New insights into the characterization of the mechanism of action of hyoscine butylbromide in the human colon ex vivo.

INTRODUCTION: Hyoscine butylbromide (HBB) is one of the most used antispasmodics in clinical practice. Recent translational consensus has demonstrated a similarity between human colonic motor patterns studied ex vivo and in vivo, suggesting ex vivo can predict in vivo results. It is unclear whether the mechanism of action of antispasmodics can predict different use in clinical practice. The aim of the present study is to bridge this gap dissecting HBB's role in excitatory and inhibitory neural pathways. METHODS: 309 colon samples from 48 patients were studied in muscle bath experiments. HBB was tested on: 1-spontaneous phasic contractions (SPCs); 2-carbachol-induced contractility; electrical field stimulation (EFS)-induced selective stimulation of 3-excitatory and 4-inhibitory pathways and 5- SPCs and EFS-induced contractions enhanced by neostigmine. Atropine, AF-DX116 (M2 blocker) and DAU-5884 (M3 blocker) were used as comparators. RESULTS: In the presence of tetrodotoxin (TTX), HBB and atropine 1 µM reduced SPCs. HBB and atropine concentration-dependently reduced carbachol- and EFS-induced contractions. Inhibitory effects of DAU-5884 on EFS-induced contractions were more potent than of AF-DX116. HBB did not affect the off-response associated to neural inhibitory responses. Neostigmine enhanced both SPCs and EFS-induced contractions. In the presence of TTX and ω-conotoxin (GVIA), neostigmine still enhanced SPCs. Addition of HBB and atropine reduced these responses. CONCLUSIONS: This study demonstrates that HBB inhibits neural cholinergic contractions associated to muscarinic (mainly M3) receptors. HBB has a potential role in reducing colonic spasm induced by the release of acetylcholine from enteric motor neurons and from an atypical source including a potential non-neuronal origin.

Hyoscine butylbromide mode of action on bowel motility: From pharmacology to clinical practice.

BACKGROUND: Hyoscine butylbromide (HBB) has been available for use as an antispasmodic since 1951 and is indicated for the treatment of abdominal pain associated with cramps. A previous review in 2007 summarized the evidence on the mode of action of HBB in vitro and in vivo in both animal and human studies. However, since then, novel publications have appeared within the literature and also our knowledge of what represents normal motility in humans has evolved. PURPOSE: This review is the result of the collaboration between a basic scientist and clinicians with the aim of providing an updated overview of the mechanisms of action of HBB and its clinical efficacy to guide not only use in clinical practice, but also future research.

Functional Abdominal Cramping Pain: Expert Practical Guidance.

Functional abdominal cramping pain (FACP) is a common complaint, which may present either on its own or in association with a functional gastrointestinal disorder. It is likely caused by a variety of, probably partly unknown, etiologies. Effective management of FACP can be challenging owing to the lack of usable diagnostic tools and the availability of a diverse range of treatment approaches. Practical guidance for their selection and use is limited. The objective of this article is to present a working definition of FACP based on expert consensus, and to propose practical strategies for the diagnosis and management of this condition for physicians, pharmacists, and patients. A panel of experts on functional gastrointestinal disorders was convened to participate in workshop activities aimed at defining FACP and agreeing upon a recommended sequence of diagnostic criteria and management recommendations. The key principles forming the foundation of the definition of FACP and suggested management algorithms include the primacy of cramping pain as the distinguishing symptom; the importance of recognizing and acting upon alarm signals of potential structural disease; the recognition of known causes that might be addressed through lifestyle adjustment; and the central role of antispasmodics in the treatment of FACP. The proposed algorithm is intended to assist physicians in reaching a meaningful diagnostic endpoint based on patient-reported symptoms of FACP. We also discuss how this algorithm may be adapted for use by pharmacists and patients.

Mesalamine foam enema versus mesalamine liquid enema in active left-sided ulcerative colitis.

AIM: To determine in a noninferiority study whether mesalamine foam is as effective as mesalamine liquid enema for inducing clinical remission in patients with active left-sided ulcerative colitis (UC). METHODS: In a multicenter investigator-blind trial, 375 patients with mild-to-moderate UC were randomized to receive mesalamine foam 1 g/80 mL/day or mesalamine liquid enema 1 g/100 mL/day for 4 wk (W). Inclusion criteria were: disease extension at least 5 cm from anorectal junction and not above splenic flexure and Clinical Activity Index (CAI) 1-4 > or = 4. Primary end point was clinical remission at W4 defined as a CAI 1-4 < or = 2. Noninferiority of the foam to liquid enema was declared if the lower limit of the 97.5% unilateral confidence interval (97.5% CI) of the difference in remission rates between foam and liquid enema groups was greater than -15% . RESULTS: Remission rates at W4 in foam versus liquid were 68.3%versus 73.6% in per protocol (PP) population (lower limit of 97.5% CI -15.1%) and 66.7%versus 70.5% in intention-to-treat (ITT) population (97.5% CI -13.4%). Remission rates at W2 were 48.1 %versus 50.6% in ITT (97.5% CI -12.8%) and 49.1%versus 52.1% in PP (97.5% CI -13.8%) in foam versus liquid, respectively. Both treatments were well tolerated. CONCLUSIONS: A 4-wk treatment of 1 g mesalamine foam induced a clinical remission in 68% patients versus 73% with 1 g mesalamine liquid enema. Although the noninferiority of mesalamine foam could not be strictly demonstrated at W4 in the PP analysis, it was achieved in the ITT population and at W2 in both populations. Mesalamine foam represents a therapeutic alternative to mesalamine liquid enema in patients with mild-to-moderate active proctitis and proctosigmoiditis.