Your body uses nausea to let you know that you’ve ingested something bad. Or, at least, that it thinks you’ve ingested something bad—it doesn’t always get it right. These are the four major pathways that produce the feeling of nausea:
- The cerebral cortex and limbic system: remember that thing that made you really sick, and now even the smell or thought of it makes you nauseous? That’s your body’s first defence against toxic ingestions.
- The GI tract: it contains chemoreceptors and mechanoreceptors that try to guess when you’ve eaten something bad or dangerous. It often involves serotonin (5-HT3) receptors in the GI tract.
- The vestibular system: disruptions to your inner ear and sense of balance can cause nausea, as anyone who has experienced motion sickness can attest. This pathway uses histamine (H1) and muscarinic acetylcholine (M1) receptors.
- Finally, the chemoreceptor trigger zone: this is a specialized bundle of chemoreceptors that sample the blood, responding to drugs, certain metabolites, and bacterial toxins. It mainly uses central dopamine (D2) receptors, but also serotonin (5-HT3) and NK1 receptors.
In order to treat nausea, then, you should target the pathway that’s acting up. For motion sickness, anti-histamines like diphenhydramine; for chemotherapy, serotonin antagonists like ondansetron; for decreased GI motility, prokinetic dopamine antagonists like metoclopramide; and when you don’t know, haloperidol, which mainly blocks dopamine but also affects the other pathways.
Read more: Palliative and End-of-Life Care > Nausea, Harrison’s Principles of Internal Medicine 19e.