Metoclopramide

Class Dopamine receptor antagonist
Chemistry

Benzamide

Routes of administration

Oral, IV, IM, s/c

Absorption

Rapidly and completely absorbed, bioavailability ~ 80%

Solubility

pKa 9.27, highly water soluble

Distribution

VOD = 3.5L/kg; minimally protein-bound (13-22%)

Metabolism

Undergoes some hepatic metabolism, mainly by CYP 2D6

Elimination

About 20-50%of the drug dose is eliminated unchanged

Time course of action

Half-life is about 4-6 hours, but the duration of antiemetic effect is only 1-2 hours

Target receptor

D2 dopamine receptor antagonist (Gi-protein coupled);
also has activity as a muscarinic agonist (mainly peripherally)

Mechanism of action

Antiemetic/antinausea effect is mainly exerted by the antidopaminergic effects centrally. Side effects (eg. dystonic reaction and galactorrhoea) are also mainly antidopaminergic. Prokinetic effects are mainly due to the peripheral muscarinic agonist effects

Clinical effects

- Increased lower oesophageal sphincter tone
- increased gastric emptying rate
- risk of dystonic reaction, especialy with children under 10
- Galactorrhoea due to dopamine antagonist effects

Literature reference

Albibi et al, 1983

CICM details of understanding Level 3
Mentioned around Deranged Physiology
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