Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nonsteroidal anti-inflammatory drugs(NSAIDs) are clinically effective against the inflammatory symptoms of rheumatoid arthritis. Recent attention has been focused on selective cyclooxygenase(COX)-2 inhibitors, a type of NSAID that inhibits a subtype of COX. Because of the different actions of COX-1 and COX-2, selective COX-2 inhibitors were expected to reduce adverse reactions such as gastrointestinal disorders. Various clinical studies have confirmed that the efficacy of COX-2 inhibitors for RA is similar to that of conventional NSAIDs, but they cause fewer severe gastrointestinal disorders. The incidence of complications related to renal dysfunction, such as edema and hypertension, is not different. Patients using selective COX-2 inhibitors have recently been reported to show an increase in thrombotic complications such as myocardial infarction. Therefore, more data on adverse events should be collected in the future from large-scale clinical studies to further clarify the actual value of selective COX-2 inhibitors.
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PMID:[Recent development of selective cyclooxygenase-2 inhibitors]. 1251 Mar 64

The purpose of this review is to provide an overview of the effect of traditional nonsteroidal anti-inflammatory drugs (NSAIDs) and cyclooxygenase (COX)-specific-2 inhibitors (coxibs) on renal function. Both COX isoforms (COX-1 and COX-2) constitutively are expressed in the adult mammalian kidney and contribute to the biosynthesis of prostaglandins (PGs). Inhibition of COX activity in the kidney by NSAIDs has relatively mild consequences in healthy individuals, but can lead to serious adverse events in patients whose renal function is PG dependent. Most studies have reported transient decreases in sodium excretion upon initiation of therapy with either traditional NSAIDs or coxibs. In patients whose renal function is dependent on prostanoids, both nonselective NSAIDs and coxibs can affect the glomerular filtration rate. Changes in renal function may result in hypertension and edema. Several studies have compared the effects of traditional NSAIDs, celecoxib, and rofecoxib on blood pressure and incidence of edema, but the results have not been consistent, as the trials used different clinical models and study designs. No trials to date have been performed with rigorous study designs that allow meaningful drug comparisons at comparably effective doses. In consequence, patients who are at risk for adverse renal events should be monitored with the same caution when receiving coxibs as when receiving treatment with nonselective NSAIDs. They include patients with congestive heart failure or renal or hepatic disease, as well as those of advanced age receiving therapy with diuretics or angiotensin-converting enzyme (ACE) inhibitors.
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PMID:Anti-inflammatory agents and renal function. 1252 72

With the development and clinical implementation of the new cyclooxygenase (COX)-2 inhibitors, their safety, including the effects on renal function and blood pressure, is attracting increasing attention. In the kidney, COX-2 is constitutively expressed and is highly regulated in response to alterations in intravascular volume. COX-2 metabolites have been implicated in mediation of renin release, regulation of sodium excretion, and maintenance of renal blood flow. Similar to conventional nonsteroidal anti-inflammatory drugs, inhibition of COX-2 may cause modest elevations in blood pressure in a minority of subjects. COX-2 inhibitors may also exacerbate pre-existing hypertension or interfere with other antihypertensive drugs. Special caution should be taken in patients with volume depletion or decreased organ perfusion.
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PMID:Does cyclooxygenase-2 affect blood pressure? 1253 Sep 41

Heme oxygenase (HO) regulates cellular heme levels and catalyzes the formation of bilirubin and carbon monoxide. We hypothesize that the status of the endothelial HO system influences the angiotensin (Ang) II-induced increase in the endothelial production of prostaglandin I2 (PGI2) (measured as 6-keto-PGF1alpha) and prostaglandin E2 (PGE2), eicosanoids that modulate the vascular actions of Ang II. In the present study, we determined the effect of interventions that suppress HO activity or induce HO-1 gene expression on Ang II-mediated increase in 6-keto-PGF1alpha and PGE2 in cultures of human femoral artery endothelial cells. Incubation of endothelial cells with Ang II (100 ng/mL) for 24 hours increased the levels of both 6-keto-PGF1alpha and PGE2 in the culture media. This effect of Ang II on prostaglandin production by endothelial cells was attenuated in cells treated with SnCl2 (10 micromol/L), an inducer of HO-1, but was magnified in cells treated with the HO inhibitor ZnDPP or heme. Upregulation of HO-1 gene expression by retrovirus-mediated delivery of the human HO-1 gene also attenuated heme and Ang II-induced prostaglandin synthesis. Of note, prostaglandin synthesis by lysates of endothelial cells stimulated with heme or Ang II appear to involve COX-2, because it was blunted by NS-398, which is presumed to inhibit COX-2 specifically. These results indicate that overexpression of the HO system exerts an inhibitory influence on Ang II-induced synthesis of prostaglandins by endothelial cells.
Hypertension 2003 Mar
PMID:Heme oxygenase attenuates angiotensin II-mediated increase in cyclooxygenase-2 activity in human femoral endothelial cells. 1262 85

Heart failure constitutes an increasing public health problem because of the growing incidence and prevalence, poor prognosis and high hospital (re)admission rates. Myocardial infarction is the underlying cause in the majority of patients, followed by hypertension, valvular heart disease and idiopathic cardiomyopathy. Nonsteroidal anti-inflammatory drugs (NSAIDs), which inhibit the enzymes cyclo-oxygenase (COX) 1 and 2, have been associated with the occurrence of symptoms of heart failure in several case reports and quantitative studies, mainly in patients with a history of cardiovascular disease or left ventricular impairment. NSAIDs may impair renal function in patients with a decreased effective circulating volume by inhibiting prostaglandin synthesis. Consequently, water and sodium retention, and decreases in renal blood flow and glomerular filtration rate may occur, affecting the unstable cardiovascular homeostasis in these patients. In patients with pre-existing heart failure, this may lead to cardiac decompensation. Putative renal-sparing NSAIDs, such as COX-2 selective inhibitors have similar effects on renal function as the traditional NSAIDs, and can likewise be expected to increase the risk of heart failure in susceptible patients. NSAIDs are frequently prescribed to elderly patients, who are particularly at risk for the renal adverse effects. If treatment with NSAIDs in high risk patients cannot be avoided, intensive monitoring and patient education is important.
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PMID:Nonsteroidal anti-inflammatory drugs and heart failure. 1265 51

Antithrombotic therapy is the cornerstone of the treatment of acute coronary syndromes, but there is now evidence which indicates that by blocking inflammation, thrombosis and thus, acute coronary events, could be lowered. The concept of athero-inflammation emerges as the meeting point of different morbidities; dyslipemia, diabetes, hypertension, obesity, immunity, infection, hyperhomocyteinemia, smoking, etc. usual named as risk factors. Thus, beside specific drugs, earliest treatment, in the stage of inflammation, using anti-inflammatory drugs, should be considered since in patients with increased risk of acute coronary process are likely to have many point of origen throughout the coronary arteries. There are a body of evidences for supporting the potential of anti-inflammatory therapy to the prevention of inflammation and atherosclerosis. COX-2 inhibition may decrease endothelial inflammation reducing monocytes infiltration improving vascular cells function, plaque stability and probably resulting in a decrease of coronary atherothrombotic events.Trials including large numbers of patients in prospective double-blind randomized studies worthwhile to confirm the efficacy of NSAID, mainly, COX-2 inhibitors, together with aspirin in the prevention of coronary events in patients with acute coronary disease.
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PMID:Acute coronary disease Athero-Inflammation: Therapeutic approach. 1290 61

Advantages and risks related to the use of selective COX-2 inhibitors when treating arthritis are currently being scrutinized by authorities and public. The discussion tends towards exaggerated claims for or against their usefulness. The issue of cardiovascular safety is still not finally settled. In an experimental study using patients with severe coronary disease, administration of celecoxib resulted in improved endothelial function together with reduced CRP levels. Gastrointestinal tolerance was studied in patients who had recently recovered from peptic ulcer bleeding. In this group of high risk patients, celecoxib was as safe as combined therapy using omeprazol and diclofenac when given for 6 months. However, both COX inhibitors caused hypertension and adverse renal effects. The second generation of selective inhibitors is being launched. Etoricoxib--related to rofecoxib--was shown to be as potent as indomethacin in the treatment of acute gout, but it caused fewer adverse reactions. In general, however, any advantage of second generation as compared to first generation COX-2 inhibitors remains to be proven. The Swedish Council on Technology Assessment in Health Care, in its "SBU Alert", has published an appraisal of celecoxib and rofecoxib, in which the need for further long-term safety studies is emphasized.
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PMID:[New studies of COX-inhibitors, yet issues remain]. 1455 11

A 62-year-old man with a past medical history notable for hypertension, osteoarthritis, and calf deep vein thrombosis at age 55 following a total hip arthroplasty presents to the emergency department with acute-onset dyspnea and right-sided pleuritic chest pains. His medications consist of a calcium channel blocker and a COX-2 inhibitor. Pretest clinical suspicion for pulmonary embolism (PE) is high. Ventilation and perfusion lung scintigraphy are interpreted as being high-probability for PE. The nurse asks if a stat transthoracic echocardiogram should be ordered.
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PMID:Patients with acute pulmonary embolism should have an echocardiogram to guide treatment decisions. 1468 Mar 5

Selective cyclooxygenase (COX)-2 inhibitors that are in widespread clinical use were developed to avoid side effects of conventional NSAIDs, including gastrointestinal and renal toxicity. However, COX-2 is constitutively expressed in the kidney and is highly regulated in response to alterations in intravascular volume. COX-2 metabolites have been implicated in maintenance of renal blood flow, mediation of renin release, and regulation of sodium excretion. COX-2 inhibition may transiently decrease urine sodium excretion in some subjects and induce mild to moderate elevation of blood pressure. Furthermore, in conditions of relative intravascular volume depletion and/or renal hypoperfusion, interference with COX-2 activity can have deleterious effects on maintenance of renal blood flow and glomerular filtration rate. In addition to physiological regulation of COX-2 expression in the kidney, increased renal cortical COX-2 expression is seen in experimental models associated with altered renal hemodynamics and progressive renal injury (decreased renal mass, poorly controlled diabetes), and long-term treatment with selective COX-2 inhibitors ameliorates functional and structural renal damage in these conditions.
Hypertension 2004 Mar
PMID:Cyclooxygenases, the kidney, and hypertension. 1473 22

Non-steroidal anti-inflammatory drugs (NSAIDs) and selective cyclooxygenase (COX)-2 inhibitors are commonly used to control pain and inflammation in osteoarthritis. However, these agents have been associated with gastrointestinal, renal and cardiovascular adverse effects. Together, these complications indicate a clear unmet need in the safety of current treatment options for the management of osteoarthritis. NSAIDs are known to have adverse gastrointestinal effects, and more recently it has been suggested that some selective COX-2 inhibitors are also associated with serious gastrointestinal complications. Selective COX-2 inhibitors have a similar capacity to NSAIDs to delay ulcer healing, and may not significantly decrease the incidences of perforation, ulceration and bleeding (the most clinically relevant gastrointestinal endpoints) compared with NSAIDs. These effects may be due to overlapping roles of COX-1 and COX-2 in physiological and pathophysiological processes. Furthermore, as COX-2 is integrally involved in renal homeostasis, selective COX-2 inhibitors are associated with negative effects on kidney function similar to those seen with NSAIDs. Electrolyte disturbances, oedema and hypertension have been correlated with the use of both drug classes. Additionally, selective COX-2 inhibitors have the potential to increase cardiovascular events, although further research is required to clearly determine such a risk. With the current unmet needs in the treatment of osteoarthritis, the opportunity exists for the development of new therapies. Novel agents include the COX-inhibiting nitric oxide donors and the lipoxygenase (LOX)/COX inhibitor licofelone. Initial results suggest that these therapies may have tolerability advantages over the NSAIDs and selective COX-2 inhibitors.
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PMID:Osteoarthritis therapy--are there still unmet needs? 1475 70


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