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Re: Sildenafil in gastrointestinal dysmotility disorders

Dear Editor

We read with interest the article by Ehrer A J, et al.[1] the authors have conclusively proven the benefit of sildenafil citrate in reducing the lower oesophageal sphincter pressure and propulsive forces in the body of oesophagus in both healthy subjects and patients with esophageal dysmotility disorders. The beneficial effect was shown to last for upto 8 hours after a single, daily dose of 50 mg.

We have done a similar study in patients with irritable bowel syndrome (IBS) and wish to share our results.

Irritable bowel syndrome is characterized by disturbances of gastrointestinal functions that occur in everybody from time to time in response to dietary indiscretions or psychological upheavals, but present to a greater extent and with greater frequency in patients with IBS.[3] the abnormal patterns of motor activity have been demonstrated in colon [4] but also in jejunum, ileum [5] and esophagus.[6]

Nitric oxide (NO) is a major inhibitory neurotransmitter in gastrointestinal tract.[2] NO activates soluble guanylate cyclase thereby enhancing the production of guanosine 3’, 5’- cyclic mono phosphate (cGMP). Sildenafil blocks the degradation of NO by blocking phosphodiesterase type 5. This results in increased levels of NO, leading to increased level of cGMP and cGMP dependent protein kinase. This causes relaxation of smooth muscles in various organs. We thought of utilizing this effect of sildenafil citrate and study its effects on IBS patients having colonic dysmotility.

A prospective, open label, intention to treat study was planed. 58 married male, patients with irritable bowel disease, diagnosed on the basis of Rome II criterion,[7] were screened. Out of these 18 reported erectile dysfunction (ED) along with symptoms of IBS. These 18 patients were enrolled for the study. They were aged between 20-40 years with mean age of 29 ±9.54 years. After explaining the nature of the study 17 patients consented for participation in the study. All the drugs were discontinued for a period of 2 weeks run in period, except fiber supplements, which were continued throughout the study period. Baseline characteristics were recorded along with the symptoms. The patients were asked to score theirs symptoms (IBS and ED symptoms) on a scale of 1 to 10 at the beginning of the study and on every follow up, to compare the improvement after treatment. The patients were started on 12.5 mg of sildenafil citrate once daily at bed time. They were asked to note down improvement in their symptoms and any untoward effects. The patients were followed up at 2 weekly intervals for 6 weeks and the drug dose was increased at every follow up. The maximum dose given was 37.5 mg / day. Compliance was measured by pill count. All the patients complied with the therapy. Only 2 patients reported minor side effects like headache and flushing with 37.5 mg dose. All the patients experienced significant improvement in their ED but none of them reported any improvement in any IBS symptoms.

Though sildenafil citrate in known to relax smooth muscle cells in various organs and has been found to be effective in improving esophageal dysmotility1 patients of IBS with erectile dysfunction did not report any improvement in their symptoms with 37.5 mg/day dose. The reason for this lack of response could be the lower dose used by us in the study group. Since there are no studies available till date regarding the use of sildenafil in IBS and no guidelines are available regarding the minimum / maximum dose of sildenafil to be used in gastrointestinal dysmotility, we gradually hiked up the dose so as to avoid significant side effects.

References

(1) Ehrer AJ, Schwartz I, Hammer HF, Petnehazy T, Scheidl SJ, Weber K, Krejs G. Effect of sildenafil on oesophageal motor function in healthy subjects and patients with esophageal motor disorders. Gut 2002;50:758-64.

(2) Sanders KM, Ward SM. Nitric oxide as a mediator of non adrenergic, non cholinergic neurotransmitter. Am J Physiol 1995;489: 735-43.

(3)Read NW. Irritable bowel syndrome, (Chapter 91). In Feldman M, Friedman LS, Sleisenger (Eds) Gastrointestinal and liver disease, 7th edition. London: Saunders, 2002. Pp.1794-1806.

(4) McKee DP, Quigley EMM. Intestinal motility in irritable bowel syndrome: Is IBS a motility disorder? Dig Dis Sci 1993;38:1761-82.

(5) Kellow JE, Gill RC, Wingate DL. Prolonged ambulant recording of small bowel motility demonstrates abnormality in irritable bowel syndrome. Gastroenterology 1990;98:1208-18.

(6) Read NW. Visceral afferent information and functional bowel disease: Evidence of dyssensation and altered reflux function. In Mayer EA, Raybould NE (Eds) Basic and clinical aspects of chronic abdominal pain. Amstredum: Elsevier, 1993. Pp.87-96.

(7) Drossman DA. Rome II: The functional intestinal disorders. McLean, Va, Degnan Associates, 2002.