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

Non-steroidal anti-inflammatory drugs (NSAIDs) represent a clinically important class of agents. NSAIDs are commonly used in treatment of conditions such as headache, fever, inflammation and joint pain. Complications often arise from chronic use of NSAIDs. Gastrointestinal (GI) toxicity in the form of gastritis, peptic erosions and ulcerations and GI bleeds limit usage of NSAIDs. These toxicities are thought to be due to cyclooxygenase (COX)-1 blockade. COX-1 generates cytoprotective prostanoids such as prostaglandin (PG) E2 and prostacyclin (PGI2). COX-2 inhibitors, commonly referred to as coxibs, were developed to inhibit inflammatory prostanoids without interfering with production of COX-1 prostanoids. Concerns over cardiovascular safety, however, have evolved based on the concept of inhibition of COX-2-derived endothelial prostanoids without inhibition of platelet thromboxane A2, leading to increased cardiovascular risk. The Celecoxib Long-Term Arthritis Safety Study (CLASS) trial did not show a significant increase in cardiovascular risk for celecoxib (Celebrex), but results of the Vioxx Gastrointestinal Outcomes Research (VIGOR) study showed an increased cardiovascular risk with long-term daily usage of rofecoxib in patients with rheumatoid arthritis. The Adenomatous Poly Prevention on Vioxx (APPROVe) trial further evaluated cardiovascular effects of rofecoxib and recently led to removal of this drug from the marketplace. Coxibs affect renal function via blockade of normal COX-2 functions. COX-2 expression increases in high renin states and in response to a high-sodium diet or water deprivation. PGI2 and PGE2 are the most important renal prostanoids. PGI2 inhibition results in hyperkalemia. PGE2 inhibition results in sodium retention, which leads to hypertension, peripheral edema and potentially exacerbation of heart failure. This review article discusses beneficial and deleterious effects associated with prostanoids produced by COX-1 and COX-2 in various organs and how blockade of these products translates into clinical medicine.
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PMID:Cyclooxygenase-2 inhibitors: a painful lesson. 1678 94

Although uncommon, presentation of juxtaglomerular cell tumor is distinct and should allow a correct preoperative diagnosis in most patients. Typical clinical presentations include headaches, polyuria, or isolated, asymptomatic, severe hypertension. The diagnosis of a juxtaglomerular apparatus (JGA) tumor typically results from identification of plasma renin levels two- to sevenfold greater than the normal value. Although JGA tumors are considered benign, with no reports of metastases or recurrence, they are potentially lethal if left untreated. Surgical excision is curative.
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PMID:Juxtaglomerular apparatus tumor: a rare, surgically correctable cause of hypertension. 1698 80

Aliskiren is a novel, orally active direct renin inhibitor that lowers blood pressure alone and in combination with existing antihypertensive agents. As aliskiren does not affect cytochrome P450 enzyme activities, is minimally metabolised, and is not extensively protein bound, the potential for drug interactions is predicted to be low. Four open-label studies investigated the pharmacokinetic interactions between aliskiren 300 mg and the antihypertensive drugs amlodipine 10 mg (n = 18), valsartan 320 mg (n = 18), hydrochlorothiazide 25 mg (HCTZ, n = 22) and ramipril 10 mg (n = 17) in healthy subjects. In each study, subjects received multiple once-daily doses of aliskiren and the test antihypertensive drug alone or in combination in two dosing periods separated by a drug-free washout period. Plasma concentrations of drugs were determined by liquid chromatography and mass spectrometry methods. At steady state, relatively small changes in exposure to aliskiren were observed when aliskiren was co-administered with amlodipine (AUC(tau) increased by 29%, p = 0.032), ramipril (C(max,ss) increased by 31%, p = 0.043), valsartan (AUC(tau) decreased by 26%, p = 0.002) and HCTZ (C(max,ss) decreased by 22%, p = 0.039). Co-administration with aliskiren resulted in small changes in exposure to ramipril (AUC(tau) increased by 22%, p = 0.002), valsartan (AUC(tau) decreased by 14%, p = 0.062) and HCTZ (AUC(tau) decreased by 10% and C(max,ss) by 26%, both p < 0.001). All other changes in pharmacokinetic parameters were also small, and not statistically significant. None of the observed pharmacokinetic changes was considered clinically relevant. Aliskiren inhibited plasma renin activity (PRA) and also prevented the reactive rise in PRA induced by valsartan. The most commonly reported adverse events were headache, dizziness and gastrointestinal symptoms (all mild in severity), which were similar in frequency during antihypertensive drug treatment alone and in combination with aliskiren except for an increase in dizziness during treatment with the combination of aliskiren and HCTZ. In conclusion, aliskiren shows no clinically relevant pharmacokinetic interactions and is generally well tolerated when administered in combination with amlodipine, valsartan, HCTZ or ramipril.
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PMID:Lack of pharmacokinetic interactions of aliskiren, a novel direct renin inhibitor for the treatment of hypertension, with the antihypertensives amlodipine, valsartan, hydrochlorothiazide (HCTZ) and ramipril in healthy volunteers. 1707 28

Patients with severe hypertension (>180/110 mm Hg) require large blood pressure (BP) reductions to reach recommended treatment goals (<140/90 mm Hg) and usually require combination therapy to do so. This 8-week, multicenter, randomized, double-blind, parallel-group study compared the tolerability and antihypertensive efficacy of the novel direct renin inhibitor aliskiren with the angiotensin converting enzyme inhibitor lisinopril in patients with severe hypertension (mean sitting diastolic blood pressure (msDBP)>or=105 mm Hg and <120 mm Hg). In all, 183 patients were randomized (2:1) to aliskiren 150 mg (n=125) or lisinopril 20 mg (n=58) with dose titration (to aliskiren 300 mg or lisinopril 40 mg) and subsequent addition of hydrochlorothiazide (HCTZ) if additional BP control was required. Aliskiren-based treatment (ALI) was similar to lisinopril-based treatment (LIS) with respect to the proportion of patients reporting an adverse event (AE; ALI 32.8%; LIS 29.3%) or discontinuing treatment due to AEs (ALI 3.2%; LIS 3.4%). The most frequently reported AEs in both groups were headache, nasopharyngitis and dizziness. At end point, ALI showed similar mean reductions from baseline to LIS in msDBP (ALI -18.5 mm Hg vs LIS -20.1 mm Hg; mean treatment difference 1.7 mm Hg (95% confidence interval (CI) -1.0, 4.4)) and mean sitting systolic blood pressure (ALI -20.0 mm Hg vs LIS -22.3 mm Hg; mean treatment difference 2.8 mm Hg (95% CI -1.7, 7.4)). Responder rates (msDBP<90 mm Hg and/or reduction from baseline>or=10 mm Hg) were 81.5% with ALI and 87.9% with LIS. Approximately half of patients required the addition of HCTZ to achieve BP control (ALI 53.6%; LIS 44.8%). In conclusion, ALI alone, or in combination with HCTZ, exhibits similar tolerability and antihypertensive efficacy to LIS alone, or in combination with HCTZ, in patients with severe hypertension.
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PMID:A comparison of the tolerability of the direct renin inhibitor aliskiren and lisinopril in patients with severe hypertension. 1754 89

Hypertension is a common chronic disease that leads to significant cardiovascular morbidity and mortality worldwide. Blood pressure control is critical in reducing the end-organ complications, such as stroke, myocardial infarction, heart failure, or kidney disease. Currently available antihypertensive agents work by different mechanisms to reduce blood pressure. Aliskiren, a novel direct renin inhibitor, lowers blood pressure by decreasing renin activity, and angiotensin I and II levels. At the approved dosage (150-300 mg once daily), it reduces systolic blood pressure by 12-16 mm Hg and diastolic blood pressure by 2-12 mm Hg. In studies its efficacy was comparable to losartan 100 mg, irbesartan 150 mg, and valsartan 80-320 mg. When used adjunctively with ramipril, an angiotensin-converting enzyme (ACE) inhibitor, valsartan, an angiotensin II receptor blocker (ARB), or hydrochlorothiazide, a diuretic, it provides additional blood pressure reduction compared with placebo or monotherapy. Aliskiren is well tolerated, with the most common side effects being gastrointestinal symptoms, fatigue, weakness, and headache. In short-term clinical trials, aliskiren caused fewer disturbances in potassium levels when compared with hydrochlorothiazide, ACE inhibitors and ARBs. Long-term data on morbidity and mortality outcomes are not currently available, thus it is unknown whether aliskiren would join ACE inhibitors and ARBs as the preferred hypertensive agents for end organ protection. At this time, aliskiren should be considered as an alternative agent for mild-to-moderate hypertension, or as an adjunctive therapy when preferred agents fail to maintain optimal blood pressure control. It is also an option for those patients who have contraindications or intolerability to other antihypertensive agents, including dry cough induced by ACE inhibitors.
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PMID:Aliskiren: an oral renin inhibitor for the treatment of hypertension. 1809 68

A rare case of combined unilateral adrenal hyperplasia and paraganglioma is reported. A 27-year-old woman presented with hypertension, palpitation, dizziness, and headache for about 3 months. Elevated plasma aldosterone with low renin and a high level of urine vanillylmandelic acid (VMA) were found. Computed tomography showed a microadenoma of the left adrenal gland and a well demarcated left retroperitoneal para-aortic mass. Adrenal vein sampling for aldosterone and renin levels suggested left adrenal lesion. Surgical removal of the left adrenal gland and para-aortic mass was performed. Pathologic examination of the resected left adrenal gland showed adrenal cortical hyperplasia and the left retroperitoneal para-aortic mass showed a paraganglioma. Postoperatively, blood pressure, plasma renin, aldosterone and urine VMA all returned to within normal ranges. The possible relationship of these two diseases is discussed.
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PMID:Hypertension due to co-existing paraganglioma and unilateral adrenal cortical hyperplasia. 1819 11

This is a case report of a woman who showed headache, weakness, upper-limb edema and a generalized convulsive seizure after chronic ingestion of liquorice. She was taking oral contraceptives which can predispose to liquorice toxicity. Plasma potassium, aldosterone, renin activity and albumin were below the normal level. The abdominal echography and computerized tomography scan demonstrated a perihepatic and perisplenic thin liquid layer with liquid collection in the pelvis. The bioelectrical impedance suggested a hyperhydration state. After stopping the liquorice, the laboratory and bioelectrical values normalized and clinical upper-limb edema and the liquid in the abdomen disappeared in a few days.
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PMID:Liquorice-induced hypokalaemia and water retention in the absence of hypertension. 1838 59

Several conditions are comorbid with migraine; our review is focused on the relation between migraine, and cerebrovascular and cardiovascular diseases. Despite many studies showed an association between migraine and patent foramen ovale, it is still not known whether its presence might be causal for the migraine pathogenesis and currently its closure cannot be recommended for migraine prevention. On the contrary, conflicting epidemiological data link migraine to arterial hypertension and the use of antihypertensive agents acting on the renin-angiotensin system sounds promising in migraine prevention. A complex bidirectional relation exists between migraine and stroke, and new evidences show a clear association between migraine and coronary heart disease. In both conditions, migraine represents a defined risk factor although the magnitude of the risk varies across the different studies. However, since the risk is low in the general population, it is not possible to identify which migraineurs will develop a cardiovascular or a cerebrovascular event making difficult to apply preventive measures.
J Headache Pain 2008 Aug
PMID:Comorbid neuropathologies in migraine: an update on cerebrovascular and cardiovascular aspects. 1860 Mar

Intensive efforts have been spent to discover therapeutic, non-peptide and orally effective hypertensive drugs. One drug that emerged from this effort is aliskiren, a direct human renin inhibitor that blocks the conversion of angiotensinogen to angiotensin I (Ang I). In contrast to other antihypertensive agents, aliskiren decreases plasma renin activity (PRA). In healthy human subjects, doses of between 40 and 640 mg of aliskiren exert a dose-dependent reduction in PRA and Ang I and Ang II levels. The bioavailability of aliskiren is low (2%), peak plasma concentrations are reached within one to three hours and the binding with plasma proteins achieves approximately 47-51%. Aliskiren is slightly metabolized (20%) by CYP3A4. The most common adverse events include diarrhea, headache, back pain and gastrointestinal disorders. Aliskiren is well tolerated, and may be used alone or in combination with other antihypertensive agents. Aliskiren belongs to a new class of agents that effectively and specifically inhibit the RAS. This drug functions through a novel mechanism of action and has the potential to become a true alternative to angiotensin converting enzyme inhibitors and angiotensin receptor blockers in the therapy of hypertension and other cardiovascular and renal disorders.
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PMID:Pharmacokinetics and pharmacodynamics of aliskiren, an oral direct renin inhibitor. 1906 8

Migraine is a chronic disease with episodic attacks, which, when frequent or severe, can be associated with poor quality of life, increased health resource utilization, lost productivity, and significant disability. Preventive therapy can therefore have a significant beneficial clinical and economic impact. However, many migraineurs are treated suboptimally. There is increasing evidence that activation and degranulation of meningeal mast cells result in meningeal irritation, vascular dilation, and stimulation of nearby nociceptive nerve endings of the trigeminal nerve, thus potentially contributing to the pathogenesis of migraine headache. The renin angiotensin system and its peptides are well represented in the mammalian central nervous system and can also promote neurogenic inflammation. Interestingly, mast cells are capable of releasing renin and increasing local production of Angiotensin II. We therefore hypothesize that mast cells contribute to migraine headache through activation of the renin angiotensin system. This hypothesis may help explain the association between migraine and cardiovascular disease as well as observations that medications that modulate the renin angiotensin system can reduce migraine-related morbidity in patients with frequently recurring migraine attacks.
Headache
PMID:Mast cells activate the renin angiotensin system and contribute to migraine: a hypothesis. 1907 48


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