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1
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Fuggle N, Laslop A, Rizzoli R, Al-Daghri N, Alokail M, Balkowiec-Iskra E, Beaudart C, Bruyère O, Bemden ABV, Burlet N, Cavalier E, Cerreta F, Chandran M, Cherubini A, da Silva Rosa MMC, Conaghan P, Cortet B, Jentoft AC, Curtis EM, D'Amelio P, Dawson-Hughes B, Dennison EM, Hiligsmann M, Kaufman JM, Maggi S, Matijevic R, McCloskey E, Messina D, Pinto D, Yerro MCP, Radermecker RP, Rolland Y, Torre C, Veronese N, Kanis JA, Cooper C, Reginster JY, Harvey NC. Treatment of Osteoporosis and Osteoarthritis in the Oldest Old. Drugs 2025; 85:343-360. [PMID: 39969778 PMCID: PMC11891106 DOI: 10.1007/s40265-024-02138-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/01/2024] [Indexed: 02/20/2025]
Abstract
Osteoporosis and osteoarthritis are key diseases of musculoskeletal ageing and are increasing in prevalence and burden with the progressively ageing population worldwide. These conditions are thus particularly common in 'the oldest old', and there are complexities of managing them within the context of extensive multimorbidity, physical and mental disability, and polypharmacy, the rates for all of which are high in this population. In this narrative review, we explore the epidemiology of osteoporosis and osteoarthritis in the oldest old before examining trials and real-world data relating to the pharmacological treatment of these diseases in older adults, including anti-resorptives and bone-forming agents in osteoporosis and symptomatic slow-acting drugs for osteoarthritis, paracetamol, and non-steroidal anti-inflammatory drugs in osteoarthritis, recognising that the oldest old are usually excluded from clinical trials. We then review the potential benefits of nutritional interventions and exercise therapy before highlighting the health economic benefits of interventions for osteoporosis and osteoarthritis. The high prevalence of risk factors for both disease and adverse events associated with treatment in the oldest old mean that careful attention must be paid to the potential benefits of intervention (including fracture risk reduction and improvements in osteoarthritis pain and function) versus the potential harms and adverse effects. Further direct evidence relating to such interventions is urgently needed from future research.
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Affiliation(s)
- Nicholas Fuggle
- MRC Lifecourse Epidemiology Centre, University of Southampton, Southampton, SO16 6YD, UK
| | - Andrea Laslop
- Scientific Office, Austrian Medicines and Medical Devices Agency, Vienna, Austria
| | - René Rizzoli
- Division of Bone Diseases, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland
| | - Nasser Al-Daghri
- Chair for Biomarkers of Chronic Diseases, Biochemistry Department, College of Science, King Saud University, 11451, Riyadh, Saudi Arabia
| | - Majed Alokail
- Protein Research Chair, Biochemistry Department, College of Science, King Saud University, 11451, Riyadh, Saudi Arabia
| | - Ewa Balkowiec-Iskra
- Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Warsaw, Poland
- The Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Warsaw, Poland
| | - Charlotte Beaudart
- Clinical Pharmacology and Toxicology Research Unit, Department of Biomedical Sciences, Faculty of Medicine, NARILIS, University of Namur, Namur, Belgium
| | - Olivier Bruyère
- Research Unit in Public Health, Epidemiology and Health Economics, University of Liège, Liège, Belgium
| | | | - Nansa Burlet
- The European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO), Liege, Belgium
| | - Etienne Cavalier
- Department of Clinical Chemistry, CIRM, University of Liège, CHU de Liège, Liège, Belgium
| | | | - Manju Chandran
- Osteoporosis and Bone Metabolism Unit, Department of Endocrinology, Singapore General Hospital, Singapore, Singapore
- DUKE NUS Medical School, Singapore, Singapore
| | - Antonio Cherubini
- Geriatria, Accettazione geriatrica e Centro di ricerca per l'invecchiamento, IRCCS INRCA, Ancona, Italy
- Department of Clinical and Molecular Sciences, Università Politecnica delle Marche, Ancona, Italy
| | | | - Philip Conaghan
- Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK
- NIHR Leeds Biomedical Research Centre, Leeds, UK
| | - Bernard Cortet
- Department of Rheumatology, University of Lille, Lille, France
| | - Alfonso Cruz Jentoft
- Servicio de Geriatría. Hospital Universitario Ramón y Cajal (IRYIS), Madrid, Spain
| | - Elizabeth M Curtis
- MRC Lifecourse Epidemiology Centre, University of Southampton, Southampton, SO16 6YD, UK
| | - Patrizia D'Amelio
- Department of Geriatrics and Geriatric Rehabilitation, Lausanne University Hospital, Lausanne, Switzerland
| | - Bess Dawson-Hughes
- Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA
| | - Elaine M Dennison
- MRC Lifecourse Epidemiology Centre, University of Southampton, Southampton, SO16 6YD, UK
| | - Mickaël Hiligsmann
- Department of Health Services Research, CAPHRI Care and Public Health Research Institute, Maastricht University, Maastricht, the Netherlands
| | - Jean-Marc Kaufman
- Department of Endocrinology, Ghent University Hospital, Ghent, Belgium
| | | | - Radmila Matijevic
- Faculty of Medicine, Clinic for Orthopedic Surgery and Traumatology, Clinical Center of Vojvodina, University of Novi Sad, Novi Sad, Serbia
| | - Eugene McCloskey
- Division of Clinical Medicine, School of Medicine and Population Health, Centre for Integrated Research in Musculoskeletal Ageing, University of Sheffield, Sheffield, UK
| | - Daniel Messina
- IRO Investigaciones Reumatologicas y Osteologicas SRL Collaborating Centre WHO, University of Buenos Aires, Buenos Aires, Argentina
| | - Daniel Pinto
- Department of Physical Therapy, Marquette University, Milwaukee, WI, USA
| | | | - Régis Pierre Radermecker
- Department of Diabetes, Nutrition and Metabolic disorders, Clinical pharmacology, University of Liège, CHU de Liège, Liège, Belgium
| | - Yves Rolland
- IHU Health Age, CHU Toulouse, INSERM 1295, Toulouse, France
| | - Carla Torre
- Faculdade de Farmácia, Universidade de Lisboa, Avenida Professor Gama Pinto, 1649-003, Lisbon, Portugal
- Laboratory of Systems Integration Pharmacology, Clinical and Regulatory Science, Research Institute for Medicines of the University of Lisbon (iMED.ULisboa), Avenida Professor Gama Pinto, 1649-003, Lisbon, Portugal
| | - Nicola Veronese
- Chair for Biomarkers of Chronic Diseases, Biochemistry Department, College of Science, King Saud University, 11451, Riyadh, Saudi Arabia
- Geriatric Unit, Department of Medicine, University of Palermo, 90127, Palermo, Italy
| | - John A Kanis
- Division of Clinical Medicine, School of Medicine and Population Health, Centre for Integrated Research in Musculoskeletal Ageing, University of Sheffield, Sheffield, UK
- Mary McKillop Institute for Health Research, Australian Catholic University, Melbourne, Australia
| | - Cyrus Cooper
- MRC Lifecourse Epidemiology Centre, University of Southampton, Southampton, SO16 6YD, UK
- NIHR Southampton Biomedical Research Centre, University of Southampton, Southampton, UK
- NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK
| | - Jean-Yves Reginster
- Protein Research Chair, Biochemistry Department, College of Science, King Saud University, 11451, Riyadh, Saudi Arabia
- Research Unit in Public Health, Epidemiology and Health Economics, University of Liège, Liège, Belgium
| | - Nicholas C Harvey
- MRC Lifecourse Epidemiology Centre, University of Southampton, Southampton, SO16 6YD, UK.
- NIHR Southampton Biomedical Research Centre, University of Southampton, Southampton, UK.
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2
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Coetzee E, Absalom AR. Pharmacokinetic and Pharmacodynamic Changes in the Older Adults: Impact on Anesthetics. Clin Geriatr Med 2025; 41:19-35. [PMID: 39551539 DOI: 10.1016/j.cger.2024.03.004] [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: 11/19/2024]
Abstract
Anesthesiologists are increasingly required to care for frail older adults patients. A detailed knowledge of the influence of age on the pharmacokinetics and dynamics of the anesthetic drugs is essential for optimal safety and care. For most of the anesthetic drugs, the older adults need lower doses to achieve the same plasma concentrations, and at any given plasma and effect-site concentration, they will have more profound clinical effects than younger patients. Caution is required, with close monitoring of clinical effects and active titration of dose administration to achieve the desired level of effect, ideally following the "start low, go slow" principle.
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Affiliation(s)
- Ettienne Coetzee
- Department of Anaesthesia and Perioperative Medicine, Groote Schuur Hospital, D23, Observatory, Cape Town 7925, Republic of South Africa
| | - Anthony Ray Absalom
- Department of Anesthesiology, University of Groningen, University Medical Center Groningen, Post Box 30.001, Groningen 9700 RB, the Netherlands.
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3
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Pickering G, Kotlińska-Lemieszek A, Krcevski Skvarc N, O'Mahony D, Monacelli F, Knaggs R, Morel V, Kocot-Kępska M. Pharmacological Pain Treatment in Older Persons. Drugs Aging 2024; 41:959-976. [PMID: 39465454 PMCID: PMC11634925 DOI: 10.1007/s40266-024-01151-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/16/2024] [Indexed: 10/29/2024]
Abstract
Pharmacological pain treatment in older persons is presented by a multi-disciplinary group of European pain experts. Drugs recommended for acute or chronic nociceptive pain, also for neuropathic pain and the routes of administration of choice are the same as those prescribed for younger persons but comorbidities and polypharmacy in older persons increase the risk of adverse effects and drug interactions. Not all drugs are available or authorised in all European countries. For mild-to-moderate pain, non-opioids including paracetamol and non-steroidal anti-inflammatory drugs are first-line treatments, followed by nefopam and metamizole. Codeine, dihydrocodeine and tramadol are prescribed for moderate to severe pain and 'strong' opioids, including morphine, hydromorphone, oxycodone, fentanyl, buprenorphine, methadone and tapentadol, for severe pain. Chronic neuropathic pain treatment relies on coanalgesics, including anti-epileptics (gabapentinoids) and anti-depressants with additional option of topical lidocaine and capsaicine. The choice of analgesic(s) and the route of administration should be guided by the pain characteristics, as well as by the patient's comorbidities, organ function and medications. Several directions have been highlighted to optimise pharmacological pain management in older individuals: (1) before starting pain treatment adequately detect and assess pain and always perform a full geriatric assessment, (2) consider kidney function systematically to adjust the doses of analgesics and avoid the risks of overdose, (3) start with the lowest dose of an analgesic and increase it gradually under the control of the effect, (4) involve the older persons and family in their treatment, (5) reevaluate pain regularly during treatment and (6) combine pharmacological treatment with non-pharmacological approaches.
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Affiliation(s)
- Gisèle Pickering
- Clinical Pharmacology Department, PIC/CIC Inserm 1405-University Hospital CHU and Faculty of Medicine, Université Clermont Auvergne, Clermont-Ferrand, France.
| | - Aleksandra Kotlińska-Lemieszek
- Department of Palliative Medicine, Pharmacotherapy in Palliative Care Laboratory, Poznan University of Medical Sciences, Poznań, Poland
| | - Nevenka Krcevski Skvarc
- Institute for Palliative Medicine and Care, Faculty of Medicine of University Maribor, Maribor, Slovenia
| | - Denis O'Mahony
- Department of Medicine, University College Cork, Cork University Hospital, Cork, Ireland
- Department of Geriatric and Stroke Medicine, Cork University Hospital, Cork, Ireland
| | | | - Roger Knaggs
- University of Nottingham, University Park, Nottingham, UK
- Pain Centre Versus Arthritis, Clinical Sciences Building, City Hospital, Nottingham, UK
- Primary Integrated Community Services, Nottingham, UK
| | - Véronique Morel
- Clinical Pharmacology Department, PIC/CIC Inserm 1405-University Hospital CHU and Faculty of Medicine, Université Clermont Auvergne, Clermont-Ferrand, France
| | - Magdalena Kocot-Kępska
- Department for Pain Research and Treatment, Medical College Jagiellonian University, Krakow, Poland
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Tu JJ, Yu ZZ, Ou ML, Cen JX, Xue K, Zhou J, Li SJ, Lu GD. Differential impacts of nonsteroidal anti-inflammatory drugs on lifespan and healthspan in aged Caenorhabditis elegans. J Appl Toxicol 2024; 44:1528-1539. [PMID: 38840409 DOI: 10.1002/jat.4655] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2024] [Revised: 05/23/2024] [Accepted: 05/24/2024] [Indexed: 06/07/2024]
Abstract
Aging and age-related diseases are intricately associated with oxidative stress and inflammation. Nonsteroidal anti-inflammatory drugs (NSAIDs) have shown their promise in mitigating age-related conditions and potentially extending lifespan in various model organisms. However, the efficacy of NSAIDs in older individuals may be influenced by age-related changes in drug metabolism and tolerance, which could result in age-dependent toxicities. This study aimed to evaluate the potential risks of toxicities associated with commonly used NSAIDs (aspirin, ibuprofen, acetaminophen, and indomethacin) on lifespan, healthspan, and oxidative stress levels in both young and old Caenorhabditis elegans. The results revealed that aspirin and ibuprofen were able to extend lifespan in both young and old worms by suppressing ROS generation and enhancing the expression of antioxidant SOD genes. In contrast, acetaminophen and indomeacin accelerated aging process in old worms, leading to oxidative stress damage and reduced resistance to heat stress through the pmk-1/skn-1 pathway. Notably, the harmful effects of acetaminophen and indomeacin were mitigated when pmk-1 was knocked out in the pmk-1(km25) strain. These results underscore the potential lack of benefit from acetaminophen and indomeacin in elderly individuals due to their increased susceptibility to toxicity. Further research is essential to elucidate the underlying mechanisms driving these age-dependent responses and to evaluate the potential risks associated with NSAID use in the elderly population.
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Affiliation(s)
- Jia-Jun Tu
- Department of Toxicology, School of Public Health, Guangxi Medical University, Nanning, Guangxi Province, China
| | - Zhen-Zhen Yu
- Department of Toxicology, School of Public Health, Guangxi Medical University, Nanning, Guangxi Province, China
| | - Mei-Ling Ou
- Department of Toxicology, School of Public Health, Guangxi Medical University, Nanning, Guangxi Province, China
| | - Jin-Xiong Cen
- Department of Toxicology, School of Public Health, Guangxi Medical University, Nanning, Guangxi Province, China
| | - Kun Xue
- School of Public Health, Fudan University, Shanghai, China
| | - Jing Zhou
- Department of Physiology, School of Basic Medical Sciences, Guangxi Medical University, Nanning, Guangxi Province, China
| | - Shao-Jun Li
- Department of Toxicology, School of Public Health, Guangxi Medical University, Nanning, Guangxi Province, China
- Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, School of Public Health, Guangxi Medical University, Nanning, Guangxi, China
| | - Guo-Dong Lu
- Department of Toxicology, School of Public Health, Guangxi Medical University, Nanning, Guangxi Province, China
- School of Public Health, Fudan University, Shanghai, China
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5
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Roberts BM, Geddis AV, Ciuciu A, Reynoso M, Mehta N, Varanoske AN, Kelley AM, Walker RJ, Munoz R, Kolb AL, Staab JS, Naimo MA, Tomlinson RE. Acetaminophen influences musculoskeletal signaling but not adaptations to endurance exercise training. FASEB J 2024; 38:e23586. [PMID: 38568858 DOI: 10.1096/fj.202302642r] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2023] [Revised: 03/01/2024] [Accepted: 03/19/2024] [Indexed: 04/05/2024]
Abstract
Acetaminophen (ACE) is a widely used analgesic and antipyretic drug with various applications, from pain relief to fever reduction. Recent studies have reported equivocal effects of habitual ACE intake on exercise performance, muscle growth, and risks to bone health. Thus, this study aimed to assess the impact of a 6-week, low-dose ACE regimen on muscle and bone adaptations in exercising and non-exercising rats. Nine-week-old Wistar rats (n = 40) were randomized to an exercise or control (no exercise) condition with ACE or without (placebo). For the exercise condition, rats ran 5 days per week for 6 weeks at a 5% incline for 2 min at 15 cm/s, 2 min at 20 cm/s, and 26 min at 25 cm/s. A human equivalent dose of ACE was administered (379 mg/kg body weight) in drinking water and adjusted each week based on body weight. Food, water intake, and body weight were measured daily. At the beginning of week 6, animals in the exercise group completed a maximal treadmill test. At the end of week 6, rats were euthanized, and muscle cross-sectional area (CSA), fiber type, and signaling pathways were measured. Additionally, three-point bending and microcomputer tomography were measured in the femur. Follow-up experiments in human primary muscle cells were used to explore supra-physiological effects of ACE. Data were analyzed using a two-way ANOVA for treatment (ACE or placebo) and condition (exercise or non-exercise) for all animal outcomes. Data for cell culture experiments were analyzed via ANOVA. If omnibus significance was found in either ANOVA, a post hoc analysis was completed, and a Tukey's adjustment was used. ACE did not alter body weight, water intake, food intake, or treadmill performance (p > .05). There was a treatment-by-condition effect for Young's Modulus where placebo exercise was significantly lower than placebo control (p < .05). There was no treatment by condition effects for microCT measures, muscle CSA, fiber type, or mRNA expression. Phosphorylated-AMPK was significantly increased with exercise (p < .05) and this was attenuated with ACE treatment. Furthermore, phospho-4EBP1 was depressed in the exercise group compared to the control (p < .05) and increased in the ACE control and ACE exercise group compared to placebo exercise (p < .05). A low dose of ACE did not influence chronic musculoskeletal adaptations in exercising rodents but acutely attenuated AMPK phosphorylation and 4EBP1 dephosphorylation post-exercise.
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Affiliation(s)
- Brandon M Roberts
- Military Performance Division, US Army Research Institute of Environmental Medicine, Natick, Massachusetts, USA
| | - Alyssa V Geddis
- Military Performance Division, US Army Research Institute of Environmental Medicine, Natick, Massachusetts, USA
| | - Alexandra Ciuciu
- Department of Orthopaedic Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
| | - Marinaliz Reynoso
- Military Performance Division, US Army Research Institute of Environmental Medicine, Natick, Massachusetts, USA
| | - Nikhil Mehta
- Department of Orthopaedic Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
| | - Alyssa N Varanoske
- Military Performance Division, US Army Research Institute of Environmental Medicine, Natick, Massachusetts, USA
- Oak Ridge Institute for Science and Education, Belcamp, Maryland, USA
| | - Alyssa M Kelley
- Military Performance Division, US Army Research Institute of Environmental Medicine, Natick, Massachusetts, USA
| | - Raymond J Walker
- Military Performance Division, US Army Research Institute of Environmental Medicine, Natick, Massachusetts, USA
| | - Rigoberto Munoz
- Military Performance Division, US Army Research Institute of Environmental Medicine, Natick, Massachusetts, USA
| | - Alexander L Kolb
- Military Performance Division, US Army Research Institute of Environmental Medicine, Natick, Massachusetts, USA
| | - Jeffery S Staab
- Military Performance Division, US Army Research Institute of Environmental Medicine, Natick, Massachusetts, USA
| | - Marshall A Naimo
- Military Performance Division, US Army Research Institute of Environmental Medicine, Natick, Massachusetts, USA
| | - Ryan E Tomlinson
- Department of Orthopaedic Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
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6
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Edwina AE, Dreesen E, Hias J, Koch BCP, Van den Eede N, Pauwels S, Allegaert K, Van der Linden L, Spriet I, Tournoy J. Agreement Between a Colorimetric Assay and Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry for Quantifying Paracetamol Plasma Concentrations. AAPS J 2024; 26:23. [PMID: 38302833 DOI: 10.1208/s12248-024-00890-1] [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: 09/19/2023] [Accepted: 12/21/2023] [Indexed: 02/03/2024] Open
Abstract
Special populations, like geriatric patients, experience altered paracetamol pharmacokinetics (PK), complicating pain management. More PK research is essential to optimize paracetamol (acetaminophen) dosing. Yet, the reference method ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) is not readily available. Therefore, we aimed to evaluate the agreement between UPLC-MS/MS and the more accessible colorimetric Roche acetaminophen (ACETA) assay in quantifying paracetamol plasma concentrations, to facilitate PK studies and therapeutic drug monitoring for pain management. Patient data and plasma samples were obtained from a prospective study including geriatric patients admitted to the geriatric wards. ACETA and UPLC-MS/MS assays were performed in two separate laboratories. Bland-Altman plot and Passing-Bablok regression were used to assess agreement. Accuracy was evaluated using the McNemar test for a threshold value of 10 mg/L. Population PK modeling was employed to bridge PK data obtained from both methods (NONMEM 7.5). A total of 242 plasma sample pairs were available from 40 geriatric patients (age range, 80-95 years). Paracetamol plasma concentrations from ACETA (median 9.8 [interquartile range 6.1-14.4] mg/L) and UPLC-MS/MS (9.5 [6.2-14.8] mg/L) did not differ significantly (P > 0.05). No significant proportional nor additive bias was observed between both assay methods. The classification accuracy (at threshold 10 mg/L) was 85% (P = 0.414). The conversion factor between ACETA and UPLC-MS/MS was estimated at 1.06 (relative standard error 5%), yet with a 13.4% (relative standard error 23%) interindividual variability. ACETA assay showed no systematic bias in comparison with the UPLC-MS/MS assay in determining paracetamol exposure in geriatric blood samples despite the imprecision.
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Affiliation(s)
- Angela Elma Edwina
- Gerontology and Geriatrics, Department of Public Health and Primary Care, KU Leuven - University of Leuven, UZ Herestraat 49, Box 7003, 3000, Leuven, Belgium
| | - Erwin Dreesen
- Clinical Pharmacology and Pharmacotherapy, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven - University of Leuven, Leuven, Belgium
| | - Julie Hias
- Clinical Pharmacology and Pharmacotherapy, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven - University of Leuven, Leuven, Belgium
- Pharmacy Department, University Hospitals Leuven, Leuven, Belgium
| | - Birgit C P Koch
- Department of Hospital Pharmacy, Erasmus University Medical Center, Rotterdam, Netherlands
| | | | | | - Karel Allegaert
- Clinical Pharmacology and Pharmacotherapy, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven - University of Leuven, Leuven, Belgium
- Department of Hospital Pharmacy, Erasmus University Medical Center, Rotterdam, Netherlands
- Department of Development and Regeneration, KU Leuven - University of Leuven, Leuven, Belgium
| | - Lorenz Van der Linden
- Clinical Pharmacology and Pharmacotherapy, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven - University of Leuven, Leuven, Belgium
- Pharmacy Department, University Hospitals Leuven, Leuven, Belgium
| | - Isabel Spriet
- Clinical Pharmacology and Pharmacotherapy, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven - University of Leuven, Leuven, Belgium
- Pharmacy Department, University Hospitals Leuven, Leuven, Belgium
| | - Jos Tournoy
- Gerontology and Geriatrics, Department of Public Health and Primary Care, KU Leuven - University of Leuven, UZ Herestraat 49, Box 7003, 3000, Leuven, Belgium.
- Department of Geriatric Medicine, University Hospitals Leuven, Leuven, Belgium.
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7
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Coetzee E, Absalom AR. Pharmacokinetic and Pharmacodynamic Changes in the Elderly: Impact on Anesthetics. Anesthesiol Clin 2023; 41:549-565. [PMID: 37516494 DOI: 10.1016/j.anclin.2023.02.006] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/31/2023]
Abstract
Anesthesiologists are increasingly required to care for frail elderly patients. A detailed knowledge of the influence of age on the pharmacokinetics and dynamics of the anesthetic drugs is essential for optimal safety and care. For most of the anesthetic drugs, the elderly need lower doses to achieve the same plasma concentrations, and at any given plasma and effect-site concentration, they will have more profound clinical effects than younger patients. Caution is required, with close monitoring of clinical effects and active titration of dose administration to achieve the desired level of effect, ideally following the "start low, go slow" principle.
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Affiliation(s)
- Ettienne Coetzee
- Department of Anaesthesia and Perioperative Medicine, Groote Schuur Hospital, D23, Observatory, Cape Town 7925, Republic of South Africa
| | - Anthony Ray Absalom
- Department of Anesthesiology, University of Groningen, University Medical Center Groningen, Post Box 30.001, Groningen 9700 RB, the Netherlands.
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8
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Baud F, Ladjouzi N, Ben Hassen J, El Omeiri N, Raveloson H, Brondin L, Ben Rahal C, Ould Ouali C, Zouloumis G, Schlatter J. Paracetamol prescriptions in older people hospitalized in a French geriatric hospital. Health Sci Rep 2023; 6:e1565. [PMID: 37732103 PMCID: PMC10507803 DOI: 10.1002/hsr2.1565] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2023] [Revised: 08/30/2023] [Accepted: 08/31/2023] [Indexed: 09/22/2023] Open
Affiliation(s)
- Frederic Baud
- Médecine gériatrique aigue, Hôpital Paul DoumerAssistance Publique des Hôpitaux de ParisLabruyèreFrance
| | - Nadia Ladjouzi
- Médecine gériatrique aigue, Hôpital Paul DoumerAssistance Publique des Hôpitaux de ParisLabruyèreFrance
| | - Jihène Ben Hassen
- Médecine gériatrique aigue, Hôpital Paul DoumerAssistance Publique des Hôpitaux de ParisLabruyèreFrance
| | - Nesrine El Omeiri
- Médecine gériatrique aigue, Hôpital Paul DoumerAssistance Publique des Hôpitaux de ParisLabruyèreFrance
| | - Hendriniainia Raveloson
- Médecine gériatrique aigue, Hôpital Paul DoumerAssistance Publique des Hôpitaux de ParisLabruyèreFrance
| | - Lucile Brondin
- Médecine gériatrique aigue, Hôpital Paul DoumerAssistance Publique des Hôpitaux de ParisLabruyèreFrance
| | - Camille Ben Rahal
- Médecine gériatrique aigue, Hôpital Paul DoumerAssistance Publique des Hôpitaux de ParisLabruyèreFrance
| | - Cid Ould Ouali
- Service de soins et réadaptation, Hôpital Paul DoumerAssistance Publique des Hôpitaux de ParisLabruyèreFrance
| | - Georges Zouloumis
- Service de long séjour, Hôpital Paul DoumerAssistance Publique des Hôpitaux de ParisLabruyèreFrance
| | - Joël Schlatter
- Pharmacie, Hôpital Paul DoumerAssistance Publique des Hôpitaux de ParisLabruyèreFrance
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9
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Dowd LA, Cross AJ, Liau SJ, Jadczak AD, Visvanathan R, Veal FC, Bell JS. Identifying Residents Who May Benefit from an Analgesic Review: Applying Analgesic Indicators in Residential Aged Care Services. Drugs Aging 2023; 40:449-459. [PMID: 37147416 DOI: 10.1007/s40266-023-01025-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/21/2023] [Indexed: 05/07/2023]
Abstract
BACKGROUND Ensuring safe and effective analgesic use in residential aged care services is important because older adults are susceptible to analgesic-related adverse drug events (ADEs). OBJECTIVE The aim of this study was to identify the proportion and characteristics of residents of aged care services who may benefit from analgesic review based on indicators in the 2021 Society for Post-Acute and Long-Term Care Medicine (AMDA) Pain Management Guideline. METHODS Cross-sectional analyses of baseline data from the Frailty in Residential Sector over Time (FIRST) study (N = 550 residents) across 12 South Australian residential aged care services in 2019 were conducted. Indicators included the proportion of residents who received > 3000 mg/day of acetaminophen (paracetamol), regular opioids without a documented clinical rationale, opioid doses > 60 mg morphine equivalents (MME)/day, more than one long-acting opioid concurrently, and a pro re nata (PRN) opioid on more than two occasions in the previous 7 days. Logistic regression was performed to investigate factors associated with residents who may benefit from analgesic review. RESULTS Of 381 (69.3%) residents charted regular acetaminophen, 176 (46.2%) were charted > 3000 mg/day. Of 165 (30%) residents charted regular opioids, only 2 (1.2%) had no prespecified potentially painful conditions in their medical record and 31 (18.8%) received > 60 MME/day. Of 153 (27.8%) residents charted long-acting opioids, 8 (5.2%) received more than one long-acting opioid concurrently. Of 212 (38.5%) residents charted PRN opioids, 10 (4.7%) received more than two administrations in the previous 7 days. Overall, 196 (35.6%) of 550 residents were identified as potentially benefiting from analgesic review. Females (odds ratio [OR] 1.87, 95% confidence interval [CI] 1.20-2.91) and residents with prior fracture (OR 1.62, 95% CI 1.12-2.33) were more likely to be identified. Observed pain (OR 0.50, 95% CI 0.29-0.88) was associated with a lower likelihood of being identified compared with residents with no observed pain. Overall, 43 (7.8%) residents were identified based on opioid-related indicators. CONCLUSIONS Up to one in three residents may benefit from a review of their analgesic regimen, including 1 in 13 who may benefit from a specific review of their opioid regimen. Analgesic indicators represent a new approach to target analgesic stewardship interventions.
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Affiliation(s)
- Laura A Dowd
- Centre for Medicine Use and Safety, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Parkville, VIC, Australia.
| | - Amanda J Cross
- Centre for Medicine Use and Safety, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Parkville, VIC, Australia
| | - Shin J Liau
- Centre for Medicine Use and Safety, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Parkville, VIC, Australia
- National Health and Medical Research Council (NHMRC) Centre of Research Excellence in Frailty and Healthy Ageing, Adelaide, SA, Australia
| | - Agathe D Jadczak
- National Health and Medical Research Council (NHMRC) Centre of Research Excellence in Frailty and Healthy Ageing, Adelaide, SA, Australia
- Faculty of Health and Medical Sciences, Adelaide Geriatrics Training and Research with Aged Care (GTRAC) Centre, Adelaide Medical School, University of Adelaide, Adelaide, SA, Australia
| | - Renuka Visvanathan
- National Health and Medical Research Council (NHMRC) Centre of Research Excellence in Frailty and Healthy Ageing, Adelaide, SA, Australia
- Faculty of Health and Medical Sciences, Adelaide Geriatrics Training and Research with Aged Care (GTRAC) Centre, Adelaide Medical School, University of Adelaide, Adelaide, SA, Australia
- Aged and Extended Care Services, The Queen Elizabeth Hospital, Central Adelaide Local Health Network, Adelaide, SA, Australia
| | - Felicity C Veal
- Unit for Medication Outcomes Research and Education (UMORE), School of Pharmacy and Pharmacology, University of Tasmania, Hobart, TAS, Australia
| | - J Simon Bell
- Centre for Medicine Use and Safety, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Parkville, VIC, Australia
- National Health and Medical Research Council (NHMRC) Centre of Research Excellence in Frailty and Healthy Ageing, Adelaide, SA, Australia
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10
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Alsaeedi A, Welham S, Rose P, Zhu YZ. The Impact of Drugs on Hydrogen Sulfide Homeostasis in Mammals. Antioxidants (Basel) 2023; 12:antiox12040908. [PMID: 37107283 PMCID: PMC10135325 DOI: 10.3390/antiox12040908] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2023] [Revised: 04/04/2023] [Accepted: 04/09/2023] [Indexed: 04/29/2023] Open
Abstract
Mammalian cells and tissues have the capacity to generate hydrogen sulfide gas (H2S) via catabolic routes involving cysteine metabolism. H2S acts on cell signaling cascades that are necessary in many biochemical and physiological roles important in the heart, brain, liver, kidney, urogenital tract, and cardiovascular and immune systems of mammals. Diminished levels of this molecule are observed in several pathophysiological conditions including heart disease, diabetes, obesity, and immune function. Interestingly, in the last two decades, it has become apparent that some commonly prescribed pharmacological drugs can impact the expression and activities of enzymes responsible for hydrogen sulfide production in cells and tissues. Therefore, the current review provides an overview of the studies that catalogue key drugs and their impact on hydrogen sulfide production in mammals.
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Affiliation(s)
- Asrar Alsaeedi
- School of Biosciences, University of Nottingham, Loughborough, Leicestershire LE12 5RD, UK
| | - Simon Welham
- School of Biosciences, University of Nottingham, Loughborough, Leicestershire LE12 5RD, UK
| | - Peter Rose
- School of Biosciences, University of Nottingham, Loughborough, Leicestershire LE12 5RD, UK
- State Key Laboratory of Quality Research in Chinese Medicine, School of Pharmacy, Macau University of Science and Technology, Macau, China
| | - Yi-Zhun Zhu
- State Key Laboratory of Quality Research in Chinese Medicine, School of Pharmacy, Macau University of Science and Technology, Macau, China
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11
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Valsamaki A, Xanthoudaki M, Oikonomou KG, Vlachostergios PJ, Papadogoulas A, Katsiafylloudis P, Voulgaridi I, Skoura AL, Komnos A, Papamichalis P. Prevention, diagnostic evaluation, management and prognostic implications of liver disease in critically ill patients with COVID-19. World J Clin Cases 2023; 11:514-527. [PMID: 36793637 PMCID: PMC9923862 DOI: 10.12998/wjcc.v11.i3.514] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2022] [Revised: 12/05/2022] [Accepted: 01/10/2023] [Indexed: 01/23/2023] Open
Abstract
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, broke out in December 2019 in Wuhan city of China and spread rapidly worldwide. Therefore, by March 2020, the World Health Organization declared the disease a global pandemic. Apart from the respiratory system, various other organs of the human body are also seriously affected by the virus. Liver injury in patients with a severe form of COVID-19 is estimated to be 14.8%-53.0%. Elevated levels of total bilirubin, aspartate aminotransferase and alanine aminotransferase and low levels of serum albumin and prealbumin are the main laboratory findings. Patients with pre-existing chronic liver disease and cirrhosis are much more prone to develop severe liver injury. This literature review presented the recent scientific findings regarding the pathophysiological mechanisms responsible for liver injury in critically ill patients with COVID-19, the various interactions between drugs used to treat the disease and the function of the liver and the specific tests providing the possibility of early diagnosis of severe liver injury in these patients. Moreover, it highlighted the burden that COVID-19 put on health systems worldwide and its effect on transplant programs and the care provided to critically ill patients in general and particularly to those with chronic liver disease.
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Affiliation(s)
- Asimina Valsamaki
- Intensive Care Unit, General Hospital of Larissa, Larissa 41221, Greece
| | - Maria Xanthoudaki
- Intensive Care Unit, General Hospital of Larissa, Larissa 41221, Greece
| | | | - Panagiotis J Vlachostergios
- Division of Hematology and Medical Oncology, Department of Medicine, Weill Cornell Medicine, New York, NY 10065, United States
| | | | | | - Ioanna Voulgaridi
- Department of Microbiology, General Hospital of Larissa, Larissa 41221, Greece
| | | | - Apostolos Komnos
- Intensive Care Unit, General Hospital of Larissa, Larissa 41221, Greece
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12
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Saeedi BJ, Hunter-Chang S, Luo L, Li K, Liu KH, Robinson BS. Oxidative stress mediates end-organ damage in a novel model of acetaminophen-toxicity in Drosophila. Sci Rep 2022; 12:19309. [PMID: 36369211 PMCID: PMC9652370 DOI: 10.1038/s41598-022-21156-w] [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: 02/04/2022] [Accepted: 09/23/2022] [Indexed: 11/13/2022] Open
Abstract
Acetaminophen is the most common cause of acute drug-induced liver injury in the United States. However, research into the mechanisms of acetaminophen toxicity and the development of novel therapeutics is hampered by the lack of robust, reproducible, and cost-effective model systems. Herein, we characterize a novel Drosophila-based model of acetaminophen toxicity. We demonstrate that acetaminophen treatment of Drosophila results in similar pathophysiologic alterations as those observed in mammalian systems, including a robust production of reactive oxygen species, depletion of glutathione, and dose-dependent mortality. Moreover, these effects are concentrated in the Drosophila fat body, an organ analogous to the mammalian liver. Utilizing this system, we interrogated the influence of environmental factors on acetaminophen toxicity which has proven difficult in vertebrate models due to cost and inter-individual variability. We find that both increasing age and microbial depletion sensitize Drosophila to acetaminophen toxicity. These environmental influences both alter oxidative stress response pathways in metazoans. Indeed, genetic and pharmacologic manipulations of the antioxidant response modify acetaminophen toxicity in our model. Taken together, these data demonstrate the feasibility of Drosophila for the study of acetaminophen toxicity, bringing with it an ease of genetic and microbiome manipulation, high-throughput screening, and availability of transgenic animals.
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Affiliation(s)
- Bejan J Saeedi
- Department of Pathology, Emory University School of Medicine, 615 Michael Street, Atlanta, GA, 30322, USA
| | - Sarah Hunter-Chang
- Department of Pathology, Emory University School of Medicine, 615 Michael Street, Atlanta, GA, 30322, USA
| | - Liping Luo
- Department of Pathology, Emory University School of Medicine, 615 Michael Street, Atlanta, GA, 30322, USA
| | - Kaiyan Li
- Department of Pathology, Emory University School of Medicine, 615 Michael Street, Atlanta, GA, 30322, USA
| | - Ken H Liu
- Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, GA, 30322, USA
| | - Brian S Robinson
- Department of Pathology, Emory University School of Medicine, 615 Michael Street, Atlanta, GA, 30322, USA.
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13
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Recent Updates on Risk and Management Plans Associated with Polypharmacy in Older Population. Geriatrics (Basel) 2022; 7:geriatrics7050097. [PMID: 36136806 PMCID: PMC9498769 DOI: 10.3390/geriatrics7050097] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2022] [Revised: 09/08/2022] [Accepted: 09/09/2022] [Indexed: 11/17/2022] Open
Abstract
The concept of polypharmacy encompasses adverse drug reactions and non-adherence factors in elderly individuals. It also leads to the increased use of healthcare services and negative health outcomes. The problem is further alleviated by the odds of potentially inappropriate medications (PIM), which lead to the development of drug-related problems. Since polypharmacy is more commonly observed in the elderly population, urgency is required to introduce operative protocols for preventing and managing this problem. The family medicine model of care can be associated with favorable illness outcomes regarding satisfaction with consultation, treatment adherence, self-management behaviors, adherence to medical advice, and healthcare utilization. Hence, interventions built on family medicine models can provide significant support in improving the outcomes of the older population and their quality of life. In this regard, the authors have taken up the task of explaining the accessible resources which can be availed to improve the application of health care services in the field of geriatric medicine.
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14
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Yin F, Ma W, Liu Q, Xiong LL, Wang TH, Li Q, Liu F. Efficacy and safety of intravenous acetaminophen (2 g/day) for reducing opioid consumption in Chinese adults after elective orthopedic surgery: A multicenter randomized controlled trial. Front Pharmacol 2022; 13:909572. [PMID: 35935863 PMCID: PMC9355325 DOI: 10.3389/fphar.2022.909572] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Accepted: 06/29/2022] [Indexed: 11/13/2022] Open
Abstract
Background: Acetaminophen is an important component of a multimodal analgesia strategy to reduce opioid consumption and pain intensity after an orthopedic surgery. The opioid-sparing efficacy of intravenous acetaminophen has been established at a daily dose of 4 g. However, it is still unclear for the daily dose of 2 g of acetaminophen, which is recommended by the China Food and Drug Administration Center for Drug Evaluation, in terms of its efficacy and safety.Objectives: This study aimed to evaluate the efficacy and safety of intravenous acetaminophen at a daily dose of 2 g for reducing opioid consumption and pain intensity after orthopedic surgery.Methods: In this multicenter, randomized, double-blind, placebo-controlled phase III trial, 235 patients who underwent orthopedic surgery were randomly assigned to receive intravenous acetaminophen 500 mg every 6 h or placebo. Postoperative morphine consumption, pain intensity at rest and during movement, and adverse events were analysed.Results: For the mean (standard deviation) morphine consumption within 24 h after surgery, intravenous acetaminophen was superior to placebo both in the modified intention-to-treat analysis [8.7 (7.7) mg vs. 11.2 (9.2) mg] in the acetaminophen group and the placebo group, respectively. Difference in means: 2.5 mg; 95% confidence interval, 0.25 to 4.61; p = 0.030), and in the per-protocol analysis (8.3 (7.0) mg and 11.7 (9.9) mg in the acetaminophen group and the placebo group, respectively. Difference in means: 3.4 mg; 95% confidence interval: 1.05 to 5.77; p = 0.005). The two groups did not differ significantly in terms of pain intensity and adverse events.Conclusion: Our results suggest that intravenous acetaminophen at a daily dose of 2 g can reduce morphine consumption by Chinese adults within the first 24 h after orthopedic surgery, but the extent of reduction is not clinically relevant.Clinical Trial Registration: [ClinicalTrials.gov], identifier [NCT02811991].
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Affiliation(s)
- Feng Yin
- Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Wei Ma
- Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Qiao Liu
- Department of Anesthesiology, Chenzhou No. 1 People’s Hospital, Chenzhou, Hunan, China
| | - Liu-Lin Xiong
- Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Ting-Hua Wang
- Institute of Neurological Disease, Translational Neuroscience Centre, West China Hospital, Sichuan University, Chengdu, Sichuan, China
- Institute of Neuroscience, Kunming Medical University, Kunming, Yunnan, China
| | - Qian Li
- Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
- *Correspondence: Qian Li, ; Fei Liu,
| | - Fei Liu
- Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
- *Correspondence: Qian Li, ; Fei Liu,
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15
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Abstract
Pain is common among older people. However, it remains underrecognised and under-treated. A comprehensive assessment of pain involves identifying its cause, establishing its severity, determining its impact on the person experiencing it and reviewing the person's response to treatment. Addressing their pain requires a different approach compared to a younger person because there is usually concomitant frailty, multimorbidity, polypharmacy, sensory deficits and cognitive impairment. This review will summarise a comprehensive approach to pain management in the older person.
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16
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Fu JL, Perloff MD. Pharmacotherapy for Spine-Related Pain in Older Adults. Drugs Aging 2022; 39:523-550. [PMID: 35754070 DOI: 10.1007/s40266-022-00946-x] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/05/2022] [Indexed: 12/12/2022]
Abstract
As the population ages, spine-related pain is increasingly common in older adults. While medications play an important role in pain management, their use has limitations in geriatric patients due to reduced liver and renal function, comorbid medical problems, and polypharmacy. This review will assess the evidence basis for medications used for spine-related pain in older adults, with a focus on drug metabolism and adverse drug reactions. A PubMed/OVID search crossing common spine, neck, and back pain terms with key words for older adults and geriatrics was combined with common drug classes and common drug names and limited to clinical trials and age over 65 years. The results were then reviewed with identification of commonly used drugs and drug categories: nonsteroidal anti-inflammatories (NSAIDs), acetaminophen, corticosteroids, gabapentin and pregabalin, antispastic and antispasmodic muscle relaxants, tricyclic antidepressants (TCAs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tramadol, and opioids. Collectively, 138 double-blind, placebo-controlled trials were the focus of the review. The review found a variable contribution of high-quality studies examining the efficacy of medications for spine pain primarily in the geriatric population. There was strong evidence for NSAID use with adjustments for gastrointestinal and renal risk factors. Gabapentin and pregabalin had mixed evidence for neuropathic pain. SNRIs had good evidence for neuropathic pain and a more favorable safety profile than TCAs. Tramadol had some evidence in older patients, but more so in persons aged < 65 years. Rational therapeutic choices based on geriatric spine pain diagnosis are helpful, such as NSAIDs and acetaminophen for arthritic and myofascial-based pain, gabapentinoids or duloxetine for neuropathic and radicular pain, antispastic agents for myofascial-based pain, and combination therapy for mixed etiologies. Tramadol can be well tolerated in older patients, but has risks of cognitive and classic opioid side effects. Otherwise, opioids are typically avoided in the treatment of spine-related pain in older adults due to their morbidity and mortality risk and are reserved for refractory severe pain. Whenever possible, beneficial geriatric spine pain pharmacotherapy should employ the lowest therapeutic doses with consideration of polypharmacy, potentially decreased renal and hepatic metabolism, and co-morbid medical disorders.
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Affiliation(s)
- Jonathan L Fu
- Department of Neurology, Boston University School of Medicine, Boston Medical Center, 85 E. Concord St, 1122, Boston, MA, 02118, USA
| | - Michael D Perloff
- Department of Neurology, Boston University School of Medicine, Boston Medical Center, 85 E. Concord St, 1122, Boston, MA, 02118, USA.
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Alchin J, Dhar A, Siddiqui K, Christo PJ. Why paracetamol (acetaminophen) is a suitable first choice for treating mild to moderate acute pain in adults with liver, kidney or cardiovascular disease, gastrointestinal disorders, asthma, or who are older. Curr Med Res Opin 2022; 38:811-825. [PMID: 35253560 DOI: 10.1080/03007995.2022.2049551] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Acute pain is among the most common reasons that people consult primary care physicians, who must weigh benefits versus risks of analgesics use for each patient. Paracetamol (acetaminophen) is a first-choice analgesic for many adults with mild to moderate acute pain, is generally well tolerated at recommended doses (≤4 g/day) in healthy adults and may be preferable to non-steroidal anti-inflammatory drugs that are associated with undesirable gastrointestinal, renal, and cardiovascular effects. Although paracetamol is widely used, many patients and physicians still have questions about its suitability and dosing, especially for older people or adults with underlying comorbidities, for whom there are limited clinical data or evidence-based guidelines. Inappropriate use may increase the risks of both overdosing and inadequate analgesia. To address knowledge deficits and augment existing guidance in salient areas of uncertainty, we have researched, reviewed, and collated published evidence and expert opinion relevant to the acute use of paracetamol by adults with liver, kidney, or cardiovascular diseases, gastrointestinal disorders, asthma, or/and who are older. A concern is hepatotoxicity, but this is rare among adults who use paracetamol as directed, including people with cirrhotic liver disease. Putative epidemiologic associations of paracetamol use with kidney or cardiovascular disease, hypertension, gastrointestinal disorders, and asthma largely reflect confounding biases and are of doubtful relevance to short-term use (<14 days). Paracetamol is a suitable first-line analgesic for mild to moderate acute pain in many adults with liver, kidney or cardiovascular disease, gastrointestinal disorders, asthma, and/or who are older. No evidence supports routine dose reduction for older people. Rather, dosing for adults who are older and/or have decompensated cirrhosis, advanced kidney failure, or analgesic-induced asthma that is known to be cross-sensitive to paracetamol, should be individualized in consultation with their physician, who may recommend a lower effective dose appropriate to the circumstances.
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Affiliation(s)
- John Alchin
- Pain Management Centre, Burwood Hospital, Burwood, New Zealand
| | - Arti Dhar
- GlaxoSmithKline Consumer Healthcare Pte. Ltd, Singapore
| | | | - Paul J Christo
- Department of Anesthesiology and Critical Care Medicine, Division of Pain Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
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18
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Wilson SH, Wilson PR, Bridges KH, Bell LH, Clark CA. Nonopioid Analgesics for the Perioperative Geriatric Patient: A Narrative Review. Anesth Analg 2022; 135:290-306. [PMID: 35202007 DOI: 10.1213/ane.0000000000005944] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Management of acute perioperative pain in the geriatric patient can be challenging as the physiologic and pharmacokinetic changes associated with aging may predispose older patients to opioid-related side effects. Furthermore, elderly adults are more susceptible to postoperative delirium and postoperative cognitive dysfunction, which may be exacerbated by both poorly controlled postoperative pain and commonly used pain medications. This narrative review summarizes the literature published in the past 10 years for several nonopioid analgesics commonly prescribed to the geriatric patient in the perioperative period. Nonopioid analgesics are broken down as follows: medications prescribed throughout the perioperative period (acetaminophen and nonsteroidal anti-inflammatory drugs), medications limited to the acute perioperative setting (N-methyl-D-aspartate receptor antagonists, dexmedetomidine, dexamethasone, and local anesthetics), and medications to be used with caution in the geriatric patient population (gabapentinoids and muscle relaxants). Our search identified 1757 citations, but only 33 specifically focused on geriatric analgesia. Of these, only 21 were randomized clinical trials' and 1 was a systematic review. While guidance in tailoring pain regimens that focus on the use of nonopioid medications in the geriatric patient is lacking, we summarize the current literature and highlight that some nonopioid medications may extend benefits to the geriatric patient beyond analgesia.
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Affiliation(s)
- Sylvia H Wilson
- From the Department of Anesthesia and Perioperative Medicine, Medical University of South Carolina, Charleston, South Carolina
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19
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Jasat H, Thompson J, Sonneborn O, Dayment J, Miller C. Prolonged use of paracetamol and the prescribing patterns on rehabilitation facilities. J Clin Nurs 2021; 31:3605-3616. [PMID: 34957612 DOI: 10.1111/jocn.16188] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2021] [Revised: 12/14/2021] [Accepted: 12/16/2021] [Indexed: 11/30/2022]
Abstract
AIMS AND OBJECTIVES The study investigated: (a) the usage patterns of paracetamol, and (b) the association between paracetamol use and patient outcomes such as liver and kidney functions among older people. BACKGROUND Paracetamol is a well-known analgesic and antipyretic drug, with an excellent safety profile when used within its recommended dose. It is a commonly used drug by people aged over 65 years to treat chronic pain. Prolonged use of paracetamol in the elderly is poorly understood. As such, there is a genuine risk among older people of unintentional overdose. METHODS A retrospective analysis of medical records in rehabilitation wards was undertaken from 1 July 2016 to 30 June 2017. Patients' paracetamol use, prescribing patterns and biochemical results were analysed to assess for differences in admission and discharge biochemistry results. The TREND Statement was utilised to guide study reporting (Enhancing the QUAlity and Transparency Of health Research, 2021). RESULTS A total of 1119 patients were admitted for seven or more days in a metropolitan tertiary hospital in Melbourne. Almost three-quarters (74%) of patients were administered paracetamol; 76.1% received Immediate-Release Paracetamol (IRP), and 23.9% were given Sustained-release paracetamol (SRP). A proportion (4.5%) of patients in both the IRP and SRP groups received more than the daily recommended dose. There were limited statistically significant differences between patients' admission and discharge biochemistry results; group or time differences were observed, which were indicative of improvements within the paracetamol group. CONCLUSION Paracetamol was a commonly used medication among long-stay elderly patients. Precaution to ensure paracetamol use does not exceed recommended daily doses is required. This study suggests that paracetamol used at a therapeutic level in older patients had limited, negative associations with liver and kidney function. RELEVANCE TO CLINICAL PRACTICE The clinical practice regarding prolonged use of paracetamol is ambitious. The increased risk of paracetamol toxicity among the frail elderly is a concern. Optimising the dose adjustment in the elderly is important to avoid adverse outcomes.
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Affiliation(s)
- Homairah Jasat
- La Trobe University, Bundoora, Victoria, Australia.,Austin Health, Heidelberg, Victoria, Australia
| | - John Thompson
- Department of Nursing, The University of Melbourne, Carlton, Victoria, Australia.,Royal Melbourne Hospital, Melbourne, Victoria, Australia
| | - Olivia Sonneborn
- La Trobe University, Bundoora, Victoria, Australia.,Alfred Health, Melbourne, Victoria, Australia
| | | | - Charne Miller
- La Trobe University, Bundoora, Victoria, Australia.,Department of Nursing, The University of Melbourne, Carlton, Victoria, Australia
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20
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Kronfol MM, Abudahab S, Dozmorov MG, Jahr FM, Halquist MS, McRae M, Wijesinghe DS, Price ET, Slattum PW, McClay JL. Histone acetylation at the sulfotransferase 1a1 gene is associated with its hepatic expression in normal aging. Pharmacogenet Genomics 2021; 31:207-214. [PMID: 34320608 PMCID: PMC8490294 DOI: 10.1097/fpc.0000000000000443] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
OBJECTIVES Phase II drug metabolism is poorly studied in advanced age and older adults may exhibit significant variability in their expression of phase II enzymes. We hypothesized that age-related changes to epigenetic regulation of genes involved in phase II drug metabolism may contribute to these effects. METHODS We examined published epigenome-wide studies of human blood and identified the SULT1A1 and UGT1A6 genes as the top loci showing epigenetic changes with age. To assess possible functional alterations with age in the liver, we assayed DNA methylation (5mC) and histone acetylation changes around the mouse homologs Sult1a1 and Ugt1a6 in liver tissue from mice aged 4-32 months. RESULTS Our sample shows a significant loss of 5mC at Sult1a1 (β = -1.08, 95% CI [-1.8, -0.2], SE = 0.38, P = 0.011), mirroring the loss of 5mC with age observed in human blood DNA at the same locus. We also detected increased histone 3 lysine 9 acetylation (H3K9ac) with age at Sult1a1 (β = 0.11, 95% CI [0.002, 0.22], SE = 0.05, P = 0.04), but no change to histone 3 lysine 27 acetylation (H3K27ac). Sult1a1 gene expression is significantly positively associated with H3K9ac levels, accounting for 23% of the variation in expression. We did not detect any significant effects at Ugt1a6. CONCLUSIONS Sult1a1 expression is under epigenetic influence in normal aging and this influence is more pronounced for H3K9ac than DNA methylation or H3K27ac in this study. More generally, our findings support the relevance of epigenetics in regulating key drug-metabolizing pathways. In the future, epigenetic biomarkers could prove useful to inform dosing in older adults.
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Affiliation(s)
- Mohamad M. Kronfol
- Department of Pharmacotherapy and Outcomes Science, School of Pharmacy, Virginia Commonwealth University, Richmond, Virginia
| | - Sara Abudahab
- Department of Pharmacotherapy and Outcomes Science, School of Pharmacy, Virginia Commonwealth University, Richmond, Virginia
| | - Mikhail G. Dozmorov
- Department of Biostatistics, School of Medicine, Virginia Commonwealth University, Richmond, Virginia
| | - Fay M. Jahr
- Department of Pharmacotherapy and Outcomes Science, School of Pharmacy, Virginia Commonwealth University, Richmond, Virginia
| | - Matthew S. Halquist
- Department of Pharmaceutics, School of Pharmacy, Virginia Commonwealth University, Richmond, Virginia
| | - MaryPeace McRae
- Department of Pharmacotherapy and Outcomes Science, School of Pharmacy, Virginia Commonwealth University, Richmond, Virginia
| | - Dayanjan S. Wijesinghe
- Department of Pharmacotherapy and Outcomes Science, School of Pharmacy, Virginia Commonwealth University, Richmond, Virginia
| | - Elvin T. Price
- Department of Pharmacotherapy and Outcomes Science, School of Pharmacy, Virginia Commonwealth University, Richmond, Virginia
- Geriatric Pharmacotherapy Program, School of Pharmacy, Virginia Commonwealth University, Richmond, Virginia
- Institute for Inclusion, Inquiry and Innovation: Health and Wellness in Aging Populations Core, Virginia Commonwealth University, Richmond, Virginia
| | - Patricia W. Slattum
- Department of Pharmacotherapy and Outcomes Science, School of Pharmacy, Virginia Commonwealth University, Richmond, Virginia
- Geriatric Pharmacotherapy Program, School of Pharmacy, Virginia Commonwealth University, Richmond, Virginia
- Institute for Inclusion, Inquiry and Innovation: Health and Wellness in Aging Populations Core, Virginia Commonwealth University, Richmond, Virginia
| | - Joseph L. McClay
- Department of Pharmacotherapy and Outcomes Science, School of Pharmacy, Virginia Commonwealth University, Richmond, Virginia
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21
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Hias J, Van der Linden L, Walgraeve K, Gijsen M, Mian P, Koch BCP, Allegaert K, Annaert P, Tournoy J, Spriet I. Pharmacokinetics of 2 oral paracetamol formulations in hospitalized octogenarians. Br J Clin Pharmacol 2021; 88:1020-1030. [PMID: 34418143 DOI: 10.1111/bcp.15049] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2020] [Revised: 04/02/2021] [Accepted: 05/26/2021] [Indexed: 11/29/2022] Open
Abstract
AIMS It is currently unclear how paracetamol should be dosed in order to increase its efficacy while warranting safety in very old adults. The objective was to evaluate the pharmacokinetics of 2 oral paracetamol formulations and its metabolites in hospitalized octogenarians. METHODS Geriatric inpatients aged 80 years and older received a 1000-mg paracetamol tablet or granulate at 08.00, 14.00 and 20.00. After at least 4 consecutive gifts, plasma samples were collected around the 08.00 dose (trough, +0.5, +1, +2, +4, +5 and +6 h). Plasma concentrations of paracetamol and its metabolites were determined and individual pharmacokinetic parameters were derived. The Edmonton Frail Scale was used to assess frailty. An analgesic plasma target was defined as an average plasma concentration (Cavg ) of 10 mg/L. RESULTS The mean (±standard deviation) age was 86.78 (±4.20) years. The majority (n = 26/36, 72%) received the tablet, 10 (28%) the granulate. Thirty patients (85%) were classified with moderate to severe frailty. Seven (21%) patients had a Cavg above 10 mg/L. The median [interquartile range] time to reach the peak concentration was 50.5 [31.50-92.50] and 42.50 [33.75-106.75] min for the tablet and granulate, respectively. The coefficient of variation was 95% for time to reach the peak concentration and 30% for Cavg of paracetamol. A correlation of Cavg of paracetamol was observed with female sex and total serum bilirubin. CONCLUSION Large interindividual differences were found for pharmacokinetic parameters of oral paracetamol in frail inpatients after multiple dosing. Female sex and higher total serum bilirubin concentrations were associated with paracetamol exposure. No significant differences were observed between the tablet and granulate.
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Affiliation(s)
- Julie Hias
- Pharmacy Department, University Hospitals Leuven, Leuven, Belgium
| | - Lorenz Van der Linden
- Pharmacy Department, University Hospitals Leuven, Leuven, Belgium.,Department of Pharmaceutical and Pharmacological Sciences, KU Leuven - University of Leuven, Leuven, Belgium
| | | | - Matthias Gijsen
- Pharmacy Department, University Hospitals Leuven, Leuven, Belgium.,Department of Pharmaceutical and Pharmacological Sciences, KU Leuven - University of Leuven, Leuven, Belgium
| | - Paola Mian
- Department of Clinical Pharmacy, Medisch Spectrum Twente, Enschede, The Netherlands
| | - Birgit C P Koch
- Department of Hospital pharmacy, Erasmus MC University Medical Center, Rotterdam, The Netherlands
| | - Karel Allegaert
- Department of Pharmaceutical and Pharmacological Sciences, KU Leuven - University of Leuven, Leuven, Belgium.,Department of Hospital pharmacy, Erasmus MC University Medical Center, Rotterdam, The Netherlands.,Department of Development and Regeneration, KU Leuven - University of Leuven, Leuven, Belgium
| | - Pieter Annaert
- Drug Delivery and Disposition, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven - University of Leuven, Leuven, Belgium
| | - Jos Tournoy
- Department of Geriatric Medicine, University Hospitals Leuven, Leuven, Belgium.,Department of Public Health and Primary care, KU Leuven - University of Leuven, Leuven, Belgium
| | - Isabel Spriet
- Pharmacy Department, University Hospitals Leuven, Leuven, Belgium.,Department of Pharmaceutical and Pharmacological Sciences, KU Leuven - University of Leuven, Leuven, Belgium
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22
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TRPM2 Non-Selective Cation Channels in Liver Injury Mediated by Reactive Oxygen Species. Antioxidants (Basel) 2021; 10:antiox10081243. [PMID: 34439491 PMCID: PMC8389341 DOI: 10.3390/antiox10081243] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2021] [Revised: 07/25/2021] [Accepted: 07/26/2021] [Indexed: 12/12/2022] Open
Abstract
TRPM2 channels admit Ca2+ and Na+ across the plasma membrane and release Ca2+ and Zn2+ from lysosomes. Channel activation is initiated by reactive oxygen species (ROS), leading to a subsequent increase in ADP-ribose and the binding of ADP-ribose to an allosteric site in the cytosolic NUDT9 homology domain. In many animal cell types, Ca2+ entry via TRPM2 channels mediates ROS-initiated cell injury and death. The aim of this review is to summarise the current knowledge of the roles of TRPM2 and Ca2+ in the initiation and progression of chronic liver diseases and acute liver injury. Studies to date provide evidence that TRPM2-mediated Ca2+ entry contributes to drug-induced liver toxicity, ischemia–reperfusion injury, and the progression of non-alcoholic fatty liver disease to cirrhosis, fibrosis, and hepatocellular carcinoma. Of particular current interest are the steps involved in the activation of TRPM2 in hepatocytes following an increase in ROS, the downstream pathways activated by the resultant increase in intracellular Ca2+, and the chronology of these events. An apparent contradiction exists between these roles of TRPM2 and the role identified for ROS-activated TRPM2 in heart muscle and in some other cell types in promoting Ca2+-activated mitochondrial ATP synthesis and cell survival. Inhibition of TRPM2 by curcumin and other “natural” compounds offers an attractive strategy for inhibiting ROS-induced liver cell injury. In conclusion, while it has been established that ROS-initiated activation of TRPM2 contributes to both acute and chronic liver injury, considerable further research is needed to elucidate the mechanisms involved, and the conditions under which pharmacological inhibition of TRPM2 can be an effective clinical strategy to reduce ROS-initiated liver injury.
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23
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Clare D, Zink KL. Geriatric Trauma. Emerg Med Clin North Am 2021; 39:257-271. [PMID: 33863458 DOI: 10.1016/j.emc.2021.01.002] [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: 10/21/2022]
Abstract
Geriatric trauma patients will continue to increase in prevalence as the population ages, and many specific considerations need to be made to provide appropriate care to these patients. This article outlines common presentations of trauma in geriatric patients, with consideration to baseline physiologic function and patterns of injury that may be more prevalent in geriatric populations. Additionally, the article explores specific evidence-based management practices, the significance of trauma team and geriatrician involvement, and disposition decisions.
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Affiliation(s)
- Drew Clare
- Department of Emergency Medicine, University of Florida, 655 W 8th st, Jacksonville, FL 32209, USA.
| | - Korie L Zink
- Johns Hopkins University, 1830 E. Monument St, St 6-100, Baltimore, MD 21224, USA. https://twitter.com/koriezinkmd
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24
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Pietruk K, Gbylik-Sikorska M, Łebkowska-Wieruszewska B, Gajda A, Giorgi M, Sartini I, Jedziniak P. Development of a Multimatrix UHPLC-MS/MS Method for the Determination of Paracetamol and Its Metabolites in Animal Tissues. Molecules 2021; 26:molecules26072046. [PMID: 33918518 PMCID: PMC8038326 DOI: 10.3390/molecules26072046] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2021] [Revised: 03/29/2021] [Accepted: 03/30/2021] [Indexed: 11/16/2022] Open
Abstract
Paracetamol/acetaminophen (APAP) is one of the most popular pharmacologically active substances used as an analgesic and antipyretic agent. The metabolism of this drug occurs in the liver and leads to the formation of two main metabolites-glucuronic acid and sulfate derivate. Despite the wide use of paracetamol in veterinary medicine, a handful of analytical methods were published for the determination of paracetamol residues in animal tissues. In this paper, a multimatrix method has been developed for the determination of paracetamol and two metabolites-paracetamol sulfate (PS) and p-Acetamidophenyl β-D-glucuronide (PG). A validation procedure was conducted to verify method reliability and fit purpose as a tool for analyzing acetaminophen and metabolites in muscle, liver, lung, and kidney samples from different species of animals. Established validation parameters were in agreement with acceptable criteria laid by the European legislation. The initial significant matrix effect was successfully reduced by implementing an internal standard-4-Acetamidophenyl β-D-glucuronide-d3 (PG-d3, IS). The usefulness of the developed method was verified by analyzing samples from an experiment in which paracetamol was administrated to geese.
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Affiliation(s)
- Konrad Pietruk
- Department of Pharmacology and Toxicology, National Veterinary Research Institute, 24-100 Pulawy, Poland; (M.G.-S.); (A.G.); (P.J.)
- Correspondence: ; Tel.: +48 81-889-3169
| | - Małgorzata Gbylik-Sikorska
- Department of Pharmacology and Toxicology, National Veterinary Research Institute, 24-100 Pulawy, Poland; (M.G.-S.); (A.G.); (P.J.)
| | - Beata Łebkowska-Wieruszewska
- Department of Pharmacology, Toxicology and Environmental Protection, University of Life Sciences, 20-950 Lublin, Poland;
| | - Anna Gajda
- Department of Pharmacology and Toxicology, National Veterinary Research Institute, 24-100 Pulawy, Poland; (M.G.-S.); (A.G.); (P.J.)
| | - Mario Giorgi
- Department of Veterinary Sciences, University of Pisa, 56126 Pisa, Italy;
- Department of Veterinary Medicine, PhD School, University of Sassari, 07100 Sassari, Italy;
| | - Irene Sartini
- Department of Veterinary Medicine, PhD School, University of Sassari, 07100 Sassari, Italy;
| | - Piotr Jedziniak
- Department of Pharmacology and Toxicology, National Veterinary Research Institute, 24-100 Pulawy, Poland; (M.G.-S.); (A.G.); (P.J.)
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25
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Rotundo L, Pyrsopoulos N. Liver injury induced by paracetamol and challenges associated with intentional and unintentional use. World J Hepatol 2020; 12:125-136. [PMID: 32685105 PMCID: PMC7336293 DOI: 10.4254/wjh.v12.i4.125] [Citation(s) in RCA: 54] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2019] [Revised: 12/26/2019] [Accepted: 02/17/2020] [Indexed: 02/06/2023] Open
Abstract
Drug induced liver injury (DILI) is a common cause of acute liver injury. Paracetamol, also known as acetaminophen, is a widely used anti-pyretic that has long been established to cause liver toxicity once above therapeutic levels. Hepatotoxicity from paracetamol overdose, whether intentional or non-intentional, is the most common cause of DILI in the United States and remains a global issue. Given the increased prevalence of combination medications in the form of pain relievers and antihistamines, paracetamol can be difficult to identify and remains a significant cause of acute hepatotoxicity, as evidenced by its contribution to over half of all acute liver failure cases in the United States. This is especially concerning given that, when co-ingested with other medications, the rise in serum paracetamol levels may be delayed past the 4-hour post-ingestion mark that is currently used to determine patients that require medical therapy. This review serves to describe the clinical and pathophysiologic features of hepatotoxicity secondary to paracetamol and provide an update on current available knowledge and treatment options.
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Affiliation(s)
- Laura Rotundo
- Department of Medicine, Rutgers New Jersey Medical School, Newark, NJ 07103, United States
| | - Nikolaos Pyrsopoulos
- Department of Gastroenterology and Hepatology, Rutgers New Jersey Medical School, Newark, NJ 07103, United States.
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26
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Affiliation(s)
- Bruno T Saragiotto
- Masters and Doctoral Programs in Physical Therapy, Universidade Cidade de São Paulo, São Paulo, Brazil
- Institute for Musculoskeletal Health, University of Sydney, Camperdown, New South Wales, Australia
- Faculty of Medicine and Health, School of Public Health, University of Sydney, New South Wales, Australia
| | - Christina Abdel Shaheed
- Institute for Musculoskeletal Health, University of Sydney, Camperdown, New South Wales, Australia
- Faculty of Medicine and Health, School of Public Health, University of Sydney, New South Wales, Australia
| | - Chris G Maher
- Institute for Musculoskeletal Health, University of Sydney, Camperdown, New South Wales, Australia
- Faculty of Medicine and Health, School of Public Health, University of Sydney, New South Wales, Australia
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27
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Abstract
The management of acute pain in older adults (age 65 or greater) requires special attention due to various physiologic, cognitive, functional, and social issues that may change with aging. Especially in the postoperative setting, there are significant complications that can occur if pain is not treated adequately for elderly patients. In this article, the authors describe these changes in detail and discuss how pain should be assessed appropriately in older patients. In addition, the authors detail the unique risks and benefits of several mainstream analgesic medications as well as interventional treatments for elderly patients. The authors' goal is to provide recommendations for health care providers on appropriately recognizing and treating pain in a safe, effective manner for aging patients.
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Affiliation(s)
- Jay Rajan
- Department of Anesthesia and Perioperative Care, University of California, San Francisco, 513 Parnassus Avenue, S-455, San Francisco, CA 94143, USA
| | - Matthias Behrends
- Department of Anesthesia and Perioperative Care, University of California, San Francisco, 513 Parnassus Avenue, S-455, San Francisco, CA 94143, USA.
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28
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Mian P, van Esdonk MJ, Olkkola KT, de Winter BCM, Liukas A, Spriet I, Tibboel D, Petrovic M, Koch BCP, Allegaert K. Population pharmacokinetic modelling of intravenous paracetamol in fit older people displays extensive unexplained variability. Br J Clin Pharmacol 2019; 85:126-135. [PMID: 30321459 PMCID: PMC6303215 DOI: 10.1111/bcp.13770] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2018] [Revised: 09/10/2018] [Accepted: 09/16/2018] [Indexed: 02/06/2023] Open
Abstract
AIMS Paracetamol is the analgesic most used by older people. The physiological changes occurring with ageing influence the pharmacokinetics (PK) of paracetamol and its variability. We performed a population PK-analysis to describe the PK of intravenous (IV) paracetamol in fit older people. Simulations were performed to illustrate target attainment and variability of paracetamol exposure following current dosing regimens (1000 mg every 6 h, every 8 h) using steady-state concentration (Css-mean ) of 10 mg l-1 as target for effective analgesia. METHODS A population PK-analysis, using NONMEM 7.2, was performed based on 601 concentrations of paracetamol from 30 fit older people (median age 77.3 years, range [61.8-88.5], body weight 79 kg [60-107]). All had received an IV paracetamol dose of 1000 mg (over 15 min) after elective knee surgery. RESULTS A two-compartment PK-model best described the data. Volume of distribution of paracetamol increased exponentially with body weight. Clearance was not influenced by any covariate. Simulations of the standardized dosing regimens resulted in a Css of 9.2 mg l-1 and 7.2 mg l-1 , for every 6 h and every 8 h respectively. Variability in paracetamol PK resulted in Css above 5.4 and 4.1 mg l-1 , respectively, in 90% of the population and above 15.5 and 11.7, respectively, in 10% at these dosing regimens. CONCLUSIONS The target concentration was achieved in the average patient with 1000 mg every 6 h, while every 8 h resulted in underdosing for the majority of the population. Furthermore, due to a large (unexplained) interindividual variability in paracetamol PK a relevant proportion of the fit older people remained either under- or over exposed.
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Affiliation(s)
- P. Mian
- Intensive Care and Department of Paediatric SurgeryErasmus MC Sophia Children's HospitalRotterdamThe Netherlands
| | - M. J. van Esdonk
- Division of Systems Biomedicine and Pharmacology, Leiden Academic Centre for Drug ResearchLeiden UniversityLeidenThe Netherlands
- Centre for Human Drug ResearchLeidenThe Netherlands
| | - K. T. Olkkola
- Department of AnaesthesiologyIntensive Care and Pain Medicine University of Helsinki and Helsinki University Central HospitalHelsinkiFinland
| | | | - A. Liukas
- Department of AnaesthesiologyTurku University HospitalTurkuFinland
| | - I. Spriet
- Clinical Pharmacology and Pharmacotherapy, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven and Pharmacy DepartmentUniversity Hospital LeuvenLeuvenBelgium
| | - D. Tibboel
- Intensive Care and Department of Paediatric SurgeryErasmus MC Sophia Children's HospitalRotterdamThe Netherlands
| | - M. Petrovic
- Department of GeriatricsGhent University HospitalGhentBelgium
| | - B. C. P. Koch
- Department of Hospital PharmacyErasmus MCRotterdamThe Netherlands
| | - K. Allegaert
- Intensive Care and Department of Paediatric SurgeryErasmus MC Sophia Children's HospitalRotterdamThe Netherlands
- Department of Development and RegenerationKU LeuvenLeuvenBelgium
- Department of Paediatrics, Division of NeonatologyErasmus MC Sophia Children's HospitalRotterdamThe Netherlands
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