Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Obesity is associated with an increased concentration of inflammatory mediators, which in turn, in adults, reduces the response to calcium channel blockers (CCBs). We reviewed the medical charts of 263 pediatric nephrology patients with renal conditions, with the aim of studying the effect of obesity on the response to L-type CCBs, angiotensin interrupting agents (ANGIs), or a combination of the two. Forty-eight patients were ultimately enrolled in the study: 25 obese and 23 non-obese patients. The effect of the treatments on lowering the blood pressure was compared in obese versus non-obese patients. The systolic response to CCBs, measured as at least a 10% reduction from the baseline, was significantly lower in the obese (12.5%) patients than in the non-obese (52.9%) ones. The differences in diastolic response (58.8 and 25% for non-obese and obese patients, respectively) did not reach significance. The percentage response to CCBs, however, was significantly less in the obese patients than in the non-obese patients for both systolic and diastolic blood pressure. Corticosteroids also significantly influenced the response to CCBs in terms of diastolic pressure (62.9 and 25% for non-obese and obese patients, respectively). None of the tested covariates, including obesity, was found to significantly influence the response to ANGIs alone or in various combinations with CCBs. In conclusion, obesity and corticosteroid therapy should be considered when initiating antihypertensive drug treatment in children with kidney disease as both may contribute to a reduced efficacy of the antihypertensive therapy.
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PMID:Effect of obesity on response to cardiovascular drugs in pediatric patients with renal disease. 1908 22

Active rheumatoid arthritis (RA), obesity, and old age are associated with reduced responsiveness to the calcium channel antagonist verapamil despite increased drug concentrations. The diminishing effect appears to be associated with the severity of inflammation. We examined pharmacodynamics and pharmacokinetics of verapamil in patients with controlled RA. Volunteers included RA patients in remission: 12 on infliximab, 8 on other antirheumatic therapy, and 12 healthy subjects. Verapamil plasma concentrations and selected inflammatory mediators as well as blood pressure and electrocardiographic parameters were recorded after a single 80-mg dose of verapamil. Inflammatory mediators were all below what is reported for active RA, confirming that RA was controlled. The tumor necrosis factor-alpha concentration, however, was significantly higher in the infliximab group compared with other groups and the literature value for active RA. No significant difference was observed between groups in terms of percentage prolongation of PR interval despite a trend toward a lower response in the RA groups, the mean plasma concentrations, and the total and unbound area under the curve of verapamil. However, the slope of the S-verapamil concentration-effect curve was steeper for controls compared with the RA patients. Remission from active disease appears to restore plasma protein levels and hepatic drug metabolism activity in patients with RA, resulting in relatively normal verapamil pharmacokinetics.
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PMID:Influence of controlled rheumatoid arthritis on the action and disposition of verapamil: focus on infliximab. 1916 2

Obesity is a major risk factor for hypertension. Adipose tissue releases numerous substances that act on the pathophysiologic mechanisms of blood pressure. Management of obese patients with high blood pressure includes weight loss efforts, but antihypertensive treatment is most often necessary. Beta-blockers, alone or with thiazide diuretics, increase the risk of diabetes in hypertensive patients. Treatment against hypertension must include a renin-angiotensin system blocker, with a calcium channel blocker or a thiazide diuretic, if necessary.
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PMID:[Hypertension in obese patients: Pathophysiology and management]. 1923 4

Cardiomyocyte apoptosis is a critical process in the pathogenesis of ischemic and diabetic cardiomyopathy, but the mechanisms are not fully understood. Thioredoxin-interacting protein (TXNIP) has recently been shown to have deleterious effects in the cardiovascular system and we therefore investigated whether it may also play a role in diabetes-associated cardiomyocyte apoptosis. In fact, TXNIP expression was increased in H9C2 cardiomyocytes incubated at high glucose, and cardiac expression of TXNIP and cleaved caspase-3 were also elevated in vivo in streptozotocin- and obesity-induced diabetic mice. Together, these findings not only suggest that TXNIP is involved in diabetic cardiomyopathy but also that it may represent a novel therapeutic target. Surprisingly, testing putative TXNIP modulators revealed that calcium channel blockers reduce cardiomyocyte TXNIP transcription and protein levels in a dose-dependent manner. Oral administration of verapamil for 3 wk also reduced cardiac TXNIP expression in mice even in the face of severe diabetes, and these reduced TXNIP levels were associated with decreased apoptosis. To determine whether lack of TXNIP can mimic the verapamil-induced decrease in apoptosis, we used TXNIP-deficient HcB-19 mice, harboring a natural nonsense mutation in the TXNIP gene. Interestingly, we found significantly reduced cleaved caspase-3 levels in HcB-19 hearts, suggesting that TXNIP plays a critical role in cardiac apoptosis and that the verapamil effects were mediated by TXNIP reduction. Thus our results suggest that TXNIP reduction is a powerful target to enhance cardiomyocyte survival and that agents such as calcium channel blockers may be useful in trying to achieve this goal and prevent diabetic cardiomyopathy.
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PMID:Diabetes induces and calcium channel blockers prevent cardiac expression of proapoptotic thioredoxin-interacting protein. 1925 88

Increasing lifespan and progressive aging of the Polish population results in rising demands on health care. Chronic diseases with a leading position of arterial hypertension (HA) prevail in morbidity rates of adult seniors. The aim of the study is to characterize hypertension in the elderly with regard to other risk factors, complications and therapeutic control. The study was carried out in 2002 within the framework of the CINDI WHO Programme. A total of 1460 persons were randomly selected among residents of Lodz aged > or = 65 years. The response rate was 57%. All participants underwent questionnaire interview, two blood pressure (BP) measurements, anthropometric and physical examination, ECG and laboratory tests. After final verification, we analysed data collected from 828 persons (289 men and 539 women). Mean values of systolic and diastolic BP were 147.6 and 83.6 mmHg, respectively. The increase of systolic BP with age of studied seniors was observed. Hypertension was diagnosed in 669 persons (79% men, 82% women). In most cases there were systolic-diastolic or isolated systolic hypertension. About 60% of seniors with elevated BP declared suffering from HA, while 73% were under antihypertensive treatment. Normalization of BP (< 140/ 90 mmHg) was achieved in 28% of treated patients. Most often prescribed medications were: ACE-inhibitors (51%), beta-blockers (40%), calcium channel blockers (31%) and diuretics (30%). Mean values of plasma lipids and prevalence of lipid disorders were comparable in hypertensive and normotensive persons. Among patients with HA there were significantly smaller percentage of smokers (8.6% vs 18.7%, p < 0.05). The prevalence of obesity, visceral obesity and metabolic syndrome was higher in hypertensive seniors. As a result, incidents of myocardial infarction and morbidity due to coronary artery disease were twice as cantly more often hospitalised and visited family doctors (7 vs 4.6 visits/year) in comparison to normotensive subjects.
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PMID:[Arterial hypertension as a medical and social problem in the older urban population. The CINDI WHO Program study]. 1944 75

Diabetes mellitus and hypertension frequently coexist in patients with the insulin resistance syndrome (IRS). Patients with both diabetes and hypertension typically have widespread endothelial dysfunction, increased oxidative stress, an activated sympathoadrenal system, and an elevated systemic burden of inflammatory mediators. Patients with diabetes and hypertension also have concomitant mixed dyslipidemia and obesity with significant frequency, and are at high risk for the development of macro- and microvascular disease, congestive heart failure, and nephropathy. Current data suggest that ACE inhibitors or angiotensin receptor blockers with or without a diuretic are important, if not preferred, initial therapies for the patient with diabetes and hypertension. Other drug classes such as combined alpha-/beta-adrenoceptor antagonists, dihydropyridine calcium channel antagonists (CCAs), and peripheral alpha-adrenoceptor antagonists are also useful therapeutic options in these patients. In order to optimally reduce the risk for cardiovascular events in the patient with diabetes and hypertension, optimal BP control should be coupled with comprehensive lifestyle modification and aggressive management of dyslipidemia and hyperglycemia.
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PMID:A guide to the management of blood pressure in the diabetic hypertensive patient. 1946 21

High blood pressure is often difficult to control. Resistant hypertension is blood pressure above goal despite adherence to a combination of at least three antihypertensive medications of different classes, optimally dosed and usually including a diuretic. The approach to blood pressure that is apparently difficult to control begins with an assessment of the patient's adherence to the management plan, including lifestyle modifications and medications. White-coat hypertension may need to be ruled out. Suboptimal therapy is the most common reason for failure to reach the blood pressure goal. Once-daily fixed-dose combination pills may improve control through the synergism of antihypertensive agents from different classes and improved adherence. Truly drug-resistant hypertension is commonly caused by chronic kidney disease, obstructive sleep apnea, or hyperaldosteronism, all of which can lead to fluid retention. Higher doses of diuretics (or a change to a loop diuretic) are usually needed. Other strategies include adding an alpha blocker, alpha-beta blocker, clonidine, or an aldosterone antagonist (e.g., spironolactone). Particularly in patients with diabetes or renal disease, combining a long-acting nondihydropyridine with a dihydropyridine calcium channel . blocker can also be considered. Obesity, heavy alcohol intake, high levels of dietary sodium, and interfering substances (especially nonsteroidal anti-inflammatory drugs) contribute to hypertension that is resistant or difficult to control.
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PMID:Evaluation and management of the patient with difficult-to-control or resistant hypertension. 2070 61

1. Obesity is increasingly common among liver transplantation (LT) recipients and donors. Outcomes following LT for selected patients with class I-III obesity are similar to those for nonobese recipients. In patients who are otherwise satisfactory candidates for LT, a high body mass index, as long as it does not present a technical barrier, should not be considered to be an absolute contraindication to LT. 2. The most common causes of death beyond the first year of LT are, in descending order of frequency, graft failure (especially secondary to hepatitis C virus recurrence), malignancy, cardiovascular disease, infections, and renal failure. Metabolic syndrome is an important risk factor for each of these etiologies of posttransplant death. Posttransplant diabetes, posttransplant hypertension, and an original diagnosis of cryptogenic cirrhosis, which is commonly associated with metabolic syndrome, are all associated with an increased risk of post-LT mortality. Features of metabolic syndrome should be screened for and treated in LT recipients. 3. Because of the physiological mechanism of post-LT hypertension, which includes renal arteriolar constriction secondary to calcineurin inhibition, calcium channel blocking agents are a good pharmacological treatment modality and have been shown to be effective in renal protection in randomized controlled trials of posttransplant hypertension. 4. It is rare for dietary changes and weight reduction to result in normalization of the lipid profile. Statins should thus be initiated early in the course of management of post-LT dyslipidemia. Forty milligrams of simvastatin per day, 40 mg of atorvastatin per day, and 20 mg of pravastatin per day are reasonable starting doses for post-LT hypercholesterolemia. It is important to remember that the effects of statin therapy are additive to those of a controlled diet (eg, a Mediterranean diet rich in omega-3 fatty acids, fruits, vegetables, and dietary fiber). 5. Nonalcoholic steatohepatitis, an increasingly common etiology of cirrhosis and liver failure, recurs commonly after LT and may also arise de novo. Treatment should be directed at managing obesity and complications of metabolic syndrome. Optimal immunosuppression in patients with nonalcoholic steatohepatitis is still evolving but should include steroid minimization.
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PMID:Obesity, hyperlipidemia, and metabolic syndrome. 1987 24

Atrial fibrillation (AF) is very common within the first 5 days of cardiac surgery. It is associated with significant morbidity including stroke, ventricular arrhythmias, myocardial infarction, heart failure, acute kidney injury, prolonged hospital stay, and also short- and long-term mortality. The underlying mechanisms of developing AF after cardiac surgery are multifactorial; risk factors may include advanced age, withdrawal of beta-blockers and angiotensin-converting-enzyme inhibitors, valve surgery, obesity, increased left atrial size, and diastolic dysfunction. There are many pharmacological options in preventing AF, but none of them are effective for all patients and they all have significant limitations. Beta-blockers may reduce the incidence of AF by more than a third, but bradycardia, hypotension, or exacerbation of heart failure often limit their utility postoperatively. Recent evidence suggests that class III antiarrhythmic drugs, sotalol and amiodarone, are more effective than beta-blockers, but they both share similar hemodynamic side effects of beta-blockers. Magnesium, antiinflammatory drugs such as statins, omega fatty acids, and low-dose corticosteroids also have some efficacy and they have the advantages of not causing significant hemodynamic side effects. Data on effectiveness of calcium channel blockers, digoxin, alpha-2 agonists, sodium nitroprusside, and N-acetylcysteine are more limited. Because the pathogenesis of AF is multifactorial, a combination of drugs with different pharmacological actions may have additive or synergistic effect in preventing AF after cardiac surgery. Randomized controlled trials evaluating the effectiveness of a multimodality pharmacological approach in patients at high-risk of AF after cardiac surgery are needed.
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PMID:Prevention of atrial fibrillation in cardiac surgery: time to consider a multimodality pharmacological approach. 2007 60

Insulin resistance, dyslipidemia, hypertension, obesity, cardiovascular disease, and chronic kidney disease cluster together, and the incidence of all of these disease states is increasing throughout the world. Current strategies for hypertension management-including the use of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, calcium antagonists, and thiazide diuretics-are effective for most patients. However, as the incidence of hypertension increases in this target population, so does that of resistant hypertension. As such, significant research and effort must be put forth to bring blood pressure to goal and delay or prevent target organ damage. Such efforts should frequently include a dihydropyridine calcium channel blocker such as amlodipine. Other agents that are currently underused in this population for the treatment of resistant hypertension include nebivolol, carvedilol, aliskiren, and aldosterone antagonists. Finally, significant potential is seen for darusentan, an endothelin antagonist, if it comes to market.
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PMID:Best strategies for hypertension management in type 2 diabetes and obesity. 2042 73


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