Where is the vomiting centre?
In the medulla
The vomiting centre receives impulses from 4 different pathways.
What are they?
How does it pick up these impulses?
GI tract
Vestibular apparatus
Higher centres
Chemoreceptor trigger zone
Picks up impulses from all these places via its muscarinic receptors on its surface
Describe the steps in the process of GI tract problems causing vomiting.
- Enterochromaffin cells in the gastric mucosa release serotonin in response to irritation, cytotoxic agents etc.
- The serotonin binds to 5HT3 receptors of sensory nerves nearby
- These take signals via the vagus nerve to the muscarinic receptors of the vomiting centre
Where is the chemoreceptor trigger zone?
In the medulla
It’s part of the vomiting centre
Describe the steps in the process of cytotoxic agents causing vomiting.
- The CTZ is in the medulla but is located outside the blood-brain barrier
- It has 5HT3 and D2 receptors which detects biochemical upset in blood and CSF, caused cytotoxic agents
- When it detects these it sends an impulse to stimulate the muscarinic receptors of the vomiting centre
- This triggers the vomiting reflex
Describe the steps in the process of emotion, pain, sights and smells causing vomiting?
- Brain processes emotion, pain, smell or sights
- The higher brain centre sends signals to the vomiting centre
- Which are picked up by the muscarinic receptors of vomiting centre
- Triggering the vomiting reflex
Describe the steps in the process of vestibular problems causing vomiting.
- Vestibular apparatus sends signals about balance status to the vestibular nuclei in the pons
- The vestibular nuclei contains H1 and muscarinic receptors which pick up these signals from the v. apparatus
- The v. nuclei then sends signals to the CTZ’s D2 and 5HT3 receptors
- This then sends signals to the vomiting centre’s muscarinic receptors
- Which then triggers vomiting reflex
Which neurotransmitters and corresponding receptors are involved in each vomiting pathway?
GI: Dopamine (D2), Serotonin (5HT3)
CTZ: Dopamine (D2), Serotonin (5HT3)
Higher: histamine (H1)
Vestibular: histamine (H1), Ach (muscarinic)
Substance P: Neurokinin 1 receptor
What are some causes of each vomiting pathway?
- GI tract
- CTZ
- Higher centre
- Vestibular
GI tract: gastric irritation, gastric stasis, intestinal obstruction, cytotoxic agents in the stomach
CTZ: cytotoxic agents in blood (chemotherapy) electrolyte imbalance
Higher centre: smells, sights, emotion, pain, raised ICP
Vestibular: motion sickness, labyrinthitis, morning sickness
Describe the steps in the process of raised ICP causing vomiting?
- Brain senses raised ICP
- The higher brain centre sends signals to the vomiting centre
- which are picked up by the muscarinic receptors of vomiting centre
- Triggering the vomiting reflex
What happens when the vomiting reflex is triggered?
Relaxation of lower oesophageal sphincter
Contraction of diaphragm and abdominal muscles
Which results in raised intra-abdominal pressure
Epiglottis closes
Autonomic changes: tachycardia, salivation
Then vomit can be expelled
What are some non-pharmacological ways which can help reduce nausea and vomiting in a palliative patient?
Control odours from wounds, urine and faeces, food
Small snacks not large meals
Acupressure wrist bands
Name the classes of anti-emetic drugs.
Give examples.
Histamine 1 receptor antagonists: cyclizine, promethazine
5HT3 receptor antagonists: ondansetron
D2 receptor antagonists:
- Butyrophenones
- Prokinetic agents
- Phenothiazines
Muscarinic receptor antagonists: hyoscine
Neurokinin receptor antagonists
Histamine 1 receptor antagonists.
Mechanism of action?
Which causes of N+V are they effective in?
Name some drugs.
- Block H1 receptors in the vestibular nuclei
- Preventing impulse getting from v. apparatus to v. nuclei
- Meaning no impulse gets from v, nuclei to CTZ to vomiting centre
- So no vomiting reflex triggered.
They are effective against vomiting caused by vestibular problem (motion sickness, morning sickness)
Cyclizine, promethazine
5-HT3 receptor antagonists.
Mechanism of action?
Which causes of N+V are they effective in?
Name some drugs.
- Block 5HT-3 receptors on the CTZ so serotonin cannot bind. No impulse receieved by CTZ means no impulse sent from CTZ to vomiting centre
- Also block 5-HT3 in the nerves of the GI tract so serotonin cannot bind and send an impulse up to the vomiting centre
- No impulse received by vomiting centre means no vomiting reflex triggered
Effective against N+V caused by cytotoxic agents, drugs, electrolyte imbalances (uraemia)
AND
GI problems
Ondansetron, dolasetron
There are 3 different classes of D2 receptor antagonists.
What are they?
What are the differences in mechanism of action?
Phenothiazines:
Prochlorperazine, Chlopromazine
Reduces dopamine action in CTZ and other parts of brain
Pro-kinetics:
Metoclopromide (inhibits dopamine action in CTZ but stimulates gastric motility)
Butyrophenones: Haloperidol (inhibits dopamine action in brain)
Muscarinic receptor antagonists.
Mechanism of action?
Which causes of N+V are they effective in?
Name some drugs.
- Inhibit muscarinic receptors on the vomiting centre
- So no impulses from any of the pathways can get to vomiting centre
- So vomiting reflex not triggered
Good for all types of vomiting
Hyoscine
Histamine 1 receptor antagonists.
Example
Benefits
Side effects
Cyclizine
Benefits:
Good for motion sickness and morning sickness (vestibular pathway)
Side effects:
Drowsiness, sedation
5-HT3 receptor antagonists.
Example
Benefits
Side effects
Ondansetron
Benefits:
Good for patients undergoing chemo, radiotherapy and for PONV
Side effects:
Headache, GI upset
D2 receptor antagonists.
Example
Benefits
Side effects
Prochlorperazine
Metoclopramide
Benefits:
Good for patients undergoing chemo, radiotherapy
Reflux, hepato-biliary disorders
Side effect:
Sedation, HTN, Extra-pyramidal side effects
What are the extra-pyramidal side effects?
Akathasia Oculogyric crisis Tardive dyskinesia Torticolis Parkinsonism Neuroleptic malignant syndrome.
Muscarinic receptor antagonists.
Example
Benefits
Side effects
Hyoscine
Benefits: good for prophylaxis and motion sickness
Side effects: dry mouth, blurry vision, drowsiness
Draw out how the 4 vomiting pathways link up with the vomiting centre.
https://www.youtube.com/watch?v=zD_CWMlrb5s
Neurokinin receptor antagonists.
Mechanism of action?
Which causes of N+V are they effective in?
Name some drugs.
- Inhibit neurokinin 1 receptors which are found in the C and PNS
- Substance P cannot bind with NK1 receptors
- No impulse to vomiting centre
Effective in preventing chemotherapy induced N+V, no evidence on efficacy in treating established N+V
Aprepitant
Fosaprepitant
