Possible mechanism for the gastro-intestinal adverse effects upon topical application of Prostaglandin F2α analogs

Abstract

Prostaglandin F2α analogs (PGAs), including latanoprost, travoprost and bimatoprost, the first choice for the pharmaceutical treatment of glaucoma, are gaining more attention on their systemic side effects in recent years. The gastro-intestinal effects are among the most reported adverse effects upon topical application of PGAs. Yet, the underlying mechanism remains to be unknown. In the current study, we performed a molecular genetic analysis on the patient reported by Yu et al. (BMJ Case Rep, 2009), who developed nausea, vomiting and diarrhea after topical application of travoprost and latanoprost, but not bimatoprost, and then speculated that the mechanism underlying the gastro-intestinal distress secondary to PGA topical application should be attributed to their stimulation of smooth muscles of the gastric and intestinal tract via prostanoid receptors. We postulate that the diversified receptor selectivity of various PGAs might mediate their diversified gastro-intestinal effects. To further verificate the speculation, other three glaucoma patients who exhibited different gastro-intestinal responses to different PGA medications were enrolled. The results suggested that the relative expression level of FP receptor, versus EP receptors, might be associated with the severity of gastro-intestinal effects incurred by PGAs. Owing to the differed expression levels of FP receptor, the responses of various patients to different PGAs can be variable.