Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042963 (vomiting)
 31,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nearly 30% of patients treated with metformin experience gastrointestinal side effects. Since release of 5-hydroxytryptamine (5-HT) from the intestine is associated with nausea, vomiting, and diarrhea, we examined whether metformin induces 5-HT release from the intestinal mucosa. In 40% of tissue biopsy specimens of human duodenal mucosa, metformin (1, 10, and 30 microM) caused an increase in 5-HT outflow by 35, 70, and 98%, respectively. Peak increases in 5-HT outflow were observed after 10-15 min exposure to metformin, returning to baseline levels after 25 min. Tetrodotoxin (1 microM) reduced by about 50% the metformin-evoked increase in 5-HT outflow (P<0.05). Metformin-evoked release was not affected by scopolamine + hexamethonium, propranolol, the 5-HT3 receptor antagonist dolasetron, naloxone, or the NK1 receptor antagonist L703606. In the presence of tetrodotoxin (1 microM), somatostatin (1 microM) further reduced metformin-induced 5-HT release by 15-20%. In view of the 5-HT releasing effects of selective 5-HT3 receptor agonists to which metformin (N-N-dimethylbiguanide) is structurally related, we investigated whether metformin directly interacts with 5-HT3 receptors. Receptor binding (inhibition of [3H]-GR65630 binding) and agonist effects (stimulation of [14C]-guanidinium influx) at 5-HT3 receptors were studied in murine neuroblastoma N1E-115 cells, which express functional 5-HT3 receptors. Metformin up to 0.3 mM failed to inhibit [3H]-GR65630 binding and to modify displacement of [3H]-GR65630 binding induced by 5-HT. 5-HT (3 microM) stimulated the influx of [14C]-guanidinium in intact N1E-115 cells. Metformin up to 1 mM failed to modify basal influx, 5-HT-induced influx, and 5-HT+ substance P-induced influx of [14C]-guanidinium. Our results indicate that metformin induces 5-HT3 receptor-independent release of 5-HT from human duodenal mucosa via neuronal and non-neuronal mechanisms. Part of the gastrointestinal side effects observed during treatment with metformin could, thus, be produced by the release of 5-HT and other neurotransmitter substances within the duodenal mucosa.
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PMID:Effects of metformin on intestinal 5-hydroxytryptamine (5-HT) release and on 5-HT3 receptors. 1065 Nov 52

Metformin belongs to a class of drugs known as the biguanides that are widely used in the treatment of type 2 diabetes mellitus. Its association with lactic acidosis is well established, although rare. Metformin-associated lactic acidosis is recognized as a potentially lethal condition that can occur in patients with contraindications to the drug, such as renal dysfunction, liver diseases, alcoholism, and cardiopulmonary diseases. In these cases, the plasma concentration of metformin is not necessarily abnormally high. We describe a 75-year-old diabetic woman with acute renal failure and life-threatening lactic acidosis due to metformin intoxication. Clinical manifestations included vomiting, diarrhea, hypothermia, hypotension and transitory blindness. Her initial renal function was recovered after hemodialysis and she was discharged 3 months after admission.
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PMID:Metformin-associated lactic acidosis and acute renal failure in a type 2 diabetic patient. 1460 17

Treatment with metformin is associated with a high incidence of gastrointestinal side effects of unknown mechanism. Metformin is a biguanide derivative, which resembles 5-HT3-receptor agonists in its structure. Activation of 5-HT3 receptors is known to induce nausea, vomiting, and diarrhea. In this study, we investigated if the gastrointestinal side effects produced by metformin were antagonized by ondansetron, a selective antagonist of 5-HT3 receptors. Patients experiencing gastrointestinal side effects were randomized to ondansetron (4 mg bid p.o.) or placebo while maintained on metformin (double-blind, parallel-group design). If side effects persisted or worsened, metformin was discontinued and the patient considered a therapeutic failure. Of the 98 subjects treated with metformin, 22 developed side effects to match the study entry criteria. Diarrhea was the most frequent side effect. Subjects were randomized to ondansetron (10/2 F/M, 42.8 +/- 2.3 years, 28.6 +/- 1.1 kg/m2, 2585 +/- 35 mg/d metformin) or placebo (9/1 F/M, 43 +/- 4.3 years, 29.7 +/- 1.8 kg/m2, 2715 +/- 71 mg/d metformin). Ondansetron showed no efficacy against metformin-induced side effects. A comparable number of therapeutic failures were observed in ondansetron (8/12; 66%) and placebo-treated subjects (5/10; 50%) (P<0.1). Mean nausea scores (numeric analog scale) before and during treatment with ondansetron were 6.3 +/- 1 and 6.9 +/- 1 cm, respectively. Nausea scores averaged 7.3 +/- 1.5 and 5.9 +/- 1.5 cm, before and during treatment with placebo (P>0.1). In conclusion, 5-HT3 receptors do not seem to play a role in metformin-induced gastrointestinal side effects.
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PMID:Ondansetron and metformin-induced gastrointestinal side effects. 1462 84

Metformin is an oral antidiabetic drug that improves control of glycemia primarily by inhibiting hepatic gluconeogenesis and glycogenolysis. This study evaluated the usefulness of metformin for the treatment of diabetes mellitus in cats. The study consisted of 3 phases. Phase I was a dose-finding study performed in healthy cats that were randomly administered varying doses of metformin to determine the approximate dose that would yield plasma concentrations known to be effective in humans. Phase 2 was a 3-week safety study performed in healthy cats to determine if cats could tolerate the daily oral dose and administration protocol identified during phase 1. Phase 3 was a clinical trial evaluating the clinical response of diabetic cats to oral metformin treatment. Five cats with newly diagnosed, naturally acquired diabetes mellitus were enrolled in phase 3. Plasma metformin concentrations in the therapeutic range of 0.5-2 microg/mL were achieved with doses of 50 mg/cat PO q12h without dramatic drug accumulation. Intermittent lethargy, inappetence, vomiting, and weight loss were identified, and the results of the CBC, serum biochemical analysis, plasma lactate concentration, and urinalysis remained within the reference range during phase 2 of the study. During phase 3, control of glycemia was achieved in 1 of 5 diabetic cats after 8 weeks of metformin treatment; 3 cats failed to respond to metformin, and treatment with insulin was initiated after 7-8 weeks of metformin treatment; 1 cat died unexpectedly 11 days after starting metformin treatment. The cause of death was not determined. The serum insulin concentration was within or greater than the reference range in the responder diabetic cat and was undetectable or at the low end of the reference range in the nonresponder diabetic cats. The results of this study suggest that metformin is beneficial only in those diabetic cats with detectable concentrations of insulin at the time metformin treatment is initiated.
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PMID:Evaluation of the oral antihyperglycemic drug metformin in normal and diabetic cats. 1476 27

A 39-year-old woman with type-2 diabetes mellitus presented with metabolic acidosis due to an attempted suicide with metformin. Despite treatment with activated charcoal and laxation, she experienced cardiac arrest, which required resuscitation. After transfer to another hospital, she was treated with high-volume continuous venovenous haemofiltration. However, she died due to multiple organ failure. Metformin is the most widely used oral antidiabetic agent in the world and the first-choice treatment for patients with type-2 diabetes mellitus. Metformin overdose can cause lactic acidosis, which usually manifests as abdominal pain, vomiting and diarrhoea. Although rare, metformin-associated lactic acidosis carries a high mortality risk. The treatment of choice is immediate haemodialysis and orally administered activated charcoal. If a patient treated with metformin presents with metabolic acidosis, lactic acidosis due to metformin overdose should be suspected and appropriate treatment should be initiated immediately.
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PMID:[Fatal autointoxication with metformin]. 1782 56

The objective of this case report is to highlight presentation, complications and treatment of metformin poisoning. Patient after ingestion of 45gms of metformin developed colicky abdominal pain, severe tachypnea and vomiting. He developed severe lactic acidosis, cardiac arrest, pancreatitis and hemolytic anemia which was treated with charcoal, sodium bicarbonate, early initiation of high volume continuous veno-venous hemofiltration and supportive therapy. Metformin poisoning is a rare presentation and we discuss course of events in the management of metformin poisoning and its associated complications.
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PMID:Metformin poisoning: A complex presentation. 2171 82

We describe the case of a patient with severe lactic acidosis, as well as presenting some data on its incidence, diagnosis, prognostic factors, and the most appropriate treatment. A 76 year-old male patient with diabetes on treatment with metformin, hypertension, dyslipaemia, and with mild cognitive impairment, was admitted to the Intensive Care Unit in a state of circulatory shock, requiring aggressive treatment with vasopressors and volume. The patient had acute kidney injury with an anuria of 3 days, probably secondary to dehydration to vomiting and to NSAIDs. As a result of the acute renal damage, the patient suffered a severe metformin-associated lactic acidosis. The rest of the causes of metabolic acidosis with an increased anion gap were ruled out, as well as a possible sepsis or rhabdomyolysis. Metformin-associated lactic acidosis is an uncommon metabolic condition, but with a high mortality. To reduce the mortality of these patients, it is important to make an early diagnosis using the clinical records, physical examination, and laboratory tests, with an early resuscitation with volume, vasopressors, bicarbonate, and renal replacement therapy.
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PMID:[Metformin-associated lactic acidosis: incidence, diagnosis, prognostic factors and treatment]. 2260 63

Metformin is a biguanide group oral antidiabetic drug used for the treatment of type 2 diabetes mellitus. Nausea, vomiting, diarrhea, abdominal pain, and anorexia are the most common adverse effects encountered during treatment. Lactic acidosis is a serious side effect seen with metformin use, and while the incidence of lactic acidosis is similar to other oral antidiabetics, metformin is not recommended to patients with certain risk factors, such as cardiovascular, pulmonary, and renal and liver failure. We describe a chronic hemodialysis patient treated with metformin, presenting to the nephrology department with altered mental status.
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PMID:Lactic acidosis induced by metformin in a chronic hemodialysis patient with diabetes mellitus type 2. 2429 54

This meta-analysis examined the effectiveness and safety of metformin to prevent or treat weight gain and metabolic abnormalities associated with antipsychotic drugs. We systematically searched in both English- and Chinese-language databases for metformin randomized controlled clinical trials (RCTs) using placebo in patients taking antipsychotics. Twenty-one RCTs (11 published in English and 10 in Chinese) involving 1547 subjects (778 on metformin, 769 on placebo) were included in this meta-analysis. Metformin was significantly superior to placebo (standard mean differences, -0.69 to -0.51; P = 0.01-0.0001) in the primary outcome measures (body weight, body mass index, fasting glucose, fasting insulin, triglycerides, and total cholesterol). Metformin was significantly superior to placebo in some secondary outcome measures but not in others. Significantly higher frequencies of nausea/vomiting and diarrhea were found in the metformin group, but no differences were found in other adverse drug reactions. In the metformin group, the frequency of nausea/vomiting was 14%, and of diarrhea, 7%. Subgroup and sensitivity analyses demonstrated that primary outcomes were influenced by ethnicity, treatment style (intervention vs prevention), metformin dose, study duration, and mean age. Body weight standard mean difference was -0.91 (confidence interval [CI], -1.40 to -0.41) in 3 prevention RCTs in naive patients, -0.66 (CI, -1.02 to -0.30) in 5 intervention RCTs during the first year, and -0.50 (CI, -0.73 to -0.27) in 9 intervention RCTs in chronic patients. This meta-analysis suggests that adjunctive metformin is an effective, safe, and reasonable choice for antipsychotic-induced weight gain and metabolic abnormalities.
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PMID:Metformin for Weight Gain and Metabolic Abnormalities Associated With Antipsychotic Treatment: Meta-Analysis of Randomized Placebo-Controlled Trials. 2628 Aug 37

Metformin is a common medication used for the treatment of type 2 diabetes, especially in obese subjects. Clinical studies show that, in addition to the lowering effect of blood glucose, metformin reduces cardiovascular risk, does not induce weight gain and additionally, provides a unique safety strategy and efficacy in patients with diabetes and heart disease. However, this treatment is not without risks. The most feared metabolic complication is lactic acidosis that often occurs with complex and severe clinical symptoms and is associated with a high mortality risk. We detail our experience, during one year, regarding four patients with diabetes treated with metformin who developed such acute renal failure and lactic acidosis as to require hemodialysis treatment. The patients selected had previous normal renal function but a history of serious cardiovascular disease (hypertensive cardiomiopathy, ischemic revascularized and/or dilated, chronic obstructive arterial disease). We observed in all four of our patients an onset of non-related symptoms (fever, fatigue, vomiting and gastrointestinal disorders), a rapid deterioration in renal function, anuria and very high levels of lactic acid. In two patients we found acute pancreatitis. In addition to rehydration therapy, hemodialysis was started instantly with progressive rebalancing of the biohumoral status, effective recovery of spontaneous diuresis and improvement of the clinical status in three patients. Unfortunately, we had a failure during the initial hours of ward admittance, with an important clinical situation complicated by acute cardiac ischemia, abnormal heart rhythm, ending in death. Our experience provides us with elements to reflect on. Lactic acidosis is a serious metabolic disorder because it is associated with a high mortality risk. So a rapid diagnosis and a complete recognition of all the fundamental elements are important for its management. Starting hemodialysis early and prolonged treatment can solve complicated clinical status, correct acidosis and restore kidney function in patients with serious comorbidity.
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PMID:[Lactic acidosis, acute renal failure and heart failure during treatment with metformin: what do we know?]. 2648 Feb 56


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