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Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Within the last decade it became obvious that the treatment of angina pectoris alone is not sufficient. Modern goals include the optimization of anti-ischemic treatment ("silent myocardial ischemia") without compromising quality of life, as well as the reduction of fatal and non-fatal cardiac events. The failure of nitrates to continuously protect from myocardial ischemia ("nitrate tolerance") requires a modification of the current step-care recommendations for medical treatment. Numerous combinations of nitrates, betablockers and calcium channel blockers compensate for each other regarding their effects on heart rate, contractility, peripheral resistance and coronary blood flow. Recommendations for combination therapy decisively depend on the choice of the first-line drug. Only nitrates reduce myocardial preload by venodilation and substitute for EDRF-deficiency. After headaches disappear, nitrates do not affect quality of life and they are cheap. The nitrate-induced acceleration of heart rate should be compensated by the addition of beta-blockers or heart rate-decreasing calcium channel blockers. Therefore, the combination of nitrates with heart-rate-increasing calcium channel blockers, such as nifedipine, should be avoided. Many studies have proven the superiority of different double and triple therapies, as compared to their single components. A few reports, however, did not confirm this increase of anti-ischemic efficacy with combination therapy. The improvement of prognosis is proven for beta blockers without ISA in subgroups of patients with acute or post myocardial infarction and can be assumed for nitrates as well. With regard to prognosis, calcium channel blockers were inferior to nitrates and beta blockers. The combination of nitrates with a non-ISA betablocker should be preferred in post myocardial infarction patients with ventricular arrhythmias, whereas the combination of nitrates with a heart rate decreasing calcium channel blocker should be preferred in patients with COPD, severe peripheral arterial disease or severe diabetes. The combination of nitrates with a heart-rate-increasing calcium channel blocker should be considered in patients with sinus bradycardia, first degree AV-block, or proven coronary spasm. In patients with congestive heart failure, betablockers and calcium channel blockers should be avoided. To optimize medical treatment of ischemic heart disease, intermittent high dosage ISDN plus a beta blocker without ISA or ISDN plus a calcium channel blocker like verapamil are recommended. Frequently, however, the patient decides by himself, based on unacceptable side effects.
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PMID:[Combination of anti-angina drugs]. 257 81

We conducted a randomized controlled hemodynamic study to evaluate the effect of placebo and 20 mg isosorbide-5-mononitrate, a long-acting organic nitrate, in 19 patients with HBsAg-positive cirrhosis by the simultaneous measurement of portal venous pressure and wedged hepatic venous pressure. Baseline values for the two groups were similar. One hour after oral administration of 20 mg isosorbide-5-mononitrate in 10 patients, mean arterial pressure, mean pulmonary arterial pressure and pulmonary capillary wedge pressure significantly decreased from 92 +/- 13 (mean +/- S.D.) to 82 +/- 14 mmHg, from 12.9 +/- 4.5 to 9.3 +/- 2.4 mmHg and from 6.9 +/- 3.4 to 4.3 +/- 1.8 mmHg, respectively. However, both portal venous pressure gradient (from 18.1 +/- 3.6 to 17.5 +/- 3.0 mmHg) and hepatic venous pressure gradient (from 17.8 +/- 5.2 to 16.6 +/- 5.3 mmHg) remained unchanged during the study. In six patients who received 20 mg isosorbide-5-mononitrate twice daily for 7 days, hepatic venous pressure gradient remained unaltered as compared to basal and 1-hr values. There was no significant change in cardiac index, heart rate or systemic vascular resistance in either immediate (1-hr) or delayed (7-day) studies. Three patients (30%) developed mild headache or dizziness and two patients (20%) demonstrated systolic hypotension (less than mmHg) during the immediate study. This study shows that isosorbide-5-mononitrate appears to have no effect in treating portal hypertension in patients with HBsAg-positive cirrhosis. In addition, the isosorbide-5-mononitrate may affect the systemic circulation more than the portal circulation.
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PMID:Lack of effects of isosorbide-5-mononitrate on hepatic hemodynamics in HBsAg-positive cirrhosis. 275 46

Nitrate usage worldwide is on the increase as the indications for therapy expand. Present indications for nitrate therapy include chronic stable angina pectoris, unstable angina pectoris, complications of acute myocardial infarction, and 'unloading' therapy for acute and chronic congestive heart failure. Nitrates are also being used in the operating suite by anaesthesiologists to control systolic blood pressure during various surgical procedures. New nitrate delivery systems have recently become available which provide considerable dosing flexibility, further increasing the interest in this group of compounds. The dominant action of nitrates is a direct effect on vascular smooth muscle, producing vasodilation of the veins and arteries. These drugs decrease myocardial work by lowering systolic blood pressure, systemic vascular resistance, and reducing intracardiac dimensions. In addition, nitrates have a potent effect on cardiac preload as a result of systemic venodilatation. There is also some evidence that nitrates exert direct effects on the coronary circulation (vasodilatation of coronary arteries and coronary collateral vessels, and direct atherosclerotic stenosis dilatation). These actions may play a role in relieving myocardial ischaemia. Adverse sequelae of nitrate therapy are well known and serious adverse reactions are uncommon. Headache and dizziness are the most frequent side effects. Nitrate tolerance is a definite problem - present evidence indicates that long acting formulations, high doses, or frequent dosing regimens are particularly likely to induce vascular tolerance to nitrates. Consequently, provision of a nitrate-free interval has taken on increasing significance as a strategy to avoid tolerance. Nitrate delivery systems are numerous. Although availability varies from country to country, in most countries there are a wide variety of formulations of glyceryl trinitrate (nitroglycerin) available, including sublingual and oral tablets, oral spray, topical ointment as well as discs or patches for transdermal administration, a transmucosal tablet and an intravenous formulation. Similar formulations of isosorbide dinitrate, except buccal tablets, are available in some countries. Isosorbide 5-mononitrate, a potent metabolite of isosorbide dinitrate, is achieving increasing popularity as an antianginal drug. Optimum nitrate therapy requires a good understanding of the properties of the various formulations, particularly onset and duration of action and propensity to induce tolerance.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Glyceryl trinitrate (nitroglycerin) and the organic nitrates. Choosing the method of administration. 311 8

Tolerance development to organic nitrates, with respect to blood pressure reduction and precipitation of headache, had been assumed for almost a century but it was not until 1980 that the anti-ischemic effect was proven to be subject to this phenomenon, in a placebo-controlled, double-blind study carried out by our group exemplarily employing long-term treatment with isosorbide dinitrate (ISDN) in sustained-release form. Subsequent studies showed that tolerance development was also incurred during administration of ISDN, nonsustained-release form, 40 mg q.i.d. and on application of transdermal nitroglycerin patch systems. Both changes in the pharmacokinetics and activation of counter-regulatory mechanisms can be excluded as meaningful etiologic factors for the development of nitrate tolerance. It must be assumed that intracellular changes in the target organ which are associated with a diminished responsiveness for guanylate cyclase activation are at the basis of tolerance development. Prerequisite, according to laboratory experiments and clinical observations, are high concentrations of nitrates. After development of tolerance, on allowing a nitrate-free interval to intervene, the attenuated effects rapidly resume. Consequently, we investigated the hypothesis that tolerance could be avoided by an intermittent administration of nitrates which prevented accumulation of high serum concentrations. This was confirmed in two placebo-controlled, double-blind studies. Both during treatment with 20 mg ISDN in the morning and at midday as well as with the once-daily administration of 120 mg ISDN sustained-release form in the morning, there was an unequivocal anti-ischemic effect without tolerance development together with a significant reduction in the rate of anginal attacks and nitrate consumption.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Avoidance of tolerance development to long term therapy with nitrates through correct dosage]. 354 18

Nitrates are vasodilators of venous and arterial smooth muscle commonly prescribed both for angina and congestive heart failure. Primarily venodilators, nitrates also affect the systemic circulation if administered in sufficient dosage. In the coronary circulation, the principal effect is on the large epicardial and collateral vessels. Blood is shunted toward the ischemic subendocardium. In the majority of patients with angina, relief of symptoms by nitrates is primarily due to hemodynamic effects on preload and afterload, unless the patient has coronary spasm. In patients with congestive heart failure, nitrates decrease the resistance to the emptying of blood from the left ventricle as well as the filling pressure. Nitrates are relatively well tolerated, except for an initial throbbing headache which rapidly resolves as tolerance develops. Nitrates are available in a multitude of forms including sublingual, oral, topical, transmucosal, intravenous, and spray preparations. Oral preparations undergo a first-pass effect in the liver, requiring larger doses. Other forms avoid this problem by direct transdermal absorption or the intravenous route. The latter has the advantage of rapid administration and ease of titration. The choice of nitrate depends upon the clinical situation.
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PMID:Nitrate therapy in angina and congestive heart failure. 390 32

Dermal nitrate preparations are claimed to be useful in the treatment of angina, as their slow absorption by-passing the liver leads to a sustained action. Ten patients with angina were exercised on a treadmill after dermal application of 16.64 mg glyceryl trinitrate or 100 mg isosorbide dinitrate or placebo. Exercise duration was significantly increased at one and three hours for both nitrate preparations but not at six hours after application. The calculated workload achieved was significantly increased (p less than 0.01) at one and three hours for both preparations and at six hours (p less than 0.05) for isosorbide dinitrate. Headaches were common with glyceryl trinitrate cream. The dermal nitrate preparations studied had a duration of antianginal action similar to that of oral nitrate tablets. Aside from their value when the oral route cannot be used or absorption may be delayed, dermal nitrate preparations have no advantage over oral preparations for angina pectoris.
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PMID:Assessment of dermal glyceryl trinitrate and isosorbide dinitrate for patients with angina pectoris. 391 53

Organic nitrates are available in a remarkably diverse variety of formulations, including sublingual, buccal and oral tablets, capsules, topical creams, ointments, patches, tapes, inhalable sprays and intravenous solutions. Although not all of these formulations are available in the United States, the array of drugs and dosages approved for use is extensive. It is only by weighing the pharmacologic properties of these agents against the patient's clinical status and needs that a concise and appropriate treatment regimen may be derived. Numerous recent studies have confirmed the protracted efficacy of the organic nitrates in the treatment of patients with angina pectoris and congestive heart failure (CHF) as evidenced by improvements in cardiac hemodynamics and desired clinical parameters. It is appropriate that the patient's dosage of nitrates be administered with a formulation most likely to be both clinically effective and well tolerated. The use of nitroglycerin and isosorbide dinitrate in the acute and chronic treatment of CHF will be discussed in the context of their unique pharmacologic and pharmacokinetic properties. A rationale for the most efficacious use of these agents will be presented. Tolerance phenomena and adverse effects (i.e., headache) will also be discussed from the perspective of their significance in chronic nitrate therapy.
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PMID:Pharmacology of nitroglycerin and long-acting nitrates. 392 50

In a double-blind, within-patient, randomized, placebo-controlled, acute study, the effects at rest and on exercise capacity of two doses of a new transdermal therapeutic system (TTS), releasing respectively 10 and 20 mg of nitroglycerin (NTG) over 24 hours, were assessed in 15 outpatients with stable exercise-induced angina pectoris. A symptom-limited exercise test was performed 4 and 24 hours after the application of each system. In comparison with placebo, both TTS-NTG doses induced a statistically significant (p less than 0.01) increase in total duration of exercise, in exercise duration to 1 mm ST segment depression, in maximal workload and in total work performed, at both 4 and 24 hours after dosing. Furthermore, both TTS-NTG doses induced a significant rise in the pressure-rate product, both 4 and 24 hours after dosing (p less than 0.01 and p less than 0.05, respectively). No statistical difference was found between the two doses of active drug in any of the above-mentioned evaluation parameters. The only unpleasant side effect was the typical nitrate headache, which occurred in 11 of 15 patients. In conclusion, a single application of TTS-NTG, 20 cm2 or 40 cm2, may improve exercise capacity over a 24-hour period in patients with stable exercise angina due to atherosclerotic heart disease.
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PMID:Effect of a new transdermal therapeutic system containing nitroglycerin on exercise capacity in patients with angina pectoris. 392 79

Cocainization of the sphenopalatine fossa region has been shown to abort acute cluster headaches rapidly. Whether this response occurs by sympathomimetic action or via local anesthetic effect has been unknown. In this study, lidocaine hydrochloride was given as a therapeutic abortive agent to patients with cluster headache to elucidate cocaine's mechanism of action in relieving symptoms and to search for a safe, nonaddicting agent for self-administration. Using a 4% lidocaine solution applied to the sphenopalatine fossa, four of five patients obtained rapid relief of nitrate-induced cluster headaches and associated signs. Lidocaine was also effective in relieving spontaneous attacks. These results indicated that anesthetic rather than sympathomimetic effects are responsible for cocaine-medicated abortion of cluster headache, that transmission of pain in cluster headache likely occurs via the sphenopalatine fossa, and that topical lidocaine is effective in rapidly aborting acute cluster headache.
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PMID:Cluster headache. Local anesthetic abortive agents. 399 68

A total of 250 patients with coronary heart disease diagnosed clinically, by ECG and in some cases by coronary angiography, was treated with isosorbide 5-mononitrate, 221 of the patients being treated for up to 6 months. In 181 patients previously treated with isosorbide dinitrate (ISDN)-retard, the mean daily dosage of nitrate was reduced from 77 mg (200 mg maximum) ISDN to 45 mg (120 mg maximum) isosorbide 5-mononitrate in long-term treatment. During previous treatment with ISDN-retard (with high doses in some cases: 80 to 200 mg daily in 48.6% of patients and 40 mg or less daily in only 33.1%), 4.5% of the patients were totally free of angina pectoris attacks. In the same patients, this proportion was 53.6% after administration of isosorbide 5-mononitrate for 6 months (dosage 40 mg daily or less in 67.4% of patients, 80 mg or more in 8.8% of patients). A substantial increase in subjective exercise tolerance and the reduction in incidence of angina pectoris was associated with a marked reduction in nitrate consumption for acute attacks. Isosorbide 5-mononitrate lowered slightly the blood pressure and heart rate. Treatment with isosorbide 5-mononitrate was withdrawn in 22 (8.8%) patients due to nitrate intolerance (headache in 7.6%) and in a further 7 (2.8%) patients for other reasons. Of patients completing 6-months' treatment, 9.9% reported one or more reversible undesirable reactions typical of nitrates at the start of the trial (compared with 6.8% in the pre-trial period). The incidence of such effects decreased to 1.4% after 6 months. The incidence of tolerable headache was 7.7% during the first week on isosorbide 5-mononitrate, decreasing to 0.9% after 24 weeks (5.9% in the pre-trial period). The laboratory parameters and subjective tolerability data confirmed the therapeutic safety of isosorbide 5-mononitrate.
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PMID:An open, long-term, multi-centre study of the anti-anginal efficacy and safety of isosorbide 5-mononitrate at low doses in patients with coronary heart disease. 634 4


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