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Antiemetics: Nursing Pharmacology



ondansetron (Zofran)
metoclopramide (Reglan)
aprepitant (Cinvanti, Emend)
5-HT3 receptor antagonist
D2 dopamine receptor antagonist
Neurokinin receptor antagonist
Decreases vagal nerve stimulation (peripheral action); blocks chemoreceptor trigger zone
Blocks dopamine D2 receptors → decreases dopamine levels; crosses blood-brain-barrier
Blocks substance P from acting at the neurokin-1 receptors
  • Postoperative nausea / vomiting
  • Chemotherapy / radiotherapy-induced nausea / vomiting 
  • Diabetic gastroparesis
  • Postoperative nausea / vomiting
  • Chemotherapy-induced nausea / vomiting
  • PO
  • IV
  • IM
  • PO
  • NAS
  • IV
  • IM
  • SubQ
  • PO
  • IV (fosaprepitant)
  • Headaches
  • Gastrointestinal disturbances
  • QT prolongation
  • Serotonin syndrome
  • CNS toxicity → hyperprolactinemia, parkinsonism (more common with metoclopramide)
  • Gastrointestinal disturbances
  • Restlessness
  • Fatigue
  • Drowsiness
  • Depression
  • Dry mouth, rash, pruritus, and urticaria, or hives, arrhythmias (domperidone)
  • EPS symptoms (e.g., pseudoparkinson-ism, acute dystonia)
  • Headaches
  • Dizziness
  • Fatigue
  • Hiccups
  • Gastrointestinal disturbances
  • Hair loss
  • Skin rash
  • Blood disorders
  • Clients with risk factors for QT prolongation
  • Combination with other medications that increase serotonin levels (e.g., SSRIs, MAOIs)
  • Prolonged use (>12 weeks)
  • Severe hepatic disease
  • Interacts with warfarin, grapefruit juice
DRUG NAMEprochlorperazine (Compro), promethazine
*High Alert Medication*
diphenhydramine (Benadryl)
dronabinol (Marinol)
Antihistamine; H1 receptor antagonist
Blocks dopamine, cholinergic and histamine receptors
Blocks histamine H1 receptors
Activates cannabinoid receptors in the brain
  • Chemotherapy- induced nausea / vomiting
  • Motion sickness
  • Motion sickness
  • Nausea / vomiting
  • Allergic reactions
  • Chemotherapy- induced nausea / vomiting

  • PO
  • PR
  • IV
  • IM
  • PO
  • IV
  • IM
  • PO
  • Antidopaminergic effects: hyperprolactinemia, parkinsonism
  • Anticholinergic effects
  • Antihistamine effects: sedation
  • Boxed warning (promethazine):  vesicant
  • Antihistamine effects: sedation, increased appetite, weight gain
  • Anticholinergic effects
  • Anti-α-adrenergic effects: orthostatic hypotension, dizziness
  • CNS effects: drowsiness, dizziness, confusion, delusions, anxiety, euphoria
  • Increased appetite
  • Gastrointestinal disturbances
  • Boxed warning (prochlorperazine): increased mortality in elderly clients with dementia-related psychosis

All antiemetics
  • Client history, current medications
  • Symptoms
    • Onset, duration and frequency; emesis characteristics; fluid intake; urine output; associated symptoms; e.g., abdominal pain, lightheadedness, fever
  • Vital signs; note signs of dehydration; abdominal assessment
  • Laboratory and diagnostic test results
    • CBC, electrolytes, renal and hepatic function; ECG for QT prolongation
  • Monitor for side effects
    • Drowsiness, QT prolongation, anticholinergic, extrapyramidal, serotonin syndrome
  • Evaluate for desired outcomes
    • Reduced nausea and vomiting, balanced hydration and electrolytes, adequate nutritional intake increased comfort
All antiemetics
  • Explain the purpose of medication
  • Take as directed
  • Side effects
    • Drowsiness, anticholinergic effects
  • Comfort measures
    • Cleansing face and with cool washcloth; performing mouth care between episodes of vomiting
  • Drink clear liquids as tolerated, sipping small amounts every 15 to 20 minutes is better tolerated; try eating foods with a lot of liquid in them (e.g., gelatin or popsicles);  crackers or dry toast can help settle their stomach
  • For postoperative nausea / vomiting: demonstrate how splint incision site
  • Contact healthcare provider if worsening vomiting, decreased urinary output, extrapyramidal side effects
ondansetron (Zofran)
prochlorperazine (Compro), promethazine
*High Alert Medication*

Ondansetron disintegrating tablet
  • Take with or without food, allow the tablet to dissolve in their mouth without chewing or swallowing whole
  • Remind them to protect unused tablets from moisture
  • Ensure proper IV catheter placement into a large vein
  • Instruct the client to immediately report pain / burning if extravasation is suspected
  • Stop the infusion for suspected extravasation
  • Extravasation management measures

Antiemetics are a group of medications that are used to treat nausea and vomiting. These include ondansetron, metoclopramide, aprepitant, prochlorperazine, and promethazine, as well as antihistamines like diphenhydramine, and cannabinoids, such as dronabinol.

Let’s start with ondansetron, which can be administered orally, intravenously, and intramuscularly. Once administered, ondansetron acts as a 5-HT3 receptor antagonist peripherally by decreasing vagal nerve stimulation, but it is also a very powerful central acting antiemetic blocking an area in the brain called chemoreceptor trigger zone, or CTZ for short.

Ondansetron is primarily used to control nausea and vomiting after surgical anesthesia, as well in individuals undergoing chemotherapy or radiotherapy.

Next, metoclopramide can be administered orally, intranasally, intravenously, and intramuscularly, and subcutaneously. Once administered, it acts by blocking dopamine receptors in the CTZ.

As a result, the levels of dopamine decrease, preventing nausea and vomiting after surgical anesthesia as well as chemotherapy-induced nausea and vomiting.

Okay, another antiemetic is aprepitant, which can be given orally, as well as intravenously in the form of fosaprepitant. Once administered, it acts as a neurokinin receptor antagonist that blocks neurokinin-1, or NK-1, receptors in the CTZ, and thus, it can be used to prevent chemotherapy-induced nausea and vomiting.

Alright, moving onto prochlorperazine, which is a phenothiazine, and can be given orally, rectally, intravenously, and intramuscularly. Phenothiazines block dopamine receptors in the CNS and they’re mostly used as antipsychotics.

However, most phenothiazines also have antiemetic effects, and in fact, prochlorperazine is used solely as an antiemetic. The mechanism of the antiemetic effects is complex.

They’re primarily due to the blockage of D2 receptors in the CTZ, as well as due to anticholinergic and antihistamine effects. Prochlorperazine is mainly used to treat nausea and vomiting associated with motion sickness.

Okay, now antihistamines, or H1 antagonists, like diphenhydramine can be given orally, intravenously, and intramuscularly. These medications are primarily used to treat allergic reactions, but diphenhydramine is unique in that it can also be used to treat motion sickness.

Finally, there’s dronabinol, which is the pharmaceutical form of cannabinoid that can be administered orally. Dronabinol activates cannabinoid receptors in the brain, which seems to cause appetite stimulation and antiemetic effects, and can be used to treat clients who experience chemotherapy-induced nausea and vomiting.

Alright, now moving onto side effects. Ondansetron can cause headaches, gastrointestinal disturbances like constipation, and can prolong the QT interval, leading to arrhythmias.

A life-threatening side effect of ondansetron is serotonin syndrome, which is caused by serotonin accumulation that results in overstimulation of the nervous system.

This syndrome is characterized by skin flushing, muscle rigidity, hyperthermia, agitation, seizure, and coma. It can occur in clients treated with a combination of ondansetron and other medications that increase serotonin level, such as antidepressants.

Okay, now metoclopramide can cause CNS toxicity. In females, it can lead to hyperprolactinemia, which can present with galactorrhea, which is the increase in milk production, and anovulatory amenorrhea, which is the absence of ovulation and menses.

On the other hand, in males, metoclopramide can cause gynecomastia and erectile dysfunction. Decreasing the effects of dopamine can also lead to the development of extrapyramidal symptoms within the first few days of treatment, such as acute dystonia and pseudoparkinsonism.

Now, metoclopramide can also cause restlessness, fatigue, drowsiness, and depression. Finally, metoclopramide can cause gastrointestinal disturbances, such as abdominal cramps and diarrhea.

Similarly, prochlorperazine can decrease dopamine effects, leading to hyperprolactinemia and parkinsonism. In addition, it can result in anticholinergic side effects, such as dry mouth, blurred vision, tachycardia, urinary retention, and constipation.

Finally, prochlorperazine can also cause extrapyramidal symptoms, and may have antihistamine effects, which can lead to sedation.

On the other hand, aprepitant may cause side effects like headaches, dizziness, fatigue, and hiccups! Other common side effects may include anorexia, nausea, vomiting, heartburn, and constipation.

Finally, less common but still important side effects of aprepitant include hair loss and a skin rash, as well as blood disorders like neutropenia.

Moving onto antihistamines, their side effects can be subdivided into antihistaminic effects, such as sedation, increased appetite, and weight gain; anticholinergic side effects, such as dry mouth, blurred vision, tachycardia, urinary retention, and constipation; and anti-α-adrenergic effects, like orthostatic hypotension and dizziness.

Finally, dronabinol can cause side effects from cannabinoids. These include drowsiness, dizziness, confusion, delusions, anxiety, and euphoria. In addition, dronabinol can also increase appetite and cause gastrointestinal disturbances, such as abdominal pain.

As far as contraindications go, ondansetron should be avoided in clients with risk factors for QT prolongation or in combination with other medications that increase serotonin levels, and should be used with caution in clients with electrolyte abnormalities.

On the other hand, metoclopramide is contraindicated in clients with Parkinson’s disease, as well as in those with mechanical bowel obstruction or perforation.

Additionally, as a boxed warning, metoclopramide should not be used for more than 12 weeks, as it may cause tardive dyskinesia, which can be irreversible.

Aprepitant should be used with caution in clients with severe hepatic disease, as well as those who also take warfarin. Finally, prochlorperazine has a boxed warning, contraindicating it for elderly clients with dementia-related psychosis.

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  3. "Mosby's 2021 Nursing Drug Reference" Mosby (2020)
  4. "Saunders Comprehensive Review for the NCLEX-RN Examination" Saunders (2019)
  5. "Goodman & Gilman's: The Pharmacological Basis of Therapeutics, 13e" McGraw-Hill Education (2018)