Five neurotransmitter receptor sites are known to be involved in the physiology of nausea and vomiting (control the vomiting reflex). Several classes of antiemetic drugs are available that antagonize these neurotransmitter receptors. These antiemetic drugs are classified according to their primary action; however, some agents act on multiple receptors.
“The area postrema is an important site for M1, D2, 5-HT3, and NK1 receptors, although other central and peripheral sites play a role, including H1 receptors in the vestibular nucleus and 5-HT3 receptors on vagal afferent neurons.”
| Neurotransmitter (NT) Receptors (that are antagonized) & Drug Class | Drugs | Common Uses | Side Effects |
| Receptors: M1 – muscarinic Drug class: Anticholinergic agents -The M1-muscarinic receptor antagonists |
–Scopolamine 1.5mg patch q72hrs | Prophylaxis against motion sickness | Dry mouth, drowsiness, and vision disturbance |
| Receptors: H1–histamine Drug class: Antihistamines |
-Diphenhydramine, 25 to 50 mg PO Q6h or 10 to 50 mg IV or IM -Dimenhydrinate (Dramamine) 50 mg PO Q4H -Cyclizine, 50 mg PO or IM every four hours or 100 mg by suppository every four hours -Meclizine, 25 to 50 mg PO every 24 hours -Promethazine 12.5 to 25 mg PO or IM every four hours or 12.5 to 25 mg rectally every 12 hours. -hydroxyzine -Promethazine (both an antihistamine & Phenothiazine) |
Motion Sickness Prevention | Sedation |
| Receptors: D2 – dopamine Drug Class: Dopamine Receptor Antagonists.There are 3 classes of DA receptor antagonists used in treating N/V: –Phenothiazines -Butyrophenones -Benzamides |
Phenothiazines: -Prochlorperazine -Chlorpromazine -Promethazine (Phenergan) -Perphenazine |
Extrapyramidal reactions such as dystonia and with prolonged use, tardive dyskinesia. Acute dystonia can be treated with diphenhydramine 25 to 50 mg IV or IM. Hypotension can also occur, particularly in older adults or with intravenous infusion. | |
| Butyrophenones: -Droperidol -Haloperidol |
The side effect profile and antiemetic efficacy of the butyrophenones appear to be similar to those of the phenothiazines. IV haloperidol and droperidol carry a dose-dependent risk of QT prolongation and torsades de pointes and patients who are medically ill, older adults, or receiving other agents that prolong QT interval should be monitored before and for two to three hours after drug administration. Additional side effects include hypotension, alpha blockade, and acute dystonia. | ||
| Benzamides: Metoclopramide |
-Tx N/V 2/2 Gastroparesis – Tx of Gastroparesis b/c it speeds gastric emptying in patients with gastroparesis and increases tone in the lower esophageal sphincter. |
Metoclopramide has central side effects such as anxiety, restlessness, and depression, hyperprolactinemia, and QT interval prolongation. Metoclopramide has a black box warning from the FDA related to risks of irreversible tardive dyskinesia with higher dosing and long-term use. | |
| Receptors: 5HT-3 [5-hydroxytryptamine-3 – serotonin Drug Class: Drug Class: 5 HT-3 receptor antagonists (Serotonin Receptor Antagonists)1st Generation: Ondansetron, Granisetron, and Dolasetron2nd Generation: Palonosetron |
–Ondansetron, -Granisetron, -Dolasetron, |
Ondansetron is used to tx N/V in general including chemo. Granisetron and Dolasetron are used to tx N/V 2/2 to Chemo. |
Mild headaches in 15-20% of pts. Asthenia and constipation in 5-10%. Dizziness in ~ 10%. ECG interval changes are a class effect of the first-generation 5-HT3 antagonists, including ondansetron, granisetron, and dolasetron. They appear to be most prominent one to two hours after a dose of these agents, are mostly small and clinically insignificant, and return to baseline within 24 hours. However, potentially fatal cardiac arrhythmias, including torsade de pointes, have been reported in association with QTc prolongation. The FDA recommends ECG monitoring in patients with electrolyte abnormalities such as hypokalemia or hypomagnesemia, heart failure, bradyarrhythmias, or patients taking concomitant medications that prolong the QT interval. |
| -Palonosetron | Chemotherapy-Induced Emesis (CIE) | ||
| Neurokinin 1 (NK1) receptor – substance P | -aprepitant, -fosaprepitant, |
Used in combination with palonosetron for chemo-induced n/v. | |
Other Agents for Tx N/V |
|||
| Glucocorticoids (MOA unknown.) |
Dexamethasone is the most commonly used and studied | Chemotherapy-Induced Emesis (CIE) | Insomnia, increased energy, and mood changes are common side effects. |
| Cannabinoids | Dronabinol 5 to 10 mg PO Q6-8H. Nabilone 1 to 2 mg Q12H (is usually given as a dose). | As adjunctive tx in selected patients. | -Vertigo, xerostomia, hypotension, dysphoria. – sedation and euphoria may be beneficial |
| Benzodiazepines (Used in combination with other antiemetics, not as single agents) |
Lorazepam & Alprazolam most commonly used. | Given primarily as adjunctive agents to reduce anxiety and akathisia associated with dexamethasone and metoclopramide, respectively. Maybe helpful in reducing anticipatory emesis. | Sedation is the main side effect. |
The 5-HT3 receptor antagonists are the most useful class of antiemetics for chemotherapy-induced emesis
“Substance P is a mammalian neuropeptide found in neurons that innervate the brainstem nucleus tractus solitarius and the area postrema, two areas intimately involved in the induction of vomiting. The emetogenic effects of substance P are mediated through the neurokinin-1 (NK1) receptor, a member of the G protein receptor superfamily”
Reference:
Practical Selection of Antiemetics in the Ambulatory Setting, AAFP
http://www.aafp.org/afp/2012/0601/p1054.html
https://www.uptodate.com/contents/characteristics-of-antiemetic-drugs
Dynamed
Epocrates