ANTIEMETIC AGENTS

 

Introduction:  Nausea and vomiting may be manifestations of a wide variety of conditions, including adverse effects from medications; systemic disorders or infections; pregnancy; vestibular dysfunction; central nervous system infection or increased pressure; peritonitis; hepatobiliary disorders; radiation or chemotherapy; and gastrointestinal obstruction, dysmotility, or infections.  

Pathophysiology:  The brainstem “vomiting center” is a loosely organized neuronal region within the lateral medullary reticular formation and coordinates the complex act of vomiting through interactions with cranial nerves VIII and X and neural networks in the nucleus tractus solitarius that control respiratory, salivatory, and vasomotor centers.  High concentrations of muscarinic M₁, histamine H₁, neurokinin1 (NK1), and serotonin 5-HT3  receptors have been identified in the vomiting center.  There are four important sources of afferent input to the vomiting center:  

1)    The “chemoreceptor trigger zone” or area postrema is located at the caudal end of the fourth ventricle.  This is outside the blood-brain barrier but is accessible to emetogenic stimuli in the blood or cerebrospinal fluid.  The chemoreceptor trigger zone is rich in dopamine D₂ receptors and opioid receptors, and possibly serotonin 5-HT₃ receptors and NK1 receptors.  

2)     The vestibular system is important in motion sickness via cranial nerve VIII.  It is rich in muscarinic M1  and histamine H1 receptors.  

3)     Vagal and spinal afferent nerves from the gastrointestinal tract are rich in 5-HT3 receptors.  Irritation of the gastrointestinal mucosa by chemotherapy, radiation therapy, distention, or acute infectious gastroenteritis leads to release of mucosal serotonin and activation of these receptors, which stimulate vagal afferent input to the vomiting center and chemoreceptor trigger zone.  

4)     The central nervous system plays a role in vomiting due to psychiatric disorders, stress, and anticipatory vomiting prior to cancer chemotherapy.   Identification of the different neurotransmitters involved with emesis has allowed development of a diverse group of antiemetic agents that have affinity for various receptors.

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