Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011168 (dysphagia)
 15,644 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Risedronate sodium is an orally active antiresorptive agent and a member of the pyridinyl class of bisphosphonates. It has been approved for the treatment of Paget's disease of the bone and is under development as a chronic therapy for the treatment and prevention of osteoporosis. A novel cellulose film-coated tablet formulation was developed to optimize esophageal transit of this bisphosphonate. The aim of the present study was to compare the esophageal transit of the film-coated tablet formulation of risedronate with its original gelatin capsule dose form. A total of 25 elderly, healthy volunteers (mean 66 years), who were dysphagia-free, participated in this randomized cross-over study. On separate occasions, volunteers swallowed radiolabeled placebo formulations with 50 ml water. Dynamic images with participants in a sitting position were recorded for 10 min using a gamma camera. Scintigraphic imaging showed a delay in esophageal transit (greater than 15 s) in 28% of patients in the capsule group but in none of the tablet group (P<0.05). The mean transit times of the capsules and tablets were 23.8 and 3.3 s, respectively. Esophageal transit of film-coated tablets was faster than gelatin capsules, suggesting that film-coated tablets would be the appropriate formulation for all pivotal trials with risedronate and for subsequent commercialization.
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PMID:Esophageal transit of risedronate cellulose-coated tablet and gelatin capsule formulations. 1048 35

The bisphosphonate, alendronate sodium (e.g. Fosamax) is a bone resorption inhibitor used to treat postmenopausal osteoporotic women and osseous Paget's disease. Esophagitis is one of the adverse effects (AE) associated to its use. Five (5) patients with alendronate-associated esophagitis assisted in the Gastroenterologic Center, Rosario, Argentina, between October 1996 and December 1999 are described. The aim is to correlate the clinical, endoscopic and histopathological findings in 5 women (ages 57-71) complaining for upper digestive symptoms (dysphagia, epigastralgia, retrosternal pain.). All had osteoporosis treated with alendronate 10 mg/day and received detailed instructions about how to take the medication. The time from the beginning of alendronate intake and the appearance of the symptoms was elapsed 30, 35, 67, 85 and 90 days. The esophagitis was graded according to the Savary-Miller Classification. The videoscopy disclosed esophagitis of III and IV grades. Three patients had also antral and antroduodenal lesions, one of them associated to Helicobacter Pylori. Anatomopathologic findings confirm esophagitis and esophagic ulceration. Some authors claim that bisphosphonates as a new class of gastrotoxic drugs with AE similar to aspirin. Even when it is administrated according to the instructions of the manufacturers it should be used with caution. Our contribution emphasize the importance of this AE and suggest measures to diminish or suppress them, and take into consideration those patients who are taking aspirin. With alendronate, as well as with other potentially corrosive agents, is very important to take in mind the measures to prevent AE.
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PMID:[Esophagitis associated with use of alendronate in 5 postmenopausic patients]. 1147 18

Alendronate is a potent bisphosphonate that is effective in preventing osteoporotic fractures. Clinical trial data involving over 17,000 women provide a large, placebo-controlled experience from which alendronate has been demonstrated to be safe and well tolerated. We review the safety profile of alendronate in the context of its pharmacology, preclinical information and published literature on bisphosphonates. The clinical data include information from 1) the two primary Phase III osteoporosis treatment studies involving 994 women with postmenopausal osteoporosis treated with alendronate for up to 3 years; 2) upper gastrointestinal (GI) tolerability data (including special subgroup analyses) from the Fracture Intervention Trial (FIT), involving 2027 women with prior vertebral fractures; 3) an endoscopy study, and 4) postmarketing experience. Because all bisphosphonates have the potential to irritate the upper GI mucosa, we specifically investigated the safety and tolerability profile with respect to the upper GI tract. In the Phase III trials, alendronate 5 or 10 mg/day was well tolerated, with no increase relative to placebo in the incidence of overall adverse experiences (ie, inclusive of all events, not just those related to the GI tract). In the Phase III trials, alendronate 5 mg/day or 10 mg/day was well tolerated, with no increase relative to placebo in the incidence of overall adverse experiences. The incidence of upper gastrointestinal adverse experiences, overall, was similar among alendronate 5 mg or 10 mg and placebo, with abdominal pain and dysphagia being the only individual adverse experiences that were significantly increased (with alendronate 10 mg). Esophageal adverse experiences were uncommon, being reported in 8 (2.0%) patients receiving placebo and 9 (4.6%) patients taking alendronate 10 mg. None of the events occuring on alendronate therapy were serious or resulted in discontinuation. Tolerability was not affected by a wide range of concomitant medications including nonsteroidal anti-inflammatory drugs. Additional analyses of the 2027 postmenopausal women with vertebral fractures enrolled in FIT demonstrated that alendronate use was not associated with a significant increase in upper GI events, esophageal events, or gastroduodenal adverse events, even among women at high risk for upper GI complications (those older than 75 yr, those with previous upper GI disease, or those using NSAIDs). Esophageal adverse experiences (including esophagitis and esophageal ulcers) have been reported with alendronate in postmarketed use. A high proportion of these reports involved patients who did not follow the dosing instructions and probably relate to the irritant potential of refluxed gastric acid containing alendronate. Consistent with the antiresorptive mechanism of action of alendronate, asymptomatic decreases in serum calcium and phosphate were observed with alendronate treatment in the clinical trials. There were no other laboratory changes noted with alendronate. Now marketed in 78 countries and used by over 3 million women, the safety profile of alendronate, when dosed appropriately, has been consistent with that of the clinical trial experience. In view of the increased morbidity and mortality associated with fractures, and the proven efficacy of alendronate to reduce fracture risk, the benefit/risk ratio of alendronate remains highly favourable.
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PMID:The clinical tolerability profile of alendronate. 1266 41

Two patients affected by esophagitis arised during therapy with alendronate, an aminobiphosphonate often used today in the treatment of the postmenopausal osteoporosis are presented. Two osteoporotic women, without gastroenterological past history, developed dysphagia, odynophagia and retrosternal pain shortly after starting therapy. Endoscopy demonstrated ulcerative esophagitis affecting circumferentially the distal portion of the esophagus. Biopsies showed aspecific inflammatory changes and no sign of fungi or viral inclusions. The discontinuation of alendronate, with additional use of a protonic pump inhibitor and sucralfate, led to complete recovery and normalization of endoscopic findings. In both patients esophagitis was associated with incorrect intake of alendronate, resulting in prolonged mucosal exposure to the noxious effect of the drug. In order to prevent it the necessity is stressed to inform adequately patients on how to take the drug correctly and to select carefully the cases to treat, excluding those having reflux symptoms or other esophageal disorders that would facilitate the drug induced damage.
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PMID:[Esophagitis due to alendronate. Report of two cases]. 1649 98

The relationship between osteoporosis and magnesium (Mg) deficiency is still controversial. Here we report a case of an 82-year-old woman with a giant adenomatous goiter and severe osteoporosis with multiple vertebral fractures, whose clinical course indicated that her osteoporosis was probably due to Mg deficiency. She visited our hospital for treatments of tetany. Laboratory data showed the existence of hypomagnesemia, hypocalcemia, hypokalemia, vitamin D deficiency, and slightly elevated intact PTH. Intravenous administration of Mg not only improved these electrolyte abnormalities but also increased serum levels of intact PTH, bone formation markers, 1,25-dihydroxyvitamin D, as well as bone resorption markers in the urine, and lowered urinary phosphate reabsorption. Hypomagnesemia on admission seemed to arise from long-lasting poor food intake and malnutrition, because it improved after the disappearance of dysphagia with a goiter resection. After the operation, BMD values at the lumbar spine and femoral neck obviously increased during 6 months of Mg supplementation without any specific therapies for osteoporosis. Mg deficiency in this case seemed to cause impaired secretion of PTH from the parathyroid and the refractoriness of bone and kidney to the hormone, which led to the suppression of both bone remodeling and renal vitamin D production. These processes were probably linked to her severe osteoporosis, which was reversed by Mg supplementation.
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PMID:A case of magnesium deficiency associated with insufficient parathyroid hormone action and severe osteoporosis. 1804 93

We report a 94-year-old woman, who underwent percutaneous endoscopic Jejunostomy (PEJ) tube feeding for enteral nutrition, developed the intussusception of the small intestine. She suffered from nontuberculous mycobacterium (NTM), and her lung inflammation deteriorated due to aspiration pneumonia and malnutrition. Because of old age, dysphagia, esophageal hiatus hernia, gastro-esophageal reflux and her bedridden condition due to severe osteoporosis, oral nutritional supplementation is nearly impossible. To reduce the aspiration risk, we chose PEJ instead of percutaneous endoscopic gastrostomy (PEG) as the route of tube feeding. Six months after the placement of a PEJ tube, aspiration pneumonia was diagnosed and she was readmitted to our hospital. During hospitalization, she had sudden diarrhea, vomiting, and lower abdominal pain. Abdominal CT scan and radiographs using contrast medium showed small intestinal intussusception related to the PEJ tube. We observed the clinical course without performing surgery, pulling it back towards the stomach and placing an ileus tube, because the small intestine was not completely obstructed. Two months later, although she suffered from aspiration pneumonia once more, she remained in a stable condition without further intervention so that she could move to aother hospital. Recently PEJ has been expected to prevent aspiration pneumonia, but we believe that it can be a risk factor for intussusception. Although the PEJ can be a good parenteral nutrition route for frail elderly with dysphagia, we need to consider possible complications including intussusception.
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PMID:[A 94-year-old woman with nontuberculous mycobacterium who developed small intestinal intussusception associated with a percutaneous endoscopic jejunostomy tube]. 1804 13

Myasthenia gravis is often difficult to diagnose and treat in older subjects due to complications, previous history and reciprocal interaction with drugs used to treat complications. An 84-year-old woman with slowly progressive 2-year dysphagia and dysarthria had reached critical condition with aspiration pneumonia. She was diagnosed with thymoma-free myasthenia gravis and her respirator removed after being administrated an anticholinesterase drug. Her dysphagia and dysarthria did not improve. Because of severe osteoporosis with two previous lumbar compression fractures and excessive thinness, she could not be given prednisolone or immunosuppressive drugs. Following cricopharyngeal myotomy and bilateral lateral palatopharyngeal wall narrowing, she could eat without misdeglutition and speak clearly.
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PMID:[Dysphagia and dysarthria surgery for advanced-age myasthenia gravis]. 2106 68

Human size and shape vary widely. Relative obesity or apparent under nutrition may not limit survival into old age. Normal body appearance can mask gross malnutrition, particularly mineral and vitamin deficiency, problems of measurement in the elderly. Obesity is associated with joint degeneration and systemic disease but with reduced incidence of fractures. Undenutrition is associated with skin breakdown, poor wound healing and fractures. Body composition changes due to disease include dysphagia, myxoedema, anaemia, chronic cardiac and renal disease. Skeletal changes include osteoporosis and Paget's disease. Body composition can change due to treatment, control of dietary energy intake and tube-feeding.
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PMID:Body composition and aging: a practising clinician's point of view. 2439 52

Osteoporosis is a growing public health problem and several drugs have been developed in the past two decades to offer pharmacological solutions both in prevention and in therapy. Alendronate was the first compound registered as an anti-fracture agent and also the most prescribed drug worldwide for osteoporosis. Patient compliance is a major problem with alendronate, with studies demonstrating that 50-60% of patients discontinue treatment within one year. Dysphagia and swallowing difficulties are common especially among elderly people and the perceived potential for upper GI problems is a barrier to good long-term adherence. As non-persistence and non-compliance are linked to increased risk of fractures, efforts have been made to develop forms of alendronate which are more acceptable to patients. Among these, the drinkable formulations have the potential great convenience, simplicity of administration and reduction in gastro-intestinal side effects. In addition these novel soluble products are equivalent in cost to generic alendronate tablets. The approaches to improve adherence to an old and effective medication for osteoporotic patients will be reviewed in this report, with a special focus on the recently marketed product Bonasol 70 mg oral solution.
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PMID:A drinkable formulation of alendronate: potential to increase compliance and decrease upper GI irritation. 2455 29

Osteoporotic fractures are a public health problem and their incidence and subsequent economic and social costs are expected to rise in the next future. Different drugs have been developed to reduce osteoporosis and the risk of osteoporotic fractures, and among them, antiresorptive agents, and in particular oral alendronate, are the most widely utilized. However, one of the most common problems with antiresorptive drugs is poor adherence to treatment, which is associated with a high fracture incidence and with an increase in hospitalization costs. One of the main reasons of poor adherence to these treatments is the occurrence of adverse events, mainly at gastrointestinal (GI) level, including dyspepsia, dysphagia, and esophageal ulcers. In light of these considerations the aim of this paper is to perform a literature review to show the pathophysiologic bases of GI alendronate-induced adverse events and how new bisphosphonate formulations like effervescent alendronate can improve compliance and persistence to treatment and decrease the fracture rate incidence in osteoporotic patients.
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PMID:The potential impact of new effervescent alendronate formulation on compliance and persistence in osteoporosis treatment. 2499 88


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