Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The metabolism of serotonin was studied in cancer patients of their first day of their first course of chemotherapeutic drugs either with strongly or moderately emetogenic regimens. It was observed that strongly emetogenic treatments induce greater increases in serotonin release than moderately emetogenic regimens. High-dose cisplatinum (75 +/- 5 or 83.8 +/- 5 mg m-2) produced a marked increase in the plasma levels and in the urinary excretion of 5-hydroxyindole acetic acid (5-HIAA). Neither platelet nor plasma (platelet-free plasma) serotonin were significantly modified by high-dose cisplatinum. Dacarbazine (283 +/- 22 mg m-2), another strongly emetogenic agent, induced acute nausea and emesis paralleled by marked increases in the urinary excretion of 5-HIAA. Both for high-dose cisplatinum and dacarbazine, the increases in serotonin metabolism occurred with a similar time-course than those of vomiting, and lasted for a period of 4 to 8 h. Low-dose cisplatinum (30.8 +/- 3 mg m-2) as well as cyclophosphamide-based chemotherapies (520 +/- 30 mg m-2) produced very small increases in the urinary excretion of 5-HIAA. Platelet and plasma serotonin levels failed to increase in cyclophosphamide-treated patients. Octreotide, a long-acting somatostatin analog, did not inhibit the increase in urinary 5-HIAA and the nausea and vomiting produced by high-dose cisplatinum. These results suggest that for treatments that induce marked increases in serotonin release such as high-dose cisplatinum or dacarbazine: (a) the amount and time course of serotonin release induced by chemotherapeutic drugs determines the severity, time of onset and pattern of emesis observed; (b) platelet serotonin play no role in chemotherapy-induced emesis; (c) strongly emetogenic regimens release serotonin from enterochromaffin cells; and (d) intestinal release of serotonin is the consequence of the damage induced by the chemotherapeutic drugs on the gut mucosa.
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PMID:Changes in serotonin metabolism in cancer patients: its relationship to nausea and vomiting induced by chemotherapeutic drugs. 137 60

Octreotide is an analogue of somatostatin. Like endogenous somatostatin, it exerts a potent inhibitory effect on the release of anterior pituitary growth hormone and thyroid-stimulating hormone, and peptides of the gastroenteropancreatic endocrine system, while overcoming some of the shortcomings of exogenously administered somatostatin, namely a short duration of action, a need for intravenous administration and postinfusion rebound hypersecretion of hormone. Clinical studies have shown that octreotide is effective in the treatment of acromegaly and thyrotrophinomas. In comparative trials octreotide was significantly superior to bromocriptine in patients with acromegaly. Octreotide also appears to provide a significant advantage over existing therapies in the management of the carcinoid syndrome and offers considerable therapeutic potential in reversing carcinoid crises which may be life-threatening. Trials in patients with tumours producing vasoactive intestinal peptide demonstrated that octreotide may be an effective first-line choice for this condition, which has usually metastasised and become refractory to traditional symptomatic therapy. In limited studies in patients with high-output secretory diarrhoea, including cryptosporidium-related diarrhoea associated with AIDS and in patients with small bowel fistulas, octreotide has been shown to be effective in reducing stool/fistula output. However, well-designed clinical trials are still required to confirm its long term usefulness in these disorders. Similarly, although the use of octreotide in other conditions such as neonatal hypoglycaemia caused by nesidioblastosis, reactive pancreatitis, insulin-dependent diabetes mellitus, postprandial hypotension and the dumping syndrome has provided encouraging preliminary results, more studies are needed to clarify the place of octreotide in their treatment. Overall, octreotide appears to be well tolerated with the most frequently reported reactions being pain at the site of injection and gastrointestinal symptoms such as abdominal cramps, nausea, bloating, flatulence, diarrhoea and steatorrhoea. These adverse effects usually abate with time. Additionally, octreotide, like endogenous somatostatin, may also result in cholelithiasis, presumably by altering fat absorption and possibly by decreasing motility of the gallbladder. Thus, octreotide represents a new departure from traditional therapies in the treatment of various pathophysiological states associated with excessive peptide production and secretion. It offers a significant advantage over existing therapies in the medical management of patients with acromegaly, thyrotrophinomas, the carcinoid syndrome, tumours producing vasoactive intestinal peptide and severe secretory diarrhoea in whom conventional management options have either become exhausted or have provided suboptimal symptomatic relief.
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PMID:Octreotide. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in conditions associated with excessive peptide secretion. 268 36

The purpose of this study was to evaluate the therapeutic potential of the somatostatin analog octreotide in patients with orthostatic hypotension. Octreotide was administered sc, and its pressor effect was assessed while the patients were semirecumbent and on the tilt table. We also studied the effect of octreotide on blood pressure while patients walked. The efficacy of therapy was assessed by measuring the duration of walking (walking time) before the onset of hypotension. Low doses of octreotide (0.2-0.4 micrograms/kg) had a pressor effect in all patients with progressive autonomic failure (n = 7), multiple system atrophy (n = 7), and diabetic autonomic neuropathy (n = 8), but not in patients with sympathotonic orthostatic hypotension (n = 6). Larger doses (0.4-1.6 micrograms/kg) resulted in a sustained (greater than or equal to 50 min) increase in blood pressure during walking in four of six patients with progressive autonomic failure and in one of six patients with multiple system atrophy. Some patients in whom octreotide failed to stabilize upright blood pressure had a satisfactory response to the drug after pretreatment with dihydroergotamine (10 micrograms/kg, sc). Patients with diabetic autonomic neuropathy, although sensitive to the pressor effect of octreotide, often developed nausea or abdominal cramps after moderate doses (greater than 1.0 micrograms/kg). These results indicate that the pressor effect of octreotide is sufficiently potent to prevent orthostatic hypotension in some patients with autonomic neuropathy. Others require treatment with both dihydroergotamine and octreotide to achieve a stable upright blood pressure.
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PMID:Treatment of orthostatic hypotension with octreotide. 272 26

Treatment of chronic intestinal pseudoobstruction with prokinetic agents has been disappointing. Our study was designed to determine if octreotide and erythromycin would provide sustained relief from nausea, abdominal pain, and bloating in pseudoobstruction. Using gastrointestinal manometry, quantitative parameters of the activity front of the migrating motor complex at baseline and after prokinetic therapy with erythromycin and octreotide were determined in 14 patients with intestinal pseudoobstruction who had nausea, abdominal pain, and bloating. Patients were treated with erythromycin and octreotide for 20-33 weeks. Octreotide increased the frequency, duration, and motility index of activity fronts (AFs) from 1.2 +/- 0.3 AFs/4 hr, 2.7 +/- 0.7 min, and 85 +/- 23 min mm Hg to 4.1 +/- 0.8 AFs/4 hr, 5.5 +/- 0.7 min, and 152 +/- 24 min mm Hg, respectively (P < 0.05). Antral activity was decreased from 63 +/- 14 to 23 +/- 8% by octreotide (P < 0.05). Erythromycin induced antral activity; however, small intestinal motor activity was suppressed. While on erythromycin and octreotide, five patients had long-term improvement of nausea and abdominal pain. All responders had at least 5 AFs/4 hr induced by octreotide. We conclude that octreotide and erythromycin relieve abdominal pain and nausea in pseudoobstruction. Patients who have at least 5 AFs/4 hr after octreotide administration are most likely to clinically respond.
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PMID:Effect of octreotide and erythromycin on idiopathic and scleroderma-associated intestinal pseudoobstruction. 755 39

One hundred and three acromegalic patients from 14 medical centers were enrolled in this study to determine the efficacy and safety of the somatostatin analog, octreotide acetate, during long term treatment. Seventy percent of the patients had undergone previous surgery or radiation treatment. Octreotide was initiated at a dose of 100 micrograms, sc, every 8 h and gradually increased to a maximum of 1500 micrograms daily depending upon the individual patient's clinical and biochemical response [GH and insulin-like growth factor I (IGF-I) reduction]. The mean duration of treatment was 24 months (range, 3-30 months). However, most patients were treated for a mean of 30 months, because this study took place after an initial 6-month study previously reported. Mean serum GH fell from 30.9 micrograms/L (range, 2.7-350) to 5.7 micrograms/L (range, 0.6-59) at the 3 months visit and remained suppressed (P < 0.001). Plasma IGF-I concentrations were also significantly reduced and remained in the normal range for at least half of the treatment visits in 56 of 87 patients (64%) treated for 12-30 months. Patients with higher initial GH concentrations were less likely to normalize IGF-I concentrations during treatment (P < 0.001). There was no evidence of drug tachyphylaxis in those patients who continued taking stable doses of medication. With some exceptions, dose increments above 800 micrograms daily in 31 patients did not provide additional benefit in terms of GH and IGF-I reduction. Headache, excessive perspiration, fatigue, and joint pain were ameliorated in 83-95% of patients. Mean finger circumference was decreased significantly at the 12 month visit (P < 0.05). The most common adverse events reported were diarrhea, abdominal discomfort, loose stools, and nausea; these symptoms usually disappeared within 3 months of treatment. Five patients discontinued octreotide because of adverse events. Of 102 patients with normal baseline ultrasound examinations of the gallbladder, 24 patients (23.5%) developed gallstones (usually during the first year of treatment), and 21 patients developed sludge alone. Gallstone formation was not related to the dose of octreotide. Most patients with cholelithiasis were asymptomatic, and none developed cholecystitis. These observations suggest that octreotide is a valuable long term medical treatment for acromegaly.
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PMID:Safety and efficacy of long-term octreotide therapy of acromegaly: results of a multicenter trial in 103 patients--a clinical research center study. 767 22

The effects of octreotide on six normal subjects and five patients with scleroderma were investigated. Changes in intestinal motility and in plasma motilin were examined after a single injection of octreotide. Octreotide stimulated intense intestinal motor activity in normal subjects. Motility patterns in the scleroderma patients were chaotic and non-propagative, but, after octreotide was given, became well coordinated, aborally directed, and nearly as intense as in normal volunteers. Clinical responses and changes in breath hydrogen were also evaluated in the five scleroderma patients who had further treatment with octreotide at a dose of 50 micrograms/day subcutaneously for three weeks. A reduction in symptoms of abdominal pain, nausea, vomiting, and bloating was seen. Additionally, there was an improvement in bacterial overgrowth as objectively measured by breath hydrogen testing. The effects of octreotide (100 micrograms/day subcutaneously) on the perception of rectal distension were investigated in a double blind, placebo controlled study in healthy volunteers. Octreotide was shown to reduce the perception of rectal distension without affecting motor pathways or local rectal reflexes. This enhanced tolerance to volume distension seems to result from inhibition of sensory afferent pathways as shown by electroencephalographic studies showing diminished evoked spinal and cortical potentials after octreotide. In irritable bowel syndrome patients with rectal urgency, octreotide reduces rectal pressures and perception after rectal distension to near normal values.
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PMID:Octreotide in gastrointestinal motility disorders. 820 95

GH and IGF-I levels are elevated in patients with acromegaly. At the time of diagnosis patients present with macroadenomas with a high surgical failure rate or microadenomas. Administration of octreotide (100 micrograms, three times daily) suppressed GH secretion during 8 h to < 5 micrograms/l in 47% and to < 2 micrograms/l in 26% of acromegalic patients after two weeks. IGF-I levels were normalized in up to 70% of patients. Increasing the dose of octreotide to 250 micrograms three times daily did not further improve results. Tumour shrinkage occurred in 37% after six months of treatment, while symptoms improved in 70%. Transient diarrhoea and nausea were noted in 88%, but after six months only 10% reported these symptoms. Gallbladder sludge and gallstones were noted in 19% of patients. IGF-I levels were normalized in 82% of patients with microadenoma and in 50% with macroadenoma. Well-defined pituitary adenomas are usually surgically removed. Invasive tumours are difficult to remove surgically but preoperative octreotide may shrink adenomas and improve response. Octreotide therapy, unlike surgery and irradiation, does not compromise pituitary function. This study suggests that octreotide therapy could be a viable primary management of small discreet adenomas. Where surgery and octreotide fail, other treatments of adenoma include bromocriptine and radiotherapy.
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PMID:Medical management of acromegaly--what and when? 837 5

In the present study, we have updated our results with chemotherapy, alpha-interferon, octreotide and combinations of treatment modalities in patients with malignant endocrine pancreatic tumor (EPT). In our patient material of 134 EPT, 92 subjects had malignant tumors as evidenced by the presence of metastases or growth into adjacent organs. Seventy-eight patients had liver metastases. Streptozotocin plus 5-fluorouracil produced objective responses in 17/31 (54%) patients with a median duration of response of 23 months. The use of 5-HT3-antagonists as antiemetics has dramatically improved the quality of life during treatment by reducing the frequency of nausea to only 12.5%. The objective response rate to alpha-interferon (alpha-IFN) treatment, given as first-line treatment in 29 patients and after chemotherapy in 28 patients, was 51% (29/57) with a median duration of response of 20 months. Octreotide, which is still used as third-line treatment in most patients, produced significant biochemical responses in 6/19 (31%) patients with a median duration of 16 months. Combinations of alpha-IFN plus chemotherapy and a alpha-IFN plus octreotide in a small number of patients might indicate additive or synergistic effects. The median survival from start of treatment in the 92 malignant cases was 56.5 months, and for those with liver metastases (n = 78) at start of treatment 50 months. In conclusion, there are at least three effective therapies for malignant EPT and by combining them simultaneously or consecutively, a median survival of more than four years can be obtained.
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PMID:An update of the medical treatment of malignant endocrine pancreatic tumors. 839 32

In advanced cancer patients with inoperable bowel obstruction, the administration of antisecretive and antiemetic drugs has proved to be effective in controlling gastrointestinal symptoms caused by bowel obstruction. However, controlled studies concerning the most effective antisecretive drug are lacking. The aim of this randomized controlled study was to determine whether octreotide or hyoscine butylbromide was the more effective antisecretive drug for use in states of inoperable bowel obstruction. Eighteen patients with inoperable bowel obstruction randomly received octreotide 0.3 mg daily (n = 9) or hyoscine butylbromide (HB) 60 mg daily (n = 9) s.c. The following parameters were measured: episodes of vomiting, nausea, drowsiness, continuous and colicky pain, using a Likert scale corresponding to a numerical value: (none 0, slight 1, moderate 2, severe 3) recorded before starting the treatment (T0) and 24 h (T1), 48 h (T2) and 72 h after (T3), and the mean daily amounts of fluids administered i.v. or s.c. during the period of study. Three patients dropped out of the study because data were incomplete. Octreotide treatment induced a significantly rapid reduction in the number of daily episodes of vomiting and intensity of nausea compared with HB treatment at the different time intervals examined. No relevant changes were found in dry mouth, drowsiness and colicky pain. Lower levels of hydration were associated with nausea regardless of the treatment. At the doses used in this study, octreotide was more effective than HB in controlling gastrointestinal symptoms of bowel obstruction. Further studies are necessary to understand the role of hydration more clearly in such a clinical situation.
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PMID:Comparison of octreotide and hyoscine butylbromide in controlling gastrointestinal symptoms due to malignant inoperable bowel obstruction. 1078 58

Patients with chronic intestinal pseudoobstruction (CIP) experience a constellation of symptoms including abdominal pain, nausea, fullness, and malaise which fluctuates in severity and invariably result in a diminished quality of life. Though surgical resection or transplantation may be an option for some, there currently is no cure for CIP. Thus, management strategies utilize pharmacologic, intravenous, endoscopic, and surgical techniques to promote transit, minimize painful bloating, reduce complications of stasis, and improve quality of life. Prokinetic agents such as erythromycin, metoclopramide, cisapride, neostigmine, and tegaserod may be effective for acute exacerbations. Octreotide may reduce symptoms of bacterial overgrowth and bloating by stimulating migrating motor complexes. Enteral tubes for venting and nutritional support may reduce hospitalizations. Total parenteral nutrition (TPN), fraught with well-known complications, may be the only tolerated source for nutrients and fluid. Advanced disease may magnify nutritional problems, difficulties of long term intravenous and intestinal access, and poor symptom control. Because the initial process may manifest in other intestinal regions following surgery, resection of involved segments should be performed with caution. Small intestinal transplantation is a high-risk surgery performed in persons unable to tolerate intravenous (IV) nutrition. Optimal management for persons with CIP should not only provide nutritional and symptom focused care but should be part of a supportive network which links patients to their appropriate healthcare needs.
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PMID:Chronic Intestinal Pseudoobstruction. 1523 7


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