Review article: the pharmacology of the internal anal sphincter and new treatments of ano-rectal disorders T.

Surgical options for faecal incontinence in the presence of intact sphincte rs are limited. Furthermore, in patients with fissures, lateral sphincterot omy reduces anal sphincter hypertonia but there has been concern about comp lications, A greater understanding of the basic pharmacology of the interna l anal sphincter has led to the development of novel treatments for both th ese disorders. A Medline review was undertaken for internal anal sphincter pharmacology, anal fissures and faecal incontinence. This review is based o n these articles and those found by further cross-referencing. Nitric oxide released from non-adrenergic non-cholinergic nerves is the mai n inhibitory agent in the internal anal sphincter. Relaxations are also med iated through beta -adrenoceptors and muscarinic receptors, Stimulation of alpha -receptors results in contraction. Calcium and its entry through L-ty pe calcium channels is important for the maintenance of tone. Nitric oxide donors produce reductions in resting anal tone and heal fissures but are as sociated with side-effects. Muscarinic agents and calcium channel antagonis ts show promise as low side-effect alternatives. Botulinum toxin appears mo re efficacious than other agents in healing fissures. To date, alpha -recep tor agonists have been disappointing at improving incontinence. Further understanding of the pharmacology of the internal anal sphincter ma y permit the development of new agents to selectively target the tissue wit h greater efficacy and fewer side-effects.