Antiemetic Drug Therapy

Antiemetics are a class of medications used to treat nausea and vomiting. There are seven classes of antiemetics: antihistamines, like meclizine; anticholinergics, like scopolamine; dopamine antagonists, like promethazine; serotonin antagonists, like ondansetron; cannabinoids, like dronabinol; glucocorticoids, like dexamethasone; and substance P/Neurokinin 1 antagonists, like aprepitant.
So, nausea is the uneasy feeling that often occurs before vomiting, or emesis. Emesis occurs when an area of the body, like the inner ear, the GI tract, or the cerebral cortex, sends a message to the chemoreceptor trigger zone in the brain, which then stimulates the vomiting center. Okay, let’s look closer at how some of these antiemetics work. Dopamine antagonists, like promethazine, block the dopamine 2 or D2 receptors in the chemoreceptor trigger zone, preventing nausea and vomiting. Promethazine also has anticholinergic and antihistamine effects. On the other hand, serotonin antagonists, like ondansetron, block type 3 serotonin or 5-HT3 receptors centrally in the chemoreceptor trigger zone and peripherally, on the vagal nerve in the upper GI tract, leading to suppression of nausea and vomiting. So, since promethazine blocks D2 receptors, it can cause extrapyramidal symptoms like muscle rigidity and a shuffling gait, restlessness, and facial grimacing; as well as neuroleptic malignant syndrome, an emergency condition which includes changes in mental status, hyperthermia, and muscle rigidity.
In addition, anticholinergic side effects can include dry mouth, blurred vision, tachycardia, urinary retention, and constipation. Lastly, promethazine’s antihistamine effects can lead to dizziness and sedation. Common side effects of ondansetron include headache, dizziness, and constipation, and it can prolong the QT interval, leading to dysrhythmias. It can also cause a life-threatening side effect called serotonin syndrome, which is caused by an accumulation of serotonin that results in overstimulation of the nervous system, characterized by skin flushing, tachycardia, and agitation. It can occur in patients treated with a combination of ondansetron and other medications that increase serotonin levels, such as antidepressants. As far as contraindications go, ondansetron should be used with caution in patients who have long QT syndrome, or who are taking other medications that prolong the QT interval, which could degenerate into torsades de pointes, a potentially life-threatening dysrhythmia. It also should be used with caution in patients at risk of dysrhythmias, such as those with electrolyte imbalances. Promethazine shouldn’t be used in patients with hepatic impairment, bone marrow suppression, or conditions that could be affected by anticholinergic effects, like glaucoma and myasthenia gravis. Also, it should not be given to children with Reye syndrome, a serious condition that causes swelling in the brain and liver. Importantly, promethazine is considered a high-risk medication in pediatrics, older adults, and when given IV. In fact, it has two Black Box warnings including tissue necrosis with IV use and respiratory depression in children younger than 2 years old.