Kontinuierliche Therapie mit der Apomorphinpumpe

Zusammenfassung

Die kontinuierliche subkutane Infusion mit Apomorphin gehört neben der duodenalen Infusion von L-Dopa via PEG (perkutane enterale Gastrostomie) und der tiefen Hirnstimulation mit intrazerebralen Elektroden zu den 3 ressourcenintensiveren Therapien der Parkinsonkrankheit. Von diesen Therapien ist die Apomorphinpumpe für den Patienten die am schnellsten und einfachsten „ausprobierbare” Therapie, weil sie keinen operativen Eingriff wie den einer PEG oder Hirnoperation erfordert. Die kontinuierliche subkutane Infusion mit Apomorphin kann Off-Zeiten um mehr als 50 % (bis zu 85 %) reduzieren. Außerdem werden bestehende L-Dopa-induzierte Dyskinesien längerfristig signifikant gelindert. Es finden sich Verlaufsbeobachtungen von über 100 Monaten mit nachhaltiger Wirksamkeit. Hauptproblem der kontinuierlichen subkutanen Infusion sind die Hauterscheinungen an den Injektionsstellen, während unerwünschte psychiatrische Probleme eine geringe Rolle spielen. In anderen europäischen Ländern ist die Therapie mit der Apomorphinpumpe viel weiter verbreitet als in Deutschland. Ziel dieses Artikels ist es, Indikationen, praktisches Vorgehen sowie den Umgang mit Problemen der kontinuierlichen subkutanen Apomorphintherapie vorzustellen.

Abstract

The continuous subcutaneous infusion of apomorphine represents together with the duodenal infusion of levodopa via percutaneous gastrostomy and deep brain stimulation one of the three resource dependent therapeutic interventions in Parkinson’s disease. Among these therapeutic options the apomorphine pump is the treatment which is most easily and readily tested, because it does not need any surgical procedure. The continuous subcutaneous infusion of apomorphine can reduce Off-time by more than 50 % (up to 85 %) and lessen preexisting levodopa dyskinesias significantly. There are reports with a mean follow up of up to more than 100 months. The main side effects of subcutaneous apomorphine treatment are cutaneous nodules, whereas sedation and psychiatric complications play a lesser role. In other European countries the use of the apomorphine pump is by far more extended than in Germany. The aim of this article is to present the indications, practical issues and handling of problems with subcutaneous apomorphine treatment.

Parkinsonsyndrom - Medikamentenpumpen - Apomorphin - Dopaminagonisten - Dopa

Parkinson disease - medication pumps - apomorphine - dopamine agonists - levodopa, L-dopa

Literatur

• 1 Struppler A, Uexkuell T v. Untersuchungen ueber die Wirkungsweise von Apomorphine auf den Parkinsontremor.  Z Klin Med. 1953;  152 46-57
• 2 Cotzias G C, Papavasiliou P S, Fehling C et al. Similarities between neurologic effects of L-dopa and of apomorphine.  N Engl J Med. 1970;  282 31-33
• 3 Corsini G U, Del Zompo M, Gessa G L et al. Therapeutic efficacy of apomorphine combined with an extracerebral inhibitor of dopamine receptors in Parkinson’s disease.  Lancet. 1979;  1 954-956
• 4 Stibe C M, Lees A J, Kempster P A et al. Subcutaneous apomorphine in parkinsonian on-off oscillations.  Lancet. 1988;  1 403-406
• 5 Luginger E, Wenning G K, Bosch S et al. Beneficial effects of amantadine on L-dopa-induced dyskinesias in Parkinson’s disease.  Mov Disord. 2000;  15 873-878
• 6 Manson A J, Hanagasi H, Turner K et al. Intravenous apomorphine therapy in Parkinson’s disease: clinical and pharmacokinetic observations.  Brain. 2001;  124 331-340
• 7 Dewey Jr R B, Hutton J T, LeWitt P A et al. A randomized, double-blind, placebo-controlled trial of subcutaneously injected apomorphine for parkinsonian off-state events.  Arch Neurol. 2001;  58 1385-1392
• 8 Manson A J, Turner K, Lees A J. Apomorphine monotherapy in the treatment of refractory motor complications of Parkinson’s disease: long-term follow-up study of 64 patients.  Mov Disord. 2002;  17 1235-1241
• 9 Katzenschlager R, Hughes A, Evans A et al. Continuous subcutaneous apomorphine therapy improves dyskinesias in Parkinson’s disease: A prospective study using single-dose challenges.  Mov Disord. 2004;  20 151-157
• 10 Tyne H L, Parsons J, Sinnott A et al. A 10 year retrospective audit of long-term apomorphine use in Parkinson’s disease.  J Neurol. 2004;  251 1370-1374
• 11 Hughes A J, Lees A J, Stern G M. Challenge tests to predict the dopaminergic response in untreated Parkinson’s disease.  Neurology. 1991;  41 1723-1725
• 12 Factor S A, Brown D L, Molho E S. Subcutaneous apomorphine injections as a treatment for intractable pain in Parkinson’s disease.  Mov Disord. 2000;  15 167-169
• 13 Reuter I, Ellis C M, Ray Chaudhuri K. Nocturnal subcutaneous apomorphine infusion in Parkinson’s disease and restless legs syndrome.  Acta Neurol Scand. 1999;  100 163-167
• 14 Tison F, Wiart L, Guatterie M et al. Effects of central dopaminergic stimulation by apomorphine on swallowing disorders in Parkinson’s disease.  Mov Disord. 1996;  11 729-732
• 15 Kempster P A, Lees A J, Crichton P et al. Off-period belching due to a reversible disturbance of oesophageal motility in Parkinson’s disease and its treatment with apomorphine.  Mov Disord. 1989;  4 47-52
• 16 Bailbe M, Bataille B, Paquereau J et al. Improvement in swallowing difficulties treated by subcutaneous apomorphine infusion after deep brain stimulation in Parkinson’s disease.  Rev Neurol. 2004;  160 352-353
• 17 Christmas T J, Kempster P A, Chapple C R et al. Role of subcutaneous apomorphine in parkinsonian voiding dysfunction.  Lancet. 1988;  2 1451-1453
• 18 Edwards L L, Quigley E M, Harned R K et al. Defecatory function in Parkinson’s disease: response to apomorphine.  Ann Neurol. 1993;  33 490-493
• 19 O’Sullivan J D. Apomorphine as an alternative to sildenafil in Parkinson’s disease.  J Neurol Neurosurg Psychiatry. 2002;  72 681
• 20 O’Sullivan J D, Hughes A J. Apomorphine-induced penile erections in Parkinson’s disease.  Mov Disord. 1998;  13 536-539
• 21 Di Rosa A E, Epifanio A, Antonini A et al. Continuous apomorphine infusion and neuropsychiatric disorders: a controlled study in patients with advanced Parkinson’s disease.  Neurol Sci. 2003;  24 174-175
• 22 Garcia Ruiz P J. Nocturnal subcutaneous apomorphine infusion for severe insomnia in Parkinson’s disease.  Mov Disord. 2006;  21 727-728
• 23 Eggert K et al. Parkinson-Syndrome – Diagnostik und Therapie. Leitlinien für Diagnostik und Therapie in der Neurologie. 4. überarbeitete Auflage. Stuttgart: Thieme Verlag; 2008
• 24 Chaudhuri K R, Critchley P, Abbott R J et al. Subcutaneous apomorphine for on-off oscillations in Parkinson’s disease.  Lancet. 1988;  2 1260
• 25 Pollak P, Champay A S, Hommel M et al. Subcutaneous apomorphine in Parkinson’s disease.  J Neurol Neurosurg Psychiatry. 1989;  52 544
• 26 Kreczy-Kleedorfer B, Wagner M, Bosch S et al. Long-term results of continuous subcutaneous apomorphine pump therapy in patients with advanced Parkinson disease.  Nervenarzt. 1993;  64 221-225
• 27 Stocchi F, Bramante L, Monge A et al. Apomorphine and lisuride infusion. A comparative chronic study.  Adv Neurol. 1993;  60 653-655
• 28 Hughes A J, Bishop S, Kleedorfer B et al. Subcutaneous apomorphine in Parkinson’s disease: response to chronic administration for up to five years.  Mov Disord. 1993;  8 165-170
• 29 Gancher S T, Nutt J G, Woodward W R. Apomorphine infusional therapy in Parkinson’s disease: clinical utility and lack of tolerance.  Mov Disord. 1995;  10 37-43
• 30 Pietz K, Hagell P, Odin P. Subcutaneous apomorphine in late stage Parkinson’s disease: a long-term follow up.  J Neurol Neurosurg Psychiatry. 1998;  65 709-716
• 31 Kanovsky P, Kubova D, Bares M et al. Levodopa-induced dyskinesias and continuous subcutaneous infusions of apomorphine: results of a two-year, prospective follow-up.  Mov Disord. 2002;  17 188-191
• 32 Morgante L, Basile G, Epifanio A et al. Continuous apomorphine infusion (CAI) and neuropsychiatric disorders in patients with advanced Parkinson’s disease: a follow-up of two years.  Arch Gerontol Geriatr Suppl. 2004;  9 291-296
• 33 De Gaspari D, Siri C, Landi A et al. Clinical and neuropsychological follow-up at 12 months in patients with complicated Parkinson’s disease treated with subcutaneous apomorphine infusion or deep brain stimulation of the subthalamic nucleus.  J Neurol Neurosurg Psychiatry. 2006;  77 450-453
• 34 Garcia Ruiz P J, Sesar Ignacio A, Ares Pensado B et al. Efficacy of long-term continuous subcutaneous apomorphine infusion in advanced Parkinson’s disease with motor fluctuations: a multicenter study.  Mov Disord. 2008;  23 1130-1136
• 35 Pollak P, Champay A S, Gaio J M et al. Subcutaneous administration of apomorphine in motor fluctuations in Parkinson’s disease.  Rev Neurol. 1990;  146 116-122
• 36 Colzi A, Turner K, Lees A J. Continuous subcutaneous waking day apomorphine in the long-term treatment of levodopa induced interdose dyskinesias in Parkinson’s disease.  J Neurol Neurosurg Psychiatry. 1998;  64 573-576
• 37 Ahmad N, Keith-Ferris J, Gooden E et al. Making a case for domperidone in the treatment of gastrointestinal motility disorders.  Curr Opin Pharmacol. 2006;  6 571-576
• 38 Schoffer K L, Henderson R D, O’Maley K et al. Nonpharmacological treatment, fludrocortisone, and domperidone for orthostatic hypotension in Parkinson’s disease.  Mov Disord. 2007;  22 1543-1549
• 39 Rabinak C A, Nirenberg M J. Dopamine agonist withdrawal syndrome in Parkinson disease.  Arch Neurol. 2010;  67 58-63
• 40 van Laar T, Postma A G, Drent M. Continuous subcutaneous infusion of apomorphine can be used safely in patients with Parkinson’s disease and pre-existing visual hallucinations.  Parkinsonism Relat Disord. 2010;  16 71-72
• 41 Pinter M M, Helscher R J, Mundsperger N et al. Transient increase of pancreatic enzymes evoked by apomorphine in Parkinson’s disease.  J Neural Transm. 1998;  105 1237-1244
• 42 Todd A, James C A. Apomorphine nodules in Parkinson’s disease: best practice considerations.  Br J Community Nurs. 2008;  13 457-463
• 43 Poltawski L, Edwards H, Todd A et al. Ultrasound treatment of cutaneous side-effects of infused apomorphine: a randomized controlled pilot study.  Mov Disord. 2009;  24 115-118