Levodopa (L-Dopa)


Article Author:
Kavita Gandhi


Article Editor:
Abdolreza Saadabadi


Editors In Chief:
Andrew Sherman
Richard Kaplan


Managing Editors:
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Frank Smeeks
Kristina Soman-Faulkner
Benjamin Eovaldi
Radia Jamil
Sobhan Daneshfar
Saad Nazir
William Gossman
Pritesh Sheth
Hassam Zulfiqar
Navid Mahabadi
Steve Bhimji
John Shell
Matthew Varacallo
Ahmad Malik
Mark Pellegrini
James Hughes
Beata Beatty
Hajira Basit
Phillip Hynes


Updated:
3/21/2019 12:10:05 AM

Indications

Levodopa is the precursor to dopamine. Most commonly, Levodopa is used as a dopamine replacement agent for the treatment of Parkinson disease. It is most effectively used to control bradykinetic symptoms that are apparent in Parkinson disease. Levodopa is typically prescribed to a patient with Parkinson disease once symptoms become more difficult to control with other antiparkinsonian drugs. The drug can also be used for postencephalitic parkinsonism and symptomatic parkinsonism due to carbon monoxide intoxication.[1][2][3] Recent data have suggested that levodopa can either slow down the progression of Parkinson disease and/or have increased benefits even after drug administration has stopped. A common off-label use for levodopa is restless leg syndrome and periodic limb movement in sleep (PLMS).

Mechanism of Action

Degeneration of the substantia nigra occurs in patients with Parkinson disease. This results in the disruption of the nigrostriatal pathway and thus, decreasing the striatal dopamine levels. Unlike dopamine, levodopa can cross the blood-brain-barrier (BBB). Levodopa is converted to dopamine in both the CNS and periphery.[4] Levodopa is commonly administered with carbidopa, a dopamine decarboxylase inhibitor, to decrease the amount of levodopa that is converted to dopamine in the periphery. This would allow for more levodopa to cross the BBB. Once converted to dopamine, it activates postsynaptic dopaminergic receptors and compensates for the decrease in endogenous dopamine. Levodopa administration should be discontinued for about 12 hours before carbidopa is administered to decrease the adverse reactions.

Administration

The oral form of levodopa is given with meals to decrease gastrointestinal (GI) upset. Patients are recommended to avoid high-fat, high-calorie meals when taking levodopa as it can delay the absorption by 2 hours. Also, high protein diets can decrease the amount of levodopa absorbed due to competition with amino acid transporters. The orally disintegrating tablets need to be dissolved entirely on the tongue before swallowing. The extended-release capsule of levodopa can be administered with or without food. Patients who have trouble swallowing can open up the capsule and sprinkle the contents over food and consume immediately. Another form of administration is a 16-hour infusion through a nasojejunal tube. Research has shown that levodopa infusion is associated with low plasma trough levels seen with oral drug administration. Recent studies of such infusion have shown to decrease the negative effects of motor complications. Some studies have even shown that pulsatile administration of levodopa can cause more motor complications when compared to continuous administration of the drug. Administration of levodopa in the pediatric population has not been well researched and as a result, is not recommended to be administered to patients under the age of 18.

Adverse Effects

The common adverse effects of Levodopa treatment are nausea, dizziness, headache, and somnolence. Special precaution should be used in elderly patients because they may be more sensitive to central nervous system (CNS) effects. The most common side effects in older patients taking levodopa can be confusion, hallucinations, delusions, psychosis, and agitation. [5][6][7]There may be a greater risk of hip fractures in older adults as well due to levodopa mildly increasing homocysteine levels as an adverse effect. Patients presenting with an idiopathic parkinsonian disorder and who are on levodopa can also develop low serum vitamin B12, elevated methylmalonic acid levels, and greater chances of sensorimotor peripheral neuropathy. If levodopa is suddenly stopped, a commonly reported adverse effect is neuroleptic malignant syndrome (NMS). Hyperthermia, involuntary movements, and muscle rigidity are seen in severe NMS cases. The most common cardiovascular effects are dizziness and postural hypotension. Cardiac arrhythmias have also been reported in studies. Somnolence is another adverse effect that has been reported with levodopa use. The onset is rapid and without warning and thus, precaution is needed when operating motor vehicles. [8]Medication should be discontinued in patients that experience excessive daytime sleepiness. Long-term use of levodopa presents with other complications. The quality of life of patients can be negatively affected because of irreversible motor function changes from drug use.  These motor complications are seen in about 50% of patients using levodopa for 5 to 10 years. The motor complications increase depending on whether the onset of PD was at an early age.

Contraindications

The use of levodopa is contraindicated with the congruent use of monoamine oxidase inhibitors (MAOIs) because it can lead to hypertensive crisis. There should be a 14-day washout period when switching from levodopa to an MAOI or vice versa. Patients that are on D2 antagonists may see a reduction in the effects of levodopa, and as a result, the beneficial effects of the drug may be reduced. Individuals with narrow-angle glaucoma should use levodopa with caution as it can increase ocular pressure. Extra precaution should be taken in patients with atrial nodal or ventricular arrhythmias. It is recommended that these patients be administered levodopa in a coronary care unit. Levodopa use is also contraindicated in people with pre-existing neuropathy because symptoms have the potential to worsen. The risk of GI bleeds is heightened in patients who already have a history of peptic ulcer disease. Levodopa can increase the risk of psychosis in patients who are already diagnosed with a major psychotic disorder.

Monitoring

Frequent monitoring of BUN, creatinine levels, and hepatic function is necessary for individuals taking Levodopa. Good hepatic function is crucial in patients taking levodopa because it is where the drug is decarboxylated. Also, it is important to test for intraocular pressure in patients with glaucoma. Testing for peripheral neuropathy before and while on levodopa is also very important. Patients should also be regularly monitored for dyskinesia. Patients need to be observed for psychotic behavior and hallucinations when on dopaminergic medications. Confusion and excessive dreaming can be accompanied with hallucinations. Thus, patients with a history of past psychiatric disorders should not be treated with levodopa.  As an extra precaution, patients should be monitored for melanoma. It is not known yet whether the risk of melanoma is increased due to levodopa use or Parkinson disease.

Toxicity

Studies have shown that levodopa toxicity can damage neuronal cells. The formation of free radicals once the body oxidizes levodopa can induce apoptosis. Also, dopamine, norepinephrine, and epinephrine levels can rise in the blood when levodopa is decarboxylated in the periphery. The rise in catecholamines activate alpha and beta-adrenergic receptors and result in toxic effects. In pregnant women, levodopa does cross the placenta and can potentially be metabolized by the fetus. Unfortunately, there is insufficient information to make an appropriate decision regarding the use of levodopa in pregnant women. The drug is excreted in breast milk, and thus, caution is advised when administering the drug to women who are nursing. To treat toxicity, supportive measures should be taken such as gastric lavage, maintenance of airways, and administration of intravenous (IV) fluids.

Enhancing Healthcare Team Outcomes

While the initial treatment of a patient with Parkinson disease is by a neurologist, the outpatient monitoring and continued care is by the primary care provider and nurse practitioner. When patients are started on L-dopa, Frequent monitoring of BUN, creatinine levels, and hepatic function is necessary. In addition, the patient must be referred to the ophthalmologist for glaucoma screening. Patients on L dopa may develop mood changes and should be closely followed by a mental health nurse.

It is important for the primary care provider to know the symptoms of PD because L-dopa usually works for a short period and patients may have to be started on other medications. In addition, patients with Parkinson disease may develop a variety of autonomic symptoms and may need to be referred to the gastroenterologist and urologist. Overall, there is no cure for Parkinson disease and eventually, most patients succumb to the disorder.[9][10]


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Levodopa (L-Dopa) - Questions

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Which feature of Parkinson disease does L-dopa not relieve?



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Which of the following co-existing conditions contraindicates the use of levodopa?



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What does the optimal dose of levodopa do in the treatment of Parkinson disease?



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A patient with Parkinson disease is experiencing impaired physical functioning and is receiving levodopa. Which of the following instructions should be included regarding the potential side effects of levodopa?



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What instructions should be given to a patient in order to maximize the efficacy of levodopa?



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Which of the following is not a contraindication to the use of L-dopa?



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Select the correct statement about the use of L-dopa for Parkinson disease.



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What is the reason why L-dopa is administered to Parkinson disease patients instead of dopamine?



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A 68-year-old woman has been placed on L-dopa for Parkinson disease. What drug is routinely added to improve the effectiveness of L-dopa?



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Which of the following drugs is most effective for treating the bradykinesia associated with Parkinson disease?



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Parkinson disease results from a loss of dopaminergic neurons. Why is levodopa given instead of dopamine?



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A patient is on levodopa. Which of the following conditions does the patient most likely have?



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Why would dosage of levodopa TID to a 71-year-old female with early Parkinson disease result in sustained motor response?



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Which of the following is most likely to respond to L-dopa early in the disease process?



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Which drug is contraindicated in a patient taking L-dopa?



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The levodopa antiparkinson effect is inhibited by which one of the following?



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A 59-year old presents with a tremor in his right hand and excessive salivation. He denies the use of any medications, does not smoke, or drink. He is unable to divulge his medical history, as he appears confused. On examination, he walks with a shuffling gait, his movements are very slow and his arm does not fully swing and he appears to have postural instability. He has a flat affect and he has a resting tremor. It is decided to start him on L-dopa and carbidopa. What condition would be contraindicated to l-dopa administration?



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A 66-year-old male patient has just been diagnosed with Parkinson disease and is started on levodopa. The patient also has a long history of depression that is currently well controlled with psychotherapy and medications. Now that he has been started on levodopa, which antidepressant must he avoid?



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When dispensing one of the drugs in this list, it is recommended to the patient that they not consume any supplemental pyridoxine (vitamin B6). Which drug is it?



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A client with Parkinson's disease has been started on the drug, levodopa. Which of the following is true about this agent? Select all that apply.



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Why is L-dopa given to patients with Parkinson disease when the disease is caused by a deficiency of dopamine?



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Levodopa (L-Dopa) - References

References

Corvol JC,Mariani LL, [Therapeutic and pharmacologic perspectives in Parkinson's disease]. La Revue du praticien. 2018 May;     [PubMed]
Ebada MA,Alkanj S,Ebada M,Abdelkarim AH,Diab A,Aziz MAE,Soliman AM,Fayed N,Bahbah EI,Negida A, Safety and Efficacy of Levetiracetam for the Management of Levodopa-Induced Dyskinesia in Patients with Parkinson's Disease: A Systematic Review. CNS     [PubMed]
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