Topical diltiazem and bethanechol decrease anal sphincter pressure without side effects.
BACKGROUND
Topical nitrates lower anal sphincter pressure and heal anal fissures, but a majority of patients experience headache. The internal anal sphincter has a calcium dependent mechanism to maintain tone, and also receives an inhibitory extrinsic cholinergic innervation. It may therefore be possible to lower anal sphincter pressure using calcium channel blockers and cholinergic agonists without side effects.


OBJECTIVE
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 of increasing concentration were applied topically to lower anal pressure.


RESULTS
A single dose of 60 mg diltiazem lowered the maximum resting anal sphincter pressure (MRP) by a mean of 21%. Once daily diltiazem produced a clinically insignificant effect but a twice daily regimen reduced anal pressure by a mean of 17%. Diltiazem and bethanechol gel produced a dose dependent reduction of the anal pressure; 2% diltiazem produced a maximal 28% reduction, and 0.1% bethanechol a maximal 24% reduction, the effect lasting three to five hours.


CONCLUSIONS
Topical diltiazem and bethanechol substantially reduce anal sphincter pressure for a prolonged period, and represent potential low side effect alternatives to topical nitrates for the treatment of anal fissures.
Carapeti
E A
EA
Department of Physiology, St Mark's Hospital, Northwick Park, Watford Road, Harrow, Middlesex HA1 3UJ, UK.
Kamm
M A
MA
Evans
B K
BK
Phillips
R K
RK
D000284:Administration, Oral; D000287:Administration, Topical; D000328:Adult; D001003:Anal Canal / Q000187:drug effects*; D018723:Bethanechol / Q000008:administration & dosage* / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004110:Diltiazem / Q000008:administration & dosage* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005782:Gels; D006801:Humans; D008297:Male; D008875:Middle Aged; D018721:Muscarinic Agonists / Q000008:administration & dosage* / Q000494:pharmacology
D002121:Calcium Channel Blockers; D005782:Gels; D018721:Muscarinic Agonists; D018723:Bethanechol; D004110:Diltiazem