Anti-emetics Flashcards
How does chemotherapy cause induced nausea and vomiting?
- Chemotherapeutic agents (e.g. cisplatin) are toxic to the lining of the stomach
- Cisplatin affects enterochromaffin cells and causes destruction
- This causes the release of free radicals -> excessive 5-HT (serotonin) release from the stomach
- Free radicals contribute to the destruction of the cells themselves
What does the serotonin in the stomach act on?
5-HT3A receptors, located on:
- Nerve fibres to the nucleus tractus solitarius (NTS) (Ã nerves to the vomiting centre)
- Nerve fibres to the vomiting centre (VC)
- Nerve fibres to chemoreceptor trigger zone (CTZ)
What is the nucleus tractus solitaris?
Projects up to the vomiting centre
What happens due to increased serotonin to the VC activity?
As a result of increased serotonin, there is increased activity of the solitary tract -> increased activity of the VC -> nausea and vomiting
How is CINV treated?
The most effective strategy to prevent CINV is blocking the 5-HT receptors
- Ondansteron: 5-HT3A receptor antagonist
This is NOT just given on its own – NICE suggest that it should be given with two other things:- Glucocorticoids: this reduces free radical production -> remove effects of free radicals - Aprepitant: neurokinin-1 receptor antagonist
Aprepitant - neurokinin 1 receptor antagonist
Front line treatment for nausea and vomiting induced by chemotherapy. Ondansteron and Aprepitant are given together, to reduce the likelihood of nausea and vomiting developing within these individuals.
Neurokinin 1 receptor - what is it?
Thought to be located in the connection between the solitary tract and the vomiting centre. Substance P normally acts on these NK-1 receptors. Inhibiting these receptors will inhibit vomiting.
What causes motion sickness?
- In motion sickness, there is a neural mismatch between the labyrinth and central nervous system
- A signal from the labyrinth is mediated through muscarinic receptors
- This signal is received by the hypothalamus
- The hypothalamus can communicate with the chemoreceptor trigger zone via histamine receptors
- This signal says that there is a mismatch -> activation of the CTZ -> nausea and vomiting
What is the pathophsyiology of motion sickness? (What could be affected/damaged?)
Auditory labyrinth – neural mismatch – Vestibular system (via muscarinic (M) receptors)
Increased hypothalamic histamine (H) release – activates H1 receptors in CTZ
Vestibular system & hypothalamus may also activate the VC though cholinergic system
How is motion sickness treated?
- promethazine
- hyoscine
How does promethazine work?
- H1 receptor antagonist
- This blocks the histamine H1 receptors
- These receptors may be pre-synaptic or post-synaptic
- involved in the signalling process from the hypothalamus to the CTZ
- By blocking histamine receptors, you reduce the likeliness of vomiting being triggered
How does hyoscine work?
- Non-selective muscarinic receptor antagonist
- Most effective way to treat motion sickness
- No one is entirely sure how the cholinergic system plays a role in vomiting
- Because hyoscine is such an effective agent against motion sickness, we know ACh is involved
- Muscarinic receptors are most likely to be involved in signalling from labyrinth -> vestibular
What are people with diabetes likely to have and how does this lead to vomiting?
Gastroparesis: delayed emptying of the stomach (it cannot contract properly)
Food remains in the stomach, which triggers the vomiting reflex
Pathophysiology of gastropariesis
Delayed stomach emptying -> reduced stomach contraction -> 5-HT release -> activation of 5-HT receptors on:
- Nerves fibres to vomiting centre (VC)
- Nerve fibres to chemoreceptor trigger zone (CTZ)
The nucleus tractus solitarius hasn’t been included in this case, because it is not that relevant in terms of the pathophysiology for gastroparesis.
How are nausea and vomiting induced by gastroparesis treated?
- 5-HT antagonists may be effective but not first line
- First line is D2 antaginist
