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)

Nicorandil belongs to the class of compounds known as potassium channel activators which are characterised by their arterial vasodilator properties. In addition, nicorandil has venodilating properties which are attributable to a nitrate group in its chemical structure. Therefore, by combining these two vasodilator mechanisms, nicorandil represents a novel type of compound for use in the treatment of angina pectoris. Furthermore, increasing experimental evidence suggests that potassium channel activation may also exert a direct cytoprotective effect by augmenting normal physiological processes which protect the heart against ischaemic events. Comparative studies of up to 3 months' duration suggest that nicorandil is equivalent in efficacy to isosorbide dinitrate, propranolol, atenolol, nifedipine or diltiazem in the treatment of stable angina. Preliminary evidence suggests that an improvement of anginal and ischaemic symptoms is maintained for up to 1 year. Whilst the efficacy of nicorandil in other types of angina has not been extensively studied, preliminary results indicate that intravenous nicorandil is as effective as isosorbide dinitrate in the treatment of unstable angina and is also effective in patients with variant angina. In addition, the limited data available indicate that nicorandil may be effective in patients with unstable and variant angina who are refractory to therapy with conventional antianginal agents, a potentially important area for further study. Headache, mostly of mild to moderate intensity was the most commonly reported adverse event, occurring in one-third of patients receiving the recommended therapeutic regimen of nicorandil 10 to 20mg twice daily. In comparative trials involving a total of 84 patients who received nicorandil, the incidence of headache was similar to that produced by isosorbide mononitrate and isosorbide dinitrate. Headache was most frequent on initiating therapy but declined with continued treatment. To date, approximately 5% of patients participating in European trials have withdrawn due to headache, although this rate may be reduced by using a lower starting dose of nicorandil (5 mg twice daily). In summary, clinical experience thus far indicates that nicorandil, with its novel combination of two distinct vasodilator mechanisms, offers an effective alternative to established vasodilator therapy with conventional nitrates and calcium antagonists in the long term treatment of stable angina pectoris. Further studies are warranted to establish whether the unique pharmacodynamic profile of nicorandil is advantageous for the treatment of other types of angina and/or the ischaemic myocardium.
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PMID:Nicorandil. A review of its pharmacology and therapeutic efficacy in angina pectoris. 128 Oct 76

The hemodynamics influencing effect of Nitromint sublingual tablet and aerosol (EGIS Pharmaceuticals) has been examined in 22 ischaemic heart disease patients during heart catheterisation. The patients were hospitalized and took also the earlier prescribed drugs. On the basis of the results of examinations it may be concluded that Nitromint aerosol has a therapeutic action comparable to other short-acting nitrate preparations such as sublingual nitroglycerin tablet. According to the observations of the patients the drug action develops within a significantly shorter period. Considering the type of side-effects there was no difference between the two drug forms. Primarily, Nitromint tablet caused systemic effects (headache, dizziness, throbbing head) while aerosol caused predominantly local symptoms (burning of the tongue, disagreeable taste). These effects were only temporary and ceased within 10 minutes. According to the above described observations Nitromint aerosol may successfully be used as a new nitroglycerin containing drug form in all forms of angina pectoris: in rest angina, effort angina, as a prophylaxis, in mixed type angina pectoris, as a first-aid in emergency cases in acute left heart failure, preceding the application of infusion.
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PMID:Comparative haemodynamic examination of Nitromint (sublingual tablet and aerosol). 158 77

1. Nitrates have a place in the prophylactic treatment of patients with angina pectoris. Their efficacy is not in doubt. 2. However, there may be some practical problems associated with their use, such as unreliable absorption, short duration of action, treatment-induced headache, development of nitrate tolerance and a suggested rebound phenomenon observed during intermittent dosing. Furthermore, patient convenience with treatment schedule and patient compliance have to be considered during prophylactic treatment. The present article discusses how many of these problems may be solved by selection of formulation as well as nitrate compound. 3. The development of controlled-release formulations producing sufficiently high nitrate plasma concentration during part of the day followed by nitrate-poor rather than nitrate-free interval, have the potential to prevent both nitrate tolerance and rebound phenomenon, and produce a sufficiently long duration of action with a convenient once daily regimen.
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PMID:Prophylactic nitrate therapy in angina pectoris--is there an optimal treatment regimen? 163 74

Nitrates have a place in the prophylactic treatment of patients with angina pectoris. Their efficacy is not in doubt. However, there may be some practical problems associated with their use, such as unreliable absorption, short duration of action, treatment-induced headache, development of nitrate tolerance and a suggested rebound phenomenon observed during intermittent dosing. This article discusses how many of these problems may be solved by selection of formulation as well as nitrate compound. Thus, the development of a controlled-release formulation producing sufficiently high nitrate plasma concentrations during part of the day, followed by a low nitrate level rather than a nitrate-free interval, seems to have the potential to prevent both nitrate tolerance and rebound phenomenon. This system would also offer a sufficiently long duration of action with a convenient once-daily dose regimen.
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PMID:Is there an optimal prophylactic nitrate therapy? 187 71

To assess efficacy of transdermal nitrate use, a randomized, placebo-controlled trial of continuous and intermittent use of nitroglycerin patches (10 mg/24 hours) was conducted in 127 patients with stable angina pectoris who discontinued exercise testing within 9 minutes because of angina. After a placebo run-in week, baseline (day 0) symptom-limited exercise testing was performed and repeated on day 1 and 14 before and after the administration of 0.5 mg of sublingual nitroglycerin. On day 0, total exercise duration was the same (within narrow limits) in all 3 groups and remained unchanged in the placebo group. On day 1, total exercise duration increased from 406 +/- 115 to 469 +/- 158 seconds (p less than 0.001) in the continuously treated group and from 396 +/- 105 to 475 +/- 171 seconds (p less than 0.001) in the intermittently treated group. In the intermittent group, exercise duration increased slightly to 483 +/- 140 seconds on day 14, and in the continuous group exercise duration decreased to 447 +/- 144 seconds. However, this decrease was not statistically significant. Similar treatment effects were seen for time to 1-mm ST depression. Sublingual nitroglycerin remained effective in all 3 groups and on all days. Eleven actively treated patients and 1 patient taking placebo discontinued the study because of headache. It is concluded that continuous use of transdermal nitroglycerin remains partially effective and intermittent therapy remains fully effective in improving long-term exercise capacity with acceptable adverse effects in patients with stable angina pectoris.
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PMID:Long-term efficacy of continuous and intermittent use of transdermal nitroglycerin in stable angina pectoris. 192 43

Thirty-six men (aged 18-42 years, average age 27 years) with known spinal cord lesions for 0.3-39 years and levels of the lesions from C3 incomplete to L1 complete were submitted to penile vibrations with the objective to obtain reflex ejaculation. Sperm cells were demonstrated in a total of 27 of the participants, antegrade ejaculation in 16 cases and 11 retrograde ejaculations. In general, the semen quality was very poor with reduced total number of spermatozoa and increased percentage of immobile and/or morphologically abnormal spermatozoa compared with normal values. In connection with the vibration procedures, three cases of autonomous hyperreflexia followed by transient slight headache which did not require treatment occurred while an isolated case was treated with 0.5 mg glycerine nitrate (Nitromex) administered sublingually with good effect. No other side effects were observed.
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PMID:[Vibration-induced reflex ejaculation in patients with spinal cord injuries]. 194 4

We have discussed several miscellaneous headache disorders not associated with structural brain disease. The first group included those headaches provoked by "exertional" triggers in various forms. These include benign cough headache, BEH, and headache associated with sexual activity. The IHS diagnostic criteria were discussed. Benign exertional headache and cough headache were discussed together because of their substantial similarities. In general, BEH is characterized by severe, short-lived pain after coughing, sneezing, lifting a burden, sexual activity, or other similar brief effort. Structural disease of the brain or skull was the most important differential diagnosis for these disorders, with posterior fossa mass lesions being identified as the most common organic etiology. Magnetic resonance imaging with special attention to the posterior fossa and foramen magnum is the preferred method for evaluating these patients. Indomethacin is the treatment of choice. The headache associated with sexual activity is dull in the early phases of sexual excitement and becomes intense at orgasm. This headache is unpredictable in occurrence. Like BEH, the headache associated with sexual activity can be a manifestation of structural disease. Subarachnoid hemorrhage must be excluded, by CT scanning and CSF examination, in patients with the sexual headache. Benign headache associated with sexual activity has been successfully treated with indomethacin and beta-blockers. The second miscellaneous group of headache disorders includes those provoked by eating something cold or food additives, and by environmental stimuli. Idiopathic stabbing headache does not have a known trigger and appears frequently in migraineurs. Its occurrence may also herald the termination of an attack of cluster headache. Indomethacin treatment provides significant relief. Three headaches triggered by substances that are eaten were reviewed: ingestion of a cold stimulus, nitrate/nitrite-induced headache, and MSG-induced headache. For the most part, avoidance of these stimuli can prevent the associated headache. Lastly, we reviewed headache provoked by high altitude and hypoxia. The headache is part of the syndrome of AMS during its early or benign stage and the later malignant stage of HACE. The pain can be exacerbated by exercise. The best treatment is prevention via slow ascent and avoidance of respiratory depressants. Acetazolamide and dexamethasone have proved useful in preventing this syndrome.
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PMID:Cough, exertional, and other miscellaneous headaches. 202 Feb 26

Nicorandil, a nicotinamide derivative, is an orally efficacious antianginal drug possessing a nitrate moiety in its chemical structure. This drug is an effective and well-tolerated treatment for various types of angina pectoris. Its general efficacy is similar to that of nitrates, with several unique effects on the cardiovascular system. Nicorandil causes sustained dilation of both the arterial resistance and conductive vessels, thus markedly dilating the coronary artery and increasing coronary blood flow. In addition, nicorandil, unlike nitroglycerin or isosorbide dinitrate, possesses little hemodynamic effect on heart rate, blood pressure, or cardiac contractility with clinical doses yielding antianginal effects. The mechanism causing coronary vasodilation has not been completely clarified but appears to be associated partly with increases in c-GMP, as well as the hyperpolarization of the smooth muscle membrane. Nicorandil, in single oral doses of 10-30 mg, has been shown to be effective in chronic stable angina, as assessed objectively by increases in exercise duration and/or the time to onset of ST-segment depression during treadmill exercise. In open studies and controlled efficacy evaluations, nicorandil in daily oral doses of 15-40 mg demonstrated significant effectiveness in the treatment of various types of angina pectoris. Headaches due to vasodilation may occur, and some side effects occurred in 5.1-34% of patients receiving nicorandil, but were generally minor in nature. There was no depressant effect on atrioventricular conduction, which occurs frequently in patients treated with calcium antagonists of the verapamil and diltiazem type. Nicorandil may be effective even in patients with rest and effort angina who do not respond to combination therapy with calcium antagonists and oral nitrates. Thus, nicorandil appears to be a valuable addition to the arsenal of antianginal drugs due to its low incidence of serious side effects.
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PMID:Pharmacology and therapeutic effects of nicorandil. 215 May 92

In a simple blind crossover 7-week study with a randomized beginning the authors compared in 13 patients with stable angina pectoris after exercise the action of diltiazem (Blocalcin 60, Lachema) and isosorbidedi nitrate (Isoket retard 120, Schwarz). Both drugs improved significantly, as compared with placebo, the tolerance of the load, reduced the frequency of stenocardias per 24 hours, diltiazem also the nitroglycerin consumption per 24 hours. Diltiazem reduced significantly, as compared with isosorbidedi nitrate, the pulse rate at rest, it reduced significantly Robinson's index and the diastolic pressure at rest. In none of the other investigated parameters there was a significant difference between the two drugs and both are valuable in the treatment of angina after exercise. Diltiazem was well tolerated by the patients, while headache was a frequent side-effect of isosorbide dinitrate.
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PMID:[Comparison of the effects of depot isosorbide dinitrate (Isoket Retard 120) and diltiazem in patients with exertional angina pectoris]. 218 69

The rationale for intermittent nitrate therapy is based on the pathophysiology of nitroglycerin tolerance and the diurnal pattern of symptoms encountered in patients with chronic stable angina. Nitrate tolerance was first observed as tolerance to headache in industrial toxicology. When long-acting nitrates for chronic stable angina became available, similar tolerance was observed but not thought to indicate tolerance to a haemodynamic or therapeutic effect. Subsequently, Needleman and coworkers (J Pharmacol Exp Ther 1973; 187: 324) defined in vitro the phenomenology of vascular smooth muscle tolerance to nitroglycerin-induced relaxation and reversibility was demonstrated. More recently, a potential molecular explanation for nitrate tolerance has been proposed: sulfhydryl group depletion in smooth muscle cells resulting in reduced formation of S-nitrosothiols on nitrate exposure with resultant reduced activation of cyclic GMP. In vivo, other mechanisms, including fluid retention and neurohumoral responses to vasodilation may also be important. The first demonstration that nitrate tolerance affected the therapeutic efficacy of long-acting nitrates was reported by Parker and coworkers in 1982 (Circulation 1987; 76: 572-6). This landmark study was not given much credence at the time because it appeared to be in conflict with earlier reports. However, in the past 6 years development of tolerance has been demonstrated with a variety of oral nitrates, transdermal nitroglycerin and intravenous nitroglycerin. When plasma concentrations are held constant, tolerance to antianginal effects is demonstrable within 24h, but varies markedly in severity from individual to individual.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Intermittent nitrate therapy in angina pectoris. 250 Oct 96


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