🧠 SUBSTANCE P / NEUROKININ-1 RECEPTOR ANTAGONISTS

What is Substance P?

A neurokinin peptide neurotransmitter.

What is the primary role of Substance P in chemotherapy?

It is believed to be the primary mediator of delayed chemotherapy-induced nausea and vomiting.

With which medications is Substance P often used?

It is often used with 5-HT3 blockers and corticosteroids.

What is the prototype drug for NK1 receptor antagonists?

Aprepitant (Emend, Cinvanti) - PO and Fosaprepitant (Emend IV) - IV (a prodrug converted to aprepitant).

What is the mechanism of action of Aprepitant?

It blocks NK1 receptors in the brainstem to interrupt the nausea signal.

Does Aprepitant have any effect on serotonin or dopamine receptors?

No, it has no effect on serotonin or dopamine receptors.

What are the indications for using Aprepitant?

Improves control of nausea/vomiting on days 3-5, which 5-HT3 blockers don’t fully cover.

What safety warning is associated with Fosaprepitant?

It should no longer be used in adults/peds for chemo-induced N/V due to risk of abnormal heart rhythm.

What should be monitored when using Fosaprepitant?

Monitor QT interval, especially if used with other risk drugs.

What is the effect of Aprepitant on hormonal contraceptives?

It reduces effectiveness for up to 28 days; a backup method should be used.

What is Aprepitant’s administration method for PO?

Take with or without food, 1 hour before chemo on day 1, then QAM on days 2 & 3.

Why is IV administration of Fosaprepitant discouraged?

Due to QT issues.

What combination of drugs is typically used in the antiemetic regimen including Aprepitant?

Aprepitant + 5-HT3 antagonist + corticosteroid ± olanzapine.

What should be assessed after chemotherapy when using Aprepitant?

Whether nausea/vomiting is controlled.

What are common side effects of Aprepitant?

Fatigue, dizziness, and hiccups.

What contraindications exist for using Aprepitant?

Hypersensitivity to the drug, and use with Ranolazine, Pimozide, and Cisapride due to serious QT and arrhythmia risks.

What should be monitored when Aprepitant is given IV?

Cardiac monitoring, especially if the patient is at risk for arrhythmia.

What drug interaction requires dosage adjustment with Aprepitant?

Dexamethasone dose must be reduced by 50% (oral) or 25% (IV) if given together.

What is a significant finding from Navari et al. (2021) regarding Akynzeo?

Akynzeo was found to be more effective than aprepitant regimens for delayed N/V.

What did the study about Akynzeo find regarding medication needs?

It reduced the need for rescue meds.

What lifestyle modification should be made regarding grapefruit juice when taking Aprepitant?

Avoid grapefruit juice due to its interaction with CYP3A4 drugs.

What are the common side effects of Aprepitant?

Fatigue, headache, dizziness, and hiccups.

What is the significance of the BLACK BOX warning for Fosaprepitant?

Risk of abnormal heart rhythm.

What clinical considerations are important when administering Aprepitant?

Monitor for drug interactions and QT prolongation.

What combination is essential with Aprepitant to improve treatment efficacy?

Combination with 5-HT3 antagonists and corticosteroids.

When should the backup method for birth control be used when taking Aprepitant?

For up to 28 days after the last dose.

What is the primary target of Aprepitant in chemotherapy-induced conditions?

Delayed nausea and vomiting.

What should be done if a patient experiences side effects while on Aprepitant?

Assess and monitor the patient for side effects post-chemo.

What types of patients should be particularly monitored when receiving Aprepitant?

Patients at risk for arrhythmias.

How does Aprepitant affect the nausea signal in the body?

It interrupts the signal by blocking NK1 receptors.

What should be done if nausea/vomiting is not controlled after chemotherapy?

Assess the effectiveness of the antiemetic regimen.

What is the potential impact of using other medications with Aprepitant?

Increased risk of QT prolongation and drug interactions.

What is the preferred route of administration for Fosaprepitant?

IV administration is discouraged due to associated risks.

What can patients do to avoid drug interaction issues while on Aprepitant?

Consult healthcare providers before taking additional medications.