Rectogesic Mechanism of Action

Pharmacology: The principal pharmacologic action of glyceryl trinitrate is mediated via the release of nitric oxide. When glyceryl trinitrate ointment is applied by the intra-anal route, the internal anal sphincter becomes relaxed.
Hypertonicity of the internal but not the external anal sphincter is a predisposing factor in the formation of anal fissures. The blood vessels to the anoderm course through the internal anal sphincter (IAS). Therefore hypertonicity of the IAS may thereby decrease blood flow and cause ischaemia to this region.
Distension of the rectum results in the anorector inhibitory reflex and relaxation of the internal anal sphincter. The nerves mediating this reflex lie in the wall of the gut. Release of the neurotransmitter NO from nerves of this type play a significant role in the physiology of the internal anal sphincter. Specifically, NO mediates the anorector inhibitory reflex in man, relaxing the IAS.
The link between IAS hypertonicity and spasm and the presence of an anal fissure has been established. Patients with chronic anal fissure have a significantly higher mean maximum resting anal pressure than controls and anodermal blood flow in chronic anal fissure patients was significantly lower than in controls.
In patients whose fissures healed following a sphincterotomy, a reduction in anal pressure and improvement in anodermal blood flow was demonstrated, providing further evidence for the ischaemic nature of anal fissure. Topical application of a NO donor (glyceryl trinitrate) relaxes the anal sphincter, resulting in a reduction of anal pressure and an improvement in anoderm blood flow.
Clinical trials - pharmacokinetic properties: The volume of distribution of glyceryl trinitrate is about 3 L/kg and is cleared from this volume at extremely rapid rates, with a resulting serum half-life of about 3 minutes. The observed clearance rates (close to 1 L/kg/min) greatly exceed hepatic blood flow. The known sites of extrahepatic metabolism include red blood cells and vascular walls. The initial products in the metabolism of glyceryl trinitrate are inorganic nitrate and the 1,2 and 1,3-dinitroglycerols. The dinitrates are less effective vasodilators than glyceryl trinitrate, but they are longer lived in the serum. Their contribution to the relaxation of the internal anal sphincter is unknown. The dinitrates are further metabolised to non-vasoactive mononitrates and ultimately to glycerol and carbon dioxide. In six healthy subjects, the average bioavailability of glyceryl trinitrate applied to the anal canal as a 0.2% ointment was approximately 50% of the 0.75 mg dose.