Fissure Pharmacology肛裂药理学课件.ppt

Anal Fissure Pharmacology Judd Davies Bradford Royal Infirmary Anal fissure pharmacologyChronic fissure-in-ano Ulcer in squamous epithelium just distal to mucocutaneous junction Intermittent pain during defecation and for up to 2 hours after Roughly same sex incidence 60% fissures posterior Anterior fissures more common in women Anal fissure pharmacologyPathogenesis Most consistent finding is elevated resting pressure on manometry Gibbons et al 1986 Using angiography, posterior commissure less well perfused Klosterhalfen et al 1989 Findings duplicated using doppler flowmetric studies Schouten et al 1994 Meta-analysis of RCT comparingsphincterotomy with medical therapy Lateral internal sphincterotomyRisk of incontinence 0-36% incontinence to flatus 0-21% incontinence to liquid stool 0-5% incontinence to solid stool Women at more risk due to shorter anal sphincter and occult obstetric sphincter defects Anal fissure pharmacologyRegulation of internal sphincter tone Intrinsic myogenic tone Enteric nervous system Nitric oxide is neuro-transmitter and relaxes internal sphincter Autonomic nervous system Excitatory sympathetic innervation Inhibitory parasympathetic innervation Agents used to treat chronic anal fissure GTN Other nitric oxide donors (isosorbide dinitrate, L-arginine) Calcium channel blockers (Diltiazem, nifedipine) Botulinum toxin (Botox? and Dysport?) Cholinergic agonists (bethanechol) ?1-adrenoceptor antagonists (indoramin) Hyperbaric oxygen Sildenafil (Viagra?) Meta-analysis of RCT comparing GTN with placebo Anal fissure pharmacologyGTN Limitations Limited clinical efficacy Nelson Dis Colon Rectum 2004; 47: 422-431 Headaches and dizziness Altomare et al Dis Colon Rectum 2000; 43: 174-9 Tachyphylaxis Watson et al Br J Surg 1996; 83:771-5 Mode of application Lindsey et al Dis Colon Rectum 2003; 46: 361-6 Significant reduction in MRP for 15-90 mins Lindsey et al Br J Surg 2004; 91: 270-9 Diltiazem ointment 2%Applied three times per day for 8 week