Therapeutics: Anti-Emetics
In this episode recorded in March 2020 Kunal Gohil joined the podcast to take us through anti-emetics. Featuring a whistle-stop tour of the vomiting reflex, the mechanisms of anti-emetics and a discussion on how they sound like Transformers!
Here is our Take Visually going through the vomiting reflex:
The vomiting centre (VC) sits in the medulla oblongata of the brain. In the vomiting reflex the diaphragm contracts, abdominal muscles tense, the gastric sphincter relaxes, the epiglottis closes to prevent aspiration and the stomach contracts. Outside of the blood-brain barrier (BBB) sits the chemoreceptor trigger zone (CTZ) whose job is to detect blood borne insults and send signals to the VC which sits within the BBB.
There are 5 key mechanisms which trigger the vomiting reflex
Blood-borne agent
Typically poisoning such as electrolyte disturbance, medication side effect or a noxious substance. Detected by the CTZ which signals to the VC.
Direct insult to gastrointestinal tract
Something within the GI tract such as medication or rotten food. Detected by lumen cells which signal to the VC via serotonin along the vagus nerve.
Vestibular system
‘Motion Sickness’. The labyrinth within the inner ear signals to the vestibular nuclei close to the VC via the vestibulocochlear nerve.
Higher centres
Fear, anxiety, disgust, noxious stimuli. Mediated by higher cortical centres and self-perpetuated in a vicious cycle.
Direct insult to brain
Head injury, space occupying lesion, inflammation/swelling. Increased intracranial pressure.
All of these mechanisms use different neurotransmitters and can be targeted with different agents.
The VC uses mostly muscarinic (M1) receptors and so can be blocked by antimuscarinic agents but as it sits within the BBB it is hard to reach. The CTZ mostly uses dopamine (D2) receptors and serotonin (5-HT). The vagus nerve also uses 5-HT. The vestibular nuclei use histamine (H1) receptors. Higher centres (sensory input) can be targeted with anxiolytics (especially benzodiazepines). Direct insult by inflammation can be treated with steroids, especially dexamethasone.
Here is our Take Visually going through the different anti-emetic mechanisms: