What Are the Common Antiemetics?

Antiemetics are drugs used to prevent or treat nausea and vomiting due to multiple causes. Based on their mechanism of action, the most common antiemetics are classified as follows [1]:

• Dopamine Antagonists
• Serotonin Antagonists (5HT3 Receptor Antagonists)
• Neurokinin Antagonists
• Antihistamines
• Corticosteroids
• Benzodiazepines
• Cannabinoids

1. What Are Dopamine Antagonists?

Dopamine antagonists are drugs that block the D₂ dopamine receptor in the brain and gastrointestinal neurons by preventing dopamine binding and activation of the receptor D₂ to induce the excitation of neurons.

Dopamine is an organic chemical involved in the transmission of instructions between neurons to control movement and reward-motivated behavior [2].

Dopamine performs its action by binding to dopamine-specific receptors found on the cell surface of neurons in the nervous system.

There are 6 types of dopamine receptors known as D₁, D₂, D_3, D₄, and D₅.

The activation of D₁ and D₅ through dopamine biding can induce the excitation or inhibition of the function of target neurons, while the activation of D₂, D_3, and D₄ by dopamine results in the inhibition of target neurons.

Dopamine antagonists include the following antiemetic drugs:

• Metoclopramide (Antiemetic class: Benzamides) also known as Primperan and Reglan
• Domperidone (Antiemetic class: Benzimidazoles) also known as Motilium
• Prochlorperazine (Antiemetic class: Phenothiazines) also known as Compazine and Stemetil
• Chlorpromazine (Antiemetic class: Phenothiazines) also known as Thorazine and Largactil
• Droperidol (Antiemetic class: Butyrophenones) also known as Inapsine, Droleptan, and Dridol
• Haloperidol (Antiemetic class: Butyrophenones) also known as Haldol and Serenace
• Olanzapine (Antiemetic class: Atypical Antipsychotics) also known as Zyprexa

In addition to blocking the dopamine receptor D₂, Prochlorperazine, Droperidol, Haloperidol, and Olanzapine also block serotonin, histamine, adrenergic, and muscarinic receptors [1].

2. What Are Serotonin Antagonists (5HT3 Receptor Antagonists)?

Serotonin antagonists or 5HT3 Receptor Antagonists are drugs that block 5HT3 receptors in the brain and gastrointestinal neurons by preventing serotonin binding and activation of the 5HT3 receptor to induce the excitation of neurons [3].

Serotonin is a chemical messenger involved in the neurotransmission of information related to mood, reward, learning, memory, and cognition.

Serotonin antagonists include the following antiemetic drugs:

• Ondansetron (Zofran)
• Granisetron (Kytril, Sancuso)
• Palonosetron (Aloxi)
• Tropisetron (Navoban)
• Dolasetron (Anzemet)

3. What Are Neurokinin Antagonists?

Neurokinin antagonists are drugs that block neurokinin receptor type 1 (NK₁) on neurons of the brain and peripheral nervous system by preventing substance P binding and activation of neurokinin receptor type 1 (NK₁) to induce the excitation of neurons [4].

Neurokinin receptor type 1 (NK₁) expression on cells is not limited to neurons but is also found on other non-neuronal cell types.

Substance P is a neuropeptide that functions as a neurotransmitter or neuromodulator and is involved in inflammation, vasodilatation (dilatation of vessels), pain, vomiting, mood, anxiety, and learning.

Neurokinin antagonists include the following antiemetic drugs:

• Aprepitant (Emend for oral use)
• Fosaprepitant (Emend used IV)
• Netupitant
• Netupitant/Palonosetron combination (Akynzeo)

4. What Are Antihistamines?

Antihistamines are drugs that block the H1 receptor on neurons of the brain and peripheral nervous system by preventing histamine binding and activation of the H1 receptor to induce the excitation of neurons.

The H1 receptor is also expressed on the surface of vascular endothelial cells, smooth muscles, and the heart.

Histamine is a well know actor in local immune responses, and is produced by mast cells and basophils; however, it is also an important neurotransmitter involved in itching following inflammation, and in the regulation of sleep-wakefulness cycle [5].

Antihistamines include the following antiemetic drugs:

• Doxylamine (Unisom)
• Cyclizine (Marezine, Valoid, Nausicalm)
• Pheniramine (Avil)
• Promethazine (Phenergan)

Doxylamine, Cyclizine, and Pheniramine also block muscarinic receptors, while Promethazine blocks dopamine D₂ receptors [1].

5. What Are Anticholinergics?

Anticholinergics block muscarinic receptors on neurons of the vestibular nuclei, and the vomiting and chemoreceptor center in the medulla of the brain by preventing acetylcholine binding and activation of the muscarinic receptors to induce the excitation of neurons.

Acetylcholine is an organic chemical involved in the transmission of instructions between neurons and muscles known as neuromotor or neuromuscular transmission, and between neurons that transmit information for brain organs and glands that are involved in attention, wakefulness, learning, memory (short-term memory), motivation, mood and emotion [6].

Hyoscine is an antihistamine used as an antiemetic and is also known as Transdemscop and Kwells.

6. What Are Benzodiazepines?

Benzodiazepines prevent the excitation of neurons by enhancing the effect of GABA on GABA_A receptors.

GABA (Gamma-Aminobutyric acid) is a chemical messenger and the major inhibitor of neurotransmission by reducing nerve impulses (action potential) [7].

Lorazepam is a benzodiazepine used as an antiemetic and is also known as Ativan.

7. What Are Corticosteroids?

Corticosteroids are anti-inflammatory drugs that inhibit the synthesis and release of the proinflammatory mediators, prostaglandins, by the brain.

Prostaglandins are produced and released by almost all types of cells and act on the uterus, platelets, vessels, and mast cells [8].

Dexamethasone is the anti-inflammatory drug used as an antiemetic and known by the trade names, Dextenza, Ozurdex, Cortidex, and Neofordex.

8. What Are Cannabinoids?

Cannabinoids are substances found in cannabis that activate the CB1 cannabinoid receptors in the brain and peripheral nervous system resulting in the modulation of the release of neurotransmitters [9].

Cannabinoids include the following antiemetic drugs:

• Tetrahydrocannabinol (Marinol, Syndros)
• Nabilone (Cesamet, Canemes)
• Nabiximols (Sativex)

9. When do you need an antiemetic drug?

Antiemetics are used for the treatment of nausea and vomiting associated with the following conditions:

• Gastroenteritis
• Chemotherapy-Induced Nausea and Vomiting
• Migraine-Related Nausea and Vomiting
• Vertigo
• Opioid-Induced Nausea and Vomiting
• Radiation-Induced Nausea and Vomiting
• Post-Surgery Nausea and Vomiting

9.1. Gastroenteritis

Gastroenteritis is an inflammation of the gastrointestinal tract due to viral, bacterial, or parasitic infections. It manifests with symptoms including abdominal pain, nausea, and vomiting.

Nausea and vomiting resulting from gastroenteritis can be treated using serotonin antagonists such as ondansetron and dopamine antagonists such as metoclopramide or prochlorperazine [10].

9.2. Chemotherapy-Induced Nausea and Vomiting

Chemotherapy compounds such as Paclitaxel can induce nausea and vomiting which can be blocked using the 5HT3 receptor antagonists (serotonin antagonists).

Induced nausea and vomiting by cisplatin chemotherapy require a combination of neurokinin antagonists, serotonin antagonists, and dexamethasone [11].

Some studies suggested the use of cannabinoids to reduce Chemotherapy-Induced Nausea and Vomiting [12].

9.3. Migraine-Related Nausea and Vomiting

A migraine is a severe form of headache that manifests as an excruciating pain on one side of the head accompanied by a feeling of sickness and an increased sensitivity to light and sound.

Migraine-related nausea and vomiting are treated using Metoclopramide (Primperan, Reglan) [13]. Dopamine antagonists such as prochlorperazine or chlorpromazine have also shown efficacity [14].

9.4. Vertigo

The treatment of vertigo– and motion sickness-induced nausea and vomiting, involves the use of antihistamines such as promethazine, dopamine antagonists such as prochlorperazine, and anticholinergics such as hyoscine [15].

9.5. Opioid-Induced Nausea and Vomiting

Treatment of opioid-induced nausea and vomiting is not well-defined; however, some studies showed the efficacy of some antiemetics such as the serotonin antagonist, Ondansetron (Zofran) [16].

9.6. Radiation-Induced Nausea and Vomiting

Radiation-Induced Nausea and Vomiting such as after radiotherapy, are treated with a serotonin antagonist and dexamethasone [17].

9.7. Post-Surgery Nausea and Vomiting

The treatment of post-surgery nausea and vomiting was suggested to use the serotonin antagonists, dexamethasone, the dopamine antagonist, droperidol, and the antihistamine, cyclizine [1].

Conclusion

Antiemetics are drugs used to treat nausea and vomiting associated with gastroenteritis, vertigo, migraine, surgery, opioids, radiation, and chemotherapy. Some of the antiemetics are more efficient for the treatment of a specific condition, while others have a larger effect range.