Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.15.1 (ACE)
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Cardiac failure remains a serious complication of myocardial infarction. In addition to therapeutic interventions to limit the infarct size, it would seem possible to influence the progressive changes in geometry and size of the left ventricle, known as remodeling. Experimental and clinical studies have shown beneficial effects of angiotensin converting enzyme inhibitors and the SAVE trial evaluated the prognostic consequences of this therapy, reporting a significant reduction in mortality after 10 months' treatment. Many questions remain which require further research in this field, mainly concerning the optimal time of introduction the treatment, the importance of the chemical molecule used, the most appropriate dosage and the influence of associated drug therapy. ACE inhibitors are now part of the therapeutic arsenal of myocardial infarction but their prescription should be strictly reserved for the population concerned by these trials, that is to say patients with a recent, extensive infarct with left ventricular dysfunction but without clinical signs of cardiac failure.
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PMID:[Prevention of postinfarction cardiac insufficiency: role of angiotensin converting enzyme inhibitors]. 130 44

Many practical difficulties are encountered by physicians in the medical treatment of chronic cardiac failure. They are related to the choice of drug guided by therapeutic objectives: vasodilators and angiotensin converting enzyme inhibitors are no longer drugs of secondary intention reserved for chronic cardiac failure, but there is no information as to the place of these drugs in early stages of myocardial dysfunction before the appearance of the clinical signs of cardiac failure. Other difficulties are related to the use of many different drugs, to the many secondary effects, sometimes increased by drug interactions; these difficulties are accentuated by the multiplicity of the etiologies of cardiac failure, by the frequency of associated extracardiac disease and by the risks inherent to abnormal myocardial function. In addition, the prescriber must not forget that the drug is not everything in the treatment of cardiac failure and he must be able to recognise the pathology underlying the cardiac failure which may require specific therapy. Finally, the physician must decide the optimal timing for referring patients with very severe cardiac failure for transplantation.
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PMID:[Practical difficulties in drug prescription in chronic cardiac insufficiency]. 212 18

Between 1974 and 1986, 576 patients (284 limited and 292 extensive stages) were treated at this institution. To keep multiagent chemotherapy (CT) at a uniform intensity, patients who received (a) combined modality approach of both multiagent chemotherapy and thoracic radiotherapy (RT) and (b) greater than or equal to 3 cycles of multiagent chemotherapy (greater than or equal to 3 drugs), were chosen for this analysis. Out of 284 patients with limited Stage small-cell lung carcinoma, there were 154 such patients who met these strict criteria, and the treatment methods for the remaining 130 patients were as follows: (a) chemotherapy alone with radiotherapy reserved for local failure (47 pts); (b) radiotherapy alone (20 pts); (c) surgery +/- adjuvant chemotherapy or radiotherapy (37 pts); (d) modified chemotherapy plus radiotherapy (26 pts). During the 12-year period, the therapeutic factors have evolved. Radiation-dose was increased from 30-40 Gy (time dose fractionation 49-66) in 1974-1977 to 44-52 Gy (time dose fractionation 73-86) in 1978-1986. The target volume for radiotherapy included the primary lesion with a 2-cm margin of normal lung and the mediastinum. Chemotherapy program also evolved from COP, CAV (1974-1977) to MACC, VCE-VCA, PCE-ACE (1978-1986). Fifty of 154 patients (32%) developed loco-regional recurrence (infield failure) and 98% (49/50) of these patients exhibited this by 2.5 years. Survival data of 154 patients were as follows: (a) Median survival time (MST) was 12 M; (b) actuarial survival rates at 2 and 5 years were 21% and 8%, respectively. Fifty percent of these patients died within 12 months (MST 12 M) and were not exposed to the full length of the risk period for loco-regional failure. To take into account the duration of exposure to the risk period, actuarial method was employed to measure the probability of loco-regional failure. Loco-regional failure rates at 2.5 years were 37%, 39%, 49%, 79%, and 84% for 50 Gy, 45 Gy, 40 Gy, 35 Gy, and 30 Gy, respectively. The difference between the recurrence rates of 37% and 79% by 50 Gy and 35 Gy was statistically significant, p less than 0.05. Although the recurrence rates of 37% and 49% by 50 Gy and 40 Gy were not statistically different, there was a strong trend of a better control rate of loco-regional carcinoma by higher radiation doses. The time to recurrence seems also shorter with lower radiation-dose than that of higher radiation doses.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Importance of radiation dose in achieving improved loco-regional tumor control in limited stage small-cell lung carcinoma: an update. 254 6

318 consultant physicians in Scotland were sent a questionnaire on their use of angiotensin converting enzyme (ACE) inhibitors to treat chronic heart failure (CHF). 229 (72%) replies were received. Of these 91% used ACE inhibitors for CHF; 22% were geriatricians, 58% general physicians and 20% cardiologists. All groups reserved ACE inhibitors for patients uncontrolled by diuretics alone. Compared to general physicians, cardiologists used ACE inhibitors in preference to other vasodilators and digoxin, used higher doses and commenced treatment more often on a day-patient basis. Cardiologists also commonly started treatment with captopril even if continuing with enalapril. Geriatricians used ACE inhibitors as frequently as cardiologists but at lower doses; they did not report side-effects more frequently. Further investigation of the safety and possible cost savings of supervised day-patient rather than in-patient, introduction of ACE inhibitors for CHF is now merited. To avoid an extended period of patient observation after the first dose of ACE inhibitor, captopril might also be given as the initial therapy, even if continuing with enalapril. This policy would also reduce the risk of any hypotensive response being prolonged.
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PMID:A survey of current use of angiotensin-converting-enzyme inhibitors by Scottish physicians in the treatment of chronic cardiac failure. 274 Aug 88

Persons with persisting (at least 3 measurements over several weeks) borderline blood pressure elevation or established hypertension should always be instructed to follow general non-pharmacological measures. Antihypertensive pharmacotherapy is recommended in the following situations: in hypertensive emergencies, immediately; if the hypertension is not due to a surgically remediable cause, in patients with documented (at least 3 measurements) blood pressure elevation to diastolic values greater than 100 mm Hg; in patients with "mild" hypertension (diastolic up to 104 mm Hg) which does not decrease to less than 160/95 mm Hg following 3 to 6 months of treatment with general non-pharmacological measures; in persons with borderline blood pressure values (141-159/91-94 mm Hg) that persist following 6 to 12 months of general measures and only if they have severe additional cardiovascular risk factors; in patients with pronounced isolated systolic hypertension (greater than 180 mm Hg). In elderly patients who are frail or have evidence of advanced cardiovascular disease, dementia or other debilitating illnesses, blood pressure-lowering drugs should generally be reserved for diastolic blood pressure values consistently exceeding 110 mm Hg. There have recently been important new developments in antihypertensive pharmacotherapy. Two new pharmacological principles, the calcium entry blockers and angiotensin converting enzyme (ACE) inhibitors, have been introduced widely into practical hypertension treatment. On the other hand, concern has arisen that the conventional, thiazide-diuretic based therapy, despite its established beneficial influence on blood pressure and most cardiovascular complications, may not significantly improve or may sometimes even adversely affect coronary prognosis because of metabolic side effects.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Hypertension management in practice, 1986]. 287 92

The role of imaging is to establish the cause of systemic hypertension, the main focus being the kidneys. All children require a Doppler ultrasound examination followed by a radioisotope study, usually 99mTc-DMSA. This combination will resolve most clinical situations. There is no role for the intravenous urogram in the majority of children. Arteriography and renal vein renin sampling are reserved for a small proportion of children. Imaging should always start with the least invasive procedure with the lowest radiation burden and high radiation techniques reserved for selected cases. The use of ACE inhibition may allow the diagnosis of renovascular disease in paediatrics noninvasively.
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PMID:Imaging in systemic hypertension in paediatrics. 806 86

Patients with mild to moderate hypertension require only a simple schedule of investigations, especially if there is a history of stroke or hypertension in first degree relatives. Tests are necessary to profile other cardiovascular risk factors and to detect target organ damage with only limited screening for secondary hypertension. Careful history, physical examination, repeated blood pressure measurements over months and measurements of body mass index, random cholesterol, routine blood chemistry and urinalysis using impregnated paper strips are all that are required. More detailed investigations can be reserved for special groups such as those with peripheral vascular disease or abnormal renal function before or after treatment with angiotensin converting enzyme inhibitors or significant proteinuria or hypokalaemia. Patients with essential hypertension who are smokers with lipid abnormalities may go on to develop superimposed renovascular disease. Severe hypertension at any age and especially if there is a reliable negative family history also merits special consideration. Resistance to antihypertensive treatment is more often due to non-compliance or non-steroidal anti-inflammatory drug use or alcohol abuse than to underlying secondary causes.
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PMID:Hypertension: investigation, assessment and diagnosis. 820 68

Renal disease in elderly diabetic patients is costly in terms of morbidity, mortality and medical payments. Therefore, prevention of diabetic nephropathy has become a prominent goal in the treatment of diabetic patients. Preventive treatment should begin not later than at the stage of persistent microalbuminuria, and regular screening for microalbuminuria is recommended for both elderly and younger diabetic patients. Improved metabolic control, through diet and hypoglycaemic therapy, has been demonstrated to lower urinary albumin excretion. The target level of glycated haemoglobin is < 8%, or < 2% higher than the upper limit of normal in nondiabetic people. Insulin therapy has no adverse effects on renal indices, unless it increases bodyweight and consequently raises blood pressure. To preserve renal function in elderly diabetic patients, blood pressure should be kept well below 140/90 mm Hg. Treatment with ACE inhibitors may be the 'gold standard' intervention, and should be initiated at the lowest possible dosage and then titrated until the maximum tolerated dosage has been reached. Nonchronotropic calcium antagonists have been shown to be as effective as ACE inhibitors with regard to their effects on blood pressure, renal haemodynamics and urinary albumin excretion. Most dihydropyridines have been found to increase or to have no effect on urinary albumin excretion despite significant blood pressure reduction. A renoprotective action of diuretics is generally unlikely, with the possible exception of indapamide. Although beta-blockers are effective antihypertensive agents, they may not adequately preserve kidney function in diabetic patients. Because beta-blocker treatment may mask the symptoms of hypoglycaemia, they should be reserved for patients with coronary artery disease or arrhythmias.
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PMID:Chemoprophylaxis of diabetic nephropathy in the elderly. 897 44

The therapy of portal hypertension depends to a significant extent on its clinical manifestation. In cases of acute haemorrhage from oesophageal varices in patients with portal hypertension, the objective of the therapy is to stop the haemorrhage (endoscopically, or by compression by means of a balloon probe) and to decrease the pressure and the reflux within the portal vascular bed. Urgent sclerotisation under the simultanous pharmacologic decrease of portal hypertension is successful in 93-95%. There is an alternative procedure residing in introducing a balloon probe for several hours and subsequent repeated sclerotisation until a complete eradication of varices is achieved regarding the prevention of haemorrhage exacerbation. Urgent surgical solution is on the basis of the results of various investigated studies reserved for patients in whom endoscopic sclerotisation was not successful. Indication of surgical therapy must be also deliberated in candidates for liver transplantation, regarding the possible consequent technical problems after some types of interventions. Endoscopic sclerotisation of oesophageal varices is also an appropriate preparation for transplantation of the liver in patients with liver cirrhosis included into the transplantation programme. TIPS is a perspective new method in the therapy of portal hypertension of both, non-bleeding varices, as well as in other indications. It is also a certain intermediating link in therapy in some patients with liver cirrhosis on the waiting list of candidates for liver transplantation. Pharmacotherapy is a significant part of the portal hypertension therapy. It is appropriate to combine the endoscopic treatment with pharmacotherapy of portal hypertension in both, cases of acute haemorrhage, as well as in the prevention of haemorrhage exacerbation. In cases of acute haemorrhage, the combination of glypressin with nitroglycerin is justified, as well as the therapy by somatostatin. The prevention of haemorrhage exacerbations uses a whole series of vasoactive substances, especially nitrates, beta-blockers and ACE inhibitors. The prevention of the first bleeding includes the prophylactic therapy (endoscopic, pharmacologic, or surgical) recommended only in a selected group of patients under high risk of bleeding. The possible perspective option will reside especially in the combined pharmacological therapy, the fact of which will have to be proven in the future. (Fig. 1, Ref. 25.)
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PMID:[Treatment of portal hypertension]. 958 83

Understanding the mechanism of action and the pharmacokinetic properties of vasodilatory drugs facilitates optimal use in clinical practice. It should be kept in mind that a drug belongs to a class but is a distinct entity, sometimes derived from a prototype to achieve a specific effect. The most common pharmacokinetic drug improvement is the development of a drug with a half-life sufficiently long to allow an adequate once-daily dosage. Developing a controlled release preparation can increase the apparent half-life of a drug. Altering the molecular structure may also increase the half-life of a prototype drug. Another desirable improvement is increasing the specificity of a drug, which may result in fewer adverse effects, or more efficacy at the target site. This is especially important for vasodilatory drugs which may be administered over decades for the treatment of hypertension, which usually does not interfere with subjective well-being. Compliance is greatly increased with once-daily dosing. Vasodilatory agents cause relaxation by either a decrease in cytoplasmic calcium, an increase in nitric oxide (NO) or by inhibiting myosin light chain kinase. They are divided into 9 classes: calcium antagonists, potassium channel openers, ACE inhibitors, angiotensin-II receptor antagonists, alpha-adrenergic and imidazole receptor antagonists, beta 1-adrenergic agonist, phosphodiesterase inhibitors, eicosanoids and NO donors. Despite chemical differences, the pharmacokinetic properties of calcium antagonists are similar. Absorption from the gastrointestinal tract is high, with all substances undergoing considerable first-pass metabolism by the liver, resulting in low bioavailability and pronounced individual variation in pharmacokinetics. Renal impairment has little effect on pharmacokinetics since renal elimination of these agents is minimal. Except for the newer drugs of the dihydropyridine type, amlodipine, felodipine, isradipine, nilvadipine, nisoldipine and nitrendipine, the half-life of calcium antagonists is short. Maintaining an effective drug concentration for the remainder of these agents requires multiple daily dosing, in some cases even with controlled release formulations. However, a coat-core preparation of nifedipine has been developed to allow once-daily administration. Adverse effects are directly correlated to the potency of the individual calcium antagonists. Treatment with the potassium channel opener minoxidil is reserved for patients with moderately severe to severe hypertension which is refractory to other treatment. Diazoxide and hydralazine are chiefly used to treat severe hypertensive emergencies, primary pulmonary and malignant hypertension and in severe preeclampsia. ACE inhibitors prevent conversion of angiotensin-I to angiotensin-II and are most effective when renin production is increased. Since ACE is identical to kininase-II, which inactivates the potent endogenous vasodilator bradykinin, ACE inhibition causes a reduction in bradykinin degradation. ACE inhibitors exert cardioprotective and cardioreparative effects by preventing and reversing cardiac fibrosis and ventricular hypertrophy in animal models. The predominant elimination pathway of most ACE inhibitors is via renal excretion. Therefore, renal impairment is associated with reduced elimination and a dosage reduction of 25 to 50% is recommended in patients with moderate to severe renal impairment. Separating angiotensin-II inhibition from bradykinin potentiation has been the goal in developing angiotensin-II receptor antagonists. The incidence of adverse effects of such an agent, losartan, is comparable to that encountered with placebo treatment, and the troublesome cough associated with ACE inhibitors is absent.
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PMID:Clinical pharmacokinetics of vasodilators. Part I. 964 8


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