Valor terapêutico da associaçäo de espasmolítico com analgésico contendo brometo de N-butilescopolamina com dipirona / Therapeutic value of the combination between an spasmolithic with an analgesic: scopolamine-N-butyl bromide and dipirone

A grande mioria das combinaçöes de fármacos säo irracionais e perigosas. Por outro lado, existem algumas associaçöes medicamentosas que apresentam bases farmacológicas racionais ao lado de uma adequada relaçäo benefício/risco. A associaçäo entre o brometo de N-butilescopolamina com a dipirona é aprovada pelas autoridades sanitárias em vários países apresentando claras indicações terapêuticas, No Brasil particularmente, essa combinaçäo foi aprovada há mais de trinta anos, estando mesmo padronizada em muitos hospitais, principalmente na emergência. A classe médica considera essa combinaçäo fixa como uma associação analgésica de primeira escolha, prática, de baixo custo e muito eficaz

Antispasmodic action of propinox on the isolated human gallbladder: possible mechanism of action

Propinox is an antispasmodic drug frequently used in the treatment of disorders of the gastrointestinal tract, the uterus and the galbladder, but little is known about its relaxing activity in gallbladder tissue. The main objective of this study was to determine the antispasmodic activity of propinox, compared to other antispasmodics, in the gallblader and to assess its binding affinity to receptor sites which may be involved in its mechanism of action. Antispasmodic activity of propinox, (-) scopolamine-n-butyl bromide, atropine and verapamil was determined in human gallbladders to reduce the risk of interspecies variability. Inhibitory activities (ED50) of carbachol-induced contraction were: atropine 5.03x10(-8) M>propinox 1.25x10(-7) M> verapamil 6.63x10(-6)M> (-) scopolamine-n-butyl1 bromide 5.4x10(-5) M. pD'2 for propinox was 6.94, indicating non competitive inhibition of carbachol action. Radioligand binding studies were performed to determine if the antisplasmodic action of the drug involved binding to muscarinic receptors or calciumatagonist sites. The inhibition constant (Ki) of proponix for muscarinic receptors of guinea pig ileum smoth muscle, which contains a mixed M2-M3 receptor population, was 1.6x10(-6) M. Ki for brain muscarinic receptors (M1) was 1.0x10(-4) M, for cardiac receptors (M1) was 1.0x10(-4)M, for receptors (M2) 1.2x10(-6)M and from salivary gland receptors (M3) 1.5x10(-6)M. For binding to the dihidropiridine calcium antagonist binding sites, Ki were: 4.9x10(-5)M for propinox and 2.2x10(-7)M for verapamil. For the phenylakylamine binding sites Ki were: 5.0x10(-6)M for propinox and 3.5x10(-8)M for verapamil. For the benzothiacepine binding sites, Ki for propinox was 5.2x10(-6)M. The following may be concluded: 1- The antispasmodic activity of propinox in isolated human galbladder was was comparatively less potent than of atropine and more potent than those verapamil and (-) scopolamine-n-butyl bromide. 2- Propinox showed binding to muscarinic and calcium receptors that can be related to its antisplasmodic activity; suggesting that the drug is an antispasmodic with anticholinergic and musculotropic activity. 3.- The dual mechanism of action, anticholinergic and calcium-blocking, would induce synergism of pharmacodynamic effects and minimize adverse events of pure antimuscarinic drugs or calcium antagonists.

Effect of hyoscine butylbromide and atropine on heart rate during nocturnal sleep.

This is a single blind crossover study designed to test the effects of hyoscine butylbromide (HBB), an anticholinergic which does not cross the blood brain barrier (BBB), on the temporal changes in heart rate during nocturnal sleep. The effects were compared with atropine sulphate which is known to cross the BBB. Ten healthy male volunteers slept in the JIPMER sleep disorders laboratory for three nights and received either saline, atropine sulphate (0.4 mg, i.v.) or HBB (10 mg, i.v.) just prior to sleep onset. All night polysomnography recording was done to monitor heart rate during the specific stages of sleep. The normal physiological fall in heart rate is blunted by both drugs during slow wave sleep whereas only HBB prevented the fall in rapid eye movement sleep. Therefore, HBB may be a better choice as pre-anaesthetic medication for patients with cardiac abnormalities since it does not alter heart rate during both slow wave sleep and rapid eye movement sleep.

Comparative effects of hyoscine butylbromide and atropine sulphate on sleep architecture in healthy human volunteers.

The changes in sleep architecture, heart rate and respiratory rate to hyoscine butylbromide (HBB), a peripherally acting anticholinergic was studied. These effects were compared with that of atropine sulphate, a drug known to cross the blood brain barrier. The study followed a single blind cross over design with a one week washout period. Atropine sulphate (0.4 mg) and HBB (10 mg) were given intravenously to ten adult healthy male volunteers before sleep onset. Normal saline was used as control. All night sleep polysomnography was done with the standard montage for sleep staging. Respiration and airflow were also monitored. Rapid eye movement (REM) latency was significantly increased with both the drugs whereas the duration of REM sleep was decreased only with atropine. Slow wave sleep (SWS) was also increased significantly by atropine. There was no change in heart rate, or respiratory rate during any of the sleep stages. HBB affects the initiation of REM sleep whereas atropine affects both its initiation and maintenance.