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)

Phosphodiesterase 4 (PDE4) is a major cyclic adenosine-3',5'-monophosphate-metabolizing enzyme in immune and inflammatory cells, airway smooth muscle, and pulmonary nerves. Selective inhibitors of this enzyme have been available for a number of years and show a broad spectrum of activity in animal models of COPD and asthma. The class-associated side effects, mainly nausea and emesis, appear to have been at least partially overcome by the so-called "second-generation" PDE4 inhibitors. Currently, three companies are in the later stages of development of candidate second-generation PDE4 inhibitors for the treatment of COPD patients. The preclinical profile of one of these, BAY 19-8004, is summarized below. The initial clinical data on the most advanced compound, cilomilast, were indeed encouraging. However, full knowledge of the therapeutic value of this novel compound class awaits the outcome of longer term clinical trials.
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PMID:Phosphodiesterase 4 inhibitors for the treatment of COPD. 1201 Aug 50

The Rainey Hospice House, South Carolina's first stand-alone inpatient facility opened in September 1998. During the year 2000, 220 inpatients were served in the house. Patients ranged in age from 23 to 107 years old (average age 73). Cancer was the most common hospice diagnosis, followed by congestive heart failure, cardiovascular disease and cerebrovascular disease, dementia, cirrhosis, renal failure, and COPD. Thirty-three percent of patients were in the program less than ten days. Over 98 percent of deaths under hospice care were described as peaceful. During 2000, our outpatients and our inpatients were similar in age, insurance coverage, diagnoses, and time in the program. Inpatient hospice is highly valued by families and patients alike. It is especially useful for the following patients: those with uncontrolled symptoms, those with exhausted care givers, those with no caregivers, those who require total care, and those very close to death. The symptoms most likely to precipitate inpatient admission include pain, nausea, confusion, and agitation. Given the graying of South Carolina's population and the increase in outpatient hospice care, more areas of the state will need inpatient facilities in the future.
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PMID:Comfort always. The Rainey Hospice House: South Carolina's first inpatient hospice. 1450 98

Inflammation is a hallmark of inflammatory bowel disease (IBD), and elevation of cAMP levels can inhibit the pro-inflammatory and tissue-destructive properties of leukocytes. Phosphodiesterase 4 (PDE4) is the predominant enzyme that metabolizes cAMP in inflammatory cells, and the anti-inflammatory and immunomodulatory potential of PDE4 inhibitors in human leukocytes, endothelium and epithelium is well documented. Although PDE4 inhibitors have been investigated as treatments for several inflammatory diseases, this has focused mainly on asthma and chronic obstructive disease (COPD). Historically, their clinical utility has been limited by nausea and emesis. However, the PDE4 inhibitors cilomilast and roflumilast have recently shown efficacy in asthma and COPD, with a reduced propensity to cause nausea and emesis. In this review, we summarize for the first time the evidence that PDE4 inhibitors might have therapeutic benefit in IBD, and discuss mechanisms of action beyond the inhibition of inflammatory cells.
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PMID:PDE4 inhibition: a novel approach for the treatment of inflammatory bowel disease. 1527 12

In this study, we investigated and analysed clinical efficacy and tolerability of moxifloxacin, a new quinolone antibiotic, for the outpatient treatment of bacterial respiratory infections--acute exacerbation of chronic obstructive pulmonary disease (AE-COPD), pneumonia and acute sinusitis. The study was post-marketing and observational, and was conducted after the registration and listing of moxifloxacin in commercial distribution in Croatia. A total of 84 physicians throughout Croatia participated in this study that included 440 patients, 231 with clinically confirmed diagnosis of AE-COPD, 103 with pneumonia and 46 with acute sinusitis. According to physicians, evaluation, 96.8% of the patients were cured. The improvement was recorded on the average after 3.2 days and cure after 6.4 days from the beginning of treatment. Adverse events (48 side effects) were recorded in 40 patients, most commonly suffering from milder gastrointestinal symptoms (nausea, diarrhoea). Serious adverse events were not recorded (phototoxicity, severe hepatic impairment, cardiotoxicity). Moxifloxacin tolerability and patient compliance during treatment were rated as excellent in three-quarters of the patients. Physicians stated they would again prescribe moxifloxacin in 415 or 94.3% of the patients.
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PMID:[Efficacy of moxifloxacin in the treatment of respiratory tract infections: the Croatian post-marketing study]. 1619 58

Chronic obstructive pulmonary disease is characterized by a rapid decline in lung function due to small airway fibrosis, mucus hypersecretion and emphysema. The major causative factor for COPD is cigarette smoking that drives an inflammatory process that gives rise to leukocyte recruitment, imbalance in protease levels and consequently matrix remodeling resulting in small airway fibrosis and loss of alveolar tissue. Current drug treatment improves symptoms but do not alter the underlying progression of this disease. The failure of antiinflammatory drugs like glucocorticosteroids to have a major impact in this disease has hastened the need to develop novel therapeutic strategies. Phosphodiesterase (PDE) 4 inhibitors are novel anti-inflammatory drugs that have recently been show to document clinical efficacy in this disease, although their utility is hampered by class related side-effects of nausea, emesis and diarrhea. Whilst it is not yet clear whether such drugs will prevent emphysema, this is a distinct possibility provided experimental observations from preclinical studies translate to man. This review will discuss the current standing of PDE4 inhibitors like roflumilast as novel treatments for COPD and the potential for developing nonemetic anti-inflammatory drugs.
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PMID:PDE4 inhibitors as potential therapeutic agents in the treatment of COPD-focus on roflumilast. 1804 84

Nebulized solutions of long-acting bronchodilators provide an alternative to DPI and MDI delivery, particularly for COPD patients unable to use hand-held devices easily or correctly. The long-acting beta2-agonist, formoterol fumarate, is differentiated by its onset of significant bronchodilation within 5 min of administration. In a randomized, double-blind, double-dummy trial, COPD subjects (n=351, mean forced expiratory volume FEV1=1.3 L, 44% predicted) received nebulized formoterol fumarate (Perforomist inhalation solution; FFIS 20 microg) or DPI (Foradil Aerolizer; FA 12 microg), or placebo twice daily for 12 weeks. Efficacy was assessed with 12-h pulmonary function tests, and quality of life was assessed before and after treatment with the St. George's Respiratory Questionnaire (SGRQ). At the 12-week endpoint, FFIS significantly increased FEV1 AUC0-12h relative to placebo (p<0.0001). No evidence of tachyphylaxis was observed as indicated by maintained FEV1 AUC and reduced rescue albuterol use throughout treatment. FFIS also significantly increased peak FEV1, trough FEV1, and standardized FVC AUC0-12h compared with placebo. SGRQ assessment at Week 12 demonstrated significant and clinically meaningful improvements in total score (FFIS vs placebo, -4.9, p=0.0067), symptom, and impact scores. No significant differences in efficacy were observed between the two active treatments. Drug related AEs in the FFIS arm with a frequency > or = 1% and exceeding placebo were dry mouth, nausea, and insomnia. Nebulized FFIS provided significant improvement in respiratory status and quality of life in subjects with COPD relative to placebo and was well tolerated. The efficacy and safety profile of FFIS was comparable to FA DPI.
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PMID:Efficacy and safety of formoterol fumarate delivered by nebulization to COPD patients. 1836 1

A 69-year-old man (150 cm, 57 kg)who had been diagnosed as having COPD, was admitted to our hospital because of abdominal pain and drowsiness. He was diagnosed as CO2 narcosis and perforation of appendix. When he recovered from CO2 narcosis, he was scheduled for elective ilectomy. Because his pulmonary function was impaired, combined spinal and epidural anesthesia was selected. With the patient in the right lateral position, an epidural catheter was inserted at T12-L1 interspace, and spinal anesthesia was performed at L3-4 interspace with 0.5% isobaric bupivacaine 4 ml. When the patient was positioned laterally, SpO2 decreased from 82% to 77%. After completion of injection, the patient was returned to the supine position, and SpO2 immediately recovered. Spinal block level was not satisfactory, and fentanyl 0.1 mg and 2% mepivacaine 4 ml were administered through epidural catheter to achieve a T4 level of block. Because severe intraperitoneal inflammation was observed, ilectomy was changed to drainage of intra-abdominal abscess. The patient did not complain of dyspnea, pain, or nausea, intraoperatively. SpO2 was 85-93% with O2 inhalation at 1l x min(-1) during the operation. Post-operative course was uneventful. Although lateral position is popular in performing epidural and spinal anesthesia, sitting position could be suitable for this patient. Decrease in SpO2 may have occurred due to ventilation-perfusion mismatch. Since combined spinal and epidural anesthesia can preserve spontaneous respiration and it is possible to titrate anesthetic level, it would be preferable for abdominal surgery in patients with COPD.
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PMID:[Combined spinal-epidural anesthesia for abdominal surgery in a patient with chronic obstructive pulmonary disease]. 1986 Feb 42

The search for selective inhibitors of PDE4 as novel anti-inflammatory drugs has continued for more than 30 years. Although several compounds have demonstrated therapeutic effects in diseases such as asthma, COPD, atopic dermatitis and psoriasis, none have reached the market. A persistent challenge in the development of PDE4 inhibitors has been drug-induced gastrointestinal adverse effects, such as nausea. However, extensive clinical trials with well-tolerated doses of roflumilast (Daxas; Nycomed/Mitsubishi Tanabe Pharma Corp/Forest Laboratories Inc) in COPD, a disease that is generally unresponsive to existing therapies, have demonstrated significant therapeutic improvements. In addition, GlaxoSmithKline plc is developing 256066, an inhaled formulation of a PDE4 inhibitor that has demonstrated efficacy in trials in asthma, and apremilast from Celgene Corp has been reported to be effective for the treatment of psoriasis. Despite the challenges and complications that have been encountered during the development of PDE4 inhibitors, these drugs may provide a genuinely novel class of anti-inflammatory agents, and there are several compounds in development that could fulfill that promise.
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PMID:Is PDE4 too difficult a drug target? 2041 94

Roflumilast is a selective once daily, oral phosphodiesterase-4 inhibitor that has recently been registered in all European Union countries as novel targeted therapy for COPD, while FDA approval for the USA market is expected in 2011. In several phase III trials in patients with moderate to (very) severe COPD and in patients with symptoms of chronic bronchitis and recurrent exacerbations, roflumilast showed sustained clinical efficacy by improving lung function and by reducing exacerbation rates. These beneficial effects have also been demonstrated when added to long-acting bronchodilators (both LABA and LAMA), underscoring the anti-inflammatory activity of roflumilast in COPD. Pooled data analysis showed overall mild to moderate, mostly self-limiting adverse events, mainly consisting of nausea, diarrhea and weight loss. In this review we discuss the results of the 4 registration studies showing promising effects of roflumilast in COPD and provide an overview of the topics that still need to be addressed.
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PMID:PDE4-inhibitors: a novel, targeted therapy for obstructive airways disease. 2125 72

Roflumilast is a new anti-inflammatory drug for the treatment of COPD. Studies have reported modest, but significant increase of FEV1 with roflumilast, as well as decreased rate of exacerbations. Its use is limited by drug-related nausea and weight lost occurring in some patients. Currently it is only available in Germany. Indacaterol is a new beta-2-adrenergic bronchodilator that needs only one inhalation per day. Studies with indacaterol report a good therapeutic window and the preparation is available in Switzerland. There is no reason that prevents prescription of indacaterol together with tiotropium, a once-a-day anti-cholinergic bronchodilator. However, no studies have specifically evaluated the combination of indacaterol and tiotropium in COPD.
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PMID:[Pulmonary medicine. Two new drugs for the treatment of COPD]. 2140 Sep 48


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