Levodopa/Carbidopa

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Carbidopa/levodopa (Sinemet, Duodopa) is the combination of carbidopa and levodopa and is used to treat Parkinson's disease. Parkinson’s disease is caused by low levels of a substance called dopamine in the brain. Levodopa increases the amount of dopamine and hence reduces the symptoms of Parkinson’s disease. Carbidopa improves the antiparkinson effects of levodopa.

Contents

[edit] BRAND NAMES

[edit] STRUCTURE

[edit] MECHANISM OF ACTION

Parkinson is a disease of the nervous system that mainly affects body movement. The three main symptoms are shaking (resting tremor), muscle stiffness (feeling of tension or tightness in the muscles) and slow and unsteady movement. People with Parkinson’s disease often walk with a shuffle as they have difficulty in initiating movement.

Most of the movement-related symptoms of Parkinson's disease are caused by a lack of dopamine due to the loss of dopamine-producing cells in the substantia nigra in the brain.

Levodopa is the metabolic precursor of dopamine and acts to replenish dopamine in the brain. When levodopa is administered orally it is rapidly decarboxylated to dopamine in extracerebral tissues so that only a small portion of a given dose is transported unchanged to the central nervous system. For this reason, large doses of levodopa are required for adequate therapeutic effect and these may often be accompanied by nausea and other adverse reactions, some of which are attributable to dopamine formed in extracerebral tissues.

Carbidopa inhibits decarboxylation of peripheral levodopa to dopamine. It does not cross the bloodbrain barrier and does not affect the metabolism of levodopa within the central nervous system.

Since its decarboxylase inhibiting activity is limited to extracerebral tissues, administration of carbidopa with levodopa makes more levodopa available for transport to the brain.

Levedopa/Carbidopa combination is most helpful in improving slow movement and muscle stiffness, but tremor is less likely to get better.

[edit] INDICATIONS

Levodopa/Carbidopa combination is used to treat some of the symptoms of Parkinson's disease

[edit] DOSAGE

  • SINEMET CR (50 mg carbidopa and 200 mg levodopa per tablet): The dose varies considerably from patient to patient. Most patients need 2-8 tablets per day, taken in divided doses.
  • SINEMET (25 mg carbidopa and 100 mg levodopa per tablet): The optimal initial dosage is one tablet three times a day. Dosage may be increased by one tablet every day or every other day, as necessary, to a maximum of 8 tablets per day. MAINTENANCE: The majority of patients can be maintained at a dosage from 3 to 6 tablets per day.
  • Duodopa is a new formulation of carbidopa/levodopa, which is delivered by a novel intra-intestinal pump. The system is surgically inserted and programmed to deliver doses at specific times, and the external controller makes dose adjustments simple and non-invasive

[edit] CONTRAINDICATIONS

  • Hypersensitivity to this drug or to any ingredient in the formulation
  • Nonselective monoamine oxidase inhibitors (e.g Phenelzine) are contraindicated for use with Levedopa/Carbidopa. These inhibitors must be discontinued at least two weeks prior to initiating therapy.
  • Because levodopa may activate a malignant melanoma, it should not be used in patients with suspicious, undiagnosed skin lesions or a history of melanoma.
  • Narrow-angle glaucoma

[edit] WARNINGS AND PRECAUTIONS

  • Levodopa, may cause mental disturbances. These reactions are thought to be due to increased brain dopamine. All patients should be observed carefully for the development of depression with concomitant suicidal tendencies. Patients with past or current psychoses should be treated with caution.
  • Some people feel sleepy, drowsy, or, rarely, may suddenly fall asleep without warning (i.e. without feeling sleepy or drowsy) when taking Levodopa/Carbidopa. During treatment, patients should take special care when they drive or operate a machine.
  • Levodopa/Carbidopa may increase the possibility of upper gastrointestinal hemorrhage in patients with a history of peptic ulcer
  • Melanoma: Epidemiological studies have shown that patients with Parkinson's disease have a higher risk (2- to approximately 6-fold higher) of developing melanoma than the general population. Whether the increased risk observed was due to Parkinson's disease or other factors, such as drugs used to treat Parkinson's disease, is unclear. For the reasons stated above, patients and providers are advised to monitor for melanomas frequently and on a regular basis when using Levodopa/Carbidopa
  • Neuroleptic Malignant Syndrome: A symptom complex resembling the neuroleptic malignant syndrome including muscular rigidity, elevated body temperature, altered consciousness, mental changes, autonomic instability and increased serum creatine phosphokinase has been reported in association with rapid dose reduction, withdrawal of, or changes in antiparkinsonian therapy. Therefore, patients should be observed carefully when the dosage of Levodopa/Carbidopa is reduced abruptly or discontinued, especially if the patient is receiving neuroleptics.
  • Hallucinations: Hallucinations and confusion are known side effects of treatment with dopaminergic agents, including levodopa. Patients should be aware of the fact that hallucinations (mostly visual) can occur.

[edit] INTERACTIONS

  • Antihypertensive drugs: Symptomatic postural hypotension can occur. Dosage adjustment of the antihypertensive drug may be required.
  • Dopamine D2 receptor antagonists (e.g. phenothiazines, butyrophenones, and risperidone) may reduce the therapeutic effects of levodopa.
  • selegiline: Concomitant therapy with selegiline and Levodopa/Carbidopa preparations may be associated with severe orthostatic hypotension.
  • Isoniazid: Isoniazid may reduce the therapeutic effects of levodopa.
  • Anesthetics: When general anesthesia is required, Levodopa/Carbidopa should be discontinued the night before.
  • Metoclopramide: metoclopramide may adversely affect disease control by its dopamine receptor antagonistic properties
  • Drug-Food Interactions: Since levodopa competes with certain amino acids, the absorption of levodopa may be impaired in some patients on a high protein diet.

[edit] PREGNANCY AND LACTATION

  • Pregnancy Category C (US).
  • Nursing Mothers: Levodopa has been detected in human milk. Caution should be exercised when Levodopa/Carbidopa is administered to a nursing woman.

[edit] SIDE EFFECTS

  • Levodopa-induced dyskinesia such as choreiform, dystonic, and other involuntary movements in patients with Parkinson's disease who have been on levodopa for prolonged periods of time
  • On-Off phenomena
  • Orthostatic hypotension
  • Anorexia, nausea and vomiting

[edit] RELATED LINKS

Medications for the Treatment of Parkinson's Disease

[edit] BIBLIOGRAPHY

[edit] REFERENCES