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)

We present a case of unknown fever and abnormal liver functions which developed during the course of pain management for herpes zoster with repeated epidural blocks with 0.5% lidocaine 10 ml. The patient was a 67 year old woman. At her first admission to dermatology, there were no abnormal findings in her blood examinations. She complained of severe pain from herpes zoster. She was admitted to the pain clinic. She received thoracic epidural blocks with 0.5% lidocaine 10 ml repeatedly three or four times a week. Two weeks later, she developed general fatigue, appetite loss, nausea and a high fever. Blood examinations revealed the elevation of glutamic oxalacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), alkaline phosphatase (ALP), and gamma glutamyltrans peptidase (gamma-GTP), C reactive protein (CRP), and blood sedimentation rate (BSR). Many examinations including abdominal and thoracic computer tomography and abdominal echograph could not reveal the cause of high fever and abnormal blood examinations. We continued the thoracic epidural block for her herpes zoster pain. GOT, GPT, ALP, and gamma-GTP gradually went down to normal values in next two weeks, though fever still persisted. At this time, lymphocyte cell simulation test with 0.5 % lidocaine was positive and eosinophylic cell had increased to 5%. After ceasing the epidural block, fever resolved and blood examinations returned to normal values. These findings suggest strongly that 0.5% lidocaine induced fever and hepatitis.
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PMID:[Unknown fever and abnormal liver functions after repeated epidural blocks with lidocaine for management of herpes zoster pain]. 818 88

Elevated blood pressure is a risk factor for a variety of cardiovascular disorders, including coronary heart disease, peripheral vascular disease, cardiac failure and cerebrovascular disease. The prevailing view is that an elevated systolic rather than diastolic blood pressure is the major contributor in mortality and morbidity attributed to cardiovascular disorders. Isolated high systolic blood pressure, especially in the elderly, is a major risk factor and should undoubtedly be a target for drug treatment. In the general population, systolic and diastolic blood pressure are highly correlated, and thus it is difficult to dissociate the effects of these two components of the blood pressure and specifically ascribe cardiovascular risk factors to just elevated systolic blood pressure. Therefore, the goal in therapy of an individual with hypertension must be to reduce elevated systolic and diastolic blood pressure in order to reduce mortality and morbidity. ACE and neutral peptidase inhibitors are a new class of drugs that may be beneficial in the treatment of patients with hypertension and heart failure. They may also be useful in the treatment of diabetic patients with hypertension and/or heart failure. Drugs of this class are dual inhibitors of ACE and neutral endopeptidase, and are capable of affecting vascular tone and fluid balance. They are capable of producing vasodilatation by virtue of inhibiting the production of angiotensin II, degradation of natriuretic peptides and bradykinin. They also appear to promote natriuresis and diuresis by amplifying the actions of natriuretic peptidase and reducing aldosterone effects. In addition, they should also attenuate trophogenic actions of the renin angiotensin system and the sympathetic nervous system. Omapatrilat is one drug that appears to be at the advanced stages of clinical development. This drug has been shown to be quite effective in the treatment of hypertension. Evidence also seems to indicate that treatment with omapatrilat results in a higher tendency towards preventing death and worsening heart failure when compared with treatment with a pure ACE inhibitor in patients with advanced heart failure. Overall safety with omapatrilat appears to be good, but like other ACE inhibitors the incidence of cough is higher when compared with placebo. Other common adverse effects noted are headaches, facial flushing/warm sensation, dizziness, nausea and dyspnoea. Of greater concern is the occurrence of angio-oedema, the true incidence of which remains to be fully established as part of the published medical literature.
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PMID:Dual ACE and neutral endopeptidase inhibitors: novel therapy for patients with cardiovascular disorders. 1501 94

Glucagon-like peptide-1 (GLP-1) is synthesized from proglucagon in enteroendocrine cells and regulates glucose homeostasis via multiple complementary actions on appetite, gastrointestinal motility and islet hormone secretion. GLP-1 is secreted from the distal gut in response to food ingestion, and levels of circulating GLP-1 may be diminished in patients with type 2 diabetes mellitus. GLP-1 administration stimulates glucose-dependent insulin secretion, inhibits glucagon secretion, and lowers blood glucose in normal and diabetic rodents and in humans. GLP-1 exerts additional glucose-lowering actions in patients with diabetes mellitus already treated with metformin or sulfonylurea therapy. GLP-1 inhibits gastric emptying in healthy individuals and those with diabetes mellitus, and excess GLP-1 administration may cause nausea or vomiting in susceptible individuals. Chronic GLP-1 treatment of normal or diabetic rodents is associated with bodyweight loss and GLP-1 agonists transiently inhibit food intake and may prevent bodyweight gain in humans. The potential for GLP-1 therapy to prevent deterioration of beta-cell function is exemplified by studies demonstrating that GLP-1 analogs stimulate proliferation and neogenesis of beta-cells, leading to expansion of beta-cell mass in diabetic rodents. The rapid N-terminal inactivation of bioactive GLP-1 by dipeptidyl peptidase-IV (DPP-IV) limits the utility of the native peptide for the treatment of patients with diabetes mellitus, and has fostered the development of more potent and stable protease-resistant GLP-1 analogs which exhibit longer durations of action. The importance of DPP-IV for glucose control is illustrated by the phenotype of rodents with genetic inactivation of DPP-IV which exhibit reduced glycemic excursion and increased levels of circulating GLP-1 in vivo. Inhibitors of DPP-IV potentiate incretin action by preventing degradation of GLP-1 and glucose-dependent insulinotropic peptide, and lower blood glucose in normal rodents and in experimental models of diabetes mellitus. Hence, orally available DPP-IV inhibitors also represent a new class of therapeutic agents that enhance incretin action for the treatment of patients with type 2 diabetes mellitus.
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PMID:Harnessing the therapeutic potential of glucagon-like peptide-1: a critical review. 1576 27

PT-100 upregulates cytokine expression competitively inhibiting the dipeptidyl peptidase activity of fibroblast activation protein (FAP) and dipeptidyl peptidase IV (DPP-IV). This dose-escalation study was conducted to evaluate the safety of PT-100 in patients receiving myelosuppressive chemotherapy and to assess its effects on neutrophil recovery.PT-100 was administered orally for 7 days as a 200 microg, 400 microg, 800 microg, or 1,200 microg total daily dose (divided twice daily) to 6, 6, 17, and 5 patients, respectively. Patients received 2 cycles of chemotherapy: The first cycle served as each individual patient's control. Patients had to develop Grade 3+ neutropenia in Cycle 1 in order to receive PT-100 in Cycle 2. Most patients received PT-100 on Days 2-8 of chemotherapy in Cycle 2, except at 800 microg where an additional cohort (n = 8) was treated on a Days 5-11 schedule. Five of 7 patients receiving 800 microg on Days 2-8 experienced a >/=1-day improvement in Grade 3+ neutropenia in Cycle 2 versus Cycle 1. Overall, PT-100 was well tolerated. A reduction in chemotherapy-related nausea, vomiting, fatigue, alopecia, and diarrhea was noted in patients receiving PT-100. Edema/peripheral swelling, hypotension, hypovolemia, and dizziness were the most common nonhematologic adverse events considered related to PT-100. Two Grade 3 adverse events were considered related to PT-100: syncope (1,200 microg) and orthostatic hypotension (800 microg). A maximum tolerated dose was not reached. Given the accelerated neutrophil recovery, preclinical evidence of antitumor activity, and tolerable toxicities of PT-100, additional studies to optimize the PT-100 dosing schedule in patients receiving myelosuppressive chemotherapy are needed.
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PMID:Phase I trial of PT-100 (PT-100), a cytokine-inducing small molecule, following chemotherapy for solid tumor malignancy. 1698 58

Incretin mimetics are a new class of pharmacological agents with multiple antihyperglycemic actions that mimic several of the actions of incretin hormones originating in the gut, such as glucagon-like peptide (GLP)-1. Dipeptidyl peptidase-IV (DPP-IV) inhibitors suppress the degradation of many peptides, including GLP-1, thereby extending their bioactivity. These agents seem to have multiple mechanisms of action for the treatment of type 2 diabetes mellitus (T2DM), including some or all the following: enhancement of glucose-dependent insulin secretion, suppression of inappropriately elevated glucagon secretion, slowing of gastric emptying, and decreased food intake. Exenatide (BYETTA) is the first incretin mimetic approved for clinical use by the US Food and Drug Administration. In phase 3 clinical trials, exenatide reduced HbA(1c) by approximately 1% and body weight by approximately 2 kg in T2DM patients failing to achieve glycemic control with metformin and/or a sulfonylurea, with mild-to-moderate nausea the most common side effect. Several GLP-1 analogues and DPP-IV inhibitors are in late-stage clinical testing and may soon become available for treating T2DM patients. The use of these agents may provide an opportunity to bring about new improvements in diabetes care.
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PMID:Incretin mimetics and DPP-IV inhibitors: new paradigms for the treatment of type 2 diabetes. 1709 Jul 94

Glucagon-like peptide 1 (GLP-1) is a gut-derived incretin hormone that stimulates insulin and suppresses glucagon secretion, inhibits gastric emptying, and reduces appetite and food intake. Therapeutic approaches for enhancing incretin action include degradation-resistant GLP-1 receptor agonists (incretin mimetics), and inhibitors of dipeptidyl peptidase-4 (DPP-4) activity (incretin enhancers). Clinical trials with the incretin mimetic exenatide (two injections per day or long-acting release form once weekly) and liraglutide (one injection per day) show reductions in fasting and postprandial glucose concentrations, and haemoglobin A1c (HbA1c) (1-2%), associated with weight loss (2-5 kg). The most common adverse event associated with GLP-1 receptor agonists is mild nausea, which lessens over time. Orally administered DPP-4 inhibitors, such as sitagliptin and vildagliptin, reduce HbA1c by 0.5-1.0%, with few adverse events and no weight gain. These new classes of antidiabetic agents, and incretin mimetics and enhancers, also expand beta-cell mass in preclinical studies. However, long-term clinical studies are needed to determine the benefits of targeting the incretin axis for the treatment of type 2 diabetes.
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PMID:The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. 1725 57

Type 2 diabetes mellitus is a common chronic disease that causes significant morbidity and mortality worldwide. The primary goal of treatment is to target glycemic control by maintaining the glycosylated hemoglobin level near 6-7% without predisposing patients to hypoglycemia. Diabetes results from a combination of increased hepatic glucose production, decreased insulin secretion from beta cells, and insulin resistance in the peripheral tissues. Currently available antidiabetic agents work by different mechanisms to lower blood glucose levels. Unfortunately, each of them has its tolerability and safety concerns that limit its use and dose titration. Sitagliptin is the first antidiabetic agent from the class of dipeptidyl peptidase-4 enzyme inhibitors. It increases the amount of circulating incretins, which stimulate insulin secretion and inhibit glucose production. Sitagliptin was approved by the US Food and Drug Administration (FDA) for use with diet and exercise to improve glycemic control in adult patients with type 2 diabetes. It can be used alone or in combination with metformin or a thiazolidinedione (pioglitazone or rosiglitazone) when treatment with either drug alone provides inadequate glucose control. The usual adult dose is 100 mg once daily. A dose of 25-50 mg once daily is recommended for patients with moderate-to-severe renal impairment. In randomized, placebo-controlled trials that lasted for up to 6 months, sitagliptin lowered glycosylated hemoglobin levels by 0.5-0.8%. In a 52-week clinical trial, sitagliptin was shown to be noninferior to glipizide as an add-on agent in patients inadequately controlled on metformin alone. Sitagliptin was well tolerated with the most common side effects being gastrointestinal complaints (up to 16%), including abdominal pain, nausea and diarrhea; hypoglycemia and body weight gain occurred at similar rates compared with placebo. Overall, sitagliptin provides a treatment option for patients with type 2 diabetes as a monotherapy, or as an adjunct to metformin or a thiazolidinedione when patients achieve inadequate glycemic control while on either of the agents. It is also an alternative therapy for those patients who have contraindications or intolerability to other antidiabetic agents.
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PMID:Sitagliptin: a novel drug for the treatment of type 2 diabetes. 1770 Mar 85

The incretin effect denominates the phenomenon that oral glucose elicits a higher insulin response than intravenous glucose. Glucagon like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide are the principal hormones responsible for incretin effect. In patients with type 2 diabetes the incretin effect of these hormones is impaired. Therapeutic approaches for enhancing the incretin action include degradation resistant GLP-1 receptor agonists (incretin mimetics) and inhibitors of dipeptidyl peptidase-IV (DLP-IV) activity (incretin enhancers- gliptins). These groups of medications have similar efficacy with regards to glycaemic improvement (reduction of HbA1c between 0.5 to 1.1%) and have side-effects like nausea. The incretin mimetics are injectable agents and are more likely to reduce weight or be weight neutral when compared to the oral gliptins. Long-term studies are essential to determine the real potential and role of these newer agents in the management of type 2 diabetes.
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PMID:Incretin based therapies for type 2 diabetes mellitus. 1883 49

Type 2 diabetes poses a major health challenge among African Americans. Older therapies are associated with shortcomings such as hypoglycemia and/or weight gain. In recent years the "incretin system" has become understood as offering great promise for drug development. Two drug classes-namely, the injectable glucagon-like peptide 1 (GLP-1) receptor agonists, which produce pharmacological GLP receptor activity, and the oral dipeptidyl peptidase-4 (DPP-4) inhibitors, which raise levels of endogenously produced GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) by preventing enzymatic degradation--have been available for several years. These drugs can be given as monotherapy or added to other antidiabetic drugs to lower blood glucose with very low risk of hypoglycemia without weight gain. In fact, GLP-1 receptor agonists may induce clinically significant reductions in weight and systolic blood pressure, as well as improve indices of beta-cell function. Although transient nausea occurs in some patients with GLP-1 receptor agonists, these agents are generally well tolerated, and the available clinical data are encouraging. Clinical experience shows that these treatments are acceptable to patients.
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PMID:Can therapies that target the incretin system improve our ability to treat type 2 diabetes? 2057 17

Dyspeptic syndrome is a common complication of treatment with antidiabetic drugs. This may be a trivial as well as a very serious complication. Nausea, vomiting, diarrhoea, abdominal pain, loss of appetite and taste disturbances are the most common symptoms of dyspeptic problems in patients treated with metformin. They rarely are a reason for treatment discontinuation. Dyspeptic syndrome is a common complication in patients treated with acarbose, this may be prevented by reduced intake of sucrose. Pneumatosis cystoides intestinalis is a rare complication in acarbose-treated patients. Antiobesity agent orlistat is frequently associated with dyspeptic symptoms, particularly if fat intake is not reduced. Treatment with drugs affecting the incretin system (dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists) is very rarely complicated by acute pancreatitis. Glucagon-like peptide-1 receptor agonists may cause dyspeptic symptoms (nausea, vomiting, diarrhoea) at the beginning of treatment. These complaints usually cease and the treatment usually does not need to be discontinued.
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PMID:[Dyspeptic syndrome associated with antidiabetic therapy]. 2161 66


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