Pharm 101: Metoclopramide

Class

Anti-emetic

Pharmacodynamics

• Pro-kinetic agent
• Dopamine (D2) receptor antagonist with peripheral and central actions
• Peripheral:
  • Increases oesophageal motility
  • Increases lower oesophageal sphincter pressure
  • Increases gastric emptying
  • Activation of dopamine receptors in the gastrointestinal tract inhibits cholinergic smooth muscle stimulation, thus D2 blockade acts as a pro-kinetic mechanism
• Central:
  • Potent anti-nausea and anti-emetic agent
  • Via D2 blockade in chemoreceptor trigger zone (CTZ) of medulla

Pharmacokinetics

• X

Clinical uses

• GORD
• Impaired gastric emptying
• Anti-emetic
• Postpartum lactation stimulation (domperidone)

Adverse effects

• Relate to central dopamine antagonist action
• CNS:
  • Restlessness, drowsiness, insomnia, anxiety, agitation
  • Common (10-20%), especially in elderly
• Extrapyramidal effects:
  • Acute dystonia, akathisia, parkinsonian features
  • Tardive dyskinesia* with chronic dosing
  • Due to central dopamine blockade
  • More likely with higher doses and long-term therapy
• Hyperprolactinaemia, galactorrhoea

*Late occurring syndrome of abnormal movements which is a common complication of long-term neuroleptic or metoclopramide treatment. Caused by relative cholinergic deficiency secondary to supersensitivity of dopamine receptors.

Precautions/contraindications

• X

Further Reading

• Nickson C. Acute Dystonic Reaction