Why Dopamine antagonists are unsafe anti-emetics in poison-induced acute kidney failure

Nausea and vomiting are feared and frequently very distressing symptoms that have multiple triggers including drugs and poisons, motion, pregnancy, anxiety, vestibular disease, and gastrointestinal pathology.  

Three primary pathophysiologic pathways are involved in the stimulation of the physiologic vomiting center in the medulla that directly mediates nausea and vomiting: vestibular fibers, afferent visceral fibers, and input from the chemoreceptor trigger zone.   

Nausea and vomiting from visceral and chemoreceptor trigger zone stimulation is mediated through dopamine and serotonin whereas that from vestibular and central nervous system is caused through histamine and acetylcholine receptors. Treatment is directed at these receptors. 

Antihistamines (cyclizine, meclizine) and anticholinergic agents (hyoscine butyl bromide) are most effective in patients with nausea resulting from the vestibular and central nervous system causes.   

Dopamine antagonists and serotonin antagonists (Ondansetron, Granisetron) block dopamine/serotonin in the intestines (viscera) and chemoreceptor trigger zone are most effective for treating gastrointestinal irritation and postoperative nausea and vomiting.  

The dopamine antagonists used clinically as antiemetics can be divided into three groups: phenothiazines (eg Chlorpromazine), butyrophenones (Droperidol and Domperidone) and benzamides (Metoclopramide). 

Of toxicological importance however is that in some cases nausea and vomiting co-exist with acute kidney failure (abrupt or rapid decline in renal filtration function due to many reasons including decreased blood flow to the kidney, direct damage to the kidney from poisons, among other causes).  

There exists adequate evidence that dopamine plays a role in renal physiology. Dopamine is synthesized in the kidney and released in the tubular lumen to act on dopamine receptor subtypes (D1 and D2) to promote sodium and salt excretion as well as dilatation of renal arteries that leads to an increase in renal blood flow, in urinary volume. 

It is clear thus far that dopamine antagonists will worsen any pre-existing kidney disfunction, and therefore not recommended for controlling emesis in a setting of acute kidney injury. Serotonin antagonists such as odansentron would be a safer alternative in such situations. 

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