Would doxylamine/pyridoxine (Diclegis), indicated for nausea and vomiting of pregnancy, help resolve nausea in patients undergoing chemotherapy? — Name withheld on request
The chemotherapy-induced nausea and vomiting (CINV) response is controlled in the central nervous system (CNS) by the emetic center, which lies in the brain stem. The emetic center receives input from three sources:
- Cortex The CNS cortex pathway is responsible for anticipatory emesis, and is mediated by dopamine and histamine.
- Periphery Serotonin (5-hydroxytryptamine3 [5-HT3]) and neurokinin (NK) pathways in the GI mucosa signal peripheral stimulation of the emetic center.
- Chemoreceptor trigger zone (CTZ) The CTZ is a collection of nerve cells at the base of the brain. It is exposed to the body’s blood flow, and controls signals through all of the above chemokines.
After the emetic center is triggered, signals in the above pathways activate the salivatory, vasomotor, respiratory, and cranial centers to prompt involuntary muscle organs in the GI tract that are involved in the vomiting reflex, namely the abdominal muscles, diaphragm, stomach, and esophagus.
The combination of doxylamine and pyridoxine (Diclegis) is likely to help patients with anticipatory CINV; however, it would have little effect on the more potent peripheral stimulation and CTZ mechanisms.
Currently, a variety of direct interventions are used to prevent CINV based on blocking the chemokines using the ever-so-popular 5-HT3 and NK antagonists. The antihistamine and antidopamine properties of the combination of doxylamine and pyridoxine, respectively, would help with the less significant anticipatory pathways leading to CINV, but would have inadequate control for moderate-to-highly emetogenic chemotherapy. —Donald R. Fleming, MD