• Clinical science

Medication for Parkinson disease (Antiparkinson drug)

Summary

There are many pharmacologic options available for the treatment of Parkinson disease; regimens are tailored to the patient's age, symptoms, and symptom severity. While only symptomatic treatment is available at this point in time, drugs that may slow or reverse the course of the disease are currently being investigated. Since treatment of Parkinson disease at an early stage can significantly improve a patient's subjective well-being (honeymoon period), medical therapy should be initiated as soon as symptoms begin to interfere with the patient's daily life. For most patients, first-line treatment consists of levodopa (L-DOPA) or dopamine receptor agonists, e.g., ropinirole and pramipexole. Other drugs that are used to treat Parkinson disease include amantadine, MAO-B inhibitors, and COMT inhibitors.

Overview

Substance class Agent Mode of action Indication Additional information
Dopamine precursors
  • First-line treatment for patients > 65 years of age or patients with comorbidities
  • Second-line treatment for patients < 65 years of age
  • Mostly given as monotherapy in combination with decarboxylase inhibitors
  • Most effective drug for reducing symptoms
  • However, increased risk of severe motor dysfunction with long-term use (see “Side effects” below)
  • Administer between meals (e.g., 30 minutes before a meal) to increase gastrointestinal absorption (→ avoid high-protein diets)
Decarboxylase inhibitors
  • Always administered alongside L-DOPA
Dopamine agonists Non-ergot
  • First-line treatment for patients < 65 years of age
  • Adjunctive treatment for patients of any age
  • Less effective than L-DOPA, but fewer motor side effects
  • Effective in advanced disease stages
Ergot
  • Second-line treatment for patients < 70 years of age
COMT inhibitors
NMDA antagonists
  • Loss of effect after several months of treatment → cannot be used for long-term therapy
  • May have cardiac side effects (prolonged QT interval)
MAO-B inhibitors
  • Selective inhibition of MAO-B → ↓ metabolization of dopamine into DOPAC in the brain prolonged dopamine availability and effect→ ↓ demand for L-DOPA
  • Alternative to L-DOPA or dopamine agonists for short-term therapy in patients with mild symptoms in early disease stages
  • Can also be given in combination with L-DOPA motor fluctuations

Anticholinergic drugs
(muscarinic antagonists)

  • Useful as monotherapy in patients < 65 years of age with tremor as the main symptom
  • Beneficial regarding tremor and rigidity but does not improve bradykinesia

Patients who do not respond to levodopa therapy will not respond to dopamine agonist therapy!

Selegiline has high selectivity for the monoamine oxidase B found predominantly in the brain.

To remember that anticholinergics like benztropine and trihexyphenidyl are used in the treatment of Parkinson disease, think of “A Benz for a trip to the park.”

To remember the main drugs used to treat Parkinson disease, think of A2 B2 C2 D2: Antimuscarinics and Amantadine; Bromocriptine and MAO-B inhibitors; COMT inhibitors and Carbidopa; L-DOPA and nonergot Dopamine agonists.

References:[1][2][3][4][5]

Side effects

Carbidopa-levodopa

Dopamine agonists

Other substances

NMDA antagonists can cause prolonged QT intervals! Do not administer NMDA antagonists to patients with a history of cardiac disorders!

Administration of antimuscarinic drugs to patients with mental disorders or delirium will likely worsen psychiatric symptoms!

References:[6][7]

We list the most important adverse effects. The selection is not exhaustive.

  • 1. Tarsy D, Hurtig HI, Dashe JF. Pharmacologic Treatment of Parkinson Disease. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/pharmacologic-treatment-of-parkinson-disease. Last updated September 13, 2016. Accessed March 29, 2017.
  • 2. Hisahara S, Shimohama S. Dopamine receptors and Parkinson's disease. International Journal of Medicinal Chemistry. 2011; 2011. doi: 10.1155/2011/403039.
  • 3. Loopuijt LD, Schmidt WJ. The role of NMDA receptors in the slow neuronal degeneration of Parkinson's disease. Amino Acids. 1998; 14(1-3): pp. 17–23. doi: 10.1007/BF01345237.
  • 4. Gazewood JD, Clebak K. Parkinson disease: An update. Am Fam Physician. 2013; 87(4): pp. 267–273. url: http://www.aafp.org/afp/2013/0215/p267.html.
  • 5. Mintzer J, Burns A. Anticholinergic side-effects of drugs in elderly people. J R Soc Med. 2000; 93: pp. 457–462. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1298101/pdf/11089480.pdf.
  • 6. Rolland B, Jardri R, Amad A, Thomas P, Cottencin O, Bordet R. Pharmacology of hallucinations: several mechanisms for one single symptom?. BioMed Research International. 2014; 2014. doi: 10.1155/2014/307106.
  • 7. Zhu K, van Hilten JJ, Putter H, Marinus J. Risk factors for hallucinations in Parkinson's disease: Results from a large prospective cohort study. Movement Disorders. 2013; 28(6): pp. 755–762. doi: 10.1002/mds.25389.
last updated 06/05/2020
{{uncollapseSections(['WsbPFE', 'VsbGFE', 'Usbb8E'])}}