Necrotising colitis with perforation in diarrhoic patients treated with loperamide

Olm, M.; Gonzalez, F. J.; García‐Valdecasas, Juan Carlos; Fuster, Josep; Bertran, A.; Milla, José Javier Pérez

doi:10.1007/bf00265854

Cited by 24 publications

(8 citation statements)

References 8 publications

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“…Loperamide and other mu opiate receptor agonists seem to act primarily by disrupting forward motility, thereby enhancing gut capacitance, delaying passage of fluid through the intestine, and allowing, in turn, more time for net absorption of fluid to occur (2,9,10). The fact that their antidiarrhoeal activity is always associated with an antitransit effect probably accounts for a pooling of fluid in the distended bowel lumen, which may be responsible for some of the observed symptoms, such as abdominal distension, and for an enhancement of bacterial colonization (11)(12)(13)(14). The same mechanism presumably accounts for the relatively high frequency of reactive constipation, a common side effect of loperamide found both in patients with diarrhoea (9) and in healthy volunteers (15).…”

Section: Discussionmentioning

confidence: 97%

“…In addition to the improved patient comfort (and social cost) that can be expected from the use of antidiarrhoeal agents acting via a purely antisecretory mechanism, these drugs are likely to prevent several side effects associated with the use of antimotility drugs. These include facilitation of bacterial colonization, invasion of Shigella, extension of the period of excretion of bacterial pathogens, and precipitation of ileus and bowel dilatation ('toxic megacolon') (12)(13)(14). The lower potential risk in the case of enkephalinase inhibitors, which, in addition, are devoid of respiratory depression and drug dependence potential (4,16,18) should particularly encourage the assessment of this novel therapeutic class in groups of patients, such as children or the elderly, in which the use of antimotility drugs is controversial or even contraindicated (19).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

The Enkephalinase Inhibitor, Acetorphan, in Acute Diarrhoea: A Double-Blind, Controlled Clinical Trial versus Loperamide

Rogé

Bäumer²,

Bérard³

et al. 1993

Scandinavian Journal of Gastroenterology

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The antidiarrhoeal properties of acetorphan, an inhibitor of enkephalinase (EC 3.4.24.11) that prevents endogenous enkephalin degradation, and loperamide, a mu opiate receptor agonist, were compared. The double-blind study included 69 patients with acute diarrhoea of presumed infectious origin, allocated at random to two parallel groups. Acetorphan and loperamide were both rapidly and similarly effective, diarrhoea resolving in both cases in nearly 2 days. With acetorphan, however, abdominal distension vanished significantly more rapidly, and reactive constipation was less frequent (8% versus 31% with loperamide). These differences can be accounted for by the distinct mechanisms of antidiarrhoeal activity of the two drugs--that is, primary antitransit effect for loperamide and antisecretory activity for acetorphan.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

The Enkephalinase Inhibitor, Acetorphan, in Acute Diarrhoea: A Double-Blind, Controlled Clinical Trial versus Loperamide

Rogé

Bäumer²,

Bérard³

et al. 1993

Scandinavian Journal of Gastroenterology

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“…Although this is often due to severe illness and accompanying trauma, haemorrhage, or systemic sepsis,2 non-occlusive ischaemia has been described sporadically in otherwise well patients that have taken cocaine,3 have had infectious diarrhoea,4 or ingested antidiarrhoeal drugs5; it has even been reported after long distance running 6. We report the occurrence of ischaemic enterocolitis in a patient with severe postural hypotension secondary to idiopathic autonomic neuropathy.…”

Section: Discussionmentioning

confidence: 92%

Ischaemic enterocolitis complicating idiopathic dysautonomia

Woodward

Sanders

Keighley

et al. 1998

Gut

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A previously fit 23 year old adult male who presented with a sudden onset of profound autonomic neuropathy, for which no cause could be found, is described. The patient subsequently developed ischaemic enterocolitis that ultimately necessitated colectomy and subtotal enterectomy. Potential neural and humoral mechanisms are discussed. (Gut 1998;43:285-287) Keywords: ischaemic enterocolitis; idiopathic dysautonomia Case report A previously well 23 year old male oYce worker was referred to the neurology service of this hospital in 1994 with recent onset of syncopal episodes. Apart from a brief episode of diarrhoea and mild abdominal pain one week earlier, there were no other prodromal symptoms. In addition to frequent severe postural syncope, he described abnormalities of taste and smell, blurred vision, and felt cold. His bowel habit became irregular and intermittently loose but not bloody. Micturition was normal. There was no history of significant illness in the family.On examination he was ill; he was pyrexial and had a distended abdomen and quiet bowel sounds. His blood pressure dropped from 90 mm Hg systolic on lying to unrecordable levels on standing. His pupils were unequal in size and unresponsive to light or accommodation. No other cranial or peripheral neurological abnormalities were detected. Autonomic function testing revealed a significant combined deficit of sympathetic and parasympathetic components: head up tilt table testing at 60°c aused a blood pressure drop from 116/60 to 40/20 mm Hg within two minutes, associated with only a small increase in heart rate from 66 to 82 beats per minute. A quinarizine/starch test showed almost complete anhydrosis apart from a small patch on the right side of his face, and instillation of pilocarpine 0.05% into both eyes produced meiosis after two hours. The cardiac response to the Valsalva manoeuvre was blunted, there was little R-R variation on 24 hour electrocardiography, and carotid sinus massage had no eVect on the pulse rate.Investigations performed included a normal full blood count and erythrocyte sedimentation rate. Routine biochemical profile, C reactive protein, thyroid function tests, and serum immunoglobulin electrophoresis were within the laboratory's normal range. Autoantibodies including ANCA (antineutrophil cytoplasmic antibodies), antinuclear, and antiganglioside antibodies were not detected. Blood and stool cultures were negative, as was stool optical and electron microscopy, and Clostridium diYcile toxin A was not present. The peripheral CD4:CD8 ratio was normal. Short Synacthen tests on two occasions were normal. Urine was negative for porphyrins and cerebrospinal fluid was sterile and acellular with no oligoclonal immunoglobulins. A chest radiograph, cardiac ultrasound, and computed tomography (CT) examination of the head were normal. Peripheral electrophysiology showed normal motor and sensory conduction.An acute profound autonomic neuropathy was diagnosed and several oral therapeutic interventions were tried-including xamoterol, ...

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“…26 The consequences of bacterial overgrowth are many in human clinical practice. Adverse events with antimotility agents such as loperamide can be extremely severe: paralytic ileus, sometimes complicated with necrotizing enterocolitis, 27,28 and toxic megacolon. 29±35 More frequently, they can exacerbate infectious diarrhoea whatever the causative organism: E. coli, 36 Shigella, 37 Salmonella, 38 Clostridium dicile, 34 or amoebiasis.…”

Section: Bacterial Proliferationmentioning

confidence: 99%

Effects of racecadotril and loperamide on bacterial proliferation and on the central nervous system of the newborn gnotobiotic piglet

Duval-Iflah¹,

Bérard

Bäumer

et al. 1999

Aliment Pharmacol Ther

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Methods The effects of 4 days of oral administration of different doses of two drugs, an enkephalinase inhibitor (the antisecretory agent, racecadotril) and a μ‐receptor agonist (loperamide), on intestinal growth of a bacterial nonpathogenic strain (Escherichia coli E 404) and on the central nervous system (CNS) were compared in newborn gnotobiotic piglets. Results The E. coli content of the proximal jejunum (segment S1) and the E. coli ratio of stomach:segment S1 were similar in the racecadotril (20 mg/kg b.d., n = 5) and control groups. In contrast, in the loperamide group (1 mg/kg b.d., n = 4), the E. coli content of segment S1 and the E. coli ratio stomach:S1 were both significantly higher than with racecadotril or control (P = 0.04 and 0.005, respectively, for E. coli content; P = 0.05 and 0.03, respectively, for stomach:S1). There were no clinical signs of neurotoxicity and no deaths with racecadotril given orally at a high dose of 130 mg/kg b.d. (n = 5) – nearly 60 times the paediatric dosage. In contrast, an equivalent high dose of loperamide (5 mg/kg b.d.) resulted in death in three out of four piglets. Conclusions In contrast to loperamide, racecadotril did not induce bacterial overgrowth and did not produce central neurotoxicity.

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Necrotising colitis with perforation in diarrhoic patients treated with loperamide

Abstract: Two cases of necrotising enterocolitis with perforation occurred in patients with paralytic ileus after loperamide therapy. The possible role of loperamide in the pathogenesis of the complications is suggested.

Cited by 24 publications

References 8 publications

The Enkephalinase Inhibitor, Acetorphan, in Acute Diarrhoea: A Double-Blind, Controlled Clinical Trial versus Loperamide

The Enkephalinase Inhibitor, Acetorphan, in Acute Diarrhoea: A Double-Blind, Controlled Clinical Trial versus Loperamide

Ischaemic enterocolitis complicating idiopathic dysautonomia

Effects of racecadotril and loperamide on bacterial proliferation and on the central nervous system of the newborn gnotobiotic piglet

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