Pathophysiology
Clinical meaning
Nausea and vomiting are mediated through multiple pathways, and the NP must match the antiemetic to the underlying mechanism. The vomiting center in the medulla receives input from: (1) Chemoreceptor trigger zone (CTZ) — area postrema outside the blood-brain barrier; senses circulating toxins, drugs, and metabolic derangements; D2, 5-HT3, NK1, and opioid receptors predominate; (2) Vestibular system — motion sickness, vertigo; H1 and muscarinic (M1) receptors predominate; (3) GI tract — vagal afferents from the gut; 5-HT3 receptors on vagal nerve terminals sense mucosal irritation, chemotherapy-induced serotonin release, and distension; (4) Higher cortical centers — anticipatory nausea, psychogenic vomiting; benzodiazepines and cannabinoids are effective. Antiemetic selection: chemotherapy-induced: ondansetron (5-HT3 antagonist) ± dexamethasone ± aprepitant (NK1 antagonist) — three-drug regimen for highly emetogenic chemotherapy; post-operative: ondansetron 4 mg IV; motion sickness: scopolamine patch or meclizine; gastroparesis: metoclopramide (D2 antagonist, 5-HT4 agonist — promotes gastric motility); pregnancy: pyridoxine (B6) + doxylamine first-line, then ondansetron. The NP avoids metoclopramide for >12 weeks (FDA black box warning for tardive dyskinesia) and avoids promethazine IV push (tissue necrosis risk — only IM or diluted IV...