From the Guidelines
Dopamine antagonists, particularly those blocking D2 receptors, have been shown to be effective in managing nausea and vomiting, but their use should be cautious due to potential side effects such as extrapyramidal symptoms, sedation, and metabolic changes, as evidenced by a 2022 study 1. The effects of dopamine antagonists, which block dopamine receptors in the brain, are primarily beneficial in treating psychotic disorders, nausea, and certain movement disorders. Common dopamine antagonists include antipsychotics like haloperidol, risperidone, and olanzapine for schizophrenia and bipolar disorder; metoclopramide for nausea and gastroparesis; and prochlorperazine for severe nausea and vomiting.
Mechanism of Action
These medications work by blocking dopamine receptors, particularly D2 receptors, which helps reduce symptoms caused by excess dopamine activity.
Side Effects
However, this mechanism also leads to common side effects including:
- Extrapyramidal symptoms (muscle stiffness, tremors, tardive dyskinesia)
- Sedation
- Weight gain
- Metabolic changes Patients should be monitored for these effects, particularly during the initial treatment period.
Special Considerations
In elderly patients, lower starting doses are recommended due to increased sensitivity to side effects. These medications should be used cautiously in patients with Parkinson's disease as they may worsen motor symptoms by further reducing dopamine activity in the basal ganglia. A 2017 study 1 highlighted the efficacy of olanzapine in combination with other antiemetic agents for chemotherapy-induced nausea and vomiting, but also noted the importance of careful patient selection due to potential side effects.
Dosage and Administration
The dosage of dopamine antagonists varies depending on the specific medication and condition being treated. For example, metoclopramide is typically started at a dose of 10mg three times daily for nausea and gastroparesis, while olanzapine may be started at a dose of 5-10mg daily for schizophrenia and bipolar disorder.
Recent Evidence
Recent studies, such as the 2022 review on the management of medically refractory gastroparesis 1, have provided further insight into the use of dopamine antagonists in managing nausea and vomiting, and highlight the need for careful consideration of potential side effects and interactions.
Key Takeaways
- Dopamine antagonists are effective in managing nausea and vomiting
- Potential side effects include extrapyramidal symptoms, sedation, and metabolic changes
- Careful patient selection and monitoring are necessary to minimize risks
- Recent evidence highlights the importance of cautious use and consideration of alternative treatment options.
From the FDA Drug Label
As with other drugs that antagonize dopamine D2 receptors, olanzapine elevates prolactin levels, and the elevation persists during chronic administration. As with other drugs that antagonize dopamine D2 receptors, RISPERIDONE elevates prolactin levels and the elevation persists during chronic administration.
The effects of dopamine antagonists (D2 receptor blockers) include:
- Elevation of prolactin levels: This can lead to various symptoms such as galactorrhea, amenorrhea, gynecomastia, and impotence.
- Hyperprolactinemia: This can suppress hypothalamic GnRH, resulting in reduced pituitary gonadotropin secretion and potentially inhibit reproductive function.
- Potential decrease in bone density: Long-standing hyperprolactinemia associated with hypogonadism may lead to decreased bone density in both female and male subjects.
- Increased risk of pituitary gland, mammary gland, and pancreatic islet cell neoplasia: Although the available evidence is considered too limited to be conclusive at this time, tissue culture experiments and carcinogenicity studies suggest a potential increased risk 2, 3.
From the Research
Effects of Dopamine Antagonists
The effects of dopamine antagonists, specifically D2 receptor blockers, can be understood through their application in various medical treatments.
- Dopamine antagonists are used in the treatment of psychotic illnesses, such as schizophrenia, and have been shown to be effective in reducing psychotic symptoms 4, 5, 6.
- They are also used in the treatment of nausea and vomiting, particularly in palliative care patients, as they can help alleviate symptoms mediated by the chemoreceptor trigger zone (CTZ) and impaired gastrointestinal function 7, 8.
- In addition, dopamine antagonists have been used in the treatment of migraine, especially in emergency room settings, due to their ability to block dopamine receptors and alleviate nausea and vomiting 7.
Adverse Effects
While dopamine antagonists can be effective treatments, they also carry the risk of adverse effects, including:
- Extrapyramidal symptoms, such as akathisia, dystonic reactions, and movement disorders 4, 5, 7, 8.
- Sedation, due to their antihistamine and anticholinergic properties 7.
- Neuroleptic malignant syndrome, a rare but life-threatening condition 7.
- Tardive dyskinesia, a condition characterized by involuntary movements, which can be irreversible 8.
- QTc prolongation, which can increase the risk of cardiac arrhythmias 8.
Specific Dopamine Antagonists
Different dopamine antagonists have varying affinities for dopamine receptors and other receptor sites, which can affect their efficacy and adverse effect profiles.
- Olanzapine, for example, has a high affinity for serotonin 5-HT2A receptors, which may contribute to its efficacy in treating negative symptoms of schizophrenia 4, 5, 6.
- Haloperidol, on the other hand, has a higher risk of extrapyramidal symptoms due to its strong affinity for dopamine D2 receptors 4, 5, 8.
- Metoclopramide and prochlorperazine are also used in the treatment of nausea and vomiting, but have different receptor site affinities and adverse effect profiles compared to olanzapine and haloperidol 8.