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

Nifedipine has been proven to be effective and safe in the treatment of primary oesophageal motility disorders which can cause angina-like chest pain and/or dysphagia. The effects of the calcium channel blockers nifedipine, nitrendipine, nimodipine and nisoldipine on oesophageal smooth muscle function in healthy male volunteers were studied by oesophageal manometry using the rapid pull-through-technique, in two randomized, double-blind crossover studies. Lower oesophageal sphincter pressure, oesophageal contraction amplitude and duration after a wet swallow (measured 5 cm and 10 cm above the lower oesophageal sphincter) were determined 30 min before and at 10 minute intervals up to 90 min after the administration of nimodipine and up to 120 min after nifedipine, nitrendipine and nisoldipine. The plasma drug concentration was measured at baseline (-15 min) and in parallel with the manometric measurements. Compared to placebo, lower oesophageal sphincter pressure was significantly decreased by 24% by nifedipine and 17% by nimodipine, whereas the effects of nitrendipine (decrease of 15%) and nisoldipine (9%) were not significant. Nifedipine significantly decreased by 17% the oral contraction amplitude compared to placebo and nimodipine by 11%. The duration of the contraction amplitudes was not altered. The decrease in sphincter pressure was correlated with the corresponding plasma drug levels of nifedipine r = 0.92, nitrendipine r = 0.80 and nisoldipine r = 0.79. Nimodipine showed no such correlation.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Effect of the calcium antagonists nifedipine, nitrendipine, nimodipine and nisoldipine on oesophageal motility in man. 180 45

In this paper the pharmacodynamic effects of calcium channel blockers (verapamil, nifedipine, diltiazem, fendiline, nitrendipine, nimodipine, and nisoldipine) on esophageal motility in man and their clinical effects in patients with various forms of primary esophageal motility disorders are critically analysed and summarized. The evaluation of efficacy and safety is mainly focused on nifedipine (Bay a 1040, Adalat; CAS 21829-25-4), since it has been best documented clinical pharmacologically and therapeutically in this field. Nifedipine and--with varying potency--the other calcium antagonists reduce effectively the increased lower esophageal sphincter pressure (LESP) and abnormally high and prolonged peristaltic and nonperistaltic contractions in the esophageal body in patients with achalasia, diffuse esophageal spasm (DES), and other disorders which may cause angina-like chest pain and/or dysphagia. Pharmacodynamic effects on esophageal motility are closely correlated with the plasma concentration of nifedipine in healthy volunteers and in patients. However, a final judgement on the therapeutic value of these compounds in esophageal motor abnormalities cannot be given due to conflicting results from clinical studies with fairly small numbers of patients and varying study designs. Among the different calcium antagonists investigated nifedipine represents the best investigated and the most suitable compound for the treatment of primary hypertensive esophageal motor disorders.
 ...
PMID:Clinical efficacy of nifedipine and other calcium antagonists in patients with primary esophageal motor dysfunctions. 193 Mar 46

Utilizing the rationale that the calcium channel blocker nifedipine decreases lower esophageal sphincter pressure, we performed a double-blind, placebo-controlled, crossover trial of sublingual nifedipine in achalasia, a disorder whose treatment depends on reduction in lower esophageal sphincter pressure. Ten patients participated in this trial, completed diaries, underwent manometric determinations of lower esophageal sphincter pressure, and had testing of esophageal emptying rates by a solid-meal radionuclide method. Nifedipine, titrated to a dose of 10-30 mg before meals, was well tolerated. Compared with placebo, nifedipine significantly reduced the frequency of dysphagia, but some symptoms of dysphagia, regurgitation, or nocturnal cough were still present most days. Nifedipine significantly reduced lower esophageal sphincter pressure by 28%, a value approximately one-half that achieved by successful pneumatic dilatation or myotomy. Esophageal emptying rates, as determined by the radionuclide method, were unchanged by nifedipine. We concluded that 1) nifedipine reduces symptoms of achalasia, but substantial symptoms do remain during such therapy; 2) the suboptimal effect results from the limited, although statistically significant, effect of nifedipine on reduction of lower esophageal sphincter pressure; and 3) although we believe that nifedipine may be recommended as treatment for achalasia in the subset of patients whose overall medical condition places them at high risk for forceful dilatation or surgery, it cannot be recommended as a standard alternative to these other modalities.
 ...
PMID:The role of nifedipine therapy in achalasia: results of a randomized, double-blind, placebo-controlled study. 267 48

Achalasia is a primary esophageal motor disorder characterized by lack of esophageal peristalsis and poor lower esophageal sphincter (LES) relaxation. Clinically, achalasia manifests as progressive dysphagia to solids and liquids and mild weight loss. Predisposition to esophageal cancer is not prevalent, but certain tumors may mimic achalasia. The diagnosis of achalasia is relatively easy to make with a good history, radiography, and esophageal motility testing. The esophagogram reveals a typical bird-beak narrowing of the esophagogastric junction and esophageal dilation, the degree of which depends on the stage of the disease. Esophageal manometry reveals poor LES relaxation, aperistalsis, and often elevated intraesophageal pressure. Endoscopic examination is important to rule out malignancy as the cause of achalasia. The traditional treatment of achalasia is forceful dilation of the LES. Bougienage may be helpful in some cases. Pharmacological agents, such as nitroglycerin and calcium channel blockers, provide some relief by decreasing LES pressure. However, they are not a viable, long-term choice. Surgical myotomy offers slightly better results than pneumatic dilation, but it is accompanied by some increased gastroesophageal reflux. Laparoscopic and thoroscopic myotomy are in their infancy, and, if successful, they will make surgical treatment much more attractive. Intrasphincteric botulinum toxin injection is the newest form of therapy. Its safety and ease of administration are very encouraging, but long-term results are not available.
 ...
PMID:Achalasia. 877 90

Achalasia is an esophageal motility disorder characterized by increased lower esophageal sphincter pressure and absence of peristalsis in the lower esophagus. Patients typically present with complaints of progressive difficulty swallowing over a period of several years. Diagnosis is confirmed by esophageal manometry. Complications of achalasia include esophagitis, aspiration and possibly an increased risk of esophageal carcinoma. Medical treatment options include pneumatic dilatation, esophageal bougienage, nitrates, calcium channel blockers and botulinum toxin injections. The primary method of surgical treatment is the Heller myotomy, in which longitudinal incisions are made in the muscle fibers of the lower esophageal sphincter to reduce sphincter pressure. Frequently, a fundoplication is performed in addition to the myotomy to decrease the likelihood of development of gastroesophageal reflux. In recent years, the Heller myotomy has been performed both thoracoscopically and laparoscopically. An additional development has been the placement of an endoscope in the esophagus to provide transillumination during surgery; intraoperative endoscopy allows improved assessment of the depth of myotomy incisions and reduces the risk of esophageal perforation. The case report below describes a 64-year-old-man with achalasia who presented with persistent dysphagia despite multiple attempts at medical treatment. A laparoscopic Heller myotomy with Toupet fundoplication was performed with subsequent eradication of symptoms. A discussion of the epidemiology, etiology, clinical presentation, diagnosis and treatment of achalasia follows the case report.
 ...
PMID:Achalasia in a sixty-four-year-old man. 971 52

Swallowing is a complex mechanism based on the coordinated collaboration of tongue, pharynx and esophagus. Disturbances of this interplay or disorders of one or several of these components lead to dysphagia, non-cardiac chest pain or regurgitation. The major primary esophageal motility disorders--achalasia, diffuse esophageal spasm, hypercontractile esophagus ('nutcracker esophagus') and non-specific motility disorder--are of unknown etiology. Other esophageal diseases, such as cervical diverticula or gastroesophageal reflux disease, might also be caused by a primary esophageal motility disorder. Medical treatment of esophageal disorders with esophageal hyper- or dysmotility requires agents that reduce esophageal contractile force (anticholinergic agents, nitrates, calcium antagonists). Despite the beneficial effect of the various drugs on esophageal motility parameters, the clinical benefit of medical treatment of esophageal motility disorders is rather disappointing. Calcium channel antagonist, alone or in combination with anticholinergics or nitrates, can be used as a medical trial, especially in mild achalasia. However, medical therapy is clearly inferior to pneumatic balloon dilation therapy. Recently, botulinum toxin injection was suggested as a therapeutic option in achalasia patients with good results on lower esophageal sphincter pressure (LESP) and symptom scores that were similar to the results achieved by pneumatic balloon dilation. Hypercontractile esophagus shows a good manometric response to calcium channel antagonists, but only little clinical effect in terms of improvement of symptoms. Diffuse esophageal spasm is a relatively rare disease and few clinical studies are available. The use of calcium channel antagonists can be beneficial, at least in some patients with diffuse esophageal spasm. From clinical and epidemiological studies, there is some evidence of a 'psychological' component in the pathogenesis or perception of esophageal symptoms. There is some clinical benefit from centrally acting drugs such as benzodiazepines or antidepressants. With the exception of botulinum toxin for achalasia, medical therapy of primary esophageal motility disorders is rather limited and the clinical results are poor. Further understanding of esophageal pathophysiology as well as development of new receptor-selective drugs might increase our chances of a successful treatment of primary esophageal motility disorders.
 ...
PMID:Esophageal pharmacology and treatment of primary motility disorders. 1077 Mar 58

Achalasia is a primary motility disorder of the esophagus that causes dysphagia. Normal esophageal motility and lower esophageal sphincter (LES) function can not be restored; thus treatment is directed at decreasing the pressure or disrupting the muscle fibers of the LES to allow passage of ingested material. Effective therapy for achalasia can be broadly characterized as surgery based or endoscopy based. Medications (calcium channel blockers and nitrate derivatives) do not provide adequate relief of dysphagia and have substantial side effects, and thus are rarely used as long-term therapy. Botulinum toxin injection, a recently introduced endoscopic therapy, enjoyed much enthusiasm initially but was shown to have only transient effect and is now recommended only for poor operative candidates. The mainstay of therapy remains endoscopic dilation or laparoscopic esophagomyotomy (LEM) combined with an antireflux procedure. We have found that patients who can tolerate a laparoscopic abdominal surgery are best served with an LEM and Toupet (270 degrees ) posterior fundoplication. This provides good or excellent relief of dysphagia in 90% to 95% of patients with very little morbidity.
 ...
PMID:Treatment of Achalasia. 1562 35

The goals in the treatment of achalasia are threefold: 1) relieving the symptoms, particularly dysphagia and bland regurgitation; 2) improving esophageal emptying by disrupting the poorly relaxing lower esophageal sphincter (LES); and 3) preventing the development of megaesophagus. Although achalasia cannot be permanently cured, excellent palliation is available in over 90% of patients, especially those with pneumatic dilation and laparoscopic Heller myotomy. The efficacy for short- and long-term therapy seems to be similar when performed by experts. Pneumatic dilation done as an outpatient surgery disrupts the LES muscle from within by using balloons of progressively larger diameter (3.0, 3.5, and 4.0 cm). Repeat dilations may be required; secondary severe gastroesophageal reflux disease (GERD) is rare, but approximately 2% of patients will have an esophageal perforation. A surgical Heller myotomy is now being done laparoscopically through the abdomen that cuts the LES and extends the myotomy 2 to 3 cm onto the stomach. Usually 2 days of hospitalization is required, and patients can normally return to work in 1 to 2 weeks. Severe GERD with esophagitis and peptic stricture is a common complication; therefore, most surgeons combine the myotomy with an incomplete fundoplication. Medical therapy is much less effective than these invasive procedures. Smooth muscle relaxants (nitrates and calcium channel blockers) taken immediately before meals improve dysphagia, but side effects and drug tolerance are common. The injection of botulinum toxin (100 to 200 units) endoscopically into the LES gives short-term relief of symptoms and improves esophageal emptying. This treatment is most effective in the elderly, as symptom relief can last up to 1 to 2 years with a single injection. Several studies suggest the most cost-effective management of achalasia is initial treatment with pneumatic dilation.
 ...
PMID:Modern management of achalasia. 1600 28

Achalasia is a motor disorder of the esophageal smooth muscle in which the lower esophageal sphincter does not relax normally with swallowing, and the esophageal body undergoes nonperistaltic contractions. The underlying abnormality is the loss of intramural neurons. Achalasia affects men and women of all ages. Dysphagia, chest pain, and regurgitation are the main symptoms. Information on the effects of achalasia on pregnancy outcome and the effects of pregnancy on the natural course of achalasia is limited. Two studies, including 30 patients altogether, and several case reports have been published. Treatment options include nitrates, calcium channel antagonists, botulinum toxin injection, pneumatic dilation, and esophagomyotomy.
 ...
PMID:Achalasia in pregnancy. 1649 Jan 20

Esophageal hypomotility (EH) is characterized by abnormal esophageal peristalsis, either from a reduction or absence of contractions, whereas spastic motor disorders (SMD) are characterized by an increase in the vigor and/or propagation velocity of esophageal body contractions. Their pathophysiology is not clearly known. The reduced excitation of the smooth muscle contraction mediated by cholinergic neurons and the impairment of inhibitory ganglion neuronal function mediated by nitric oxide are likely mechanisms of the peristaltic abnormalities seen in EH and SMD, respectively. Dysphagia and chest pain are the most frequent clinical manifestations for both of these dysfunctions, and gastroesophageal reflux disease (GERD) is commonly associated with these motor disorders. The introduction of high-resolution manometry (HRM) and esophageal pressure topography (EPT) has significantly enhanced the ability to diagnose EH and SMD. Novel EPT metrics in particular the development of the Chicago Classification of esophageal motor disorders has enabled improved characterization of these abnormalities. The first step in the management of EH and SMD is to treat GERD, especially when esophageal testing shows pathologic reflux. Smooth muscle relaxants (nitrates, calcium channel blockers, 5-phosphodiesterase inhibitors) and pain modulators may be useful in the management of dysphagia or pain in SMD. Endoscopic Botox injection and pneumatic dilation are the second-line therapies. Extended myotomy of the esophageal body or peroral endoscopic myotomy (POEM) may be considered in highly selected cases but lack evidence.
...
PMID:Esophageal hypomotility and spastic motor disorders: current diagnosis and treatment. 2537 46


1 2 Next >>