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)

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

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

The effects of isosorbide dinitrate single dose 120 mg daily and nifedipine 20 mg twice daily were studied in 17 patients with variant angina pectoris due to coronary artery spasm. After a placebo phase the patients were randomized to treatment with either isosorbide dinitrate or nifedipine. After six weeks the patients were crossovered for another six weeks period of treatment. There was significant decrease of number of angina attacks during both treatment regimens. Using 24 hours Holter monitoring we also proved significant decrease of number of ST segment elevation or depression, either symptomatic or asymptomatic. There was increase of performed work during exercise tests after both treatment periods. The efficacy of Isoket 120 mg and Adalat Retard 2 x 20 mg daily in the treatment of patients with active variant angina pectoris was comparable in our study. 3 patients suffered untolerable headache during isosorbide dinitrate phase and had to terminate treatment after first day only.
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PMID:[Comparison of isosorbide dinitrate and nifedipine in the treatment of variant angina pectoris. Randomized study]. 280 34

In the treatment of angina pectoris a double-blind evaluation of verapamil (Cordilox) at two dose levels-namely, 80 mg thrice daily and 120 mg thrice daily-propranolol (Inderal) 100 mg thrice daily, and isosorbide dinitrate (Vascardin) 20 mg thrice daily has been made against a placebo. The assessment was based on relief from daily attacks of angina on effort and the response to a whole-body exercise test. We can find no statistically significant difference between the effects of verapamil (120 mg three times a day) and propranolol (100 mg three times a day) in the treatment of angina of effort. Both of these preparations are more effective than a placebo both in the reduction of daily attacks (P < 0.01) and in the prolongation of exercise test (P < 0.05). Isosorbide dinitrate (20 mg three times a day) appears to be no more effective than a placebo in the treatment of angina on effort, but 14 out of 32 patients experienced headache of such severity that even when the dose was reduced to 10 mg thrice daily this drug therapy had to be withdrawn. Both propranolol (100 mg three times a day) and verapamil (120 mg three times a day) had a significant lowering effect on the diastolic blood pressure as measured with the patient standing (P < 0.01).
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PMID:Double-blind evaluation of verapamil, propranolol, and isosorbide dinitrate against a placebo in the treatment of angina pectoris. 457 Jun 71

Nitrates are effective in the management of exertional angina pectoris primarily due to their peripheral effects i.e. venodilation and arterial dilation, and thereby reduction in myocardial oxygen demand. These drugs also improve collateral blood flow in ischemic areas and in some patients may increase coronary blood flow by modifying tonus in the conductive or conduit coronary vessels. Sublingual nitroglycerin is the most effective antianginal agent but its prophylactic use is limited by its short duration of action. Until recently, the efficacy of long-acting oral nitrates was seriously questioned. However, recent data suggests that when given acutely in adequate doses, oral nitrates, transcutaneous and buccal preparations of nitroglycerin all exert prolonged hemodynamic and antianginal effects. Development of tolerance to the circulatory and antianginal effects during chronic therapy, however, remains a concern. Published literature suggests that tolerance to the circulatory effects and to headaches develops rapidly during sustained therapy with long-acting nitrates. However, reports regarding the development of tolerance to the antianginal effects and reduction of ST segment depression remain conflicting. Partial tolerance to the antianginal effects has been well-documented during chronic therapy with isosorbide dinitrate. Duration of improvement in exercise tolerance during four times daily therapy with isosorbide dinitrate has been shown to be shortened compared to prolonged effects following acute therapy. Recent data suggests that given in high doses, beneficial effects of ST segment depression during exercise may also diminish during chronic therapy with long acting nitrates. Tolerance to antianginal and circulatory effects can be reversed by withholding long-acting nitrates for 24 to 36 hours. Furthermore, initial studies suggest that tolerance to antianginal effects during sustained therapy can be avoided by giving smaller but effective doses of ISDN (20 to 40 mg) twice a day rather than prescribing larger doses more frequently.
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PMID:Nitrates for angina pectoris. A critical review of therapeutic efficacy and tolerance. 643 Jul 66

1 In a group of 23 patients with documented ischaemic heart disease who experienced angina pectoris, oral oxyfedrine (24 mg three times daily) was compared with isosorbide dinitrate (10 mg three times daily) and placebo in a double-blind double-crossover clinical trial. 2 Isosorbide dinitrate appeared no better than placebo, either in terms of symptomatic relief or ECG responses to exercise. Thirty eight per cent of patients complained of headaches and 28% had to cease taking the drug for this reason. 3 Oxyfedrine produced statistically significant improvements in both symptom level (P < 0.01) and ECG ST-segment responses to exercise (P < 0.01). The only side effect noted was a reversible loss of taste sensation by one patient. 4 Neither drug produced any adverse changes in any haematological or biochemical parameters. 5 Oxyfedrine is, therefore, to be preferred to isosorbide dinitrate, being both much better tolerated and more efficacious.
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PMID:A controlled comparison of oxyfedrine, isosorbide dinitrate and placebo in the treatment of patients suffering attacks of angina pectoris. 700 81

Isosorbide-5-mononitrate (IS-5-MN) 5, 10, 20, 30, 40 and 50 mg were administered orally to 2 healthy male volunteers. The pharmacological effect was determined using digital pulse plethysmography and the orthostatic tilting test, and at the same time side effects were monitored. The threshold of oral activity of IS-5-MN was found to be 5 mg. The maximum response was reached with doses of 20-30 mg. The duration of action of this dose was approximately 8 h. Higher doses did not lead to any further increase, but rather to a decrease in the pharmacological response, while the side-effects, such as headaches, dizziness and nausea, became more prominent. In a randomized, double-blind, three-way cross-over study in 11 female volunteers IS-5-MN 30 mg proved to be more potent with respect to pharmacological activity than sustained released ISDN 20 mg (isosorbide dinitrate), whereas there was no difference in side-effects. Thus, it can be estimated that IS-5-MN 20 mg is approximately equivalent to 20 mg sustained released ISDN. IS-5-MN is rapidly absorbed after oral administration and the maximum concentration in serum was reached 1.2 +/- 0.2 h after doses of 10 to 50 mg. The pharmacokinetics showed dose-linearity. The compound was eliminated with an average half life of 4.04 +/- 0.16 h, which is appropriate for a reasonably prolonged duration of action without the need for a sustained release formulation.
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PMID:First data on effects and pharmacokinetics of isosorbide-5-mononitrate in normal man. 725 Jan 75

1. A randomised double-blind placebo-controlled cross-over study was performed to investigate the effects of oral isosorbide dinitrate (ISDN; 20 mg twice daily for 2 weeks) on various aspects of platelet function in vivo in 20 patients with stable angina pectoris. Measurements were performed at rest and after platelet activation by physical exercise (bicycle ergometry). 2. Compared with placebo, treatment with ISDN significantly decreased systolic blood pressure at rest by 7 (-14 to -1) mm Hg (mean and 95% CI) and tended to increase exercise capacity by 7 (-1 to 14) W and attenuate perceived chest pain during maximal work. The dosage was high, as judged by side-effects reported (mainly headache). Compliance was good, as assessed by electronic counter equipped tablet bottles (Medication Event Monitoring System); only one patient had a compliance rate below 60%. 3. Exercise significantly increased platelet aggregability as measured by filtragometry ex vivo; the time taken for platelet aggregates in whole blood drawn directly from an antecubital vein to occlude a microfilter was significantly decreased from 155 to 95 s (antilog of mean log values). Platelet secretion in vivo also increased, as indicated by significant elevations of beta-thromboglobulin in plasma; from 22 to 35 ng ml-1 (P = 0.006). 4. ISDN treatment did not inhibit platelet function. Relative to placebo, filtragometry readings (ISDN/placebo ratios; mean and 95% CI) were not altered either at rest (1.05 (0.83 to 1.32)) or immediately after exercise (0.98 (0.80 to 1.20)). Similarly, beta TG in plasma was unaltered by ISDN treatment; 1.09 (0.98 to 1.21) at rest, and 1.04 (0.82 to 1.30) immediately after exercise.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of treatment with oral isosorbide dinitrate on platelet function in vivo; a double-blind placebo-controlled study in patients with stable angina pectoris. 794 39

Safety has been assessed in a total of 1680 subjects who were treated with nicorandil, with 458 patient years of exposure to treatment. Adverse events usually occurred early in the course of treatment. After 30 days of treatment, fewer than 10% of patients reported adverse events. At the recommended doses, the main side effects were limited to headaches. Nearly all episodes of headache were experienced during the first days of nicorandil treatment and were responsible for most of the study withdrawals because of clinical non-acceptability. The incidence can be diminished by a progressive titration. In comparative trials with anti-anginal agents, such as propranolol, diltiazem, nifedipine, ISDN and isosorbide 5 mononitrate, the overall incidence of adverse events was not significantly different between nicorandil and the reference drug. Side-effect distribution was comparable between nicorandil (32%) and diltiazem (30%). Nicorandil can be safely combined with other anti-anginal drugs. Furthermore, due to its favourable pharmacokinetics, nicorandil is less likely to have interactions when combined with another therapeutic agent. Nearly one-third of the patients enrolled in the nicorandil clinical programme were 65 years old or older. Age-specific side-effects were not identified, and overall, the incidence of the most frequent adverse events in the elderly was similar. There is no evidence that nicorandil induces proarrhythmia, exacerbation of myocardial ischaemia or abrupt withdrawal syndrome. With the progressive titration scheme, no symptomatic decrease in blood pressure was recorded when nicorandil was administered in the range of 10-80 mg.day-1. Heart rate was not significantly affected in the same dose range.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Safety profile of an anti-anginal agent with potassium channel opening activity: an overview. 837 Mar 73

In normal subjects or migraine patients, nitrates induce a non-specific early headache caused by vasodilation of intracranial arteries. In migraineurs a delayed headache response to nitrates may have a typical clinical profile of a spontaneous migraine attack. The cerebral vasomotor changes of this delayed response require further study. Isosorbide dinitrate (IDN), an exogenous nitric oxide (NO) donor, was given at a dose of 5 mg sublingually and a bilateral transcranial Doppler device was used to monitor bilateral mean velocity (Vm) changes at the middle cerebral artery (MCA) after IDN administration and until delayed headache occurred. Spontaneous migraine-like headache occurred only in migraine patients during the delayed phase after IDN and was accompanied by a prolonged arterial vasodilation compared to normal subjects. This vasomotor response was more evident on the customary side of the head pain of a spontaneous migraine attack. Our findings suggest a particular vasomotor response to nitrates in migraine patients. This response is associated with the nitrate-induced headache and it is not evident in healthy pain-free controls during the delayed phase after administration of an NO donor. Owing to the short half-life of NO, the neurotransmitter released by IDN, and because of the late onset of headache, we believe the mechanism is unlikely to be vascular in origin, but may have a neurogenic component.
Cephalalgia 1997 May
PMID:Haemodynamic correlates of early and delayed responses to sublingual administration of isosorbide dinitrate in migraine patients: a transcranial Doppler study. 917 Mar 41


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