PURPOSE: Topical therapies for anal fissure have largely focused on nitric-oxide donors (e.g., nitroglycerin), sometimes with undesirable side effects or inconsistent benefits. Topical phosphodiesterase inhibitors have theoretical merit but have never been reported in treatment of anal fissure. This article describes manometric analysis of the effects of a phosphodiesterase-5 inhibitor, topical sildenafil (Viagra) in 19 consecutive patients with chronic anal fissure with no previous treatment history. METHODS: Station pullthrough manometry was performed with patients in the left-lateral position. Maximum resting pressure (MRP1) was recorded, and 0.75 ml of 10 percent sildenafil was then instilled in the anal canal. Maximum resting pressure was repeated at the same distance from the anal verge. Thereafter, pressure was measured continuously. Time for initial relaxation (T1) and time to maximal relaxation (T2) were recorded. Average resting pressure (MRP2) was calculated. Results were analyzed by Student's t-test. RESULTS: Topical administration of 10 percent sildenafil was accompanied by significant reduction in anal sphincter pressure (18 percent; P < 0.01). Only one patient failed to respond. Average onset of action was less than three minutes, with maximum effect one minute later. MRP1: 119.3 +/- 18.7 cmH(2)O. MRP2: 97.8 +/- 21.3 cmH(2)O. MRP2 < MRP1, P < 0.01. MRP M vs. F, ns. T1: 168 +/- 67 seconds (M = 210 +/- 72, F = 130 +/- 53, P < 0.02). T2: 230 +/- 78 seconds (M = 271 +/- 63, F = 183 +/- 75, P < 0.02). Mild-to-moderate anal discomfort was reported by 26 percent of patients. No headaches or other side effects were reported. CONCLUSIONS: Topical administration of a phosphodiesterase-5 inhibitor (sildenafil, Viagra) significantly reduces anal sphincter pressure in patients with chronic anal fissure. A beneficial effect of nitric oxide on the spastic anal sphincter has been demonstrated previously. This study confirms that this effect need not be derived solely from nitric oxide donors. New therapeutic avenues for treatment of anal fissure through indirect enhancement of nitric oxide activity are suggested.
PURPOSE: Topical therapies for anal fissure have largely focused on nitric-oxide donors (e.g., nitroglycerin), sometimes with undesirable side effects or inconsistent benefits. Topical phosphodiesterase inhibitors have theoretical merit but have never been reported in treatment of anal fissure. This article describes manometric analysis of the effects of a phosphodiesterase-5 inhibitor, topical sildenafil (Viagra) in 19 consecutive patients with chronic anal fissure with no previous treatment history. METHODS: Station pullthrough manometry was performed with patients in the left-lateral position. Maximum resting pressure (MRP1) was recorded, and 0.75 ml of 10 percent sildenafil was then instilled in the anal canal. Maximum resting pressure was repeated at the same distance from the anal verge. Thereafter, pressure was measured continuously. Time for initial relaxation (T1) and time to maximal relaxation (T2) were recorded. Average resting pressure (MRP2) was calculated. Results were analyzed by Student's t-test. RESULTS: Topical administration of 10 percent sildenafil was accompanied by significant reduction in anal sphincter pressure (18 percent; P < 0.01). Only one patient failed to respond. Average onset of action was less than three minutes, with maximum effect one minute later. MRP1: 119.3 +/- 18.7 cmH(2)O. MRP2: 97.8 +/- 21.3 cmH(2)O. MRP2 < MRP1, P < 0.01. MRP M vs. F, ns. T1: 168 +/- 67 seconds (M = 210 +/- 72, F = 130 +/- 53, P < 0.02). T2: 230 +/- 78 seconds (M = 271 +/- 63, F = 183 +/- 75, P < 0.02). Mild-to-moderate anal discomfort was reported by 26 percent of patients. No headaches or other side effects were reported. CONCLUSIONS: Topical administration of a phosphodiesterase-5 inhibitor (sildenafil, Viagra) significantly reduces anal sphincter pressure in patients with chronic anal fissure. A beneficial effect of nitric oxide on the spastic anal sphincter has been demonstrated previously. This study confirms that this effect need not be derived solely from nitric oxide donors. New therapeutic avenues for treatment of anal fissure through indirect enhancement of nitric oxide activity are suggested.
Authors: Kellen L Meadows; Christel Rushing; Wanda Honeycutt; Kenneth Latta; Leigh Howard; Christy A Arrowood; Donna Niedzwiecki; Herbert I Hurwitz Journal: Support Care Cancer Date: 2014-10-24 Impact factor: 3.603