Antiemetics Flashcards
What is nausea?
subjective, unpleasant sensation in the throat and stomach; often precedes vomiting
- preceded by salivation, sweating and increased heart rate
What is vomiting?
forceful propulsion of stomach contents out of the mouth.
- preceded by salivation, sweating and increased heart rate
Describe the pathophysiology of chemotherapy induced nausea and vomiting (CINV)
Cisplatin affects enterochromaffin cells (toxic to them) and causes destruction of these cells - > causes the release of free radicals -> EXCESSIVE 5-HT RELEASE from the stomach
This serotonin goes on to act on 5-HT3A receptors, located on:
- Nerve fibres to the nucleus tractus solitarius (NTS) (à nerves to the vomiting centre)
- Nerve fibres to the vomiting centre (VC)
- Nerve fibres to chemoreceptor trigger zone (CTZ)
- The result of this is increased fibres in the nerve fibre
The nucleus tractus solitarius projects up to the vomiting centre. As a result of increased serotonin, there is increased activity of the solitary tract -> increased activity of the VC -> NAUSEA AND VOMITING
What is the treatment for CINV?
ondasteron - 5-HT 3A receptor antagonist
given with:
- Glucocorticoids: this reduces free radical production -> remove effects of free radicals
- Aprepitant: neurokinin-1 receptor antagonist
Describe the pathophysiology of motion sickness
- A signal from the labyrinth (in ear) 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
- increased hypothalamic histamine (H) release activates H1 receptors in CTZ
- vestibular system and hypothalamus may also activate VC through cholinergic system
What is the treatment for motion sickness?
- Promethazine: H1 receptor antagonist
- Hyoscine (scopolomine) – non-selective muscarinic receptor antagonist
Describe the pathology of gastroperesis
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)
What is used to treat gastroparesis?
Metoclopramide: Dopamine D2 receptor antagonist
- Prokinetic – stimulates gastric emptying by acting on the stomach itself (stimulates contractility)
- Inhibits D2 receptors in the vomiting centre (blocks likelihood of vomiting from D2 stimulation)
- Metoclopramide is ALSO a 5-HT3A receptor antagonist -> inhibits activation of CTZ
- 5-HT receptor antagonists can also be used
Summarise the physiological control of nausea/vomiting and identify the main mechanistic triggers
Physiological control
- Vomiting centre (area postrema): innervated by the nucleus of the tractus solitarius
- Chemoreceptor Trigger Zone: communicates with the vomiting centre
Mechanistic triggers
- Cytotoxic drugs, motion sickness, gastrointestinal problems
Identify the main classes of anti-emetic drugs
- 5-HT3A receptor antagonists
- Histamine H1 receptor antagonists
- Muscarinic receptor antagonists
- Dopamine D2 receptor antagonists
Outline their principle clinical uses and mechanism of action
- 5-HT3A receptor antagonists: chemotherapy induced N&V
- Histamine H1 receptor antagonists: motion sickness
- Muscarinic receptor antagonists: motion sickness
- Dopamine D2 receptor antagonists: gastroparesis induced N&V
Summarise the principle side effect profile of each class of anti-emetic drug
- 5-HT3A receptor antagonists: headaches and constipation
- Histamine H1 receptor antagonists: drowsiness
- Muscarinic receptor antagonists: constipation, drowsiness and dry mouth
- Dopamine D2 receptor antagonists: extra-pyramidal side effect
