Mechanisms of Chemotherapy-induced Nausea and Vomiting

Mechanisms of CINV

Chemotherapy drugs may cause emesis through effects at a number of sites within the body and brain. A simplied view is given below.^1,2

• These drugs have an effect on the upper region of the small intestine; after the administration of chemotherapy, there is a localised release of the neurotransmitter serotonin (5-HT) from specific cells lining the intestine (enterochromaffin cells).
• The released serotonin then binds to 5-HT₃ receptors on the terminals of sensory nerves (vagal afferents) situated within the walls of the intestine.
• On binding, the nerves are then activated and send signals to part of the medulla known as the chemoreceptor trigger zone (CTZ).
• Receptors for a number of neurotransmitters with potentially important roles in the emetic response are present in the CTZ, including neurokinin-1 (NK1), 5-HT₃, and dopamine D2 receptors, which bind substance P, serotonin, and dopamine, respectively.
• Efferent nerves project from the CTZ to the vomiting centre (VC), which also contains NK1, 5-HT₃ and D2 receptors.
• Efferent impulses then travel from the VC to a number of different sites within the brain and body (abdominal muscles, salivation centre, cranial nerves and respiratory centre), causing vomiting.
• It is thought that chemotherapeutic agents cause vomiting by activating neurotransmitter receptors located in the gastrointestinal tract, CTZ and VC.

Multiple transmitters are therefore involved in the genesis of CINV via their receptors within the central nervous system and gastrointestinal tract that mediate the afferent inputs to the VC.³