Antiemetics and Prokinetic Drugs

Introduction & the emetic reflex

• Antiemetics suppress nausea and vomiting; prokinetics promote coordinated GI transit and speed gastric emptying. The two classes overlap because the dopamine D₂ block that drives the antiemetic action of benzamides (metoclopramide) also disinhibits gut motility.
• Vomiting (emesis) is a protective reflex that expels upper-gut toxins; nausea is the aversive conditioning sensation. The reflex is coordinated by a vomiting centre (VC) in the lateral reticular formation of the medulla, next to the chemoreceptor trigger zone and nucleus tractus solitarius (NTS).
• Four afferent inputs converge on the VC: (1) the CTZ in the area postrema — outside the blood–brain barrier, so it samples blood/CSF emetogens (rich in D₂, 5-HT₃, NK₁, M₁, CB₁, µ-opioid receptors); (2) vagal/spinal GI afferents (5-HT₃, activated by mucosal 5-HT from enterochromaffin cells); (3) the vestibular apparatus (M₁, H₁ — motion sickness); (4) higher cortical centres (anticipatory/psychogenic vomiting).
• Key emetic mediators are 5-HT (acting on 5-HT₃) and substance P (acting on NK₁); matching each receptor to a drug class is the spine of antiemetic therapy. Because nausea is processed in higher cortical areas separate from the emetic centre, most antiemetics control vomiting better than nausea.