title: Treatment of chronic anal fissure with isosorbide dinitrate: long-term results and dose determination.
abstract: OBJECTIVE
  Anal fissure is a tear of the anoderm, which eventually can become an ulcer. Chronic anal fissure is perpetuated by contraction of the internal sphincter, believed to reduce perfusion. Nitric oxide is a neurotransmitter mediating vasodilation and internal anal sphincter relaxation. The aim of the present study was to evaluate both the effect and the effective dose regimen of isosorbide dinitrate, a nitric oxide donor, as a treatment for chronic anal fissure.
  
  
  METHODS
  Isosorbide dinitrate, Isoket spray (Schwarz-Pharma, Mannheim, Germany), was used to treat 41 patients with chronic anal fissure. Anal manometry was performed in all patients before they entered the study. The treatment program consisted of digital application of isosorbide dinitrate in a dose of 1.25 mg or 2.5 mg three times each day for four weeks. At the end of the trial, patients were followed up for an average time of 11 +/- 1 months.
  
  
  RESULTS
  In 34 (83 percent) patients, the fissure healed within one month of treatment (mean, 3 +/- 0.1 weeks). The average time for symptoms to disappear was 6.5 +/- 0.7 days. In six (14.6 percent) patients the anal fissure did not heal even after four weeks of further treatment, and they underwent lateral sphincterotomy. Six patients relapsed during the follow-up period, but responded to another course of treatment. A dose of 2.5 mg of isosorbide dinitrate caused a greater reduction in maximum anal resting pressure than a dose of 1.25 mg.
  
  
  CONCLUSIONS
  Topical isosorbide dinitrate is an effective and safe treatment for chronic anal fissure. In our experience the optimal dose regimen is 2.5 mg three times each day.
authors.affiliation: Gastroenterology Unit, Hadassah University Hospital, Jerusalem, Israel.
authors.forename: J
authors.initials: J
authors.lastname: Lysy
authors.forename: Y
authors.initials: Y
authors.lastname: Israelit-Yatzkan
authors.forename: M
authors.initials: M
authors.lastname: Sestiere-Ittah
authors.forename: D
authors.initials: D
authors.lastname: Keret
authors.forename: E
authors.initials: E
authors.lastname: Goldin
mesh_terms: D000287:Administration, Topical; D000293:Adolescent; D000328:Adult; D002908:Chronic Disease; D005260:Female; D005401:Fissure in Ano / Q000188:drug therapy*; D006801:Humans; D007548:Isosorbide Dinitrate / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008365:Manometry; D008875:Middle Aged; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D014665:Vasodilator Agents; D007548:Isosorbide Dinitrate