What are classes of anti-emetics?
- H1 antagonists
- D2 antagonists
- 5HT3 antagonists
- Hyoscine hydrobromide
- Dexamethasone
- Midazolam
What are examples of H1 antagonists?
- Cyclizine
- Cinnarizine
How do dopamine (D2) antagonists work?
Drugs that block D2 receptors have a prokinetic effect – promoting gastric emptying – which contributes to their antiemetic action. They are effective in nausea and vomiting due to CTZ stimulation (e.g. due to drugs) and reduced gut motility (e.g. due to opioids or diabetic gastroparesis).
How is dopamine involved in vomiting?
2 main actions
- Receptor is the main receptor in the chemoreceptor trigger zone (CTZ) - area responsible for sensing emetogenic substances in the blood (e.g. drugs).
- Important neurotransmitter in the gut - promotes relaxation of the stomach and LOS and inhibits gastroduodenal coordination.
Why are D2 antagonists said to have a prokinetic effect?
Drugs that block D2 receptors have a prokinetic effect – promoting gastric emptying – which contributes to their antiemetic action
How do H1 antagonists work?
. Histamine (H1) and acetylcholine (muscarinic) receptors predominate in the vomiting centreand in its communication with the vestibular system. Drugs such as cyclizine block both of these receptors.
What are H1 antagonists particularly effective at treating?
Nausea and vomiting, particularly in the context of motion sickness or vertigo
What are examples of D2 antagonists?
- Metoclopramide
- Domperidone
- Prochlorperazine
- Haloperidol
How do 5HT3 antagonists work?
5-HT3 antagonists act by blocking 5HT3 receptors in CTZ and the gut, preventing stimulation of vagus nerve which causes vomiting.
They are effective against nausea and vomiting due to CTZ stimulation (e.g. drugs) and visceral stimuli (gut infection, radiotherapy), but not in motion sickness.
What are examples of 5HT3 antagonists?
Ondansetron
How does serotonin play a role in vomiting?
- High density of 5-HT3 receptors in the CTZ
- Key neurotransmitter released by the gut in response to emetogenic stimuli -> stimulates the vagus nerve via 5HT3- > vomiting centre via the solitary tract nucleus
How does the chemoreceptor trigger zone (CTZ) polay a role in vomiting?
Receives inputs from blood-borne drugs or hormones, and communicates with other structures in the vomiting center to initiate vomiting.
What are 5HT3 antagonists particularly useful for?
Nausea and vomiting, particularly in the context of general anaesthesia and chemotherapy
What is the mechanism of action of phenotiiazines?
Blockade of various receptors, including:
- D2 receptors in the CTZ and gut
- Histamine (H1) and acetylcholine (muscarinic) receptors in the vomiting centre and vestibular system.
What are D2 antagonists particularly good at treating?
- Nausea and vomiting due to CTZ stimulation (e.g. due to drugs)
- Reduced gut motility (e.g. due to opioids or diabetic gastroparesis)
What are examples of phenothiazines?
- Prochlorperazine
- Chlorpromazine
- Levomepromazine
What are phenothiazines particularly useful for?
Nausea and vomiting in a wide range of conditions, including chemotherapy, radiotherapy and particularly when due to vertigo - Regarded as broad spectrum anti-emetic
What are adverse effects of phenothiazines?
- Drowsiness
- Postural hypotension
- Extrapyramidal syndromes - acute (oculogyric crisis) or chronic (tardive dyskinesia)
- Prolonged QT-interval
- Heptotoxicity
