Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0014848 (achalasia)
 2,804 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Early studies confirmed the beneficial effects of calcium channel blockers on the normal oesophagus, which included a decrease in lower oesophageal sphincter tone in achalasia and a decrease in oesophageal contractions and amplitude in diffuse oesophageal spasm. This resulted in the enthusiastic use of the drugs in both disorders. With further experience, and with increased recognition of side effects, the role of these drugs in the 2 disorders has been better clarified. Clinical trials in general have not reflected the improvement observed in the manometric parameters. Only a minority of patients appear to derive sustained symptomatic benefit. Calcium channel blockers may be the initial choice for high or moderate risk patients with achalasia prior to proceeding with pneumatic dilatation or surgical myotomy. In diffuse oesophageal spasm, they are a reasonable first choice for all risk categories.
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PMID:An overview of the role of calcium antagonists in the treatment of achalasia and diffuse oesophageal spasm. 137 16

Pneumatic dilatation of the cardia is an effective procedure to treat patients suffering from achalasia. Eighty percent of these patients can be expected to have excellent or good results for 6 years after the first dilatation. A repeat dilatation should be performed as soon as the patient has recurrent symptoms, usually every 2 years. Calcium channel blockers (nifedipine and verapamil) or nitrates (isosorbide dinitrate) decrease LES pressure but do little to the clinical symptomatology of patients with achalasia; however such drug therapy may be tried as an adjunct in patients who remain symptomatic after pneumatic dilatations or myotomy. Pneumatic dilatation and surgical myotomy both reduce LES pressure; with pneumatic dilatation, enough residual LES pressure is retained to prevent gastroesophageal reflux. Indeed, reflux esophagitis seems to occur more often after surgery than after forceful dilatations. We think that pneumatic dilatation should be performed as the primary therapy and surgery reserved for the failures of this procedure.
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PMID:Non-surgical management of achalasia. 163 43

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.
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PMID:Clinical efficacy of nifedipine and other calcium antagonists in patients with primary esophageal motor dysfunctions. 193 Mar 46

Calcium channel blockers have been previously shown to decrease lower esophageal sphincter (LES) pressure and improve symptoms in achalasia. We performed a placebo-controlled, double-blind, crossover study to assess the effects of oral nifedipine and verapamil on LES pressure, amplitude of esophageal body contraction, and clinical symptomatology in eight patients with symptomatic achalasia diagnosed by endoscopy, barium swallow, and manometry. Patients were randomized to receive up to 20 mg nifedipine, 160 mg verapamil, or placebo and underwent esophageal manometry before (baseline) and after four weeks on each drug. Diary cards were kept to record and grade symptoms and drug plasma level determinations were correlated with manometric and clinical findings. Both nifedipine and verapamil caused a statistically significant decrease in mean LES pressure, but only nifedipine caused a significant decrease in the amplitude of contractions of the smooth muscle portion of the esophagus. No statistically significant differences in the overall clinical symptomatology were noted with any of the drugs, although some individual improvements in dysphagia and chest pain were noted. We conclude that, despite the reduction in LES pressure and contraction amplitude of the distal esophageal body, oral nifedipine and verapamil do not significantly alter the clinical symptomatology of patients with achalasia.
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PMID:Medical treatment of esophageal achalasia. Double-blind crossover study with oral nifedipine, verapamil, and placebo. 199 57

Nervous control of gastrointestinal motility is extremely complex, is regulated by the enteric system, the "brain of the gut", and modulated by extrinsic nerves. This system with its multiplicity of transmitters and receptors does not always allow a clear interpretation of experimental data, especially with compounds lacking specificity. In this review the complex situation is described particularly in relation to receptor populations (cholinergic, adrenergic, dopamine, histamine, 5-hydroxytryptamine, opioid, gamma-aminobutyric acid (GABA), prostanoid and dihydropyridine receptors), therapeutic aspects of drugs and their usefulness in children. Newer principles with known drugs and promising new compounds with a more appropriate kinetic or fewer side-effects, deriving from distinct pharmacological groups, as candidates for the treatment of gastrointestinal disorders are considered e.g. anticholinergics (prifinium or actilonium bromide), adrenergic alpha 2-agonists (clonidine, lidamidine) for diarrhoea in diabetic neuropathy, adrenergic beta-blockers for shortening postoperative ileus (propranolol), dopamine receptor antagonists (metoclopramide, domperidone, alizapride) and another prokinetic substance (cisapride) which may be useful for a number of applications as gastro-oesophageal reflux, gastro-paresis, intestinal pseudo-obstruction, cystic fibrosis and constipation, morphine derivatives (e.g. loperamide) for intractable diarrhoea and calcium antagonists (e.g. nifedipine) for achalasia. Increasing experience in digestive tract pharmacology and reliable clinical studies will furthermore be the basis for a more specific and better tolerated therapy of gastrointestinal motility disorders in adults and children.
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PMID:Rational pharmacotherapy of gastrointestinal motility disorders. 266 4

Clinical uses of calcium channel blockers are expanding. In addition to the established uses in patients with arrhythmias, angina pectoris or hypertension, newer and to some extent investigational uses indicate widespread application. For instance, their use has been reported in hypertrophic cardiomyopathy and cold cardioplegia, as well as in pulmonary hypertension, antiplatelet therapy, asthma, achalasia and oesophageal spasm, increased intraocular pressure and in cerebral vasospasm. Their use in obstetrical practice has been proposed. Thus, the presentation of a patient who is treated with calcium channel blockers and who requires anaesthesia will become more common. Calcium channel blockers may, under certain circumstances, potentiate haemodynamic and MAC depressive effects of inhalation agents. There is also evidence that the effects of neuromuscular blocking agents may be potentiated. The anaesthetist should be aware that the potential for interactions exists with digoxin, propranolol, quinidine, theophylline or dantrolene. Of interest and some significance are the anaesthetic implications of pathophysiological alterations that can be induced by calcium channel blockers, by affecting lower oesophageal tone, intracranial hypertension, bronchomotor tone (asthma), muscular dystrophy, neuromuscular function, hypoxic pulmonary vasoconstriction, malignant hyperthermia, inhibition of platelet aggregation and hyperkalemia. Despite these significant potential anaesthetic implications and because, at this time, in some instances withdrawal has clearly demonstrated increase in the signs of myocardial ischaemia, it would not seem necessary to recommend preoperative discontinuation of calcium channel blocker medication in patients presenting for anaesthesia. It is, however, appropriate that there is a high index of awareness of potential problems, unless there is some modification in inhalation anaesthetic concentrations and neuromuscular blocker dosage. Monitoring of cardiovascular and neuromuscular functions is essential. Calcium channel blockers would appear to be currently the drugs of choice for angina pectoris, arrhythmias or hypertension in patients with associated chronic obstructive pulmonary disease.
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PMID:Anaesthetic implications of calcium channel blockers. 286 80

Various oesophageal manometric disorders have been associated with chest pain or dysphagia. The classic motility disorders are achalasia and diffuse oesophageal spasm. In achalasia, a disorder of aperistalsis in the oesophageal body and incomplete relaxation of the lower oesophageal sphincter, either surgical myotomy or pneumatic dilatation is an effective approach, although some investigators have suggested a role for pharmacological therapy. For the treatment of diffuse oesophageal spasm, a disorder of non-peristaltic motor activity in the oesophagus, various pharmacological approaches with nitrates, anticholinergics, and calcium antagonists have been used. In the presence of associated lower oesophageal sphincter dysfunction, bouginage or pneumatic dilatation may be indicated. Long oesophagomyotomy should be considered for those patients who fail to respond to these measures. Recent manometric techniques have led to the identification of patients with chest pain or dysphagia who have abnormalities of increased contractile amplitude ('nutcracker' oesophagus) or duration. An association with gastro-oesophageal reflux or with psychiatric disturbance has been suggested. Treatment directed towards these factors is indicated and may be supplemented by pharmacological intervention, e.g. by calcium antagonists or anticholinergics.
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PMID:Primary oesophageal motility disorders. Current therapeutic concepts. 286 26

Esophageal motility disorders consist of a complex array of disturbances in normal esophageal function associated with dysphagia, gastroesophageal reflux, and noncardiac chest pain. A thorough knowledge of normal esophageal anatomy and physiology is important to a full understanding of these motility derangements. Through a complicated interaction of neuromuscular and hormonal influences, the voluntary act of swallowing transforms into an automated sequence of peristaltic waves propelling food and liquids into the stomach in concert with coordinated relaxation of the sphincters. Anatomic and physiologic barriers exist within the esophagus protecting against gastroesophageal reflux and aspiration. With improvements in diagnostic tools such as barium contrast radiography, scintigraphy, pH measurements, and esophageal manometrics with provocative testing, motility disorders have become better defined and understood. Primary motility disorders consist of achalasia, diffuse esophageal spasm (DES), "nutcracker esophagus," hypertensive lower esophageal sphincter, and nonspecific esophageal motility dysfunction (NEMD). A host of secondary and miscellaneous motility disorders also affect the esophagus, including scleroderma and other connective tissue diseases, diabetes mellitus, Chagas' disease, chronic idiopathic intestinal pseudo-obstruction, and neuromuscular disorders of striated muscle. Gastroesophageal reflux disease (GERD) may also be promoted by associated motility disturbances. Treatment modalities include surgical myotomy; dilatation; and pharmacologic manipulations, including use of nitrates, calcium-channel blockers, H2-blockers, and psychotropic drugs where appropriate.
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PMID:Esophageal motility disorders. 329 77

Familial glucocorticoid deficiency is a rare multisystem disorder characterized by glucocorticoid deficiency with normal mineralocorticoid activity, achalasia of the cardia, and alacrima. Familial hypophosphatemic rickets is characterized by selective renal phosphate wasting with subsequent hypophosphatemia and an inappropriately low 1,25-dihydroxyvitamin D concentration for the degree of hypophosphatemia. A 6-year-old girl with both disorders is described. A biochemical relationship between familial glucocorticoid deficiency and familial hypophosphatemic rickets could not be defined; the influence of cortisol on her serum calcium level, phosphorus level, and rickets, as well as the natural history of these two entities, is described.
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PMID:Familial glucocorticoid deficiency in a girl with familial hypophosphatemic rickets. 339 83

In animal experiments, esophageal smooth muscle, including the lower esophageal sphincter (LES) has been shown to be dependent on extracellular calcium both for tone and agonist induced contractions. Calcium channel blockers (CCB) suppress contractile activity, and block both resting and stimulated calcium influx. In normal man as well as in patients with hypercontractility disorders of the esophagus, such as achalasia and diffuse esophageal spasm, CCBs have been shown to reduce LES pressure and esophageal contractions, and also to cause symptomatic improvement. Controlled clinical trials on their effectiveness are lacking, but the therapeutic principle seems promising.
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PMID:Calcium channel blockers and motility disorders of the esophagus. 371 28


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