Isosorbide dinitrate and nifedipine treatment of achalasia: a clinical, manometric and radionuclide evaluation. The effect of terbutaline sulfate, nitroglycerin, and aminophylline on lower esophageal sphincter pressure and radionuclide esophageal emptying in patients with achalasia.
The effects of sublingual isosorbide dinitrate (5 mg) and nifedipine (20 mg) were compared in 15 patients with achalasia. The parameters examined included the manometric measurement of the lower esophageal sphincter pressure, the radionuclide assessment of esophageal emptying and the clinical response. The mean basal lower esophageal sphincter pressure fell significantly after both drugs (p less than 0.01), with a maximum fall of 63.5% 10 min after receiving isosorbide dinitrate, but by only 46.7% 30 min after nifedipine. The esophageal radionuclide test meal retention was significantly less (p less than 0.01) only after receiving isosorbide dinitrate. The drug improved initial esophageal emptying by its effect on the lower esophageal sphincter and by relieving the test meal hold-up noted to occur at the junction of the upper and midesophagus. Eight patients cleared their test meal within 10 min after isosorbide dinitrate administration while only two did so after nifedipine. Subjectively, 13 patients had their dysphagia relieved by isosorbide dinitrate and 8 by nifedipine. However, this relief was not confirmed in 4 patients by the radionuclide study and they, as well as the other 3 patients who did not respond to therapy, were referred to pneumatic dilatation. Side effects were more prominent after nitrates. Three of the patients are currently receiving nifedipine and 5 patients received isosorbide dinitrate therapy for 8-14 mo. The radionuclide test meal is currently the best way of objectively evaluating drug therapy in patients with achalasia. Isosorbide dinitrate is more effective than nifedipine in relieving their symptoms. We studied the effects of three smooth muscle relaxants on lower esophageal sphincter (LES) pressure and radionuclide esophageal emptying in 15 untreated patients with achalasia. LES pressures were determined before and after the administration of normal saline subcutaneously, terbutaline sulfate subcutaneously, nitroglycerin sublingually, and aminophylline intravenously. All smooth muscle relaxants significantly decreased LES pressures when compared with normal saline controls and pretreatment baseline pressures (p less than 0.01). However, in normal saline controls, LES pressure actually increased over time (p less than 0.01). Control radionuclide esophageal emptying studies were performed in all patients. Subsequent esophageal emptying studies were carried out only in patients responding to smooth muscle relaxants by decreasing LES pressures by greater than or equal to 25% (terbutaline sulfate, n = 8; nitroglycerin, n = 7; and aminophylline, n = 4). Significant improvement in esophageal emptying was observed after nitroglycerin and terbutaline sulfate (p less than 0.05) but not after aminophylline. We conclude that in patients with achalasia (a) terbutaline sulfate, nitroglycerin, and aminophylline can significantly decrease LES pressure; (b) resting LES pressures vary over time; and (c) terbutaline sulfate and nitroglycerin significantly improve esophageal emptying in some subjects.
From most of the single reports we found, after intake of nitrates (either nitroglycerin or isosorbide dinitrate), there was a fall in lower oesophageal pressure and improvement of radionuclide esophageal emptying compared to the baseline. From the available evidence, we cannot provide any implications for practice. Appropriately designed, parallel group, randomised controlled trials with long term follow-up are needed to determine the effects of nitrates for achalasia.