Levodopa Pharmacokinetics From Stomach To Brain
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Levodopa Pharmacokinetics From Stomach To Brain
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Author : Maria Nord
language : sv
Publisher: Linköping University Electronic Press
Release Date : 2019-01-07
Levodopa Pharmacokinetics From Stomach To Brain written by Maria Nord and has been published by Linköping University Electronic Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2019-01-07 with categories.
Parkinson’s disease (PD) is one of the most common neurodegenerative disorders and it is caused by a loss of dopamine (DA) producing neurons in the basal ganglia in the brain. The PD patient suffers from motor symptoms such as tremor, bradykinesia and rigidity and treatment with levodopa (LD), the precursor of DA, has positive effects on these symptoms. Several factors affect the availability of orally given LD. Gastric emptying (GE) is one factor and it has been shown to be delayed in PD patients resulting in impaired levodopa uptake. Different enzymes metabolize LD on its way from the gut to the brain resulting in less LD available in the brain and more side effects from the metabolites. By adding dopa decarboxylase inhibitors (carbidopa or benserazide) or COMT-inhibitors (e.g. entacapone) the bioavailability of LD increases significantly and more LD can pass the blood-brain-barrier and be converted to DA in the brain. It has been considered of importance to avoid high levodopa peaks in the brain because this seems to induce changes in postsynaptic dopaminergic neurons causing disabling motor complications in PD patients. More continuously given LD, e.g. duodenal or intravenous (IV) infusions, has been shown to improve these motor complications. Deep brain stimulation of the subthalamic nucleus (STN DBS) has also been proven to improve motor complications and to make it possible to reduce the LD dosage in PD patients. In this doctoral thesis the main purpose is to study the pharmacokinetics of LD in patients with PD and motor complications; in blood and subcutaneous tissue and study the effect of GE and PD stage on LD uptake and the effect of continuously given LD (CDS) on LD uptake and GE; in blood and cerebrospinal fluid (CSF) when adding the peripheral enzyme inhibitors entacapone and carbidopa to LD infusion IV; in brain during STN DBSand during oral or IV LD treatment. To conclude, LD uptake is more favorable in PD patients with less severe disease and GE is delayed in PD patients. No obvious relation between LD uptake and GE or between GE and PD stage is seen and CDS decreases the LD levels. Entacapone increases the maximal concentration of LD in blood and CSF. This is more evident with additional carbidopa and important to consider in avoiding high LD peaks in brain during PD treatment. LD in brain increases during both oral and IV LD treatment and the DA levels follows LD well indicating that PD patients still have capacity to metabolize LD to DA despite probable pronounced nigral degeneration. STN DBS seems to increase putaminal DA levels and together with IV LD treatment also increases LD in brain possibly explaining why it is possible to decrease LD medication after STN DBS surgery. Parkinsons sjukdom (PS) är en av de vanligaste s.k. neurodegenerativasjukdomarna och orsakas av förlust av dopamin(DA)producerande nervceller i hjärnan. Detta orsakar motoriska symptom såsom skakningar, stelhet och förlångsammade rörelser. Levodopa (LD) är ett ämne, som kan omvandlas till DA i hjärnan och ge symptomlindring och det är oftast förstahandsval vid behandling av patienter med PS. Flera faktorer påverkar tillgängligheten av LD, bl.a. den hastighet som magsäcken tömmer sig med och denna verkar förlångsammad hos personer med PS vilket ger sämre tillgänglighet av LD i blodet och därmed i hjärnan. LD bryts även ner i hög grad av olika enzym ute i kroppen vilket leder till mindre mängd LD som hamnar i hjärnan och till fler nedbrytningsprodukter som orsakar biverkningar. Tillägg av enzymhämmare leder till ökad mängd LD som kan nå hjärnan och omvandlas till DA. Det anses viktigt att undvika höga toppar av LD i hjärnan då dessa verkar bidra till utvecklandet av besvärliga motoriska komplikationer hos patienter med PS. Om LD ges mer kontinuerligt, exempelvis som en kontinuerlig infusion in i tarmen eller i blodet, så minskar dessa motoriska komplikationer. Inopererande av stimulatorer i vissa delar av hjärnan (DBS) har också visat sig minska dessa motoriska komplikationer och även resultera i att man kan minska LD-dosen. Huvudsyftet med den här avhandlingen är att studera LD hos patienter med PS; i blod och fettvävnad då LD ges i tablettform och se om det finns något samband med LD-upptag och hastigheten på magsäckstömningen (MT) och om kontinuerligt given LD påverkar LD-upptaget eller MT; i blod och i ryggmärgsvätska då enzymhämmarna entakapon och karbidopa tillsätts LD; i hjärna vid behandling med DBS och då LD ges både som tablett och som infusion i blodet. Sammanfattningsvis kan vi se att LD-upptaget är mer gynnsamt hos patienter med PS i tidigare skede av sjukdomens komplikationsfas. MT är förlångsammad hos patienter med PS och det är inget tydligt samband mellan LD-upptag och MT eller mellan MT och sjukdomsgrad. Kontinuerligt given LD minskar LDnivåerna. Enzymhämmaren entakapon ökar den maximala koncentrationen av LD i blod och ryggmärgsvätska och effekten är mer tydlig vid tillägg av karbidopa vilket är viktigt att ta i beaktande vid behandling av PS för att undvika höga toppar av LD i hjärnan. LD ökar i hjärnan då man behandlar med LD i tablettform och som infusion i blodet och DA-nivåerna i hjärnan följer LD väl vilket visar på att patienter med PS fortfarande kan omvandla LD till DA trots trolig uttalad brist av de DA-producerande nervcellerna i hjärnan. DBS verkar öka DA i vissa områden i hjärnan och tillsammans med LD-infusion i blodet verkar det även öka LD i hjärnan och det kan förklara varför man kan sänka LDdosen efter DBS-operation.
Neuropsychopharmacotherapy
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Author : Peter Riederer
language : en
Publisher: Springer Nature
Release Date : 2022-11-04
Neuropsychopharmacotherapy written by Peter Riederer and has been published by Springer Nature this book supported file pdf, txt, epub, kindle and other format this book has been release on 2022-11-04 with Medical categories.
This book provides a reference guide describing the current status of medication in all major psychiatric and neurological indications, together with comparisons of pharmacological treatment strategies in clinical settings in Europe, USA, Japan and China. In addition, it highlights herbal medicine as used in China and Japan, as well as complementary medicine and nutritional aspects. This novel approach offers international readers a global approach in a single dedicated publication and is also a valuable resource for anyone interested in comparing treatments for psychiatric disorders in three different cultural areas. There are three volumes devoted to Basic Principles and General Aspects, offering a general overview of psychopharmacotherapy (Vol. 1); Classes, Drugs and Special Aspects covering the role of psychotropic drugs in the field of psychiatry and neurology (Vol. 2) and Applied Psychopharmacotherapy focusing on applied psychopharmacotherapy (Vol. 3). These books are invaluable to psychiatrists, neurologists, neuroscientists, medical practitioners and clinical psychologists.
Non Motor Symptoms Of Parkinson S Disease
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Author : K. Ray Chaudhuri
language : en
Publisher: Oxford University Press, USA
Release Date : 2014
Non Motor Symptoms Of Parkinson S Disease written by K. Ray Chaudhuri and has been published by Oxford University Press, USA this book supported file pdf, txt, epub, kindle and other format this book has been release on 2014 with Medical categories.
Patients with Parkinson's disease (PD) are known to suffer from motor symptoms of the disease, but they also experience non-motor symptoms (NMS) that are often present before diagnosis or that inevitably emerge with disease progression. The motor symptoms of Parkinson's disease have been extensively researched, and effective clinical tools for their assessment and treatment have been developed and are readily available. In contrast, researchers have only recently begun to focus on the NMS of Parkinson's Disease, which are poorly recognized and inadequately treated by clinicians. The NMS of PD have a significant impact on patient quality of life and mortality and include neuropsychiatric, sleep-related, autonomic, gastrointestinal, and sensory symptoms. While some NMS can be improved with currently available treatments, others may be more refractory and will require research into novel (non-dopaminergic) drug therapies for the future. Edited by members of the UK Parkinson's Disease Non-Motor Group (PD-NMG) and with contributions from international experts, this new edition summarizes the current understanding of NMS symptoms in Parkinson's disease and points the way towards future research.
Oral Drug Absorption
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Author : Jennifer B. Dressman
language : en
Publisher: CRC Press
Release Date : 2016-04-19
Oral Drug Absorption written by Jennifer B. Dressman and has been published by CRC Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2016-04-19 with Medical categories.
Oral Drug Absorption, Second Edition thoroughly examines the special equipment and methods used to test whether drugs are released adequately when administered orally. The contributors discuss methods for accurately establishing and validating in vitro/in vivo correlations for both MR and IR formulations, as well as alternative approaches for MR an
Parkinson S Disease And Nonmotor Dysfunction
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Author : Ronald F. Pfeiffer
language : en
Publisher: Springer Science & Business Media
Release Date : 2007-11-10
Parkinson S Disease And Nonmotor Dysfunction written by Ronald F. Pfeiffer and has been published by Springer Science & Business Media this book supported file pdf, txt, epub, kindle and other format this book has been release on 2007-11-10 with Medical categories.
Parkinson’s Disease and Nonmotor Dysfunction fills a major gap in the current rapidly growing body of knowledge concerning Parkinson’s disease. Drs. Pfeiffer and Bodis-Wollner have correctly perceived that many nonmotor features of Parkinson’s disease are given insufficient attention in the medical literature. Unfortunately, they are often also given insufficient attention by the practicing neurologists who see these patients. As recently pointed out, there is clearly much more to Parkinson’s disease than depletion of the nigrostriatal dopamine system (1). Parkinson’s disease (not just m- tiple system atrophy) is a multisystem disorder, both pathologically and in its clinical manifestations. This is clearly true for the various motor system abnormalities, which are not fully corrected by dopamine replacement therapy strategies, but also for the nonmotor system abnormalities that are the subject of this volume. Although recently there has been increased awareness of the cognitive, psychiatric, and sleep disorders commonly associated with Parkinson’s disease, many of their manifestations remain under-recognized and their importance in managing patients is underestimated. Even less attention is paid to the myriad of other nonmotor disturbances that plague these patients. For example, among the autonomic disorders, although orthostatic hypotension is well recognized, it is usually attributed to dopaminergic medications rather than to effects of the underlying disease. Urologic disorders are also very familiar in these patients, but may not be properly understood or well managed.
The New Parkinson S Disease Treatment Book
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Author : J. Eric Ahlskog, PhD, MD
language : en
Publisher: Oxford University Press
Release Date : 2015-08-03
The New Parkinson S Disease Treatment Book written by J. Eric Ahlskog, PhD, MD and has been published by Oxford University Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2015-08-03 with Health & Fitness categories.
The fundamental guide to the most effective treatments for Parkinson's Disease, from a Mayo Clinic doctor with thirty years of clinical and research experience. In this second edition follow-up to the extremely successful first edition, Dr. Ahlskog draws on thirty years of clinical experience to present the definitive guide to dealing with all aspects of Parkinson's Disease, from treatment options and side effects to the impact of the disease on caregivers and family. Dr. Ahlskog's goal is to educate patients so that they can better team up with their doctors to do battle with the disease, streamlining the decision-making process and enhancing their treatment. To do this, Dr. Ahlskog offers a gold mine of information, distilled from his years of experience treating people with Parkinson's at the Mayo Clinic. In addition to providing a comprehensive account of Parkinson's medications, this book also examines additional aspects of treatment, such as the role of nutrition, exercise, and physical therapy. Although many commendable texts have been written on the subject of Parkinson's Disease, their discussions of treatment have not been in depth. Dr. Ahlskog sifts through aspects of the disease in order to give the reader a comprehensive sense of Parkinson's and the best available treatment options. With a broader understanding of the disease and the available options, patients are able to make more informed choices, and doctors are able to provide more tailored care. This book delivers hopeful, helpful, and extensive information to all parties concerned: patients, caregivers, and doctors. The ultimate guide to symptoms and treatment, this thoroughly updated second edition is the first place patients should turn for reliable, easy-to-grasp information on Parkinson's Disease.
Parkinson S Disease
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Author : Ronald F. Pfeiffer
language : en
Publisher: CRC Press
Release Date : 2012-10-09
Parkinson S Disease written by Ronald F. Pfeiffer and has been published by CRC Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2012-10-09 with Medical categories.
In recent years, considerable advances have been made in our knowledge and understanding of Parkinson's disease (PD). In particular, there has been an explosion of information regarding genetic contributions to the etiology of PD and an increased awareness of the importance of the non-motor features of the disease. Theories regarding the pathogenes
Parkinsons S Disease
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Author : Peter Lewitt
language : en
Publisher: CRC Press
Release Date : 1999-05-30
Parkinsons S Disease written by Peter Lewitt and has been published by CRC Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 1999-05-30 with Medical categories.
With the general population becoming increasingly aware of new developments for the diagnosis and treatment of certain neurological disorders throught increased media coverage in the popular press and on television and with celebrities being affected, the clinician must be aware of all the latest developments inthe diagnosis and treatment of disease. Parkinson's disease is no different. Peter LeWitt and Wolfgang Oertel have assembled an international team of contributors to write on their particular areas of expertise to produce a work which will help the practising clinician. This book captures all the latest information: the most important developments in the research of Parkinson's disease in recent years and the many different approaches to the treatment of the disease. These are exciting times for the study of Parkinson's disease, and this book condenses the wealth of available information into a practical text.
Introduction To Basics Of Pharmacology And Toxicology
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Author : Abialbon Paul
language : en
Publisher: Springer Nature
Release Date : 2021-03-13
Introduction To Basics Of Pharmacology And Toxicology written by Abialbon Paul and has been published by Springer Nature this book supported file pdf, txt, epub, kindle and other format this book has been release on 2021-03-13 with Medical categories.
This book explains the pharmacological relationships between the various systems in the human body. It offers a comprehensive overview of the pharmacology concerning the autonomic, central, and peripheral nervous systems. Presenting up-to-date information on chemical mediators and their significance, it highlights the therapeutic aspects of several diseases affecting the cardiovascular, renal, respiratory, gastrointestinal, endocrinal, and hematopoietic systems. The book also includes drug therapy for microbial and neoplastic diseases. It also comprises sections on immunopharmacology, dermatological, and ocular pharmacology providing valuable insights into these emerging and recent topics. Covering the diverse groups of drugs acting on different systems, the book reviews their actions, clinical uses, adverse effects, interactions, and subcellular mechanisms of action. It is divided into 11 parts, subdivided into several chapters that evaluate the basic pharmacological principles that govern the different types of body systems. This book is intended for academicians, researchers, and clinicians in industry and academic institutions in pharmaceutical, pharmacological sciences, pharmacy, medical sciences, physiology, neurosciences, biochemistry, molecular biology and other allied health sciences.
The Gut Brain Axis
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Author : Niall Hyland
language : en
Publisher: Elsevier
Release Date : 2023-12-15
The Gut Brain Axis written by Niall Hyland and has been published by Elsevier this book supported file pdf, txt, epub, kindle and other format this book has been release on 2023-12-15 with Medical categories.
The Gut-Brain Axis: Dietary, Probiotic, and Prebiotic Interventions on the Microbiota, Second Edition presents the most advances on how the gut microbiome influences central nervous system and brain function introduced in the first edition. The book also describes how environmental influences which affect the microbiota, including, diet, exercise, and early-life, impact on the gut-brain axis. The second edition contains new chapters on metabolomics and the gut-brain-axis; dietary factors in the maintenance of a healthy brain ; the role of gut microbes in neurodegenerative disorders; the link between exercise and the gut-brain-axis; and infant Nutrition, the microbiome and neurodevelopment. In addition, the second edition presents coverage of mechanisms underlying neurological disease; approaches to investigate the role of the microbiome in brain and behavior, and 'next generation' probiotics and prebiotics. The Gut-Brain Axis: Dietary, Probiotic, and Prebiotic Interventions on the Microbiota, Second Edition continues to be the “go-to resource for further exploration of the microbiota. Includes new chapters focused on metabolomics and the gut-brain axis; dietary polyphenols to maintain healthier brain measures and cognitive function; the role of gut microbes in Parkinson’s Disease; the microbiota-gut-brain axis in psychosis; exploration of exercise and the gut-brain axis; and coverage of pediatric nutrition Updated chapters reflect on the most recent advances on the role of the microbiome and gut-brain axis in early-life, aging, cognition, metabolism, neurodevelopmental disorders, as well as on the enteric nervous system Addresses the role of diet and the gut-brain axis across several chapters with unique author insights and perspectives Examines common mechanisms and pathways by which the microbiota may influence brain and behavior Discusses strategies to explore the contribution of the microbiome to the gut-brain axis; methods to enhance therapeutic strategies targeted toward the microbiota; and presents a case study demonstrating a rational screening approach to increase translational success