What antiemetic is most likely to cause extrapyramidal reactions in a woman with nausea?

From the Guidelines

Metoclopramide is the antiemetic most likely to cause extrapyramidal reactions in a woman with nausea. This medication, which is a dopamine receptor antagonist, works by blocking D2 receptors in the chemoreceptor trigger zone and enhancing gastric emptying. However, its antagonism of dopamine receptors in the nigrostriatal pathway can lead to extrapyramidal symptoms, particularly in young adults and especially young women. These reactions may include acute dystonia (sustained muscle contractions), akathisia (restlessness), parkinsonism symptoms, and tardive dyskinesia with long-term use.

When prescribing metoclopramide, it's essential to use the lowest effective dose for the shortest duration possible (typically not exceeding 5 days) and to inform patients about potential symptoms like involuntary movements, facial grimacing, or restlessness that would warrant immediate medical attention. According to 1, alternative antiemetics with lower risk of extrapyramidal effects include ondansetron, promethazine, or dexamethasone depending on the cause of nausea.

Some key points to consider when managing nausea and vomiting include:

• Identifying and addressing the underlying cause of nausea
• Using prophylactic treatment with antiemetic agents in patients with a prior history of opioid-induced nausea
• Considering alternative agents such as scopolamine, dronabinol, or olanzapine for management of nausea, as suggested by 1
• Using corticosteroids, which can be beneficial for reducing opioid-induced nausea and vomiting, especially in combination with metoclopramide and ondansetron, as noted in 1.

It's crucial to weigh the benefits and risks of each antiemetic option and to select the most appropriate treatment based on the individual patient's needs and medical history. In this case, metoclopramide's potential to cause extrapyramidal reactions makes it a less desirable option for long-term use, and alternative antiemetics with lower risk of extrapyramidal effects should be considered.

From the FDA Drug Label

OVERDOSAGE Symptoms of overdosage may include drowsiness, disorientation and extrapyramidal reactions. The antiemetic most likely to cause extrapyramidal reactions in a woman with nausea is metoclopramide 2.

• Extrapyramidal reactions are a known side effect of metoclopramide, particularly in cases of overdosage.
• These reactions can be controlled with anticholinergic or antiparkinson drugs or antihistamines with anticholinergic properties.

From the Research

Antiemetic-Induced Extrapyramidal Reactions

• Metoclopramide is a dopamine antagonist that can cause extrapyramidal side effects, including dystonic reactions, as reported in a case study where an 18-year-old girl developed neck dystonia and upward deviation of the eyes after taking a large dose of metoclopramide for nausea and vomiting 3.
• Another study found that metoclopramide was associated with extrapyramidal symptoms in 2 out of 68 patients, highlighting the risk of this side effect 4.
• Prochlorperazine, another antiemetic, was also found to induce extrapyramidal symptoms in 6 out of 109 patients in a palliative care setting 5.
• Dopamine antagonists, such as metoclopramide, can cause extrapyramidal adverse effects, particularly in children, and can prolong the QT interval on the ECG 6.
• A case report also described prolonged extrapyramidal symptoms induced by long-term, intermittent administration of low-dose olanzapine along with metoclopramide for emesis, highlighting the risk of drug interactions 7.

Comparison of Antiemetics

• Ondansetron, a serotonin antagonist, was found to be more effective than metoclopramide in reducing acute nausea and emesis in patients receiving chemotherapy, with fewer extrapyramidal reactions 4.
• Metoclopramide and antihistamines are first-line options for nausea and vomiting in pregnancy, but metoclopramide can cause extrapyramidal side effects 6.

Risk of Extrapyramidal Reactions

• The risk of extrapyramidal reactions is higher with dopamine antagonists, such as metoclopramide, particularly in children and when used in combination with other drugs that have D2 receptor antagonism 6, 7.
• Clinicians should be aware of the potential for exacerbated adverse effects due to drug interactions, particularly in cancer patients who often require polypharmacy 7.