Der Gastrointestinaltrakt in der Parkinson-Therapie

Zusammenfassung

Gastrointestinale Funktionsstörungen sind das häufigste nicht motorische Symptom der Parkinson-Erkrankung und können den motorischen Symptomen vorausgehen. In den Krankheitsprozess sind nahezu alle Abschnitte des Magen-Darm-Trakts einbezogen. Neben dem Einfluss auf die Lebensqualität der Patienten hat die gastrointestinale Dysfunktion auch für die Therapie der Parkinson-Erkrankung erhebliche Bedeutung. Da die meisten Parkinson-Medikamente oral verabreicht werden, führen Störungen der Magenentleerung zu einer signifikanten Verzögerung der enteralen Resorption. Die irreguläre Pharmakokinetik oral verabreichter Medikamente, insbesondere von L-Dopa, erklärt die meisten der unerwarteten motorischen Fluktuationen fortgeschrittener Parkinson-Patienten. Eine Behandlung dieser Therapiekomplikationen sollte diesen Zusammenhang berücksichtigen.

Abstract

Gastrointestinal dysfunction is a common symptom in Parkinson's disease and the most common non-motor feature. The gastrointestinal dysfunction may precede the motor symptoms of the disease. The disease involves virtually all parts of the digestive tract. Beside the alterations of quality of life in most patients, gastrointestinal dysfunction has significant implications for the treatment of the disease. While most drugs in the therapy for Parkinson's disease are orally administered, disturbances in gastric emptying can cause significant delays in enteric resorption. The irregular pharmakokinetic behaviour of orally administered drugs, especially levodopa, may explain most of the unexpected motor fluctuations, seen in advanced stages of the disease. The treatment of motor fluctuations should therefore consider disturbances in gastric and enteric motility.

Schlüsselwörter

idiopathisches Parkinson-Syndrom - Gastrointestinaltrakt - Frühsymptom - Magenentleerungsstörung

Keywords

idiopathic Parkinson's syndrome - gastrointestinal tract - early symptoms - delayed gastric emptying

Literatur

• 1 Verbaan D, Marinus J, Visser M. et al . Patient-reported autonomic symptoms in Parkinson disease.  Neurology. 2007;  69 333-341
• 2 Edwards L L, Quigley E M, Pfeiffer R F. Gastrointestinal dysfunction in Parkinson's disease: frequency and pathophysiology.  Neurology. 1992;  42 726-732
• 3 Wakabayashi K. Parkinson's disease: the distribution of Lewy bodies in the peripheral autonomic nervous system.  No To Shinkei. 1989;  41 965-971
• 4 Wakabayashi K, Takahashi H, Ohama E. et al . Parkinson's disease: an immunohistochemical study of Lewy body-containing neurons in the enteric nervous system.  Acta Neuropathol. 1990;  79 581-583
• 5 Braak H, Braak E. Pathoanatomy of Parkinson's disease.  J Neurol. 2000;  247 (Suppl. 2) II3-10
• 6 Parkkinen L, Pirttila T, Alafuzoff I. Applicability of current staging / categorization of alpha-synuclein pathology and their clinical relevance.  Acta Neuropathol. 2008;  115 399-407
• 7 Jellinger K A. A critical reappraisal of current staging of Lewy-related pathology in human brain.  Acta Neuropathol. 2008;  116 1-16
• 8 Minguez-Castellanos A, Chamorro C E, Escamilla-Sevilla F. et al . Do alpha-synuclein aggregates in autonomic plexuses predate Lewy body disorders? A cohort study.  Neurology. 2007;  68 2012-2018
• 9 Phillips R J, Walter G C, Wilder S L. et al . Alpha-synuclein-immunopositive myenteric neurons and vagal preganglionic terminals: Autonomic pathway implicated in Parkinson's disease?.  Neuroscience. 2008;  153 733-750
• 10 Singaram C, Ashraf W, Gaumnitz E A. et al . Dopaminergic defect of enteric nervous system in Parkinson's disease patients with chronic constipation.  Lancet. 1995;  346 861-864
• 11 Goetze O, Woitalla D. The role of MPTP in Parkinson's disease: connecting brain and gut?.  Exp Neurol. 2008;  210 281-285
• 12 Anderson G, Noorian A R, Taylor G. et al . Loss of enteric dopaminergic neurons and associated changes in colon motility in an MPTP mouse model of Parkinson's disease.  Exp Neurol. 2007;  207 4-12
• 13 Parkinson J. An essay on the shaking palsy. London; Wittingham and Rowland 1817
• 14 Quigley E M. Gastrointestinal dysfunction in Parkinson's disease.  Semin Neurol. 1996;  16 245-250
• 15 Abbott R D, Petrovitch H, White L R. et al . Frequency of bowel movements and the future risk of Parkinson's disease.  Neurology. 2001;  57 456-462
• 16 Qualman S J, Haupt H M, Yang P. et al . Esophageal Lewy bodies associated with ganglion cell loss in achalasia. Similarity to Parkinson's disease.  Gastroenterology. 1984;  87 848-856
• 17 Siderowf A, Stern M B. Premotor Parkinson's disease: clinical features, detection, and prospects for treatment.  Ann Neurol. 2008;  64 (Suppl. 2) S139-147
• 18 Goetze O, Wieczorek J, Mueller T. et al . Impaired gastric emptying of a solid test meal in patients with Parkinson's disease using 13C-sodium octanoate breath test.  Neurosci Lett. 2005;  375 170-173
• 19 Bagheri H, Damase-Michel C, Lapeyre-Mestre M. et al . A study of salivary secretion in Parkinson's disease.  Clin Neuropharmacol. 1999;  22 213-215
• 20 Hyson H C, Johnson A M, Jog M S. Sublingual atropine for sialorrhea secondary to parkinsonism: a pilot study.  Mov Disord. 2002;  17 1318-1320
• 21 Bhatia K P, Munchau A, Brown P. Botulinum toxin is a useful treatment in excessive drooling in saliva.  J Neurol Neurosurg Psychiatry. 1999;  67 697
• 22 Pal P K, Calne D B, Calne S. et al . Botulinum toxin A as treatment for drooling saliva in PD.  Neurology. 2000;  54 244-247
• 23 Pfeiffer R F. Gastrointestinal dysfunction in Parkinson's disease.  Lancet Neurol. 2003;  2 107-116
• 24 Jost W H, Schimrigk K. Long-term results with cisapride in Parkinson's disease.  Mov Disord. 1997;  12 423-425
• 25 Astarloa R, Mena M A, Sanchez V. et al . Clinical and pharmacokinetic effects of a diet rich in insoluble fiber on Parkinson disease.  Clin Neuropharmacol. 1992;  15 375-380
• 26 Corazziari E, Badiali D, Habib F I. et al . Small volume isosmotic polyethylene glycol electrolyte balanced solution (PMF-100) in treatment of chronic nonorganic constipation.  Dig Dis Sci. 1996;  41 1636-1642
• 27 Eichhorn T E, Oertel W H. Macrogol 3350 / electrolyte improves constipation in Parkinson's disease and multiple system atrophy.  Mov Disord. 2001;  16 1176-1177
• 28 Albanese A, Brisinda G, Bentivoglio A R. et al . Treatment of outlet obstruction constipation in Parkinson's disease with botulinum neurotoxin A.  Am J Gastroenterol. 2003;  98 1439-1440
• 29 Brisinda G, Bentivoglio A R, Maria G. et al . Treatment with botulinum neurotoxin of gastrointestinal smooth muscles and sphincters spasms.  Mov Disord. 2004;  19 (Suppl. 8) S146-156
• 30 Byrne K G, Pfeiffer R, Quigley E M. Gastrointestinal dysfunction in Parkinson's disease. A report of clinical experience at a single center.  J Clin Gastroenterol. 1994;  19 11-16
• 31 Haruta S, Kawai K, Nishii R. et al . Prediction of plasma concentration-time curve of orally administered theophylline based on a scintigraphic monitoring of gastrointestinal transit in human volunteers.  Int J Pharm. 2002;  233 179-190
• 32 Kimura T, Higaki K. Gastrointestinal transit and drug absorption.  Biol Pharm Bull. 2002;  25 149-164
• 33 Stocchi F. The levodopa wearing-off phenomenon in Parkinson's disease: pharmacokinetic considerations.  Expert Opin Pharmacother. 2006;  7 1399-1407
• 34 Stocchi F, Vacca L, Ruggieri S. et al . Intermittent vs continuous levodopa administration in patients with advanced Parkinson disease: a clinical and pharmacokinetic study.  Arch Neurol. 2005;  62 905-910
• 35 Woitalla D. Relevanz der Plasmaspiegelbestimmung des L-Dopa und 3-O-Methyldopa beim Morbus Parkinson.  Relevance of Plasma Level Determination of L-Dopa and 3-O-Methyldopa in Parkinson's Disease. 1998;  25 S279-S281
• 36 Muller T, Erdmann C, Bremen D. et al . Impact of gastric emptying on levodopa pharmacokinetics in Parkinson disease patients.  Clin Neuropharmacol. 2006;  29 61-67
• 37 Goetze O, Nikodem A B, Wiezcorek J. et al . Predictors of gastric emptying in Parkinson's disease.  Neurogastroenterol Motil. 2006;  18 369-375