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)

Heart failure is a syndrome of breathlessness, fatigue and oedema. The effects of ageing on myocardial function and the prevalence of often multiple cardiac pathologies makes heart failure a disease of the elderly, usually characterized by primary or secondary myocardial systolic dysfunction. Appropriate treatment, which requires precise diagnosis, involves correction of precipitating or aggravating factors and the rational use of drug therapy. Diuretics and ACE inhibitors offer a combination of both symptom control and improvement in prognosis. Other agents such as digoxin, xamoterol and nitrates may be particularly useful in the treatment of patients with associated problems such as atrial fibrillation and angina. Because both ageing and heart failure may alter pharmacokinetics and pharmacodynamics, safe and effective treatment of heart failure in the elderly requires understanding of the clinical pharmacology of the drugs used.
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PMID:Treatment of heart failure in the elderly. 240 42

There are several first choices for mild and moderate hypertension. The selection of a drug may of course be influenced by concomitant pathology, with positive indications for particular drugs: for coexistent angina, a beta-receptor blocking drug or a calcium antagonist; for fluid retention, a diuretic; or for contraindications, e.g., asthma, a beta-adrenoceptor blocking drug. There are therefore several possible first choices: beta-adrenoceptor blocking drugs, a combined alpha/vasodilator beta-adrenoceptor blocking drug, the vasodilators (i.e., drugs acting primarily to reduce peripheral resistance), the calcium antagonists, alpha 1-blocking drugs, and, more recently, the possibility of angiotensin converting enzyme inhibitors. Diuretics are also possible first choice agents, although not quite so frequently as once was the case. The majority of cases of hypertension can usually be controlled by one drug, even if not the first agent chosen. More severe cases may require drugs from two of the three major groups: beta-blocking drugs, vasodilators, and diuretics are often required, and, in some cases, drugs from each group. Drugs such as methyldopa, clonidine, and the adrenergic neuron inhibitory drugs are now more used as reserve agents.
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PMID:Pharmacological rationale for antihypertensive drug treatment. 245 70

Calcium channel blockers are recently developed antihypertensive drugs. In terms of mechanisms of action, their specificity is not so well established as that of angiotensin converting enzyme inhibitors but is better understood than that for diuretics or adrenergic-inhibiting drugs. Calcium channel blockers were originally developed for treatment of angina but were found to lower arterial pressure as well. Three of them are now in wide use in the United States; their therapeutic spectrum in regard to type of hypertension is broad. Sublingual nifedipine has replaced intravenously administered vasodilators as immediate treatment of severe hypertension, and all three drugs, given orally, have been shown to be effective in mild, moderate, and severe hypertension. The three drugs available in this country are verapamil, diltiazem, and nifedipine. Pharmacological studies have shown that verapamil has the most negative chronotropic and inotropic effects of the three, with nifedipine producing the most vasodilation and having the potential for causing reflex tachycardia. Actually in practice, these various pharmacological differences have proved to have less significance than previously thought, and the drugs seem to have about equal antihypertensive effectiveness. Comparisons of calcium entry blockers with other drugs have shown them to be equally effective in whites as propranolol but more effective in blacks. Responsiveness appears to be related, as well, to pretreatment plasma renin activity and age. Thus, the antihypertensive effect is directly related to age and inversely related to plasma renin activity. The side effects mostly relate to vasodilation, reflex tachycardia, palpitations, headache, and edema; they are not frequent, and the drugs are well tolerated.
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PMID:Calcium channel blockers. Potential medical benefits and side effects. 249 Aug 17

The effect of angiotensin converting enzyme inhibition on myocardial ischaemia was studied in 12 normotensive patients with chronic stable angina and exercise induced ST segment depression. The study was randomised, double blind, placebo controlled, and crossover with treatment periods of two weeks. Enalapril was used to inhibit angiotensin converting enzyme. Assessment was by angina diaries and maximum symptom limited treadmill exercise tests. The results for the whole group showed a significant reduction in systolic blood pressure at rest and at peak exercise. Mean total exercise duration was 466 s (95% confidence interval 406 to 525) when the patients were taking placebo and 509 s (436 to 583) when they were taking enalapril. Four patients prolonged their total exercise time (mean 450 to mean 591 s) by more than 20%. Two patients, however, developed ischaemia earlier on exercise and reduced their total exercise duration (mean 490 to mean 390 s). Although angiotensin converting enzyme inhibition tended to reduce myocardial ischaemia in the group as a whole, some patients improved while others deteriorated. Thus the effects of enalapril are variable and this may have important implications when enalapril is used to treat heart failure in patients with underlying severe ischaemic heart disease.
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PMID:The variable effects of angiotensin converting enzyme inhibition on myocardial ischaemia in chronic stable angina. 254 48

The calcium ion is recognized as having a ubiquitous role in a wide range of physiological responses. The calcium entry blockers have assumed a greater role than first thought possible in the management of cardiovascular disorders. As a group, they have multiple effects and can be tailored to meet specific needs. The drugs are well tolerated, thus making them useful for chronic administration. The efficacy of the calcium entry blockers can be enhanced when combined with other therapies such as beta-adrenoceptor antagonists and inhibitors of angiotensin converting enzyme as applied to patients with hypertension, angina pectoris, or both. The range of indications and potential uses of the calcium entry blockers demands an understanding of the role of the slow inward current in cardiac and vascular smooth muscle. This review focuses on the pharmacological actions of the calcium entry blockers and relates these events to their clinical applications in an effort to achieve an understanding of their multiple therapeutic uses.
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PMID:Role of calcium on excitation-contraction coupling in cardiac and vascular smooth muscle. 255 75

We have synthesized an S-nitrosylated derivative of captopril, S-nitrosocaptopril, that manifests nitrosovasodilatory activity, inhibits angiotensin converting enzyme activity and inhibits platelet aggregation. The direct vasodilatory effects of S-nitrosocaptopril reflect the effects of the thionitrite bond, the presence of which does not in any way influence S-nitrosocaptopril's ability to inhibit angiotensin converting enzyme. Thionitrite stimulation of both vascular and platelet soluble guanylate cyclase activity leads to increases in intracellular cyclic GMP that are accompanied by vasodilatation and platelet inhibition, respectively. S-nitrosocaptopril is a novel hybrid molecule that has potential use in the treatment of hypertension regardless of renin status, angina pectoris and congestive heart failure.
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PMID:S-nitrosocaptopril. I. Molecular characterization and effects on the vasculature and on platelets. 265 76

In 1988 the fourth Joint National Committee (JNC IV) issued new guidelines for the detection, evaluation, and treatment of hypertension. Pharmacologic along with nonpharmacologic therapy is indicated for hypertensive patients whose diastolic blood pressures average greater than or equal to 95 mmHg over a period of time and for patients who have a diastolic blood pressure of 90 mmHg to 94 mmHg with evidence of target organ disease and/or other major risk factors. In the absence of target organ disease and/or other major risk factors, a trial of nonpharmacologic treatment is recommended for patients with a diastolic blood pressure of 90 mmHg to 94 mmHg. The JNC IV report recommends initiating pharmacologic treatment with any one of the following classes of drugs: diuretics, beta blockers, calcium channel blockers, or ACE inhibitors. In general, diuretics and calcium channel blockers are especially indicated for elderly and black patients and beta blockers and ACE inhibitors for young and white patients, but there are many exceptions. In selecting the appropriate step-one agent for a given patient, the therapeutic "two-for-one" concept is emphasized whereby one antihypertensive drug may also be beneficial for a coexisting condition. Examples are: diuretics or ACE inhibitors in congestive heart failure; calcium channel blocking drugs or beta blockers in angina pectoris or paroxysmal supraventricular tachycardia; and beta blockers for migraine headache or senile tremor.
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PMID:Mild hypertension: critical analysis of different therapeutic approaches. 266 23

In ten patients with angiographically demonstrated coronary heart disease exercise electrocardiograms were recorded before as well as two and four hours after administration of 5 or 10 mg Quinapril, an angiotensin converting enzyme inhibitor (ACEI). This reduced the sum of ST-segment depressions from 16.3 to 11.6 mV (P less than 0.001). While the heart rate remained unchanged, blood pressure fell from 147/91 to 119/79 mm Hg and the angina-free exercise time was clearly prolonged. Altogether there was a reduction of the ischaemia reaction by 35%. This perhaps speaks for an anti-anginal effect of ACEI, which could be of importance in the management of both hypertension and heart failure. In addition, the ACE inhibitors might be used as anti-angina drugs.
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PMID:[Angiotensin-converting enzyme inhibitors in angina pectoris]. 335 81

Administration of potent vasodepressor agents such as the angiotensin converting enzyme inhibitor, captopril, may precipitate myocardial ischemic events in patients with coronary artery disease, particularly if this treatment is preceded by a discontinuation of beta-blocking drugs such as propranolol. In one case studied, a patient experienced three episodes of angina pectoris under these conditions; in another, acute anterior myocardial infarction was suspect.
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PMID:Ischemic cardiovascular complications concurrent with administration of captopril. A clinical note. 624 3

We investigated the alteration of the ACE in different parts of the circulation in 21 patients with essential hypertension, who suffered from angina pectoris attacks. Blood samples were taken during diagnostic cardiac catheterisation. The ACE was fluorimetrically measured and compared to 48 normotensive patients. In 11 patients the Plasma Renin Activity (PRA) was additionally determined by means of bioassay. The ACE was significantly (p less than 0.001) elevated in all investigated regions but a different distribution was not observed. We found a positive correlation between the ACE from the left ventricle and the systolic, mean arterial and diastolic blood pressure. Furthermore, we observed a negative correlation between ACE and PRA. No relationship could be calculated between ACE and electrolytes, creatinine or haemodynamic parameters. Our results indicate that the ACE may contribute to the pathogenesis of so-called essential hypertension.
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PMID:Elevated angiotensin-I-converting enzyme (ACE) in patients with essential hypertension. 628 14


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