- Clinical science
Medication for Parkinson disease
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 | ||
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Dopamine precursors |
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Decarboxylase inhibitors |
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Dopamine agonists | Non-ergot |
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Ergot |
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COMT inhibitors |
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NMDA antagonists |
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MAO-B inhibitors |
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Patients who do not respond to levodopa therapy will not respond to dopamine agonist therapy!
References:[1][2][3][4][5]
Side effects
Carbidopa-levodopa
- Becomes less effective over time: may require a shorter interval between doses
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Vegetative symptoms
- Nausea and vomiting
- Orthostatic hypotension
- Carbidopa reduces the risk of orthostatic hypotension, nausea, and vomiting.
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Psychotic symptoms
- Hallucinations (often visual); , insomnia, anxiety, and aggressive behavior → treat with clozapine
- Increased risk in elderly patients, women, concurrent dementia or other psychiatric disorders (e.g., depression), long duration of levodopa treatment, and high doses
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Motor fluctuations
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Hypokinesia
- End-of-dose akinesia/wearing-off phenomenon
- Freezing
- On-off phenomenon
- Dyskinesia (hyperkinesia)
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Hypokinesia
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Akinetic crisis
- Definition: : condition caused by severe dopamine deficiency (e.g., after discontinuation of L-DOPA; therapy or insufficient L-DOPA absorption)
- Clinical features: complete inability to move , incomprehensible speech, possibly hyperthermia → increased risk of dehydration, deep-vein thrombosis, and pneumonia
- Treatment: : intensive medical care, volume substitution, administration of L-DOPA, apomorphine, amantadine
Dopamine agonists
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Side effects common to all dopamine agonists
- Vegetative: nausea; , vomiting, orthostatic hypotension; , dizziness, increased daytime drowsiness and sleep attacks
- Motor function: dyskinesia (rare)
- Psychiatric: unrest, hallucinations; , impulse control disorders; (e.g., compulsive gambling; , sexual activity, or shopping), psychosis
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Dopamine agonist withdrawal syndrome
- Etiology: abrupt discontinuation of dopamine agonist therapy
- Clinical features: similar to malignant hyperthermia and neuroleptic malignant syndrome → hyperthermia and rigor; akinesia; reduced vigilance; increased creatine kinase levels, transaminases, and leukocytes
- Treatment: : intensive medical care, volume substitution, administration of L-DOPA, apomorphine, amantadine
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Side effects of ergotamine-derived agonists: (e.g., bromocriptine)
- Fibrosis: cardiac fibrosis, Raynaud disease, pleural pulmonary fibrosis and retroperitoneal fibrosis
Other substances
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NMDA antagonists (amantadine)
- Side effects similar to L-DOPA, but much less pronounced
- Livedo reticularis, peripheral edema
NMDA antagonists can cause prolonged QT intervals! Do not administer NMDA antagonists to patients with a history of cardiac disorders!
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MAO-B inhibitors
- Headache, dyskinesia, psychological disorders (e.g., hallucinations)
- Inhibition of MAO-A with higher doses → reduced peripheral degradation of catecholamines → adrenergic side effects (e.g., tachycardia, sweating, nervousness)
- Muscarinic antagonists (anticholinergics): See antimuscarinic side effects.
Administration of antimuscarinic drugs to patients with mental disorders or delirium will likely worsen psychiatric symptoms!
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COMT inhibitors
- Gastrointestinal side effects
- Dyskinesia and psychiatric symptoms (e.g., hallucinations or confusion)
References:[6][7]
We list the most important adverse effects. The selection is not exhaustive.