relatives to hasten death by increasing opioiddosage.The large majority (83%) of physicians was interested in additional education about subjects related to the end of life, the most popular subject was opioid rotation (46%). CONCLUSIONS Although the basic knowledge of physicians was adequate, there seemed to be a lack of knowledge in several areas, which can be a barrier for good pain management at the end of life. From this study four areas emerge, in which it seems likely that an improvement can improve the quality of pain management at the end of life for many patients in the Netherlands: 1)palliative sedation; 2)expected effect of opioids on survival; and 3) opioid rotation.
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Affiliation(s)
- Mette L Rurup
- VU University Medical Center, EMGO Institute for Health and Care Research, Department of Public and Occupational Health, Amsterdam, The Netherlands.
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Lagas JS, Wagenaar JFP, Huitema ADR, Hillebrand MJX, Koks CHW, Gerdes VEA, Brandjes DPM, Beijnen JH. Lethal morphine intoxication in a patient with a sickle cell crisis and renal impairment: case report and a review of the literature. Hum Exp Toxicol 2010; 30:1399-403. [PMID: 21056950 DOI: 10.1177/0960327110388962] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Morphine-6-glucuronide, the active metabolite of morphine, and to a lesser extent morphine itself are known to accumulate in patients with renal failure. A number of cases on non-lethal morphine toxicity in patients with renal impairment report high plasma concentrations of morphine-6-glucuronide, suggesting that this metabolite achieves sufficiently high brain concentrations to cause long-lasting respiratory depression, despite its poor central nervous system penetration. We report a lethal morphine intoxication in a 61-year-old man with sickle cell disease and renal impairment, and we measured concentrations of morphine and morphine-6-glucuronide in blood, brain and cerebrospinal fluid. There were no measurable concentrations of morphine-6-glucuronide in cerebrospinal fluid or brain tissue, despite high blood concentrations. In contrast, the relatively high morphine concentration in the brain suggests that morphine itself was responsible for the cardiorespiratory arrest in this patient. Given the fatal outcome, we recommend to avoid repeated or continuous morphine administration in renal failure.
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Affiliation(s)
- Jurjen S Lagas
- Department of Pharmacy and Pharmacology, Slotervaart Hospital, Amsterdam, The Netherlands.
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