Gene/Protein Disease Symptom Drug Enzyme Compound
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 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Reduction of excessive neurohumoral activation in chronic heart failure (CHF) improves the prognoses. In addition to reduction of angiotensin production or angiotensin II action and the influence of the sympathoadrenal system also blocking of aldosterone effects becomes part of the therapeutic procedure in patients with CHF. Excessive systemic and probably also local aldosterone production promotes undesirable fluid retention, hypokalaemia and hypomagnesaemia, induction of hypertrophy and fibrosis of the heart muscle and blood vessels and the development of endothelial dysfunction, peripheral vasoconstriction and depression of the baroreflex. In addition to classical effects also the existence of a rapid, so-called non-genomic effect of aldosterone is assumed. Adding a blocker of aldosterone receptors to ACE inhibition was not recommended due to possibility development of hyperkalaemia. Later it was revealed that ACE inhibitors are unable to block sufficiently the action of aldosterone and that addition of spironolactone in small amounts to ACE inhibition and diuretics does not cause in patients with CHF a major increase of the potassium level. In the RALES study (Randomized Aldacton Evaluation Study) comprising 1663 patients with serious heart failure (NYHA III, IV) addition of 25 mg spironolactone to standard treatment with ACE inhibitor, diuretic and as rule also digoxin reduced the mortality by another 30% as compared with the addition of placebo. Undesirable effects were minimal. As to potential protective mechanisms of spironolactone the greatest importance is ascribed to the reduction of excessive fibrosis of the heart muscle. Spironolactone reduces the level of the circulating N-terminal aminopeptide procollagen type III the high level of which is associated with deterioration of the prognosis.
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PMID:[The significance of aldosterone in chronic heart failure: the RALES study]. 1242 9

About half of all the patients with CHF are anemic (they have a hemoglobin of < 12 g%). The prevalence and severity of this anemia increase with increasing severity of the CHF. The anemia is caused by a combination of poor nutrition, associated renal insufficiency causing inappropriately low Erythropoietin (EPO) levels, bone marrow depression and EPO resistance caused by excessive TNF alpha and other factors, gastrointestinal blood loss caused by aspirin, ACE inhibitors, EPO loss in the urine with proteinuria, and hemodilution caused by the excessive plasma volume. Studies have shown that the anemia is an independent risk factor for death in CHF, almost doubling the mortality rate. Correction of the anemia with subcutaneous EPO and IV iron improves cardiac function and functional capacity, helps prevent the progression of renal failure, markedly reduces hospitalization and diuretic doses, and improves self assessed quality of life. This so-called Cardio Renal Anemia Syndrome is very common in CHF. Its successful treatment demands close cooperation between cardiologists and nephrologists.
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PMID:The importance of anemia and its correction in the management of severe congestive heart failure. 1245 37

The association between different antihypertensive drugs and erectile dysfunction (ED) was examined in a cohort of type II diabetes patients identified in the UK General Practice Research Database (GPRD). The GPRD contains details of diagnoses, prescribing, investigations, risk factors, outcomes, and hospital referrals, together with basic demographic information for approximately six million patients from more than 450 representative general practices throughout the UK. A total of 634 cases and 2526 controls were included for analysis. Unconditional logistic regression analysis was performed to assess the risk of ED after adjusting for age at diabetes diagnosis date, cigarette smoking, depression, glycemic control, use of HMG-CoA reductase inhibitors, use of histamine receptor antagonists, use of digitalis medicines, and use of nitrates. Increased risk of ED was observed among patients taking the following antihypertensives: ACE inhibitors (OR=1.47, 95% CI=1.21, 1.80) and alpha blockers (OR=1.54, 95% CI=1.11, 2.12). However, we identified a nearly 30% reduction in risk among patients on diuretics (OR=0.73, 95% CI=0.54, 0.99). No statistically significant increase in risk was observed among users of beta blockers and calcium channel blockers (OR=1.05, 95% CI=0.85, 1.31) and (OR=1.14, 95% CI=0.91, 1.43), respectively. The results of this study confirm the strong and recognized effect of comorbidities in a diabetic population, but also require additional experimental and observational studies to further understand the potential benefit of diuretics and other ED treatments such as PDE5 inhibitors.
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PMID:Antihypertensive treatment and erectile dysfunction in a cohort of type II diabetes patients. 1456 30

Management of hypertension in the elderly should take into account, in particular, the possible negative impact of antihypertensive drugs on the patient's quality of life, the deterioration of which may result in a loss of independence and reduced treatment compliance. Quality of life is recognised as a multifactorial variable and can be subdivided into different domains (symptomatic well-being, emotional, physical, work-social, cognitive and life satisfaction), which are generally explored by means of specific questionnaires or scales. When evaluating elderly patients with hypertension, it is necessary to pay particular attention to specific domains such as symptomatic well-being, cognitive function, activity and sexual function, which have already been diminished by the age itself and the disease. The results of some large trials that specifically evaluated the quality of life effects of long-term therapy of hypertension in older people (Medical Research Council's [MRC] Trial of Hypertension in Older Adults, Systolic Hypertension in the Elderly Program [SHEP], Systolic Hypertension in Europe [Syst-Eur], Study on COgnition and Prognosis in the Elderly [SCOPE]) have shown that antihypertensive treatment as a whole either had no negative impact on quality of life, or even produced some improvement. The question whether some classes of antihypertensive agents are more beneficial or harmful than others in terms of quality-of-life effects remains largely unanswered. Results from long-term trials suggest that treatment with diuretics is not associated with adverse effects on quality of life. Nevertheless, chlortalidone and other diuretics have been more often associated with sexual dysfunction in men, including decreased libido, erectile dysfunction and difficult ejaculation, than other drug classes. Nonselective lipophilic beta-adrenoceptor antagonists, such as propranolol, have been reported to exert some negative effect on quality of life and have been associated with depression, impairment of memory function and adverse effects such as erectile problems. A less unfavourable impact has been described with beta(1)-adrenoceptor antagonists and those with vasodilating properties. Calcium channel antagonists have generally been associated with a positive effect on quality of life, although some trials have shown high rates of adverse effects and withdrawals, particularly with first-generation dihydropyridines. Concern has also been raised about the potential for adverse cognitive effects associated with the use of calcium channel antagonists, but studies on this topic are not univocal. ACE inhibitors have usually been reported to exert favourable effects on quality of life. These drugs seem to be effective in maintaining, or even improving, cognitive function through mechanisms other than blood pressure control. In addition, a number of studies reported favourable impact of ACE inhibitors on sexual function. Angiotensin II receptor antagonists have been associated with good tolerability and low withdrawal rate. They have been demonstrated not to interfere with or even improve cognitive function as well as sexual performance. Although no class of antihypertensive agents presents a clearly superior effect over the others in terms of quality of life, the current impression is that ACE inhibitors and angiotensin II receptor antagonists may offer some advantage, at least in regard to effects on cognitive function and sexual activity.
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PMID:Effect of antihypertensive agents on quality of life in the elderly. 1508 40

Fifty consecutive elderly (> 60 years) patients admitted to our department with congestive heart failure (CHF) entered a prospective database, to define their main clinical, instrumental and cognitive characteristics. In addition we evaluated the patterns of drug therapy in this aged population. Eighty percent of this sample had been previously hospitalized for CHF. Two or more associated diseases were present in 92%. Heart disease was ischemic or hypertensive in etiology in 80% of patients. Acute dyspnea was the most common presenting symptom. Atrial fibrillation or flutter were found in 38% of patients. Ultrasound evaluation evidenced left ventricular dysfunction of a systolic type in 49% and of a diastolic type in 28.6% of subjects. Diuretics and cardiac glycosides were the most widely administered drugs, followed by ACE-inhibitors, nitrates and dobutamine. Older ( >or= 75 years) patients were treated with more agents, with a trend to a lesser use of dobutamine. Moderate to severe mental deficit was present in 20.8% of our sample, while significant depression was more common (54.2%). The main implications of the clinical profile of the elderly patient hospitalized for CHF are discussed.
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PMID:Congestive heart failure in the elderly requiring hospital admission. 1537 42

The present study investigated the role of NMDA receptors in behavioral and neuroplastic changes in amygdala efferent (central amygdala to periaqueductal gray-ACE-PAG) and amygdala afferent (ventral angular bundle to basolateral amygdala-VAB-BLA) pathways in response to predator stress. Effects on brain and behavioral response to predator stress of competitive block of NMDA receptors with a dose of 10 mg/kg of CPP (3-(2-carboxypiperazin4-yl)propyl-l-phosphonic acid) were studied. Behavioral response to stress was tested with hole board, elevated plus maze, light/dark box, social interaction and acoustic startle tests. CPP was administered i.p. 30 min prior to predator stress and blocked the effects of predator on some but not all behaviors measured 8-9 days later. Effects of predator stress and CPP on potentials evoked in the PAG by single pulse stimulation of the ACE and in the BLA by single pulse stimulation of VAB were assessed 10-11 days after predator stress. Predator stress potentiated ACE-PAG evoked potentials in the right but not the left hemisphere, replicating previous work. Predator stress potentiated VAB-BLA transmission in both hemispheres 10-11 days after predator stress. Right hemisphere VAB-BLA potentiation replicated and extended past studies showing right hemisphere potentiation at 1 and 9 days after stress. Left VAB-BLA potentiation effects differed from the long term depression seen in VAB-BLA at 1 and 9 days after stress in previous studies. CPP blocked predator stress-induced potentiation of ACE-PAG and VAB-BLA evoked potentials in the right hemisphere. CPP did not block left VAB-BLA potentiation, rather CPP amplified it. Left hemisphere effects of CPP were interpreted as reflecting block of NMDA dependent long term depression, which unmasked a non-NMDA dependent potentiation. Taken together, the findings add to a body of evidence suggesting that a syndrome of behavioral changes follows predator stress. Components of this syndrome likely depend on changes in separable neural substrates. Potentiation of ACE-PAG and VAB-BLA evoked potentials in the right hemisphere likely mediates a subset of changes in behavior. Moreover, a medial ACE-PAG pathway is implicated in mediating stress-induced changes in startle amplitude. In contrast, a lateral ACE-PAG pathway is implicated in mediating changes in startle habituation. Finally, consistent with cat and human studies, the right hemisphere appears particularly important in long term response to stress.
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PMID:Role of NMDA receptors in the lateralized potentiation of amygdala afferent and efferent neural transmission produced by predator stress. 1610 87

Pain characteristics were examined in 24 patients with myophosphorylase deficiency (McArdle's disease). Pain parameters were related to mutation analyses as well as psychosocial data using a pain questionnaire including an assessment of psychosocial distress and coping measures (Beck Depression Inventory BDI; Kiel Pain Inventory KPI, Multidimensional Fatique Inventory MFI). Twenty-three patients complained of pain, which was intermittent and exercise-induced in 15 patients. Eight patients complained of permanent pain, which was superimposed by exercise-induced pain in 7 patients. Patients reported 3-7 different pain characters and various localisations. Patients with permanent pain were significantly more frequently female, experienced higher impact on general activities and sleep as well as higher scores on the MFI. Furthermore, these patients revealed higher scores regarding several psychosocial risk factors including avoidance behavior whereas patients with intermittent pain predominantly showed endurance coping. There was no correlation between age or disease duration, pain intensity as well as mutation type and development of permanent or intermittent pain. In addition, severity of the clinical phenotype did not correlate with ACE polymorphism. Although McArdle's disease is a muscle glycogenosis with marked biochemical homogeneity, the clinical presentation can be quite heterogeneous. A substantial number of patients revealed permanent pain as a major clinical symptom. As permanent pain is not related to age or disease duration, it might be a clinically important subgroup of McArdle's disease. Gender-related genetic factors as well as maladaptive pain-related coping may contribute to the development of such a chronic pain symptom.
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PMID:Muscle pain in myophosphorylase deficiency (McArdle's disease): the role of gender, genotype, and pain-related coping. 1679 8

Treatment of migraine presents special problems in the elderly. Co-morbid diseases may prohibit the use of some medications. Moreover, even when these contraindications do not exist, older patients are more likely than younger ones to develop adverse events. Managing older migraine patients, therefore, necessitates particular caution, including taking into account possible pharmacological interactions associated with the greater use of drugs for concomitant diseases in the elderly. Paracetamol (acetaminophen) is the safest drug for symptomatic treatment of migraine in the elderly. Use of selective serotonin 5-HT(1B/1D) receptor agonists ('triptans') is not recommended, even in the absence of cardiovascular or cerebrovascular risk, and NSAID use should be limited because of potential gastrointestinal adverse effects. Prophylactic treatments include antidepressants, beta-adrenoceptor antagonists, calcium channel antagonists and antiepileptics. Selection of a drug from one of these classes should be dictated by the patient's co-morbidities. Beta-adrenoceptor antagonists are appropriate in patients with hypertension but are contraindicated in those with chronic obstructive pulmonary disease, diabetes mellitus, heart failure and peripheral vascular disease. Use of antidepressants in low doses is, in general, well tolerated by elderly people and as effective, overall, as in young adults. This approach is preferred in patients with concomitant mood disorders. However, prostatism, glaucoma and heart disease make the use of tricyclic antidepressants more difficult. Fewer efficacy data in the elderly are available for selective serotonin reuptake inhibitors, which can be tried in particular cases because of their good tolerability profile. Calcium channel antagonists are contraindicated in patients with hypotension, heart failure, atrioventricular block, Parkinson's disease or depression (flunarizine), and in those taking beta-adrenoceptor antagonists and monoamine oxidase inhibitors (verapamil). Antiepileptic drug use should be limited to migraine with high frequency of attacks and refractoriness to other treatments. Promising additional strategies include ACE inhibitors and angiotensin II type 1 receptor antagonists because of their effectiveness and good tolerability in patients with migraine, particularly in those with hypertension. Because of its favourable compliance and safety profile, botulinum toxin type A can be considered an alternative treatment in elderly migraine patients who have not responded to other currently available migraine prophylactic agents. Pharmacological treatment of migraine poses special problems in regard to both symptomatic and prophylactic treatment. Contraindications to triptan use, adverse effects of NSAIDs, and unwanted reactions to some antiemetics reduce the list of drugs available for the treatment of migraine attacks in elderly patients. The choice of prophylactic treatment (beta-adrenoceptor antagonists, calcium channel antagonists, antiepileptics, and more recently, some antihypertensive drugs) is influenced by co-morbidities and should be directed at those drugs that are believed to have fewer adverse effects and a better safety profile. Unfortunately, for most of these drugs, efficacy studies are lacking in the elderly.
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PMID:Practical considerations for the treatment of elderly patients with migraine. 1687 31

Alzheimer's disease (AD) is a major problem of health in developed societies together with cardiovascular disorders and cancer. The lack of accurate diagnostic markers for early prediction and an effective therapy are the two most important problems to efficiently halt disease progression. The pharmacological treatment in AD accounts for 10-20% of direct costs, and less than 20% of AD patients are moderate responders to conventional drugs (donepezil, rivastigmine, galantamine, memantine), with doubtful cost-effectiveness. The neuropathological hallmark of AD (amyloid deposition in senile plaques, neurofibrillary tangle formation, and neuronal loss) are buth the phenotypic expression of a pathogenic process in which more than 200 genes and their products are potentially involved. Drug metabolism, and the mechanisms underlying drug efficacy and safety, are also genetically regulated complex traits in which hundreds of genes cooperatively participate. Structural and functional genomics studies demonstrate that genomic factors, probably induced by environmental factors, cerebrovascular dysfunction, and epigenetic phenomena, might be responsible for AD pathogenic events leading to premature neuronal death. The AD population exhibits a higher genetic variation rate than the control population, with absolute and relative genetic variations of 40-60% and 0.85-1.89%, respectively. AD patients also differ in their genomic architecture from patients with other forms of dementia. Functional genomics studies in AD reveal that age of onset, brain atrophy, cerebrovascular hemodynamics, brain bioelectrical activity, cognitive decline, apoptosis, immune function, lipid metabolism dyshomeostasis, and amyloid deposition are associated with AD-related genes. Pioneering pharmacogenomics studies also demonstrate that the therapeutic response in AD is genotype-specific, with APOE-4/4 carriers as the worst responders to conventional treatments. About 10-20% of Caucasians are carriers of defective CYP2D6 polymorphic variants that alter the metabolism and effects of AD drugs and many psychotropic agents currently administered to patients with dementia. There is a moderate accumulation of AD-related genetic variants of risk in CYP2D6 poor metabolizers and ultra-rapid metabolizers, which are the worst responders to conventional drugs. With diverse multifactorial therapies, combining different types of drugs and metabolic factors, it is partially possible to slow-down cognitive deterioration, improving non-cognitive symptoms, such as anxiety and depression, which currently aggravate cognition and increase the difficulties in disease management; however, the association of the APOE-4 allele with specific genetic variants of other genes (e.g., CYP2D6, ACE) negatively modulate the therapeutic response to multifactorial treatments affecting cognition, mood and behaviour. Pharmacogenetic and pharmacogenomic factors may account for 60-90% of drug variability in drug disposition and pharmacodynamics. The incorporation of pharmacogenetic/pharmacogenomic protocols to AD research and clinical practice can foster therapeutics optimization by helping to develop cost-effective pharmaceuticals and improving drug efficacy and safety.
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PMID:Molecular pathology and pharmacogenomics in Alzheimer's disease: polygenic-related effects of multifactorial treatments on cognition, anxiety and depression. 1795 77

The purpose of this study was to examine the relationship between social support and positive health practices in early adolescents and to test two variables, depression and optimism, that mediate this relationship. The final sample included 128 adolescents, ages 12 to 14, who responded to instruments measuring social support, depression, optimism, and positive health practices in classroom settings. Correlational analysis supported the five hypothesized relationships. A series of regression analyses indicated that depression and optimism each were weak mediators of the relationship between social support and positive health practices. The application of findings to nursing is addressed, using the ACE Star Model for evidence-based practice.
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PMID:Mediational models of health practices in early adolescents. 1799 10


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