(FETT) Emetogenic/Therapy adjuncts

Antiemetics

CYCLIZINE

PROCHLORPERAZINE

METOCLOPRAMIDE

DOMPERIDONE

Dopamine receptor antagonists.

• D2 antagonist

• Central antiemetic effect at the area postrema

Exerts an antipsychotic effect through blockade of the mesolimbic D1 and D2 receptors. Exerts an anticholinergic effect (e.g., constipation, blurry vision) through blockade of cholinergic receptors and alpha-adrenergic antagonism (e.g., sedation, hypotension).

• Antipsychotic agent

• Hyperemesis gravidarum

• D2 antagonist, serotonin receptor antagonist

• As a D2 antagonist and serotonin receptor antagonist, metoclopramide exerts two complementary antiemetic effects.

• Central antiemetic effect at the area postrema

• Peripheral antiemetic effect in the gastrointestinal tract (prokinetic effect); causes increase in :

  • Gastric contractions

  • Duodenal and jejunal motility

  • Resting tone of the lower esophageal sphincter

    —> Dopamine receptors are found in the brain as well as throughout the gastrointestinal tract. The prokinetic activity of metoclopramide is mediated by D2 receptor antagonist activity and 5-HT4 receptor agonist activity.

• Together with decreased pylorus sphincter activity allows food to pass more quickly through the stomach and the small intestine

• No influence on colon motility

• Prokinetic effect used to treat diabetic and postsurgery gastroparesis (delayed gastric emptying)

• Hyperemesis gravidarum

• Persistent GERD

• D2 antagonist

• Central antiemetic effect at the area postrema

• Prokinetic effect (due to blockage of peripheral dopamine receptors)

• Nausea and vomiting

• Gastrointestinal motility disorders

• Gastrointestinal

  • Diarrhea

  • Pain

• Hyperprolactinema

• Domperidone, in contrast to metoclopramide and prochlorperazine, crosses the blood-brain-barrier only minimally, hence neurological side effects are limited

• May cause cardiac arrhythmias

• Gastrointestinal

  • Diarrhea

  • Pain

• Hyperprolactinema

• Neurological

  • Depression, anxiety

  • Fatigue

  • Drowsiness

  • Restlessness

  • Lowering of seizure threshold

  • Overdose leads to reversible extrapyramidal syndrome (e.g., dystonia, parkinsonism, tardive dyskinesia, and akathisia) and neuroleptic malignant syndrome

  • Do not combine metoclopramide with antipsychotics because this increases the risk of dyskinesia!

  • Antidote: benztropine, biperiden (anticholinergic agents)

• Avoid combination with digoxin and antidiabetic drugs.

• Contraindicated in patients with suspected small bowel obstruction

• Nonspecific nausea and vomiting

• Chemotherapy-induced nausea and vomiting

• Vertigo (e.g., vestibular neuritis, Ménière's disease)

• Motion sickness

• Gastrointestinal motility disorder (e.g., due to diabetic gastroparesis)

• Postoperative nausea and vomiting

• Dopamine receptor antagonists

  • Intestinal obstruction (ileus)

  • Prolactin-dependent tumors

  • Parkinson disease: unlike domperidone, metoclopramide can cross the blood-brain barrier and exacerbate the pre-existing dopamine deficiency that causes parkinsonism.

• Serotonin receptor antagonists: severe liver disease, prolonged QT interval

• Anticholinergic agents and antihistamines

  • Tachyarrhythmias, heart failure

  • Urinary retention, BPH

  • Glaucoma

  • Pyloric stenosis

• History of tardive dyskinesia or dystonic reaction to metoclopramide.

• Mechanical obstruction or perforation or other situations in which stimulation of GI motility might be dangerous.

• GI hemorrhage [ref] (however, has been used to empty the stomach of blood prior to endoscopy in patients with acute upper GI hemorrhage). 

• Pheochromocytoma or other catecholamine-releasing paragangliomas (due to potential for hypertensive/pheochromocytoma crisis). 

• History of seizure disorders. 

• Known hypersensitivity to metoclopramide.

Restlessness, drowsiness, fatigue, lassitude, nausea, bowel disturbances (principally diarrhea). 

Adverse effects with orally disintegrating tablets and nasal spray are similar to those observed with conventional tablets, but dysgeusia is the most common adverse effect with the nasal spray.

• Comatose states or in the presence of large amounts of CNS depressants (e.g., alcohol, barbiturates, opiates). 

• Pediatric surgery. 

• Children <2 years of age or <9 kg.

• Children with conditions for which dosage has not been established. 

• Known hypersensitivity to prochlorperazine or other phenothiazines.