Topical diltiazem and bethanechol decrease anal sphincter pressure withoutside effects

Background-Topical nitrates lower anal sphincter pressure and heal anal fis sures, but a majority of patients experience headache. The internal anal sp hincter has a calcium dependent mechanism to maintain tone, and also receiv es an inhibitory extrinsic cholinergic innervation. It may therefore be pos sible to lower anal sphincter pressure using calcium channel blockers and c holinergic agonists without side effects. Aims-To investigate the effect of oral and topical calcium channel blockade and a topical cholinomimetic on anal sphincter pressure. Methods-Three studies were conducted, each involving 10 healthy volunteers. In the first study subjects were given oral 60 mg diltiazem or placebo on separate occasions. They were then given diltiazem once or twice daily for four days. In the second and third studies diltiazem and bethanechol gels o f increasing concentration were applied topically to lower anal pressure. Results-A single dose of 60 mg diltiazem lowered the maximum resting anal s phincter pressure (MRP) by a mean of 21%. Once daily diltiazem produced a c linically insignificant effect but a twice daily regimen reduced anal press ure by a mean of 17%. Diltiazem and bethanechol gel produced a dose depende nt reduction of the anal pressure; 2% diltiazem produced a maximal 28% redu ction, and 0.1% bethanechol a maximal 24% reduction, the effect lasting thr ee to five hours. Conclusions-Topical diltiazem bethanechol substantially reduce anal sphinct er pressure for a prolonged period, and represent potential low side effect alternatives to topical nitrates for the treatment of anal fissures.