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  • Parkinson's

Improving the effect of levodopa in the long term

    • Education
    • Geriatrics
    • Neurology
    • Pharmacology and toxicology
    • RX
  • 3 minute read

The treatment management of idiopathic Parkinson’s syndrome has improved significantly in recent years. Although a causal treatment is still not possible, the disease can now be treated symptomatically. In the meantime, different factors such as age, gender, leading symptoms and concomitant diseases can be addressed individually and the diminishing effect of levodopa can also be compensated for.

Idiopathic Parkinson’s syndrome is a neurodegenerative disease characterized by bradykinesia, rigidity, tremor and postural instability. The prevalence is 100 to 200 per 100,000 inhabitants. Pathologically, a degeneration of dopaminergic neurons in the substantia nigra plays a significant role. What triggers neurodegeneration is mostly unknown. An impaired degradation of misfolded α-synuclein in lysosomes, but also a dysfunction of the mitochondria seem to be involved. Genetics can play a role, but is the sole cause in less than 10% of patients. Mutations in the glucocerebrosidase gene increase the risk, while mutations in the α-synuclein gene, for example PARK1, can be directly disease-causing. The typical symptoms are preceded by a long prodomal phase, during which other symptoms such as odor or sleep disorders can occur. Only when at least half of the neurons have died and the dopamine content in the corpus striatum is reduced by at least two thirds do the typical Parkinson’s symptoms appear.

Dopamine agonists drug of choice

To date, there is no curative treatment available for Parkinson’s disease. Therapeutically, the aim is therefore to improve the quality of life with an improvement in motor, autonomic, cognitive and psychiatric symptoms and to avoid secondary complications and side effects of dopaminergic treatment. This is because the disease is characterized by cardinal motor symptoms due to a dopamine deficit, especially in the early stages, so that treatment management is mainly based on the administration of dopaminergically active substances. For younger patients in particular, the guideline recommends the use of dopamine agonists or an MAO-B inhibitor as monotherapy. However, patients who require levodopa from the outset should also receive it right at the start of therapy. Levodopa is a precursor of dopamine which, unlike dopamine, can cross the blood-brain barrier. In the CNS, levodopa is converted into dopamine by enzymatic decarboxylation. However, degradation also takes place in the periphery, so that only a fraction of the amount of levodopa administered orally reaches the CNS. For this reason, it is always combined with one of the two peripherally active dopa decarboxylase inhibitors (DDI) carbidopa or benserazide when administered orally. However, after around five years of treatment, motor fluctuations are generally to be expected. To counteract end-of-dose hypokinesia, for example, catechol-O-methyltransferase (COMT) inhibitors can be used to inhibit the breakdown of L-dopa to 3-O-methyldopa.

The first inhibitors to be introduced for add-on therapy were tolcapone and entacapone. Opicapon is now also available as a preparation that only needs to be taken once a day. All preparations are only effective in combination with levodopa and are given in combination with levodopa and one of the DDIs. It is important to adjust the original leodopa dose at the start of therapy in order to avoid excessive reactions due to an increased dopamine concentration in the brain. Typical side effects such as dizziness, gastrointestinal complaints, muscle spasms, orthostasis with a drop in blood pressure, hallucinations, constipation and dyskinesia are therefore usually also due to the increased effect of dopamine.

Further reading:

  • Kalia LV, Lang AE. Parkinson’s disease. Lancet 2015; 386: 896-912.
  • www.pharmazeutische-zeitung.de/frueh-erkennen-gezielt-behandeln-144592/seite/5/?cHash=f96e22ce03b9342412e7d4a118b15b8d (letzter Zugriff am 31.03.2024)
  • www.akdae.de/fileadmin/user_upload/akdae/Arzneimitteltherapie/NA/Archiv/201703-Ongentys.pdf (last accessed on 31.03.2024)

InFo NEUROLOGY & PSYCHIATRY 2024; 22(2): 34

Autoren
  • Leoni Burggraf
Publikation
  • InFo NEUROLOGIE & PSYCHIATRIE
Related Topics
  • Dopamine agonists
  • Levodopa
  • Parkinson's
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