
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.
Schlüsselwörter
Parkinsonsyndrom - Medikamentenpumpen - Apomorphin - Dopaminagonisten - Dopa
Keywords
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
Prof. Dr. Andres Ceballos-Baumann
Schön Klinik München-Schwabing, Neurologie u. klinische
Neurophysiologie, Zentrum für Parkinson-Syndrome und
Bewegungsstörungen
Parzivalplatz 4
80804 München
Email: ACeballos-Baumann@schoen-kliniken.de