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)

1 We have previously reported that vasodilator headache due to isosorbide dinitrate (ISDN) can be circumvented by using small 'priming' doses for an induction period of 1-2 weeks, after which it is possible to increase to dose rapidly to 360-720 mg, daily without recurrence of headache and without toxicity. The present study corroborates this earlier finding. 2. Chronic oral administration of doses of ISDN of this order of magnitude results in prolonged high plasma concentrations of the parent compound, as well as higher levels of the metabolites 2-ISMN and 5-ISMN. 3. It is our thesis that chronic high oral dosage of ISDN saturates the intrahepatic biotransformation process, and allows high concentrations of ISDN and its metabolites to enter the systemic circulation.
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PMID:Plasma concentrations of isosorbide dinitrate and its metabolites after chronic high oral dosage in man. 66 46

The aim of the present study was to compare the ability of different doses of isosorbide-5-mononitrate (5-ISMN) to cause dilatation of medium sized and small arteries, and to examine the intensity and duration of any headache produced. Ten healthy volunteers each received 3 doses of 5-ISMN and placebo on separate days. The diameters of the radial and superficial temporal arteries were repeatedly measured with high frequency ultrasound and pain was scored using a 10 point verbal scale. A clear dose-relationship was found for plasma concentrations and headache, and for changes in the diameter of the temporal artery, but not for the radial artery. It is concluded that headache after 5-ISMN is caused by arterial dilatation or by mechanisms responsible for the arterial dilatation. Ultrasound monitoring of arterial diameters is an important and sensitive tool in the evaluation of nitrates and other vasodilators.
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PMID:Dose-dependent headache response and dilatation of limb and extracranial arteries after three doses of 5-isosorbide-mononitrate. 154 14

In a multicentre double-blind crossover study the clinical efficacy and tolerability of a controlled-release formulation, Durules, of isosorbide 5-mononitrate (Imdur) 60mg once daily was compared with placebo over 2 weeks in 70 patients with stable exercise-induced angina pectoris who were receiving concomitant long term beta-blockade. Isosorbide 5-mononitrate significantly improved exercise capacity and signs of myocardial ischaemia, while reducing the number of anginal attacks and consumption of short-acting glyceryl trinitrate tablets compared with beta-blocker therapy alone. During an open follow-up period of 1 year, there was no attenuation of the antianginal efficacy of isosorbide 5-mononitrate. The drug was well tolerated during both phases of the study, and the only significant adverse effect was headache, which rapidly disappeared during continued treatment.
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PMID:Long term efficacy of a controlled-release formulation of isosorbide 5-mononitrate (Imdur) in angina patients receiving beta-blockers. 288 18

The anti-anginal effect of a controlled-release (Durules) formulation of isosorbide-5-mononitrate (5-ISMN) 60 mg, Imdur, once daily was evaluated in a randomised double-blind, placebo-controlled, crossover study with a placebo run-in period. Each period lasted for 2 weeks. A total of 70 patients (58 men and 12 women) with stable exertional angina pectoris on beta-blockade, mean age 59 years (range 39-71), were included. Exercise testing was performed on a bicycle ergometer 3 hours after the dose at the end of each period. Anginal attacks and intake of sublingual nitroglycerin tablets were noted. Imdur in combination with a beta-blocker significantly increased the total exercise capacity, the time and total work until the onset of chest pain and at 1 mm ST-depression compared with beta-blockade alone. The attack rate and the nitroglycerin consumption were significantly decreased. Headache was the only significant side-effect. In conclusion, the addition of Imdur once daily to beta-blockade significantly increased the anti-anginal effect.
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PMID:Anti-anginal efficacy of a controlled-release formulation of isosorbide-5-mononitrate once daily in angina patients on chronic beta-blockade. 289 64

Twenty-four patients with stable exercise-induced angina pectoris entered a double-blind cross-over study. Isosorbide-5-mononitrate (5-ISMN) 60 mg in a controlled release formulation (Durules) given once daily was compared with identical placebo. The exercise tolerance was determined by bicycle ergometry before and 3 h after a single dose of 5-ISMN and following one week's treatment with 5-ISMN and placebo. Nineteen patients completed the study. Exercise tolerance until the onset of chest pain and until 1 mm ST segment depression increased significantly 3 h after dose. The same increase was seen both after a single dose and the same dose under steady-state conditions. No increase was seen with placebo. The heart rate and systolic blood pressure reactions in the standing position were less pronounced 3 h after dose in steady-state than after a single dose of 5-ISMN. Headache was the only bothersome side-effect reported. The study demonstrates that 60 mg 5-ISMN in a Durules formulation given once daily has a significant anti-anginal effect and that tolerance does not develop.
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PMID:The effect of isosorbide-5-mononitrate (5-ISMN) Durules on exercise tolerance in patients with exertional angina pectoris. A placebo controlled study. 353 13

The results of 2 clinical studies of controlled-release isosorbide 5-mononitrate (Imdur) in patients with angina pectoris are presented. In an open study in 106 patients the antianginal efficacy of controlled-release isosorbide 5-mononitrate 60 mg once daily was demonstrated by a progressive reduction in the use of short-acting glyceryl trinitrate and in the number of anginal attacks over 6 months. The only significant side effect was headache, which generally disappeared rapidly (after an average of 5 to 6 days). 30 patients were treated in a 1-week single-blind crossover study comparing controlled-release isosorbide 60 mg once daily with a conventional formulation of the drug 20 mg 3 times daily. Both regimens produced similar antianginal and anti-ischaemic effects when the patients were tested by standard ergometry, and the only significant side effect (transient headache) was equally frequent with both regimens.
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PMID:Experience of long term treatment and different dosage regimens of isosorbide 5-mononitrate. 362 14

The possible kinetic and hemodynamic interactions between digoxin and nifedipine were evaluated in nine patients with atrial fibrillation who were receiving chronic digoxin. After 2 control weeks, nifedipine (20 mg b.i.d.), in a new formulation with sustained release characteristics, was added to the therapeutic regimen for 2 weeks. Trough serum digoxin concentrations and peak nifedipine concentrations were determined repeatedly. On the same days, resting blood pressure and heart rate were measured. During nifedipine administration, serum digoxin levels increased by 15% from 0.87 +/- 0.38 to 1.04 +/- 0.37 ng/ml (mean +/- SD, p less than 0.05). This was accompanied by a reduction in systolic and diastolic blood pressure of 16 +/- 6 (p less than 0.01) and 12 +/- 5 mm Hg (p less than 0.001), respectively. In two patients, noncardiac side effects were reported. In two other patients, nifedipine was discontinued because of skin rash and severe headache, respectively. In conclusion, plasma digoxin levels were elevated slightly in the presence of nifedipine, but this probably has little clinical relevance.
Ther Drug Monit 1985
PMID:Interaction between digoxin and nifedipine at steady state in patients with atrial fibrillation. 390 33

The steady-state pharmacokinetic profile of isosorbide-5-mononitrate (5-ISMN) after oral administration of an extended-release tablet formulation of 5-ISMN 60 mg or 120 mg once a day was compared with that after administration of isosorbide dinitrate (ISDN) 40 mg every 6 hours, in a randomized, open-label, three-way crossover trial in 24 healthy men. After oral administration of extended-release 5-ISMN 60 mg or 120 mg once daily, 5-ISMN was slowly absorbed, reaching mean peak plasma concentrations of 557 and 1151 ng/mL, respectively, in approximately 3 hours. Plasma concentrations of 5-ISMN were dose proportional between 60 mg and 120 mg. After oral administration of ISDN 40 mg every 6 hours, a mean peak plasma 5-ISMN concentration of 806 ng/mL was achieved in less than 2 hours (mean time to reach the maximum plasma concentration was 1.5 hours). The mean plasma apparent elimination half-life of 5-ISMN was 6.2 hours after extended-release 5-ISMN administration and 7.1 hours after ISDN. Although the maximum plasma concentration was higher and the minimum plasma concentration was lower after administration of extended-release 5-ISMN 120 mg once daily compared with ISDN 40 mg every 6 hours, there was no significant difference (P > 0.05) in the "bioavailability" of 5-ISMN between these two treatments. The most commonly reported adverse events in these "nitrate-naive" subjects were headache, dizziness, nausea, and vomiting; these were dose related and their incidence decreased with repeated exposure.
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PMID:Pharmacokinetics of isosorbide-5-mononitrate after oral administration of an extended-release mononitrate formulation versus a standard dinitrate formulation. 761 24

Magnesium ions (Mg2+) are pivotal in the transfer, storage and utilization of energy; Mg2+ regulates and catalyzes some 300-odd enzyme systems in mammals. The intracellular level of free Mg2+ ([Mg2+]i) regulates intermediary metabolism, DNA and RNA synthesis and structure, cell growth, reproduction, and membrane structure. Mg2+ has numerous physiological roles among which are control of neuronal activity, cardiac excitability, neuromuscular transmission, muscular contraction, vasomotor tone, blood pressure and peripheral blood flow. Mg2+ modulates and controls cell Ca2+ entry and Ca2+ release from sarcoplasmic and endoplasmic reticular membranes. Since the turn of this century, there has been a steady and progressive decline of dietary Mg intake to where much of the Western World population is ingesting less than an optimum RDA. Geographic regions low in soil and water Mg demonstrate increased cardiovascular morbidity and mortality. Dietary deficiency of Mg2+ results in loss of cellular K+ and gain of cellular Na+ and calcium ions (Ca2+). Blood normally contains Mg2+ bound to proteins, Mg2+ complexed to small anion ligands and free ionized Mg2+ (IMg2+). Most clinical laboratories only now assess the total Mg, which consists of all three Mg fractions. Estimation of the IMg2+ level in serum or plasma by analysis of ultrafiltrates (complexed Mg + IMg2+) is somewhat unsatisfactory, as the methods employed do not distinguish the truly ionized form from Mg2+ bound to organic and inorganic anions. Because the levels of these ligands can vary significantly in numerous pathological states, it is desirable to directly measure the levels of IMg2+ in complex matrices such as whole blood, plasma and serum. Using novel ion selective electrodes (ISE's), we have found that there is virtually no difference in IMg2+, irrespective of whether one samples whole blood, plasma or serum. These data demonstrate that the mean concentration of IMg2+ in blood is about 600 mumoles/litre (0.54-0.65 mmol/L, 95% Cl); 65-72% of total Mg being free or biologically-active Mg2+. Use of the NOVA and KONE ISE's for IMg2+ on plasma and sera from patients with a variety of pathophysiologic and disease syndromes (e.g., long-term renal transplants, liver transplants, during and before cardiac surgery, ischemic heart disease [IHD], headaches, pregnancy, neonatal period, non-insulin dependent diabetes (NIDDM), end-stage renal disease [ESRD], hemodialyse [HEM], and continuous ambulatory peritoneal dialysis (CAPD), hypertension, myocardial infarction [AMI] and after excessive dietary intake of Mg), has revealed interesting data. The results indicate that long-term renal transplant patients, headache, pregnant, NIDDM, ESRD, HEM, CAPD, AMI, hypertensive, and IHD subjects exhibit, on the average significant depression in IMg2+ but not TMg. Use of 31P-NMR spectroscopy on red blood cells, from several of these disease states, to assess free intracellular Mg ([Mg2+]i demonstrates a high correlation (r = 0.5-0.8) between IMg2+ and [Mg2+]i. Increased dietary load of Mg, for only 6 days, in human volunteers, resulted in significant elevations in serum IMg2+ but not TMg. Correlations between the clinical course of several of the above disease syndromes and the fall in IMg2+ and [Mg2+]i were found. The ICa2+/IMg2+ ratio appears, from our data, to be an important guide for signs of peripheral vasoconstriction, ischemia or spasm and possibly atherogenesis. Overall, our data point to important uses for ISE's for IMg2+ in the diagnosis and treatment of disease states.
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PMID:Role of magnesium in patho-physiological processes and the clinical utility of magnesium ion selective electrodes. 886 38

A 40-year-old Asian man, 6 months post renal transplant and receiving tacrolimus therapy, presented to the emergency department with a complaint of sudden-onset left eye pain with blurred vision, headache on the left side, and nausea and vomiting. On being admitted, the patient was intubated for respiratory depression, and erythromycin was initiated for suspected atypical pneumonia. Tacrolimus concentrations (whole blood) drawn on the 3rd day of hospitalization were reported to be > 60.0 ng/ml. Before hospitalization, tacrolimus concentrations were reported to be 9.8 ng/ml on a maintenance dose of 7 mg twice daily. Six days after discontinuation of erythromycin and a decrease in tacrolimus dose, the concentration decreased to 11.5 ng/ml and the original dose of tacrolimus was restarted. It is recommended that concurrent administration of erythromycin and tacrolimus be avoided. However, if concomitant therapy is necessary, tacrolimus concentrations, serum creatinine, blood urea nitrogen, and urine output should be monitored.
Ther Drug Monit 1997 Feb
PMID:Interaction between tacrolimus and erythromycin. 902 62


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