Describe the physiology of vomiting. Classify antiemetics and describe the choice of drug in different situations.

Physiology of Vomiting and Drug Targets

The vomiting centre in the medulla coordinates the act; it receives input from four routes → chemoreceptor trigger zone (CTZ) in the area postrema — outside the blood–brain barrier, so it samples blood-borne emetics directly; rich in D2 and 5-HT3 receptors → vagal afferents from the gut — enterochromaffin cells release 5-HT onto 5-HT3 receptors; the route for chemotherapy and radiation → vestibular apparatus — H1 and muscarinic receptors; motion sickness and labyrinthine disease → higher centres — sight, smell, memory, anxiety; anticipatory vomiting → Each input has its own receptors, which is why the antiemetic must match the cause

Classification of Antiemetics

Matching the Drug to the Cause

Prokinetic Drugs

• Metoclopramide — D2 antagonist plus 5-HT4 agonist, increasing acetylcholine release in the gut wall; increases gastric emptying and lower oesophageal sphincter tone. extrapyramidal effects — acute dystonia (particularly in children and young women), parkinsonism, and tardive dyskinesia with prolonged use, which is why courses are now limited to 5 days
• Domperidone — peripheral D2 antagonist that does not cross the blood–brain barrier, so no extrapyramidal effects; but it prolongs the QT interval and has been restricted to short courses at low dose
• Erythromycin — a motilin agonist; used in diabetic gastroparesis and to clear the stomach before endoscopy in upper gastrointestinal bleeding; tachyphylaxis limits long-term use
• Prucalopride — a selective 5-HT4 agonist for chronic constipation; cisapride was withdrawn for QT prolongation and fatal arrhythmia

Adverse Effects of the Main Antiemetics

Applied Aspects

• Identify the cause before choosing the drug — ondansetron is excellent for chemotherapy and useless for motion sickness, because the pathways differ
• Give antiemetics before emetogenic chemotherapy or travel, not after vomiting has started; prevention is far easier than rescue
• Acute dystonia from metoclopramide is frightening and easily misdiagnosed as tetanus or hysteria; it responds within minutes to a parenteral antimuscarinic, and the drug must then be avoided
• Metoclopramide is widely and freely used in India, including for long periods, and drug-induced parkinsonism and tardive dyskinesia from it are common and frequently unrecognised
• Persistent vomiting needs a diagnosis, not just an antiemetic — intestinal obstruction, raised intracranial pressure, pregnancy, diabetic ketoacidosis, Addison disease and drug toxicity all present this way
• Correct fluid and electrolyte losses — hypokalaemia and metabolic alkalosis follow prolonged vomiting and may matter more than the symptom
• Avoid metoclopramide in young women and children where an alternative exists, since acute dystonia is commonest in exactly that group
• Domperidone is preferred in parkinson disease, because it does not cross the blood–brain barrier and so does not antagonise the dopaminergic treatment; metoclopramide and prochlorperazine both worsen parkinsonism markedly
• Antiemetics in pregnancy are safe and under-used — untreated hyperemesis causes dehydration, weight loss and Wernicke encephalopathy, and thiamine must be given before any glucose-containing fluid
• Check potassium and magnesium before giving ondansetron to a vomiting patient, since both are likely to be low and both increase the risk of torsades
• Prochlorperazine is widely used for vertigo but should not be given long term, since it delays vestibular compensation and causes extrapyramidal effects
• Ask about cannabis use in cyclical vomiting — cannabinoid hyperemesis syndrome is increasingly recognised, characteristically relieved by hot showers, and resolves only on stopping
• Vomiting is a symptom, not a diagnosis; a patient given an antiemetic without an examination and a working diagnosis may be sent home with an obstruction, a myocardial infarction or raised intracranial pressure
• Hyoscine and antihistamines must be given before travel, not once nausea has begun, since the vestibular pathway is already activated by then
• Domperidone is available over the counter in India and is widely used for long periods without supervision, despite the restriction on duration because of sudden cardiac death
• Fixed-dose combinations of antiemetics with antacids or antispasmodics are common in Indian practice and are rarely justified; single agents matched to the cause are better
• Correct dehydration before worrying about the antiemetic in a child with gastroenteritis; a single dose of ondansetron improves oral rehydration success and reduces admissions, but fluid is the treatment