Antiemetic Drugs for Nausea and Vomiting | Uses, Side Effects

There are different types of antiemetic drugs used in the treatment of nausea and vomiting. These drugs act on different receptors that are responsible for triggering the vomiting center in the brain as discussed under Anti-Nausea Medication. The most common medication used for nausea are 5-HT3 receptor antagonists.

5-HT3 Antagonist

5-HT3 receptor antagonists are potent antiemetic drugs that selectively block 5-HT3 serotonin receptors in the 5-HT3 receptors in the vomiting center, CTZ and also the 5-HT3 receptors in the intestinal vagal network. The currently available 5-HT3 antagonists include ondansetron, granisetron, dolasetron and palonosetron. Ondansetron, granisetron and dolasetron are available for oral and intravenous use. Palonosetron is the latest drug in the group which is longer acting and is available only for intravenous use.

Uses of 5-HT3 Receptor Antagonists

5-HT3 antagonists provide significant improvement in patients with vomiting resulting from vagus nerve stimulation (like post-operative nausea and vomiting) and chemotherapy-induced nausea and vomiting (CINV). These drugs are currently used as the first choice agent for the prevention of acute CINV but have minimal benefits when used alone for preventing delayed CINV.

Combining 5-HT3 antagonists with adjuvants like corticosteroids or other antiemetics like NK-1 receptor antagonists have been found to increase its effectiveness in preventing nausea and vomiting. 5-HT3 antagonists are also becoming increasingly popular in prevention and treatment of post-operative and post-radiation nausea and vomiting.

Side Effects of 5-HT3 Receptor Antagonists

The 5-HT3 receptor antagonists are drugs are well-tolerated by most patients. The common adverse effects are limited to constipation, headache, diarrhea and dizziness. These drugs are known to cause minor ECG abnormalities which are not significant. Dolasetron is however, recommended to be avoided in patients with QT prolongation (an ECG abnormality).

Dopamine Receptor Antagonists

Several drugs exert antiemetic action by blocking dopamine receptors and many of the dopamine receptor antagonists have additional antihistaminic and anticholinergic actions. Dopamine receptor antagonists are drugs that block D2 dopamine receptors in primarily in the chemoreceptor trigger zone (CTZ). The dopamine receptor blockers include prokinetic drugs like metoclorpramide, and antipsychotic or neuroleptic drugs like chlorpromazine.

Prokinetic Agents

Domperidone (not available in the US) and metoclorpramide are prokinetic agents which are used for nausea and vomiting management. Prokinetic agents are primarily used to treat diseases of intestinal motility like gastroesophageal reflux disease (GERD). Prokinetic agents reduce vomiting by moving the esophageal and gastric contents further down gastrointestinal tract and by preventing the reverse peristaltic contractions.

Neuroleptic Agents

Neuroleptics or antipsychotic drugs like chlorpromazine, prochlorperazine, or droperidol are useful in treatment of schizophrenia. These drugs target multiple receptors like dopamine, histamine, and cholinergic receptors. These actions produce significant antiemetic effects and hence have been used to manage nausea and vomiting.

Uses of Dopamine Antagonists

Dopamine receptor antagonists are among the most commonly used drug for nausea and vomiting of non-specific causes. It is also useful for nausea and vomiting as part of motion sickness and are still considered to be an optional agent for CINV and post-operative nausea and vomiting. It may be used alone or in conjunction with other agents.

Side Effects of Dopamine Antagonists

The dopamine receptor antagonists can cause abnormal muscular movements like dystonias and Parkinsonism-like symptoms, often referred as extrapyramidal syndromes. Other side effects of dopamine antagonists include severe sedation, restlessness, anxiety and occasional hypotension (low blood pressure). The prokinetic agent domperidone is known for minimal neuropsychiatric side effects and extrapyramidal syndromes. Droperidol is associated with ECG abnormalities and is not recommended for routine antiemetic use.

Neurokinin (NK-1) Antagonists

Neurokinin receptor antagonists act by blocking neurokinin (NK1) receptors in the vomiting center. Aprepitant (oral) and fosaprepitant (intravenous) are selective NK1-receptor antagonists that are available in the US. Fosaprepitant is converted to aprepitant after administration.

Uses of Neurokinin Receptor Antagonists

Neurokinin receptor antagonists are used in the prevention and treatment of acute and delayed nausea and vomiting associated with chemotherapy. It may be added to standard antiemetic regimens to improve efficacy in patients on highly emetogenic chemotherapy.

Side Effects of Neurokinin Receptor Antagonists

Neurokinin receptor antagonists may be associated with hiccups, fatigue, headaches, constipation, loss of appetite, dyspepsia, dizziness, diarrhea and elevation of liver enzymes.

Antihistaminic Drugs

Antihistaminic drugs are over-the-counter (OTC) drugs that are block the histamine H1-receptor and modify the vestibular inputs to the vomiting center. Cinnarazine, cyclizine, hydroxyzine, promethazine and diphenhydramine are some of the commonly used antihistaminics. Drugs like promethazine also exert anticholinergic effects which also contribute to its antiemetic action.

Uses of Antihistaminic Drugs

Antihistaminics are useful for motion sickness and postoperative nausea and vomiting. It is also of use in vomiting during pregnancy.

Side Effects of Antihistaminic Drugs

Antihistaminics are associated with prominent sedation and many are also associated anticholinergic related side effects like dry mouth, confusion, visual disturbances, and urinary retention. Other less common side effects include low blood pressure, excitation and allergic reactions.

Anticholinergic Drugs

Anticholinergic drugs are weak antiemetic drugs that work by blocking the muscarinic receptors. Scopolamine (hyoscine) is the most commonly used anticholinergic drug. It is most commonly used as a transdermal patch but it can also be administered as tablets or injection.

Uses of Anticholinergic Drugs

Anticholinergic drugs are used in motion sickness. It may be of marginal use in postoperative nausea and vomiting.

Side Effects of Anticholinergic Drugs

Anticholinergic drugs produce prominent anticholinergic side effects including dizziness, sedation, confusion, dry mouth, visual disturbances, and urinary retention. The transdermal formulation is devoid of significant anticholinergic adverse effects that are seen with oral or injection formulations.

Cannabinoids

Marijuana plant extracts have been found to have antiemetic actions and the active compounds with antiemetic properties have been isolated. Cannabinoids stimulate the CB1 cannabinoid receptors in the vomiting center, which is responsible for its antiemetic action. Dronabinol is a major psychoactive chemical extracted from the marijuana plant which is approved as an antiemetic. It can also be synthesized chemically. Nabilone is another cannabinoid derivative approved for antiemetic use.

Uses of Cannabinoids

Dronabinol has been approved as an adjuvant antiemetic for prevention of chemotherapy-induced vomiting. It is not commonly used due to the availability of safer and better drugs, but id reserved for patients not responding to other drugs.

Side Effects of Cannabinoids

Cannabinoids can cause sedation, mood elevation, hallucinations, increased appetite, bloodshot eyes and dry mouth. It can also lead to low blood pressure and increased heart rate. Cannabinoids are avoided in patients with history of substance abuse. Abrupt withdrawal can result in insomnia, anxiety and irritability.

Adjuvant Antiemetics

Corticosteroid as Antiemetics

Corticosteroids like dexamathasone and methylpredisone have been used with 5-HT3 antagonists for the prevention of acute and delayed chemotherapy-induced nausea and vomiting in patients receiving highly or moderately emetogenic chemotherapy.

Benzodiazepines as Antiemetics

Benzodiazepines like lorazepam and alprazolam have been found to be useful along with standard antiemetics in reducing nausea and vomiting in patients undergoing chemotherapy. The benzodiazepines may produce this effect by its sedative and anti-anxiety actions and reducing the vomiting caused by anxiety.