Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.15.1 (ACE)
 18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A markedly hypertensive, 70-year-old, black man had been on captopril for 2 years when he rapidly developed obstructive angioedema. The initial sign of difficulty in understanding his speech progressed to severe laryngeal and glossal edema over a 3 1/2 h period. His airway became obstructed less than a minute after arrival at the emergency room. Oral intubation was unsuccessful, and a difficult tracheostomy was too late to save the patient. The death was reported to the medical examiner because of its sudden and unusual nature. The risk of angioedema while on angiotensin converting enzyme inhibitor therapy has been noted previously in the clinical literature. Because of the sudden onset and possible confusion with an allergic reaction, this entity is brought to the attention of the forensic medical community.
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PMID:Fatal angioedema associated with captopril. 140 66

Although endemic along the Ohio and Mississippi River valleys in the United States, histoplasmosis may occur in many parts of the world. The multisystem involvement, the presence of non-caseating granulomas, and an elevated angiotensin converting enzyme in histoplasmosis cause diagnostic confusion with sarcoidosis. A careful epidemiologic history, serological tests, and tissue cultures are helpful in establishing the correct diagnosis.
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PMID:Histoplasmosis: a masquerader of sarcoidosis. 166 32

Poisoning is a significant problem in the elderly. The majority of poisonings in older people are unintentional and may result from dementia and confusion, improper use of the product, improper storage or mistaken identities. Depression is also common in the elderly and suicide attempts are more likely to be successful in this age group. The elderly patient's recuperative abilities may be inadequate as a result of numerous factors including impaired hepatic or renal function as well as chronic disease processes. General management of poisoning in the elderly parallels management of younger adults, but it is especially important to ascertain underlying medical conditions and concurrent medications. In most poisonings, activated charcoal and cathartic are sufficient. Haemodialysis or haemoperfusion may be required at lower plasma drug concentrations in elderly patients. While the specific indications for antidotes are the same for all age groups, dosage alterations and precautions may need to be considered in the elderly. Drugs most often implicated in poisonings in the elderly include psychotherapeutic drugs, cardiovascular drugs, analgesics and anti-inflammatory drugs, oral hypoglycaemics and theophylline. Cardiovascular and neurological toxicities occur with overdoses of neuroleptic drugs and, more frequently and severely, with cyclic antidepressants. Patients with pre-existing cardiovascular disease are at particular risk of worsening ischaemic heart disease and congestive heart failure. Benzodiazepines only appear to produce significant toxicity during long term administration or in combination with other CNS depressants. Digoxin can cause both chronic and acute intoxication, most seriously cardiac toxicity including severe ventricular arrhythmias, second or third degree heart block or severe refractory hyperkalaemia. Immune Fab antibody is indicated for the management of digoxin toxicity, although patients dependent on the inotropic effect of digoxin may develop heart failure after digoxin Fab antibody administration. Nitrates can cause toxicity including headache, vomiting, hypotension and tachycardia from excessive sublingual, transdermal or intravenous doses. Conduction disturbances and hypotension occur with overdoses of antihypertensive drugs; these effects are mild with angiotensin converting enzyme (ACE) inhibitors, occasionally severe with beta-blockers and of significant concern with calcium channel antagonists. The elderly commonly use aspirin and other salicylates, are more likely to develop chronic intoxications to these agents, and are more susceptible to severe complications such as pulmonary oedema. Salicylate poisoning, recognition of which is often delayed, should be considered in elderly patients with neurological abnormalities or breathing difficulties, especially in the setting of acid-base abnormalities. The clinical effects of NSAID overdose are mild and usually involve the central nervous system and gastrointestinal tract.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Poisoning in the elderly. Epidemiological, clinical and management considerations. 179 7

The importance of age-related changes in drug sensitivity is increasingly appreciated. More conclusive evidence is now being presented in combined kinetic and dynamic studies. The type, intensity, and duration of drug action may be affected, ranging from therapeutic failure to major drug toxicity. Alterations in physiologic and homeostatic systems, including the autonomic system, baroreceptors, thermoregulation, and balance, have been described. These may explain the propensity to postural hypotension, falls, hypothermia, and confusion, particularly following drug-induced decrements in these systems. Studies on the sensitivity to individual drugs produce a varied picture emphasizing the danger of generalizations. An increased sensitivity to many agents affecting the central nervous system, including benzodiazepines, halothane, metoclopramide, and narcotic analgesics, is becoming apparent. For the latter this may also be accompanied by an age-associated qualitative difference in toxicity. Whereas there is conclusive evidence of a reduced responsiveness to propranolol, the data are conflicting for calcium antagonists. The increased hypotensive response to ACE inhibitors is more likely due to kinetic factors. The anticoagulant response to warfarin is enhanced. Evidence is also emerging of a wide divergence in the sensitivity of different systems to the same drug--with aging the inotropic effect of theophylline is increased, but the bronchodilator response is decreased. It is becoming clear also that there is a need to separately study certain subgroups of the elderly population.
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PMID:Altered pharmacodynamics in the elderly. 218 23

We have introduced enalapril, in doses equal to or less than the 2.5 mg currently recommended, as an adjuvant to digoxin and diuretics in 17 patients of mean (SD) age 83 (5) years with severe heart failure. Only eleven patients tolerated its introduction. Unlike those reported in younger patients, all but one of the adverse drug reactions occurred 8 h or more after the first dose. Aged patients started on ACE inhibitors should be observed in hospital until stabilized on a maintenance dose. Three patients had an adverse reaction which differed in nature from those previously reported: acute confusional state, ataxia and mesenteric ischaemia. Ten patients were discharged on 5 mg or 10 mg maintenance doses of enalapril. In nine of them improvement on triple therapy was sustained for a minimum of three months. ACE inhibition was lost in the other patient when her compliance with enalapril therapy fell to around 75%: monitoring compliance is essential when ACE inhibitors are used in low dosages. Enalapril was withdrawn during follow up in three patients because of symptoms of mesenteric ischaemia and in four because of dramatic deterioration of renal function. One of the latter was found subsequently to have severe bilateral atheromatous renal artery stenosis. When isosorbide dinitrate was substituted for enalapril, symptoms of mesenteric ischaemia resolved and renal function returned to baseline. Continuing surveillance for adverse effects is essential in patients of this age group with severe heart failure, and the risk of occult renal artery stenosis requires regular biochemical screening during follow up.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Evaluation of the safety of enalapril in the treatment of heart failure in the very old. 284 29

The eighties were characterized by the introduction of angiotensin converting enzyme inhibitors (ACEI) and calcium channel blockers (CCB) in the treatment of arterial hypertension. The present study investigates the side effects of antihypertensive drugs in the Toulouse University Hospital (France) between 1981 and 1990. Most of the side effects involved ACEI (45%), CCB (22%) and diuretics (18%). Central antihypertensive agents and beta-blocking drugs were involved in 8 and 9% of side effects respectively. During these 10 years, 197 side effects were reported in our hospital (3300 beds). Some of them were found more frequently: renal insufficiency (15%) or cough (9%) with ACEI, constipation (3%), gingivitis (1%) or lower limb oedema (4.5%) with CCB, hemolytic or autoimmune anemia (2.5%) and confusional state (1.5%) with central antihypertensive agents, nightmares (1.5%) with propranolol. The most frequently side effects were dermatological (20%), hydroelectrolytic (10%) and neuropsychiatric (9.6%) disturbances. In spite of the methodological problems of this kind of study (retrospective evaluation, under-notification of the side effects and different scores of imputability), these data indicate the most frequently observed side effects of antihypertensive agents during the eighties. It allows to estimate an approximate frequency of these side effects: among the antihypertensive drugs, CCB and diuretics seems the less frequently involved in the occurrence of reported side effects.
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PMID:[Evaluation of ten years of pharmacovigilance of antihypertensive drugs in the Toulouse University Regional Hospital Center (1981-1990)]. 835 83

The genetic analysis of hypertension has revealed complex and inconsistent results, making it difficult to draw clear conclusions regarding the impact of specific genes on blood pressure regulation in diverse human populations. Some of the confusion from previous studies is probably due to undetected gene-gene interactions. Instead of focusing on the effects of single genes on hypertension, we examined the effects of interactions of alleles at 4 candidate loci. Three of the loci are in the renin-angiotensin-system, angiotensinogen, ACE, and angiotensin II type 1 receptor, and they have been associated with hypertension in at least 1 previous study. The fourth locus studied is a previously undescribed locus, named FJ. In total, 7 polymorphic sites at these loci were analyzed for their association with hypertension in 51 normotensive and 126 hypertensive age-matched individuals. There were no significant differences between the 2 phenotypic classes with respect to either allele or genotype frequencies. However, when we tested for nonallelic associations (linkage disequilibrium), we found that of the 120 multilocus comparisons, 16 deviated significantly from random in the hypertensive class, but there were no significant deviations in the normotensive group. These findings suggest that genetic interactions between multiple loci rather than variants of a single gene underlie the genetic basis of hypertension in our study subjects. We hypothesize that such interactions may account for the inconsistent findings in previous studies because, unlike our study, prior studies almost always examined single-locus effects and did not consider the effects of variation at other potentially interacting loci.
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PMID:Combinations of variations in multiple genes are associated with hypertension. 1090 4

Clinical trials continue to guide patient management. However, the hypotheses generally come from observational studies. Studies on women continue to be too little and too few, particularly in light of the fact that most elderly hypertensive patients are likely to be women. Attention has been drawn to the possibility that hypertension per se may engender symptoms such as headache for example, in addition to harder endpoints such as death. The MICROHOPE study, which was not a blood pressure-lowering study, showed that angiotensin converting enzyme inhibition with ramipril in diabetic patients provided the same beneficial effects previously published for the HOPE study. The doxazosin arm of the ALLHAT study was terminated by the data monitoring and safety board because the doxazosin-treated patients developed congestive heart failure at a greater rate than diuretic-treated patients. Two extensive studies testing two different classes of calcium antagonists against primarily diuretic-based treatment showed that the calcium antagonists were no less effective in terms of preventing hard endpoints. A small, but impressive cross-over study testing the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, pravastatin, against placebo showed that statin treatment lowers blood pressure in hypercholesterolemic patients with hypertension. Meta- analyses emphasized the value of blood pressure reduction in the elderly and added to the controversy and confusion about the role of calcium antagonists in the first-line treatment of hypertension. The point may be moot since with the current recommendations few hypertensive patients will be adequately treated with a single agent.
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PMID:Recent clinical trial highlights in hypertension. 1127 95

The treatment of hypertension is proven to reduce cardiovascular and renal risk. Combination drug therapy is becoming recognized as a necessity in most patients with hypertension and kidney disease. Allegations about the safe use of calcium antagonists in patients with kidney disease have led to questions and confusion about their use in this common condition. This article reviews the cardiovascular and renal safety of the long-acting calcium antagonists from studies comparing calcium antagonists with placebo and with angiotensin converting enzyme inhibitors or angiotensin receptor blockers in patients with kidney disease and hypertension. Patients with proteinuria and kidney disease should have their blood pressure brought as close to target (< 130/80 mm Hg) as possible for cardiovascular and renal protection. Lowering blood pressure in this setting will require an average of three antihypertensive agents. In patients with hypertension and proteinuria, angiotensin converting enzyme inhibitors or angiotensin receptor blockers must be part of the regimen, and calcium antagonists are safe and effective in this condition when used with them in combination.
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PMID:The use of calcium antagonists in the treatment of hypertensive persons with kidney disease. 1200

Despite widespread availability of a large body of evidence in the area of hypertension, the translation of that evidence into viable recommendations aimed at improving the quality of health care is very difficult, sometimes to the point of questionable acceptability and overall credibility of the guidelines advocating those recommendations.The scientific community world-wide and especially professionals interested in the topic of hypertension are witnessing currently an unprecedented debate over the issue of appropriateness of using different drugs/drug classes for the treatment of hypertension. An endless supply of recent and less recent "drug-news", some in support of, others against the current guidelines, justifying the use of selected types of drug treatment or criticising other, are coming out in the scientific literature on an almost weekly basis. The latest of such debate (at the time of writing this paper) pertains the safety profile of ARBs vs ACE inhibitors.To great extent, the factual situation has been fuelled by the new hypertension guidelines (different for USA, Europe, New Zeeland and UK) through, apparently small inconsistencies and conflicting messages, that might have generated substantial and perpetuating confusion among both prescribing physicians and their patients, regardless of their country of origin.The overwhelming message conveyed by most guidelines and opinion leaders is the widespread use of diuretics as first-line agents in all patients with blood pressure above a certain cut-off level and the increasingly aggressive approach towards diagnosis and treatment of hypertension. This, apparently well-justified, logical and easily comprehensible message is unfortunately miss-obeyed by most physicians, on both parts of the Atlantic.Amazingly, the message assumes a universal simplicity of both diagnosis and treatment of hypertension, while ignoring several hypertension-specific variables, commonly known to have high level of complexity, such as:- accuracy of recorded blood pressure and the great inter-observer variability,- diversity in the competency and training of diagnosing physician,- individual patient/disease profile with highly subjective preferences,- difficulty in reaching consensus among opinion leaders,- pharmaceutical industry's influence, and, nonetheless,- the large variability in the efficacy and safety of the antihypertensive drugs.The present 2-series article attempts to identify and review possible causes that might have, at least in part, generated the current healthcare anachronism (I); to highlight the current trend to account for the uncertainties related to the fixed blood pressure cut-off point and the possible solutions to improve accuracy of diagnosis and treatment of hypertension (II).
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PMID:Beyond the Evidence of the New Hypertension Guidelines. Blood pressure measurement - is it good enough for accurate diagnosis of hypertension? Time might be in, for a paradigm shift (I). 1581 75


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