Zusammenfassung
Apomorphin ist ein seit langem bekannter hochpotenter D2-, D3- und D4-Dopaminrezeptoragonist, der sich besonders durch eine zusätzliche D1-Dopaminrezeptorwirkung auszeichnet und in der Medizin vielfältige Anwendung gefunden hat. Wegen einer weitestgehenden Inaktivierung bei der Leberpassage wird Apomorphin in der Regel subkutan angewendet. Nach raschem Wirkungseintritt ist die Wirkungsdauer auf etwa eine Stunde begrenzt. Bei seiner Wirkung ist Apomorphin unabhängig von Mechanismen der enteralen Dopaminresorption und vom präsynaptischen System der Dopaminspeicherung und Dopaminfreisetzung. Die häufigste Nebenwirkung der subkutanen Apomorphingabe sind Gewebsverhärtungen an den Injektionsstellen. Periphere dopaminerge Nebenwirkungen, wie Übelkeit und orthostatische Hypotension, treten meist nur in der Anfangsphase der Behandlung auf und lassen sich mit Domperidon weitgehend unterdrücken. Halluzinationen treten seltener auf als beim Einsatz anderer Dopaminagonisten.
Beim Apomorphintest wird durch subkutane Bolusgaben die Levodopasensitivtät einer Parkinsonsymptomatik zur Abgrenzung eines M. Parkinson von atypischen Parkinsonsyndromen ermittelt. Dabei zeigt der Apomorphintest eine Levodopasensitivität in etwa 90% der Fälle an. Falsch-negative Ergebnisse können bei gering ausgeprägter Parkinsonsymptomatik vorkommen. Eine Metaanalyse zeigt, daß durch eine intermittierende subkutane Apomorphingabe (intermittierende Apomorphintherape) mittels eines Selbstapplikationsgeräts die tägliche Dauer unvorhersehbarer kurz anhaltender Off-Phasen um 48.8±8.7% reduziert werden kann. Dazu werden durchschnittlich 3,7±1,1 × 2,9±0,8 mg Apomorphin pro Tag appliziert. Durch eine kontinuierliche subkutane Apomorphingabe mittels einer Pumpe (kontinuierliche Apomorphintherapie) während der Wachphase läßt sich die tägliche Dauer der Off-Phasen um 64,8±13,5% und die zusätzlich notwendige Levodopadosis um 30,3±31,1% reduzieren. Bei Ganztagesgabe wird die tägliche Dauer der Off-Phasen um 63,5±19,1% und die zusätzlichen Levodopadosis um 65,5±21,9% reduziert. Levodopainduzierte Dyskinesien nehmen deutlich ab. Eine langsame Umstellung der Medikation auf eine Apomorphin-Monotherapie ist möglich. Auch bei langjähriger Anwendung zeigen sich keine wesentlichen Wirkungsverluste der Apomorphintherapie. Damit stellt die Apomorphintherapie eine sehr wirkungsvolle Therapie von Off-Phasen und levodopainduzierten Dyskinesien beim fortgeschrittenen Morbus Parkinson dar, die ausgeschöpft werden sollte, bevor invasivere Therapieansätze in Betracht gezogen werden.
Summary
Apomorphine has long been used in many medical specialties. It is a highly potent D2-, D3- and D4-dopamine receptor agonist with a particularly high D1-dopamine receptor affinity. Due to its almost complete inactivation during liver passage it is usually applied subcutaneously. After rapid onset its effect is waning after about one hour. Apomorphine’s action is not dependent on enteral dopamine resorption and on praesynaptic dopamine storage and dopamine secretion mechanisms. When applied subcutaneously its most common side effect is cutaneous nodules at the injection sites. Peripheral dopaminergic side effects, such as nausea and orthostatic hypotension, usually occur only during therapy initiation and respond well to domperidone. Hallucinations occur less frequently than with other dopamine receptor agonists.
The apomorphine test determines the levodopasensitivity of a parkinsonian syndrome by application of an apomorphine bolus to distinguish between idiopathic Parkinson’s disease and atypical parkinsonian syndromes. It indicates a levodopasensitivity in about 90% of the patients tested. False-negative results can occur in mild parkinsonian syndromes. A meta analysis indicates that intermittend subutaneous apomorphine applications (intermittend apomorphine therapy) with a self application device can reduce the daily duration of unpredictable off-phases by 48.8±8.7%. For this an average of 3.7±1.1 × 2.9±0.8 mg apomorphine has to be applied per day. Continuous subcutaneous apomorphine application with an extracorporal pump (continuous apomorhine therapy) during the wake phase reduces the duration of daily off-phases by 64.8±13.5% and the additional levodopa dose by 30.3±31.1%. 24-hour application reduces the daily duration of the off-phases by 63.5±19.1% and the additional levodopa dose by 65.5±21.9%. Levodopa-induced dyskinesias are also substantially reduced. A gradual conversion to an apomorphine monotherapy is possible. Even after prolonged treatment times no significant loss of efficacy occurs. With this profile apomorphine is a highly successful treatment option for off-phases and levodopa-induced dyskinesias in advanced cases of idiopathic Parkinson’s disease which should be used before more invasive approaches are considered.
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Dressler, D. Apomorphin bei der Behandlung des Morbus Parkinson. Nervenarzt 76, 681–689 (2005). https://doi.org/10.1007/s00115-004-1830-4
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DOI: https://doi.org/10.1007/s00115-004-1830-4
Schlüsselwörter
- Apomorphin
- Morbus Parkinson
- Off-Phasen
- Dyskinesien
- Diagnostischer Gebrauch
- Therapeutischer Gebrauch
- Intermittierende Gabe
- Kontinuierliche Gabe