Towards safer treatments for benign anorectal disease: the pharmacological manipulation of the internal anal sphincter.
BACKGROUND
The internal anal sphincter (IAS) is an important structure that is responsible for the majority of resting tone of the sphincter complex. It has a central role in continence and damage to the muscle has serious implications. Injury is most frequently from obstetric trauma though iatrogenic injury from proctological surgery is also common. This review expands on how developments in understanding of the pharmacology of IAS might identify drug treatments as alternatives for proctological conditions such as anal fissure, avoiding the risk of sphincter injury. It also examines the role of pharmacology in treatment of those patients with established incontinence.


RESULTS
Much of the basic physiology and pharmacology of the IAS has been established through in vitro analysis, particularly in the superfusion organ bath. Further analysis has been undertaken using animal models such the pig. Clinical trials have established the efficacy of a number of agents for reducing IAS tone including glyceryl trinitrate and botulinum toxin. These drugs are probably safer, but less effective, than surgery for sphincter spasm, as is seen in anal fissure, though surgery alone or in combination with drug treatment may be appropriate for some patients. In vitro analysis and small-scale clinical trials suggest that phenylephrine and methoxamine may have a role in treating patients with incontinence primarily attributable to inadequate IAS function.


CONCLUSIONS
The pharmacology of IAS has been extensively studied in the laboratory, both in vitro and in animal models. In a short time, this laboratory work has been applied to clinical problems after testing in clinical trials. It is likely, however, that the best drugs and the optimal targets for manipulation have not yet been identified.
Jones
Oliver M
OM
Department of Colorectal Surgery, John Radcliffe Hospital, Headington, Oxford, UK. oliverjones10@hotmail.com
D001003:Anal Canal / Q000187:drug effects* / Q000502:physiology; D001004:Anus Diseases / Q000188:drug therapy / Q000503:physiopathology / Q000601:surgery; D001905:Botulinum Toxins / Q000627:therapeutic use; D005765:Gastrointestinal Agents / Q000627:therapeutic use*; D006801:Humans; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D020030:Nitric Oxide Donors / Q000627:therapeutic use; D005996:Nitroglycerin / Q000627:therapeutic use; D010656:Phenylephrine / Q000627:therapeutic use; D012002:Rectal Diseases / Q000188:drug therapy* / Q000503:physiopathology / Q000601:surgery
D005765:Gastrointestinal Agents; D020030:Nitric Oxide Donors; D010656:Phenylephrine; D001905:Botulinum Toxins; D005996:Nitroglycerin