Prokinetic Drugs

Prokinetic drugs accelerate gastric emptying and gut transit through dopamine D2 antagonism, serotonin 5HT4 agonism or motilin receptor agonism. They are used for gastroparesis, functional dyspepsia, reflux with delayed emptying and chronic constipation.

Classification. D2 antagonists (metoclopramide, domperidone); 5HT4 agonists (prucalopride); motilin agonists (erythromycin at low dose).

• Metoclopramide 10 mg orally, intramuscularly or intravenously up to three times daily; maximum 30 mg daily (0.5 mg/kg).
• Domperidone 10 mg up to three times daily orally; maximum 30 mg daily.
• Erythromycin 125 to 250 mg before meals.
• Prucalopride 2 mg once daily; 1 mg daily if over 65, creatinine clearance under 30 mL/min or severe liver impairment.

Differences. Metoclopramide crosses the blood-brain barrier and causes extrapyramidal effects. Domperidone does not, but prolongs QT. Erythromycin loses effect through tachyphylaxis within weeks.

• Gastroparesis: metoclopramide for no more than 5 days at usual dosing, unless a specialist continues it; domperidone or low-dose erythromycin as alternatives.
• Chronic constipation unresponsive to laxatives: prucalopride.
• Opioid or post-surgical ileus: specialist use only.

Selection. Exclude mechanical obstruction before any prokinetic.

Contraindications. Mechanical obstruction, perforation, gastrointestinal haemorrhage, phaeochromocytoma (metoclopramide), prolactinoma, QT prolongation or use with strong CYP3A4 inhibitors (domperidone), Parkinson disease (metoclopramide).

Adverse effects. Metoclopramide: acute dystonia, akathisia, parkinsonism, tardive dyskinesia (boxed warning, often irreversible, risk rises with duration), neuroleptic malignant syndrome, hyperprolactinaemia, depression, methaemoglobinaemia in neonates. Domperidone: QT prolongation and sudden cardiac death. Prucalopride: headache, diarrhoea, abdominal pain.

Interactions. Metoclopramide with antipsychotics, SSRIs (serotonin syndrome) and levodopa; it also speeds paracetamol absorption and lowers digoxin absorption. Domperidone with ketoconazole, clarithromycin, erythromycin and other QT drugs.

Special groups.

• Kidney impairment: halve metoclopramide when creatinine clearance is under 60 mL/min and reduce further when severe.
• Children and young adults: dystonia risk is highest; metoclopramide is second-line only.
• Pregnancy: metoclopramide acceptable.
• Breastfeeding: metoclopramide raises prolactin; small milk transfer.
• Older adults: lower doses; watch for parkinsonism.

Monitoring. Abnormal movements, mood, ECG and electrolytes for domperidone.

Referral and escalation. Stop at first dystonia; give procyclidine 5 to 10 mg intramuscularly or intravenously. Refer gastroparesis not controlled by diet and one prokinetic.