Saturday, October 8, 2016

How Zofran's effectiveness lends support to a sulfite theory of NVP

The chemotherapy drug ondansetron (Zofran) is frequently prescribed off-label to treat hyperemesis gravidarum (https://www.ncbi.nlm.nih.gov/pubmed/27512487), the severe form of nausea and vomiting in pregnancy (NVP). Zofran appears quite effective at decreasing severe vomiting (but not necessarily the feeling of nausea) for many women (https://www.ncbi.nlm.nih.gov/pubmed/23724526), but its use is still controversial due to possible connections to birth defects (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3299087/) and unclear evidence of relative effectiveness compared to other antiemetics (https://www.ncbi.nlm.nih.gov/pubmed/27168518).

Zofran works by antagonizing, i.e., blocking, 5-HT3 (serotonin) receptors (http://theoncologist.alphamedpress.org/content/7/5/424.full) in both the central nervous system and the gastrointestinal tract.

Signals involved in chemotherapy-induced nausea and vomiting. Image is from "Nausea and vomiting with high-dose chemotherapy and stem cell rescue therapy: a review of antiemetic regimens." M E Trigg and D M Inverso. Bone Marrow Transplant (2008) 42:501-506. (http://www.nature.com/bmt/journal/v42/n8/full/bmt2008257a.html)
In my sulfite-molybdenum theory of NVP (https://www.ncbi.nlm.nih.gov/pubmed/27692161), I compare the accumulation of toxic sulfite in the gastrointestinal tract to taking syrup of ipecac, which brings on vomiting by irritating the lining of the stomach. Interestingly, Zofran completely does away with the emetic effect of ipecac, per this study that was actually focused on marijuana (it did find a small NVP amelioration from marijuana but not one worth the side effects) (https://www.ncbi.nlm.nih.gov/pubmed/11509190). Thus, if sulfite is irritating pregnant women's stomach lining as I hypothesize is happening, Zofran could be ameliorating sulfite-related vomiting the same way it does with ipecac.

It seems to me that the less risky way to address sulfite irritation is to help the body break down sulfite into sulfate (via support of the enzyme sulfite oxidase) and pass sulfite out of the gastrointestinal tract more quickly (via measures to speed gastric emptying) rather than working to block sulfite's effects on the 5-HT3 receptors, for the 5-HT3 receptors have other jobs to do in the body (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4417587/, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4263148/, https://www.ncbi.nlm.nih.gov/pubmed/27401036, https://www.ncbi.nlm.nih.gov/pubmed/25986676, https://www.ncbi.nlm.nih.gov/pubmed/25196083) besides mediate vomiting. Also, there will still be sulfite in the stomach and intestine which could continue to damage the mucosal lining. Unless my theory is disproven, I cannot get behind widespread use of Zofran for NVP.

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