Tegaserod normalizes opioid-induced bowel dysfunction in dogs

Weber, Eckhard; Braun, Elisabeth; Forgiarini, Peter; Pfannkuche, Hans-Juergen

doi:10.1016/s0016-5085(03)82890-1

Cited by 6 publications

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“…In another study, tegaserod administered subcutaneously at 1 and 3 mg kg −1 stimulated an increase in colonic transit in a conscious guinea‐pig model 9 . Tegaserod has also been shown to increase motility in models of delayed GI transit, specifically in a rodent model of postoperative ileus 10,11 and opioid‐induced bowel dysfunction in dogs 12 . The promotility effects of 5‐HT 4 receptor agonists are considered to result at least in part from presynaptic facilitation of ACh release from enteric nerves 7,13–15 …”

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confidence: 96%

“…9 Tegaserod has also been shown to increase motility in models of delayed GI transit, specifically in a rodent model of postoperative ileus 10,11 and opioid-induced bowel dysfunction in dogs. 12 The promotility effects of 5-HT 4 receptor agonists are considered to result at least in part from presynaptic facilitation of ACh release from enteric nerves. 7,[13][14][15] As AChE inhibitors and 5-HT 4 receptor agonists work independently at cholinergic synapses to elevate synaptic levels of ACh and thus amplify cholinergic neurotransmission, we aimed to investigate the potential synergy that might occur with a combination of a 5-HT 4 agonist and a cholinesterase inhibitor on intestinal transit.…”

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confidence: 99%

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Increased colonic transit in rats produced by a combination of a cholinesterase inhibitor with a 5‐HT₄ receptor agonist

Campbell-Dittmeyer

Hicks

Earnest

et al. 2009

Neurogastroenterology Motil

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Increased cholinergic stimulation and accelerated gastrointestinal (GI) transit may be produced by direct stimulation of the acetylcholine (ACh) receptor with an appropriate agonist by increased release of ACh from cholinergic nerve terminals or by a decreased removal or breakdown of ACh within cholinergic synapses. The acetylcholinesterase inhibitor, neostigmine, and the 5-HT(4) receptor partial agonist tegaserod, are two agents with known prokinetic activity which work by different mechanisms that result in increased levels of ACh at cholinergic synapses innervating intestinal smooth muscle. Here, we aimed to investigate the potential synergistic effect on colonic transit that may occur with concomitant use of these two agents. Colonic transit was indirectly assessed in rats via measurements of fecal pellet output every 30 min for 2.5 h following administration of neostigmine (0.003-0.1 mg kg(-1), i.p.), tegaserod (0.01-1.0 mg kg(-1), i.p.), or a combination of both compounds. When administered alone, neostigmine or tegaserod caused a dose-dependent increase in fecal pellet output. In combination, low doses of the two agents which did not produce statistically significant effects alone, compared to the vehicle, caused a significant increase in fecal pellet output. Combinations of higher doses of neostigmine and tegaserod did not display synergy. In summary, when combined at low doses, neostigmine and tegaserod produce synergistic effects manifested by a statistically significant increase in the expulsion of fecal pellets. A combination of an anticholinesterase agent with a 5-HT(4) receptor agonist may prove to be a useful therapeutic approach to treat conditions associated with slow GI transit.

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confidence: 96%

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confidence: 99%

Increased colonic transit in rats produced by a combination of a cholinesterase inhibitor with a 5‐HT₄ receptor agonist

Campbell-Dittmeyer

Hicks

Earnest

et al. 2009

Neurogastroenterology Motil

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“…It is used as a prokinetic in people and has recently been evaluated for use in dogs . Tegaserod, a potent partial 5‐HT 4 agonist and a weak 5‐HT 1D receptor agonist, has been shown to increase antral, duodenal, jejunal, and colonic motility in conscious dogs . Studies by Nguyen et al using varying doses of tegaserod in dogs showed acceleration in colonic transit, although the effects on upper GI transit were more variable .…”

Section: Specific Pharmacological Interventionsmentioning

confidence: 97%

“…Tegaserod, a potent partial 5‐HT 4 agonist and a weak 5‐HT 1D receptor agonist, has been shown to increase antral, duodenal, jejunal, and colonic motility in conscious dogs . Studies by Nguyen et al using varying doses of tegaserod in dogs showed acceleration in colonic transit, although the effects on upper GI transit were more variable . Tegaserod has been investigated for postoperative ileus in horses; however, clinical trials of tegaserod in small animal veterinary medicine are lacking.…”

Section: Specific Pharmacological Interventionsmentioning

confidence: 99%

Gastrointestinal dysmotility disorders in critically ill dogs and cats

Whitehead

Cortes

Eirmann

2016

J Vet Emergen Crit Care

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Objective -To review the human and veterinary literature regarding gastrointestinal (GI) dysmotility disorders in respect to pathogenesis, patient risk factors, and treatment options in critically ill dogs and cats. Etiology -GI dysmotility is a common sequela of critical illness in people and small animals. The most common GI motility disorders in critically ill people and small animals include esophageal dysmotility, delayed gastric emptying, functional intestinal obstruction (ie, ileus), and colonic motility abnormalities. Medical conditions associated with the highest risk of GI dysmotility include mechanical ventilation, sepsis, shock, trauma, systemic inflammatory response syndrome, and multiple organ failure. The incidence and pathophysiology of GI dysmotility in critically ill small animals is incompletely understood. Diagnosis -A presumptive diagnosis of GI dysmotility is often made in high-risk patient populations following detection of persistent regurgitation, vomiting, lack of tolerance of enteral nutrition, abdominal pain, and constipation. Definitive diagnosis is established via radioscintigraphy; however, this diagnostic tool is not readily available and is difficult to perform on small animals. Other diagnostic modalities that have been evaluated include abdominal ultrasonography, radiographic contrast, and tracer studies. Therapy -Therapy is centered at optimizing GI perfusion, enhancement of GI motility, and early enteral nutrition. Pharmacological interventions are instituted to promote gastric emptying and effective intestinal motility and prevention of complications. Promotility agents, including ranitidine/nizatidine, metoclopramide, erythromycin, and cisapride are the mainstays of therapy in small animals. Prognosis -The development of complications related to GI dysmotility (eg, gastroesophageal reflux and aspiration) have been associated with increased mortality risk. Institution of prophylaxic therapy is recommended in high-risk patients, however, no consensus exists regarding optimal timing of initiating prophylaxic measures, preference of treatment, or duration of therapy. The prognosis for affected small animal patients remains unknown. (J Vet Emerg

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“…Withdrawal of cisapride has created a clear need for new gastrointestinal (GI) prokinetic agents, although cisapride continues to be available from compounding pharmacies throughout the United States. 45 Tegaserod at doses of 3 to 6 mg/kg PO normalizes intestinal transit in opioid-induced bowel dysfunction in dogs, 47 and it may prove useful in other disorders of intestinal ileus or pseudoobstruction. 37 Tegaserod is a potent partial nonbenzamide agonist at 5-HT 4 receptors and a weak agonist at 5-HT 1D receptors.…”

Section: Prognosismentioning

confidence: 99%

Constipation

Washabau¹

2013

Canine and Feline Gastroenterology

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Tegaserod normalizes opioid-induced bowel dysfunction in dogs

Cited by 6 publications

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Increased colonic transit in rats produced by a combination of a cholinesterase inhibitor with a 5‐HT₄ receptor agonist

Increased colonic transit in rats produced by a combination of a cholinesterase inhibitor with a 5‐HT₄ receptor agonist

Gastrointestinal dysmotility disorders in critically ill dogs and cats

Constipation

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Tegaserod normalizes opioid-induced bowel dysfunction in dogs

Cited by 6 publications

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Increased colonic transit in rats produced by a combination of a cholinesterase inhibitor with a 5‐HT4 receptor agonist

Increased colonic transit in rats produced by a combination of a cholinesterase inhibitor with a 5‐HT4 receptor agonist

Gastrointestinal dysmotility disorders in critically ill dogs and cats

Constipation

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Product

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Increased colonic transit in rats produced by a combination of a cholinesterase inhibitor with a 5‐HT₄ receptor agonist

Increased colonic transit in rats produced by a combination of a cholinesterase inhibitor with a 5‐HT₄ receptor agonist