A 62-year-old woman is evaluated for refractory nausea and vomiting. She was recently diagnosed with ovarian cancer and underwent total hysterectomy with bilateral salpingo-oophorectomy and pelvic lymph node dissection. The patient was started on highly emetogenic adjuvant chemotherapy. Despite taking ondansetron around the clock, she continues to have nausea and vomiting. She has no abdominal pain or constipation. Vital signs are normal. Examination shows a well-healed abdominal scar. There is no tenderness or abnormal masses. Bowel sounds are normal. Additional therapy blocking which of the following receptors would most likely be helpful in this patient?

Question

A 62-year-old woman is evaluated for refractory nausea and vomiting.  She was recently diagnosed with ovarian cancer and underwent total hysterectomy with bilateral salpingo-oophorectomy and pelvic lymph node dissection.  The patient was started on highly emetogenic adjuvant chemotherapy.  Despite taking ondansetron around the clock, she continues to have nausea and vomiting.  She has no abdominal pain or constipation.  Vital signs are normal.  Examination shows a well-healed abdominal scar.  There is no tenderness or abnormal masses.  Bowel sounds are normal.  Additional therapy blocking which of the following receptors would most likely be helpful in this patient?

Quizplus · Accepted Answer

11ec160b_3be1_120a_9249_d74aadbc7206_MD0001_00 Vomiting is a reflex that can be activated by either humoral or neuronal stimuli. The area postrema in the fourth ventricle has a chemoreceptor trigger zone that can respond to many neurotransmitters, drugs, or toxins. The nucleus tractus solitarius (NTS) in the medulla receives information from the area postrema, gastrointestinal tract via the vagus nerve, vestibular system, and central nervous system (eg, meninges, hypothalamus). Neurons from the NTS project to other medullary nuclei and coordinate the vomiting process. The 5 major receptors involved in stimulating the vomiting reflex in the area postrema and adjacent vomiting center nuclei are M₁ muscarinic, D₂ dopaminergic, H₁ histaminic, 5-HT₃ serotonergic, and neurokinin 1 (NK1) receptors. 5-HT3 receptor antagonists (eg, ondansetron) and dopamine receptor antagonists (eg, metoclopramide) are particularly helpful for chemotherapy-induced vomiting. When these do not control symptoms, NK1 receptor antagonists (prevent substance P release) can be considered; they prevent both acute vomiting and delayed emesis associated with chemotherapy. (Choice A) Opioid receptor antagonists (eg, naltrexone) competitively bind opioid receptors to prevent action of endogenous or exogenous opioids. They are used mainly for opioid dependence. (Choice B) Motilin regulates interdigestive migrating contractions. Erythromycin is a motilin receptor agonist used for gastroparesis. (Choice D) Neuropeptide Y is a polypeptide neurotransmitter found in the central and autonomic nervous systems. It is thought to play a role in appetite and pain perception. Neuropeptide Y antagonists have been investigated as potential antiobesity drugs. (Choice E) Nicotinic antagonists are primarily used for muscle paralysis during surgery. Some antihistamines (eg, promethazine, meclizine) and antimuscarinics (eg, scopolamine) have anticholinergic activity and inhibitory effects on both the vomiting center and vestibular apparatus (useful for motion sickness). Educational objective: Vomiting is a reflex regulated mainly by 5 receptors, including M₁ muscarinic, D₂ dopaminergic, H₁ histaminic, 5-HT₃ serotonergic, and neurokinin 1 (NK1) receptors. 5-HT₃ and NK1 receptor antagonists are particularly useful for chemotherapy-induced vomiting. __________ References: Nausea, vomiting, and hiccups: a review of mechanisms and treatment. (http://www.ncbi.nlm.nih.gov/pubmed/21174569) Neurokinin-1 receptor antagonists for chemotherapy-induced nausea and vomiting. (http://www.ncbi.nlm.nih.gov/pubmed/25841473)

A 62-Year-Old Woman Is Evaluated for Refractory Nausea and Vomiting