Metoclopramide Flashcards
What is this drug usually used for?
Nausea & vomiting
Hiccups
Acute migraine
Describe the pharmacodynamics of this drug
An antiemetic
Inhibits D2 (dopamine) and 5-HT3 (serotonin) in the chemoreceptor trigger zone of the area postrema (of the medulla oblangata)
Also enhances the release of ACh which increases the tone of the lower oesophageal sphincter (LES) to stop gastric contents coming back up AND increases the gastric tone to accelarate gastric emptying
Describe the pharmacokinetics of this drug
Oral bioavailabilty = 40.7% (but has a GI absorption rate of 84%)
Volume of distribution = 3.5L/kg
Half-life = 5-6 hours (prolonged in renal impairment)
Protein binding = 30% (mainly to alpha-1-acid glycoprotein)
Metabolism = hepatic - undergoes 1st pass metabolism. Metabolised by CYP2D6 (main), CYP3A4 and CYP1A2 (minor)
Excretion = kidney (85% of orally administered drug). Total clearance of 0.7 L/h/kg
What are the contraindications of this drug?
3-4 days after GI surgery
Epilepsy
GI haemorrhage/obstruction/perforation
Phaeochromocytoma
Avoid in pregnancy as it crosses the placental barrier and can cause extrapyramidal symptoms in the foetus
What are most clinically significant (common and/or potentially life threatening) side effects of the drug?
The common/very common side effects are:
- depression
- asthenia
- parkinsonism (hence why use of more than 12 weeks should be avoided)
The uncommon side effects are:
- arrythmias
- hallucinations
- hyperprolactinaemia
- decreased level of consciousness
The very rare but dangerous side effects are:
- AV block
- cardiac arrest
- QT interval prolongation
When should the dose be reduced and by how much
In severe hepatic impariment reduce by 50%
In severe renal impairment avoid using or use small dose due to increased risk of extrapyramidal reactions
What are the most clinically significant drug interactions?
Topical prilocaine + metoclopramide = increased risk of methaemoglobinaemia
