44. Emetics, antiemetics and prokinetic drugs
Introduction to vomiting
Vomiting is a defensive response intended to rid the body of toxic or irritating material. It’s regulating by a vomiting centre, comprised of the reticular formation and the area postrema/chemosensitive trigger zone in the fourth ventricle.
Many receptors are involved in stimulating vomiting, including:
- Histamine H1 receptor
- Dopamine D2 receptor
- Muscarinic receptor
- Serotonin 5-HT3 receptor
- Neurokinin NK1 receptor
The chemoreceptor trigger zone expresses D2 and 5-HT3 receptors.
Emetics
Previously, one would use drugs to induce vomiting. This was most notably useful if someone has ingested something poisonous. For this emetine and apomorphine can be used. Apomorphine is a dopamine receptor agonist. Nowadays we have safer and more effective ways of dealing with poison ingestion.
Antiemetics
Antiemetics are more important clinically than emetics. Many receptors are involved in vomiting, so many different drugs with different mechanisms of actions have antiemetic effect.
The important drugs here are:
- Dopamine D2 receptor antagonists
- Metoclopramide (Afipran®)
- Droperidol
- Serotonin 5-HT3 receptor antagonists
- Ondansetron (Zofran®)
- Granisetron
- 1st generation histamine H1 receptor antagonists
- Cyclizine
- Cinnarizine
- Promethazine
- Muscarinic receptor antagonists
- Scopolamine
- Neurokinin NK1 receptors antagonists
- Netupitant
- Aprepitant
- Others
- Cannabinoids
- Corticosteroids
Indications
Antihistamines and scopolamine are particularly affective in nausea caused by motion sickness since the vestibular system contains M1 an H1 receptors.
D2 antagonists, 5-HT3 antagonists, corticosteroids, cannabinoids and NK1 antagonists are particularly effective in nausea caused by chemotherapy or radiotherapy. Often two or more drugs from these classes are combined to give stronger antiemetic effect.
Most cytotoxic drugs induce nausea and vomiting, especially cisplatin, cyclophosphamide and doxorubicin.
Mechanism of action
The drugs act on their respective receptors.
Dosing
Scopolamine is often administered as a transdermal patch.
Side effects
The D2 antagonists can give extrapyramidal symptoms. Serotonin antagonists can give headache.
Prokinetic drugs
These drugs increase the gastrointestinal motility. This can be useful in GERD, gastrointestinal hypomotility, decreased gastric emptying or obstipation.
Compounds
- Dopamine D2 receptor antagonist
- Domperidone
- Metoclopramide
- 5-HT4 receptor agonist
- Prucalopride
- Metoclopramide
Indications
Domperidone and metoclopramide are used in GERD and disorders of gastric emptying.
Prucalopride is used as a laxative when other laxative treatments have failed.
Mechanism of action
Metoclopramide is D2 receptor antagonist and a serotonin 5-HT4 receptor agonist.
Blocking D2 receptors increases the tone of the lower oesophageal sphincter. Activating 5-HT4 receptors stimulate gastric emptying and duodenal peristalsis.