Systematic review: the use of somatostatin or octreotide in refractory diarrhoea

Szilagyi, Andrew; Shrier, Ian

doi:10.1046/j.1365-2036.2001.01114.x

Cited by 45 publications

(23 citation statements)

References 59 publications

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“…Octreotide acetate, a synthetic octapeptide, is administered parenterally for treatment of acromegaly and multiple intestinal diseases (27, 28). This somatostatin analogue has been commercially formulated in a depot form for intramuscular administration on a monthly basis.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of Peptide Acylation in PLGA Microspheres with Water-soluble Divalent Cationic Salts

2009

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Purpose To test the potential of water-soluble divalent cationic salts to inhibit acylation of octreotide encapsulated in poly(D,L-lactic-co-glycolic acid)-star (PLGA) microspheres. Methods The divalent cationic salts, calcium chloride and manganese chloride, previously shown to disrupt peptide sorption, were introduced in PLGA microspheres prepared by the double emulsion-solvent evaporation method. Peptide stability was monitored by reversed-phase high performance liquid chromatography (RP-HPLC) and identified by liquid chromatography coupled with mass spectrometry (LC-MS) during microsphere degradation under physiological conditions for four weeks. Microsphere morphology and salt content were examined by scanning electron microscopy (SEM) and inductively coupled plasma-optical emission spectroscopy (ICP-OES), respectively. Results Addition of divalent cationic salts solely to the organic phase provided marginal acylation inhibition. However, upon addition of the salt inhibitors to both the primary emulsion and the outer water phase resulted in improved drug and salt encapsulation efficiency as well as significantly decreased salt leaching and octreotide acylation. After 28 days, the extent of acylation inhibition afforded by divalent cations was > 58% relative to 13 % for the NaCl control group. Conclusions Divalent cationic salts are suitable class of stabilizers of peptide acylation in PLGA microspheres and this study provides an important formulation approach to maximize stabilizer potency.

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Section: Introductionmentioning

confidence: 99%

Inhibition of Peptide Acylation in PLGA Microspheres with Water-soluble Divalent Cationic Salts

2009

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“…AIDS [37], graft-versus-host disease [38], diabetes mellitus [39], short bowel syndrome [40], postgastrectomy dumping syndrome [41], Zollinger-Ellison syndrome [42], infectious diarrhea (e.g. cholera) [43], and CT- [11, 12, 16] and RT-induced diarrhea [21]. …”

Section: Discussionmentioning

confidence: 99%

“…The current antidiarrheal treatment approach following CRT-induced di-arrhea (CRTID) includes nonspecific agents such as loperamide, diphenoxylate/atropine, codeine or the opium preparation paregoric as well as bowel rest, intravenous hydration, and nutritional support [10, 11]. However, quite often these agents are not effective in controlling diarrhea [12]. …”

Section: Introductionmentioning

confidence: 99%

“…Octreotide functions by interacting mainly with somatostatin receptors (SRs), and, in contrast to nonselective somatostatin, mainly with SR2 and SR5 and to a lesser degree with SR3. This interaction leads to inactivation of adenylate cyclase or the inhibition of Ca 2+ influx and K + efflux via G-inhibiting proteins, which may be effective in reversing a variety of conditions induced by water malabsorption and diarrhea [12]. Octreotide has been effective in the treatment of secretory diarrhea associated with chemotherapy-induced diarrhea, AIDS, graft-versus-host disease, diabetes mellitus, Verner-Morrison syndrome, short bowel syndrome, Zollinger-Ellison syndrome, postgastrectomy dumping syndrome, and idiopathic secretory diarrhea [13,14,15].…”

Section: Introductionmentioning

confidence: 99%

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Octreotide in the Management of Chemoradiotherapy-Induced Diarrhea Refractory to Loperamide in Patients with Rectal Carcinoma

Topkan

Karaoğlu

2006

Oncology

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Objective: To evaluate the efficacy of octreotide in the treatment of chemoradiotherapy (CRT)-induced diarrhea (CRTID) refractory to conventional loperamide treatment in this pilot study. Methods: Forty-two rectal carcinoma (T_3–4N_0–2M₀) patients with grade 2 or 3 diarrhea refractory to loperamide were enrolled to receive octreotide. Eligible patients were treated with pelvic radiotherapy combined with bolus 5- fluorouracil CRT. Octreotide was administered subcutaneously, 150 µg three times daily, for 5 consecutive days. Only complete resolution of diarrhea was considered as therapeutic success. Results: Diarrhea mainly occurred in the first 4 weeks of CRT (83.3%) and completely resolved in 34 patients (80.9%) following octreotide administration. Mean time to response was 2.7 days: 27 patients (64%) responded during the first 3 days, and the remaining 7 (17%) on days 4 and 5. No significant side effect was reported. Eight patients (19.1%) with refractory diarrhea were hospitalized for additional treatment. No treatment delay was reported in complete responders, whereas an average 7.7-day delay was observed in refractory patients. Antidiarrheal treatment was administered on an outpatient basis in the response group, whereas refractory patients were hospitalized for an average of 8.8 days. Conclusion: Daily subcutaneous octreotide administration (150 µg t.i.d.) for 5 days is apparently an effective, tolerable treatment modality for concurrent CRTID refractory to loperamide.

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“…More recently there has been a systematic review of the use of octreotide and somatostatin in refractory diarrhea. The review suggests that these agents have effi cacy in post-chemotherapy and to a lesser extent in AIDS-related diarrhea [59] .…”

Section: Somatostatin and Its Analoguesmentioning

confidence: 99%

Antisecretory Drugs for Diarrheal Disease

Farthing

2006

Dig Dis

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Acute diarrhea is a major cause of morbidity and mortality worldwide. Infants and pre-school children are the most vulnerable in whom there are 2–3 million deaths each year as a result of the associated dehydration and acidosis. Although oral rehydration therapy has reduced mortality during the past 30 years ago, the search for agents that will directly inhibit intestinal secretory mechanisms and thereby reduce faecal losses in patients with high-volume watery diarrhea has continued for more than 20 years. A variety of potential targets for antisecretory agents have been explored which include loci within the enterocyte (the chloride channel, calcium-calmodulin) and other sites such as enteric nerves and endogenous mediators (such as 5-HT, prostaglandins). Although the potential of calcium-calmodulin inhibition has as yet not been realised, preliminary studies suggest that there are chloride channel blockers under development that will find a place in the management of secretory diarrheas. Recent work has highlighted the importance of neurohumoral mechanisms in the pathogenesis of acute diarrhea. Potentiation of the effects of endogenous enkephalin activity by enkephalinase inhibition has already produced a safe, effective anti-secretory drug, racecadotril. Speculative early work indicates that there may be a role for antagonists of 5-HT, substance P, and VIP receptors. There now seems to be a real possibility that antisecretory therapy will become more widely available in the future.

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Systematic review: the use of somatostatin or octreotide in refractory diarrhoea

Cited by 45 publications

References 59 publications

Inhibition of Peptide Acylation in PLGA Microspheres with Water-soluble Divalent Cationic Salts

Inhibition of Peptide Acylation in PLGA Microspheres with Water-soluble Divalent Cationic Salts

Octreotide in the Management of Chemoradiotherapy-Induced Diarrhea Refractory to Loperamide in Patients with Rectal Carcinoma

Antisecretory Drugs for Diarrheal Disease

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