cloprostenol and Diarrhea

Prostaglandin F(2)α 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.

Topics: Administration, Topical; Aged; Amides; Base Sequence; Bimatoprost; China; Cloprostenol; Diarrhea; Female; Gastrointestinal Tract; Glaucoma; Humans; Latanoprost; Male; Middle Aged; Molecular Sequence Data; Muscle, Smooth; Nausea; Prostaglandins F, Synthetic; Receptors, Prostaglandin; Receptors, Prostaglandin E; Sequence Analysis, DNA; Travoprost; Vomiting

Sixty-seven pregnant bitches were given atropine sulphate (0.025 mg kg-1), prifinium bromide (0.1 ml kg-1) and metopimazine (0.5 mg kg-1) and 15 min later 2.5 micrograms cloprostenol kg-1 s.c., three times at 48 h intervals (day 1, day 3, day 5). After one treatment, 53 of the 67 bitches had aborted, and after a second treatment, 62 of the 67 bitches had aborted. In 18 bitches, progesteronemia kinetics were followed-up: the first injection of cloprostenol resulted in a significant (P < 0.01) fall in progesteronemia. In 12 of the 18 bitches that had aborted following the first protocol, this rapid fall in progesterone was noteworthy as it decreased progesterone concentration on average from 17.07 +/- 8.20 ng ml-1 on day 1 to 1.31 +/- 0.34 ng ml-1 on day 3. The premedication administered 15 min before the injection of prostaglandins, prevented the appearance of side effects in 39 of the 67 bitches (58.2%).

Topics: Abortifacient Agents, Nonsteroidal; Abortion, Induced; Animals; Antiemetics; Atropine; Clinical Protocols; Cloprostenol; Diarrhea; Dogs; Female; Isonipecotic Acids; Parasympatholytics; Pregnancy; Premedication; Progesterone; Pyrrolidines