24.3 : 化学療法誘発性の吐き気と嘔吐：ニューロキニン 1

The central vomiting center and the chemoreceptor trigger zone in the brainstem are rich in neurokinin 1 or NK₁ receptors. During chemotherapy, the GI mucosa releases substance P, which crosses the blood-brain barrier to bind and activate the NK₁ receptor, ultimately inducing vomiting.

To combat this, several NK₁-receptor antagonists like aprepitant, netupitant, and rolapitant, are available. They selectively bind NK₁ receptors, blocking substance P binding and preventing chemotherapy-induced nausea and vomiting, or CINV.

CINV has two phases : the acute phase occurring shortly after treatment and the delayed phase arising a few days after treatment.

NK₁-receptor antagonists effectively inhibit the delayed phase of CINV. They are typically used with acute phase inhibitors – 5-HT₃ antagonists and dexamethasone.

They are primarily metabolized by hepatic CYP3A4. Notably, this may affect the CYP3A4-mediated metabolism of anti-cancer agents such as docetaxel, paclitaxel, and imatinib.

Additional adverse effects comprise fatigue, diarrhea, hiccups, and neutropenia.