Ondansetron

• A serotonin receptor antagonist, it’s effective in most cases and safer relative to the other antiemetics! However, you need to be aware of the following side effects:
  •  Headache is the most reported side effect of ondansetron; if it happens, it’s severe and typically occurs within minutes of administration and lasts minutes to hours. Acetaminophen or acetaminophen with caffeine can be used to alleviate this.
  • QT prolongation: Ondansetron prolongs all intervals not just the QT, it prolongs PR and the QRS duration as well. It may also cause bradycardia. Look at the EKG before ordering Ondansetron, and correct any hypokalemia and hypomagnesemia. Don’t use Ondansetron if prolonged QTc exists, use metoclopramide or promethazine instead.
  • Constipation is another important side effect of ondansetron especially with repetitive doses. Stool softeners and laxatives can be used.
• Comes in IV, IM, and oral, the dissolved tablet form has been discontinued in the USA. IV form is the most commonly used in inpatient settings.
• It comes in 4-8 mg and is given every 4-6-8 hours as needed.

Ondansetron is usually the first one that comes to my mind when thinking about ordering a nausea medicine with a few exceptions that I’ll discuss soon.

Metoclopramide and promethazine

• Both work by blocking dopamine receptors but with slight differences.

   

  Promethazine blocks these receptors centrally only, while Metoclopramide blocks them centrally and peripherally in the GI tract, explaining its prokinetic effect. Additionally, Promethazine has an antihistamine effect which explains its sedative effect.

   

• Their antidopaminergic activity may lead to Drug-induced extrapyramidal reaction, Drowsiness, fatigue, dizziness, and confusion.

Drug-induced extrapyramidal reactions

• Acute dystonia and akathisia are the two conditions we need to watch out for
• They may develop rapidly within 24-48 hours of administering the medication.
• Discontinue the medication immediately!
• For acute dystonia IV diphenhydramine 50 mg x1 typically results in the resolution of an acute dystonic reaction within minutes. IV diazepam 5-10 mg is a good alternative if needed! Oral diphenhydramine 50 mg PO every 6 hours x1-2 days should be given to prevent recurrence.
• There is no definitive treatment for acute akathisia, but it will eventually improve and resolve. To help alleviate the symptoms propranolol 40-80 mg x1-2 daily can be tried.

 Other CNS effects

• Drowsiness, fatigue, dizziness, and confusion. Promethazine causes more sedation given its antihistamine effect that can be prolonged particularly in elderlies.
• Please avoid giving metoclopramide or promethazine simultaneously with other sedative agents like narcotics or benzodiazepines.

Metoclopramide

• Comes in Oral, IV, and nasal spray forms.
• It comes in 5/10/20 mg doses.
• Given every 4-6 hours as needed.
• Renal adjustment is necessary if creatinine clearance is 60 mL/minute.

Promethazine

• Comes in IV/IM/Oral/rectal
• It comes in 12.5 to 25 mg
• Given every 4 to 6 hours as needed.
• Beware that IV and IM promethazine administration carries the risk of severe tissue damage and chemical irritation and should be generally avoided. I still use IV promethazine but only if ondansetron and metoclopramide are ineffective or can’t be used! And the patient needs something quick or unable to tolerate PO.

Which one to pick

• Ondansetron is a good choice to start with in most cases -if no contraindications-
• Dopamine receptor antagonists (metoclopramide & promethazine) are preferred for migraine-induced nausea and vomiting.
• Promethazine is considered the first line in hyperemesis gravidarum.
• Some avoid using metoclopramide in cases of diarrhea given its prokinetic effect! This is incorrect! It’s safe to use metoclopramide in such cases.

Other antiemetics

• Neurokinin-1 receptor antagonists such as aprepitant or second-generation receptor antagonists such as palonosetron, are mainly used in outpatient settings for the prevention and treatment of chemotherapy-induced nausea and vomiting.
• Antihistamines such as meclizine are best for vestibular neuritis-induced nausea.
• Cannabinoids such as dronabinol, benzodiazepines, particularly lorazepam, and alprazolam, and glucocorticoids such as dexamethasone, all have variable antiemtic activity. They work better as an add-on to one of the three agents we mentioned if nausea is inadequately controlled.