Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nitrates are potent relaxers of vascular smooth muscle and act by dilating veins, arteries, and arterioles (especially at high doses). Their clinical effects have been considered to be dominantly related to peripheral actions: systemic venodilatation and a decrease in systemic vascular resistance, reducing the preload and afterload of the heart. Considerable experimental work confirms potent salutary effects on the coronary circulation. These drugs are readily absorbed across mucosal surfaces; they are available in multiple formulations, including sublingual, buccal, oral, and topical delivery systems. Nitrate administration should begin with low doses and increased to doses that are often higher than previously recommended until a specific clinical end point or limiting side effects occur. Organic nitrate esters are effective in the treatment of stable angina pectoris, unstable angina, coronary vasospastic syndromes, and in vasodilator therapy in severe congestive heart failure. The pathophysiology of these syndromes is reviewed with respect to the clinical actions of nitrates on the central and peripheral circulations. The side effects of nitrates include headache, dizziness, and nausea. Nitrate tolerance, a controversial subject, does not appear to be an important clinical problem. Using the guidelines presented in this review, nitrate therapy provides effective, inexpensive, well-tolerated therapy for many patients with cardiovascular disease.
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PMID:Nitroglycerin and long-acting nitrates in clinical practice. 640 16

An open, multi-centre trial was carried out to investigate the efficacy and tolerance of isosorbide mononitrate used as anti-anginal therapy in a large group of patients under normal general practice conditions. A total of 10,229 patients with coronary heart disease of average duration of 4 years entered the trial, of whom 8769 had sufficiently severe symptoms to be included in the analysis of results. Most of the patients (92.3%) had previously been treated with cardiovascular drugs. In the trial, all patients were treated with oral isosorbide mononitrate, 20 mg 3-times daily, for a period of 14 days. Treatment resulted in an improvement of angina (compared with the situation during previous therapy) in 79.9% of the assessed patients, complete abolition of angina attacks being achieved in 52.1% and a reduction in frequency of attacks in a further 28.7%. This reduction in angina was associated with a reduced acute consumption of nitrates used for the treatment of attacks. In the smaller sub-group of patients who had received no previous anti-anginal therapy, isosorbide mononitrate treatment resulted in improvement in 91% of patients, complete abolition being achieved in 77.5%. Nocturnal angina was almost totally eliminated by isosorbide mononitrate treatment and this can probably be explained in terms of the favourable pharmacokinetic profile of the drug. 'Nitrate headache', observed in 20.5% of the patients, was the only common side-effect of treatment. The absence of hypotension or tachycardia in significant numbers of patients indicates that isosorbide mononitrate should be well tolerated, as well as efficacious, in all patients with coronary heart disease.
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PMID:Treatment of coronary heart disease with isosorbide mononitrate ('Elantan' 20). 644 48

An open, multi-centre clinical trial was carried out in 537 hospital patients and 2138 general practice patients to evaluate the efficacy and tolerance of isosorbide 5-mononitrate in the treatment of angina pectoris. Prior to entry into the trial, angina attack frequency and acute glyceryl trinitrate consumption were assessed during previous, in most cases unsatisfactory, anti-anginal therapy. After a treatment-free washout period of 3 days, graded multi-stage exercise testing was performed and then treatment started with 20 mg isosorbide mononitrate 3-times per day. Exercise testing was repeated after 14 days' therapy and, in the case of the hospital patients, also 4 to 5 hours after the first dose of isosorbide mononitrate. At the end of the 14-day treatment period, angina attack frequency and glyceryl trinitrate consumption were again assessed. Similar results were obtained for both hospital and general practice patients. Changing to isosorbide mononitrate resulted in a marked reduction in angina frequency, with complete elimination of angina attacks in approximately half of the patients; nocturnal angina, present in approximately 20% of the patients during previous therapy, virtually disappeared during isosorbide mononitrate therapy. Exercise tolerance and performance improved in the majority of patients, with a marked increase in the number of patients able to exercise to the level at which some symptom other than angina pectoris caused them to stop. ST-depression during exercise and exercise-induced arrhythmias also showed clear reductions during isosorbide mononitrate therapy. Tolerance to isosorbide mononitrate was good, the expected 'nitrate headaches' being the only common side-effect reported. The results were such that continuation of treatment with isosorbide mononitrate after the trial was recommended by the attending physician in 77% of the hospital patients and 87% of the general practice patients.
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PMID:Treatment of coronary heart disease with isosorbide mononitrate ('Elantan' 20): a multi-centre study in hospital and general practice. 644 49

Tolerance and cross-tolerance to nitrates has been known since 1900 but the actual clinical importance of this phenomenon is unclear. Vasodilator treatment of congestive heart failure has provided an important new role for long-acting nitrates. The advent of high-dose nitrate regimens for both angina and heart failure raises the possibility that nitrate tolerance could be a potential detriment to therapy. A number of older studies have documented the development of tolerance and cross-tolerance to blood pressure and heart rate responses to nitrates as well as the rapid onset of tolerance to nitrate headaches in subjects given nitrates on a regular basis. Animal experiments also confirm the ready appearance of nitrate tachyphylaxis. Needleman has proposed a cellular mechanism for nitrate tolerance based on a chemical alteration of nitrate receptors in the vascular wall. In spite of these studies, there is considerable evidence that clinically relevant tolerance to nitrates is rare. Several recent investigations designed to look at this problem using high-dose isosorbide dinitrate (ISD) failed to demonstrate tachyphylaxis to the anti-anginal or hemodynamic effect of ISD. However, very recent work in patients with angina suggests that tolerance to high dose ISD does occur and may reduce the duration of action of long-acting nitrates. Overall, the bulk of current evidence does not support tolerance to be a major problem in nitrate treatment of cardiac diseases, although attenuated vasodilator responses may occur after several weeks of nitrate therapy.
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PMID:Nitrate tolerance and dependence. A critical assessment. 677 5

A new transdermal therapeutic system (TTS) for the administration of nitroglycerin (NTG) was tested in human pharmacological studies in 26 healthy volunteers. Plasma concentrations and haemodynamic responses were determined after the application of the system in different dosages. The concentrations of NTG reached in the plasma were uniform and dose-related, i.e. dependent on the drug-release area, and showed only minor inter-individual variation. They remained almost constant as long as the system was in contact with the skin. Renewal of the system caused no appreciable change in the plasma concentration. The haemodynamic effects, like those of all nitrates, were not clearly related to the dose administered, and were not always dependent on the plasma concentration. Upon repeated application, NTG-TTS was well tolerated locally and systemically and led to no alteration in blood chemistry or haematological parameters. The typical nitrate headaches disappeared after a few days. The presence of the system on the skin caused no discomfort or inconvenience.
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PMID:Human pharmacological studies of a new transdermal system containing nitroglycerin. 681 25

Sixteen patients with severe coronary artery disease and unstable angina, refractory to standard therapy with nitrates, beta-blockers or calcium antagonists, were given intravenous nitroglycerine (500 micrograms/ml) in an open trial. The infusion was started at 0 . 17 ml/min. The final infusion rate ranged from 0 . 17 ml/min to 2 . 04 ml/min, depending on the symptomatic and haemodynamic response of the individual patient. At the slow infusion rates, the actual dose was probably only 15% of the delivered dose because of the absorption of nitroglycerine to PVC tubing. There was significant pain relief in all patients. In six patients, pain relief was complete; in ten patients, occasional episodes occurred during the nitroglycerine infusion but they were less frequent and less severe and few were associated with ST segment changes. Systolic blood pressure fell by a mean of 100 mmHg at the commencement of therapy but there was no significant change in heart rate. Apart from mild headaches, no other adverse effects were observed. The mean treatment time was 3 . 2 days (range 1-8 days). Eight patients were discharged on oral and/or cutaneous nitrate therapy and eight patients had coronary artery surgery.
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PMID:Intravenous nitroglycerine in refractory unstable angina pectoris. 681 46

Erythrityl tetranitrate, a long-acting organic nitrate, was compared with isosorbide dinitrate in a double-blind, placebo-controlled complete crossover study in 15 healthy male volunteers. A digital plethysmogram and ear densitogram were used to assess the physiologic response to these two sublingual nitrates, with the intensity and duration of drug effect calculated by differences in diastolic amplitude intensity before and after drug administration. Both 5 mg sublingual erythrityl tetranitrate and 5 mg isosorbide dinitrate produced significant increases in diastolic amplitude intensity for up to 3 hours. The erythrityl tetranitrate peak effect was less than that of the isosorbide dinitrate, but the incidence of headaches was also less. The ear densitogram was found to be an effective means of assessing the diastolic amplitude intensity changes.
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PMID:Bioavailability of organic nitrates: a comparison of methods for evaluating plethysmographic responses. 706 34

The effect of a long-acting nitrate, isosorbide dinitrate (ID) 5 mg sublingually, on the lower oesophageal sphincter was tested in 24 patients with achalasia. The drug caused a reduction in LOS pressure in all cases. The mean LOS pressure fell from 46.32.7 mmHg to 15.31.8 mmHg (p less than 0.01). The pressure began to drop after several minutes, reaching its lowest levels after 15 minutes. This measured manometric effect lasted for 60 minutes or more in 10 patients studied. The reported clinic effect lasted for two to three hours, permitting the ingestion of a meal. Twenty-three patients were followed clinically for two to 19 months while receiving the drug three times daily before meals. Nineteen reported a marked to complete relief of dysphagia. Five of these patients had previous pneumatic dilatation, cardiomyotomy, or both, and had recurrence at time of study. Side-effect, mainly headache, were reported in eight patients. In six this was alleviated by substituting oral isosorbide dinitrate, 10 mg. Two patients became refractory to treatment after two to six months. The potential role of long-acting nitrates in the treatment of achalasia has yet to be established.
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PMID:Effect of nitrates on LOS pressure in achalasia: a potential therapeutic aid. 723 23

The effect of transdermal and oral nitrates on anginal symptoms were compared in a randomized trial of 2,456 out-patients with stable angina pectoris recruited in 206 cardiological centers in Italy. Half of the patients had effort-induced angina, 12% rest angina and 38% "mixed angina". Before enrollment, all of the patients were on stable treatment with oral nitrates either as monotherapy or in combination with other antianginal agents. After a 2-week run-in period on the previous oral nitrate regimen, two thirds of the patients were randomized to receive a nitroglycerin patch 5 mg/24 hours for 2 weeks, the remaining one third continued their previous treatment. The patients subsequently reporting > or = 1 anginal attack/2 weeks were titrated to transdermal nitroglycerin 10 mg/24 hours or to the maximum dose of oral nitrates suggested by the manufacturer for the following 4 weeks; asymptomatic patients continued on the initial dosages. The 2-week anginal attack rate was reduced from 4.9 +/- 5.3 to 1.4 +/- 2.5 in the transdermal nitroglycerin group (-71%), and from 4.5 +/- 4.7 to 1.5 +/- 2.7 (-67%) in the oral nitrate group. The proportion of patients free of angina increased from 12% to 54% (+343%) with transdermal nitroglycerin and from 15% to 49% with oral nitrates (+218%) (p < 0.05). The reduction in angina frequency was similar during the day and during the night. Nocturnal angina was rare in patients with effort angina. However, about half of the patients with rest and "mixed" angina had had nocturnal episodes, the number of which was significantly reduced by both regimens: nighttime asymptomatic patients increased from 45% to 82% in the rest angina group, and from 50% to 83% in the "mixed" angina group, with no differences between treatments. Withdrawals due to side-effects were rare: 1.5% with transdermal nitroglycerin and 1.3% with oral nitrates. Headache was the most common side-effect and was more frequently reported with oral nitrates. Although the lack of a placebo control precludes an absolute evaluation of efficacy, the results of the present study suggest that both transdermal nitroglycerin and oral nitrates may provide relief of anginal symptoms over 24 hours in the majority of stable angina patients. Nocturnal angina, reported by 50% of the patients with rest and mixed angina, is effectively reduced by the administration of nitrates over 24 hours.
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PMID:Antianginal effect of transdermal nitroglycerin and oral nitrates given for 24 hours a day in 2,456 patients with stable angina pectoris. The Italian Multicenter Study. 762 Jun 88

We have compared the migraine-inducing effect of nitroglycerin ointment applied to the frontotemporal region of the head, which is innervated by the ophthalmic and maxillary divisions of the trigeminal nerve, with that of nitroglycerin applied to the chin (innervated by the mandibular division), the posterolateral region of the neck (innervated by the second and third cervical roots), the lateral surface of the proximal third of the forearm (innervated by the sixth cervical root), and the medial surface of the upper-arm region (second dorsal root). One hundred patients suffering from migraine without aura were randomly divided into five equal groups. Each group received an application of 5 mg nitroglycerin in 2% ointment on a preselected body area for 2 hours. Frontotemporal nitroglycerin induced a significantly greater number of early onset migraine attacks with respect to the arm and forearm regions. In all cases, nitroglycerin applied to the frontotemporal region resulted in subsequent migraine, whereas there was a significant number of negative trials with nitroglycerin applied to the neck, arm, and forearm vs the frontotemporal area. It, therefore, appears that the trigeminal nerve endings in the affected frontotemporal region are particularly sensitive to the migraine-inducing effect of the nitrate. This suggests a peripheral neurogenic hypothesis of migraine genesis.
Headache 1995 Mar
PMID:The frontotemporal region plays a role in the genesis of migraine without aura. 853 Feb 85


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