Levodopa Antiemetics

When levodopa is given without a peripheral decarboxylase inhibitor, anorexia and nausea and vomiting occur in about 80% of patients. These adverse effects can be minimized by taking the drug in divided doses, with or immediately after meals, and by increasing the total daily dose very slowly antacids taken 30-60 minutes before levodopa may also be beneficial. The vomiting has been attributed to stimulation of the chemoreceptor trigger zone located in the brain stem but outside the blood-brain barrier. Fortunately, tolerance to this emetic effect develops in many patients. Antiemetics such as phenothiazines should be avoided because they reduce the antiparkinsonism effects of levodopa and may exacerbate the disease. 

Levodopa and neuroleptic drugs can interfere with the effects of each other at dopamine receptors the patient should be monitored for deterioration in both parkinsonism and mental state. If an antiemetic is required in a patient taking levodopa, one that does not affect central dopamine receptors should be chosen. 

Vomiting is triggered in the chemoreceptor trigger zone of the medulla, and nearly all dopamine receptor agonists (e.g. bromocriptine), and agents that increase dopamine in the brain (e.g. levodopa), cause vomiting. Conversely, many dopamine receptor antagonists (e.g. metoclopramide, and phenothiazines, e.g. chlorpromazine and prochlorperazine) have antiemetic activity. 

The antiemetic properties of metoclopramide appear to be a result of its antagonism of central and peripheral dopamine receptors. Dopamine produces nausea and vomiting by stimulation of the medullary chemoreceptor trigger zone (CTZ), and metoclopramide blocks stimulation of the CTZ by agents like levodopa or apomorphine that are known to increase dopamine levels or to possess dopaminelike effects. Metoclopramide also inhibits the central and peripheral effects of apomorphine and abolishes the slowing of gastric emptying caused by apomorphine. 

Antihistamines, dronabinol, glucocorticoids, and metoclopramide have antiemetic actions that are useful in the management of vomiting caused by anticancer drugs. Levodopa causes nausea because it is converted to dopamine, which activates dopamine receptors in the emetic center. The answer is (C). 

Note that prochlorperazine should not be given if apomorphine is used for Parkinson s disease, as its dopamine antagonist actions can worsen the disease (see also Levodopa + Antiemetics , p.682). Because apomorphine is highly emetogenic at the doses required for the treatment of Parkinson s disease (1 to 4 mg/hour by subcutaneous infusion), patients with Parkinson s disease requiring apomorphine should be pretreated with domperidone 20 mg three times daily for at least 2 days. Rare reports of extrapyramidal adverse effects have been reported with ondansetron, which may be of relevance in patients with Parkinson s Disease. 

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