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)

Levosimendan is one of the first agents of a new class of drugs known as calcium sensitizers. These drugs are believed to increase cardiac contractility by sensitizing cardiac myofibrils to calcium, and may therefore be of clinical benefit in the treatment of low-cardiac output states, particularly congestive heart failure. In addition to sensitizing troponin to intracellular calcium, levosimendan has been shown to inhibit phosphodiesterase III, which may contribute to its positive inotropic effect, and open adenosine triphosphate (ATP)-sensitive potassium channels (K(ATP)), which may produce vasodilation. Unlike currently available intravenous inotropes, levosimendan does not increase myocardial oxygen utilization, has not been shown to be proarrhythmic, and has been used effectively in the presence of beta-blocking medications. Levosimendan also has not been shown to impair ventricular relaxation, which was an initial concern with this class of drugs. Clinical studies of levosimendan have demonstrated short-term hemodynamic benefits of levosimendan over both placebo and dobutamine. While large-scale, long-term morbidity and mortality data are scarce, the Levosimendan Infusion versus Dobutamine in severe low-output heart failure (LIDO) study suggested a mortality benefit of levosimendan over dobutamine up to 180 days after treatment. Clinical studies comparing levosimendan with other positive inotropes, namely milrinone, are lacking. Levosimendan treatment appears to be well-tolerated, with the primary adverse events being headache and hypotension. No clinically significant drug-drug interactions have been reported with levosimendan to date. The clinical future of levosimendan will depend on the results of larger, ongoing clinical trials.
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PMID:Levosimendan: a unique approach to the treatment of heart failure. 1214 86

Nesiritide, a recombinant human B-type natriuretic peptide, is the first in a new drug class for the treatment of decompensated heart failure. The drug binds to receptors in the vasculature, kidney, adrenal gland, and brain, and overcomes resistance to endogenous BNP present in patients with CHF. Nesiritide administration leads to a rapid and balanced vasodilatory effect, which results in a significant decrease in right and left ventricular filling pressures and systemic vascular resistance and at the same time in an increase in stroke volume and cardiac output without a change in heart rate. These early hemodynamic changes result in a rapid improvement in symptoms of heart failure. In addition, nesiritide lowers aldosterone, catecholamines, and endothelin-1 levels and its effect on the kidney leads to an increased natriuresis and diuresis without effect on serum potassium or renal function. Prior to its approval for clinical use, nesiritide was studied in 10 different clinical trials involving 941 patients with moderate and severe CHF, including elderly patients, patients with both systolic and diastolic dysfunction, and patients with arrhythmias, renal insufficiency, and acute ischemic syndrome. In comparative studies with available vasoactive therapies frequently used for treatment of patients with decompensated heart failure, nesiritide was proven comparable in efficacy to inotropic drugs such as dobutamine, but superior in safety. In a recent study, nesiritide was found to be more effective and better tolerated than the vasodilator, nitroglycerin. The most common side effects expected with the use of nesiritide are headaches and decrease in blood pressure. At the recommended dose of nesiritide, headache was reported during the first 24 hours of treatment in 8% of patients and symptomatic hypotension in 4% of patients, compared to 20% and 5% in nitroglycerin-treated patients.
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PMID:Nesiritide: a new drug for the treatment of decompensated heart failure. 1223 67

The present study was conducted among 719 patients enrolled by 109 doctors to evaluate the efficacy and tolerability of the combination of losartan potassium and amlodipine besylate in Indian patients with mild to moderate hypertension. Out of them 11 patients were dropped out. Of these 708 patients 643 patients received once daily dosage of the combination whereas 10 patients received 1/2 daily, 13 patients received 1 1/2 daily and 42 patients received 1 twice daily dosage of the combination. The mean SBP in the study was 172.89 +/- 19.18 mm Hg baseline. After the 10-day treatment, the mean SBP had significant reduction ie, 13.1% from basal and at the end of day 20 of the treatment, the reduction was 19.13% from the baseline which was significant. Similarly mean DBP was 105.42 +/- 10.85 mm Hg at baseline. After treatment, the mean DBP had significant reduction. After 10- day treatment, there was 12.7% reduction from the baseline and at the end of the treatment ie, after day 20, the reduction was 17.70% from basal, which was significant. Global evaluation of efficacy was done by the physicians; 93.8% of the cases had excellent to good response and 4.9% patients had fair response. Details of any adverse event reported or noted during the treatment with the combination were recorded in the appropriate section of the case record form, whether considered treatment related or not, as reported by the patients. The severity of an adverse event was graded on a 3-point scale as mild, moderate and severe. The most common side-effects reported were oedema of feet (5.08%), ankle oedema (1.98%). Remaining adverse events included some cardiovascular events such as palpitations, gastro-intestinal events such as constipation, miscellaneous events, muscular pain, weakness, generalised swelling, etc. CNS events included giddiness, headache, insomnia, etc.
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PMID:Efficacy and safety of losartan-amplodipine combination--an Indian postmarketing surveillance experience. 1240 91

Familial hemiplegic migraine (FHM) is a rare autosomal dominant disorder characterized by episodes of transient hemiparesis followed by headache. Two chromosomal loci are associated to FHM: FHM1 on chromosome 19 and FHM2 on chromosome 1q21-23. Mutations of the alpha-1A subunit of the voltage gated calcium channel (CACNA1A) are responsible for FHM1. FHM2 critical region spans 28 cM, hence hampering the identification of the responsible gene. Here, we report the FHM2 locus refining by linkage analysis on two large Italian families affected by pure FHM. The new critical region covers a small area of 0.9Mb in 1q23 and renders feasible a positional candidate approach. By mutation analysis, we excluded the calsequestrin and two potassium channel genes mapping within the narrowed FHM2 locus.
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PMID:Familial hemiplegic migraine type 2 is linked to 0.9Mb region on chromosome 1q23. 1260 5

Dofetilide is a new antiarrhythmic agent recently approved for the conversion of and maintenance of sinus rhythm in patients with atrial fibrillation (AF) and atrial flutter (AFl). Dofetilide is a selective class III antiarrhythmic drug which works by selectively blocking the rapid component of the delayed rectifier outward potassium current (I(kr)). Dofetilide has been shown to prolong the effective refractory period which is accompanied by a dose-dependent prolongation of the QT and QTc intervals, with parallel increases in ventricular refractoriness. Approximately 80% of dofetilide is excreted in the urine which requires dose adjustments in renal insufficiency. The elimination half-life is approximately 10 h in patients with normal renal function. The therapeutic blood level range of dofetilide is presently unknown and monitoring of dofetilide blood levels is not available at this time. Clinical trials have shown dofetilide to be superior to flecainide in converting AFl patients to normal sinus rhythm (NSR) (70% vs. 9%; p<0.01). It also was more effective than sotalol in converting AF and AFl patients to NSR (29% vs. 6%; p<0.05) and maintaining these patients in NSR for up to 1 year (p<0.05). Most patients convert to NSR within 24-36 h. Torsade de pointes is the most serious side effect occurring in 0.3-10.5% of patients and is dose related. Other common side effects include headache, chest pain and dizziness. To minimize the risk of induced arrhythmia, patients initiated or reinitiated on dofetilide should be hospitalized for a minimum of 3 days where continuous electrocardiographic monitoring, evaluation of renal function and serum electrolytes and cardiac resuscitation can be provided.
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PMID:Dofetilide: A new antiarrhythmic agent approved for conversion and/or maintenance of atrial fibrillation/atrial flutter. 1284 35

Twenty-eight patients were treated with Rautrax,(R) a combination of flumethiazide, rauwolfia and potassium chloride for from one to seven months. The average mean blood pressure for the group declined from 135 mm. of mercury to 107 mm. All but two of the patients had a decrease in blood pressure and 19 became normotensive. Associated symptoms of headache, dyspnea, edema and angina were completely relieved or improved in the majority of patients with these complaints. On the basis of the blood pressure response and the clinical effects seen in the patient, therapeutic results were classified as good to excellent in 22 of the 28 patients, fair in two, and poor in three. No evaluation was made in the remaining patient in the series because further adjustment in dosage was required. Three patients had side effects-moderate gastrointestinal upset in one case, headache and a sensation of the bladder's having been "wrung out" in another, and headache and paresthesia of the legs in the third. Only the third patient had persisting symptoms after the drug was discontinued. In the other two reduction of dosage sufficed.
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PMID:A new antihypertensive agent. Clinical evaluation of a Rauwolfia-flumethiazide combination (rautrax). 1442 68

Increasing knowledge of the molecular consequences of nerve injury and the availability of genome databases has greatly increased the range of potential targets for the pharmacological management of neuropathic pain. Controlling neuronal sensitization and the associated alterations in gene expression, protein modification, and neuronal excitability is the key to managing neuropathic pain. Control of neuronal sensitization can occur through inhibition of nerve injury-associated production of cytokines, activation of glial cells, modulation of potassium channel subtypes, mitogen-activated protein kinases, the ubiquitin-proteasome system, or the protection and amplification of spinal cord dorsal horn inhibitory systems. These new and already established targets promise unparalleled opportunities for the prevention, management, and resolution of persistent pain states following nerve injury.
Curr Pain Headache Rep 2004 Jun
PMID:New and emerging pharmacological targets for neuropathic pain. 1511 37

A 69-year-old woman was referred to our department for evaluation of hypokalemia, which had been treated by oral potassium for more than ten years. She complained of headache, knee joint pain, sleeplessness and paresthesia in extremities and, most prominently, depression. Laboratory data suggested Gitelman's syndrome, which is caused by mutations in the gene encoding the thiazide-sensitive Na-Cl cotransporter. Direct sequencing of the gene in this patient revealed homozygous mutation R964Q in exon 25. Intravenous supplement of MgSO4 dramatically improved both the depression and the paresthesia, suggesting that hypomagnesemia played a role in the clinical manifestations.
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PMID:Depressive state and paresthesia dramatically improved by intravenous MgSO4 in Gitelman's syndrome. 1520 44

The two inhaled long-acting beta2-adrenoceptor agonists, salmeterol and formoterol, have been studied extensively since their introduction in the early 1990s. In this review we consider the evidence for their efficacy and safety in adults with asthma and chronic obstructive pulmonary disease (COPD), by reviewing long-term prospective studies in which these drugs have been compared with placebo or an alternative bronchodilator. We have also assessed safety, including data from postmarketing surveillance studies and case-control studies using large databases. In patients with asthma, salmeterol and formoterol increase lung function, reduce asthmatic symptoms and improve quality of life when compared with placebo. Both drugs protect against exercise-induced asthma, although some tolerance develops with regular use. Tolerance to the bronchodilator effects of formoterol has also been seen, although this is small and most of the beneficial effects are maintained long-term. Both drugs have been shown to reduce asthma exacerbations but only in studies in which most patients were taking an inhaled corticosteroid. Adding a long-acting beta2-agonist provided better control than increasing the dose of inhaled corticosteroid in several studies. Long-acting beta2-agonists also provide better asthma control than use of regular short-acting beta2-agonists and theophylline. Their relative efficacy compared with leukotriene antagonists is uncertain as yet. Formoterol appears to be at least as safe and effective as a short-acting beta2-agonist when used on an 'as required' basis. In patients with COPD, both salmeterol and formoterol offer improved lung function and reduced COPD symptoms compared with placebo, and quality of life has been improved in some studies. Some tolerance to the bronchodilating effect of salmeterol was seen in one study. Most studies have not found a significant reduction in exacerbations in COPD. Both drugs have provided greater benefit than ipratropium bromide or theophylline; there are limited data on tiotropium bromide. The long-acting beta2-agonists cause predictable adverse effects including headache, tremor, palpitations, muscle cramps and a fall in serum potassium concentration. Salmeterol can also cause paradoxical bronchospasm. There is some evidence that serious adverse events including dysrhythmias and life-threatening asthma episodes can occur; however, the incidence of such events is very low but may be increased in patients not taking an inhaled corticosteroid. Salmeterol 50 microg twice daily and formoterol 12 microg twice daily are effective and safe in treating patients with asthma and COPD. Higher doses cause more adverse effects, although serious adverse events are rare.
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PMID:A benefit-risk assessment of inhaled long-acting beta2-agonists in the management of obstructive pulmonary disease. 1535 Jan 54

Carissa edulis (forssk) vahl (Apocynaceae) is used traditionally for the treatment of headache, chest complaints, rheumatism, gonorrhoea, syphilis, rabies and as a diuretic. In the present study, the diuretic activity of different extracts of Carissa edulis was investigated. The diuretic activity of the different extracts of Carissa edulis in a dose range of 50-1000 mg/kg was assessed orally in rats using hydrochlorothiazide as a standard drug. The root bark maceration extract showed no effect on the urine output up to a dose of 1000 mg/kg, while the root bark soxhlet extract produced a significant increase (P < 0.05) in urine output at a dose of 1000 mg/kg. The root wood maceration and root wood soxhlet extracts produced a significant increase in urine output at a dose of 50 mg/kg, with a P-value of <0.05. Urinary electrolyte excretion was also affected by the extracts: the root bark soxhlet extract increased urinary excretion of sodium, potassium and chloride ions; root wood maceration extract increased excretion of sodium and potassium, while root wood soxhlet extract increased excretion of potassium ion. These findings support the traditional use of Carissa edulis as a diuretic agent.
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PMID:Diuretic effect of the crude extracts of Carissa edulis in rats. 1537 7


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