Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nicardipine is currently being evaluated in clinical trials as a treatment for angina and hypertension. Over 2,000 patients have received nicardipine, most at dosages of 20 to 40 mg 3 times daily. In 12 double-blind, parallel-group studies (4 of them placebo-controlled) the efficacy of nicardipine was evaluated in mild to moderate hypertension; supine systolic blood pressure was lowered by 10 to 15 mm Hg and supine diastolic blood pressure by 10 mm Hg. A clear dose response is present at dosages from 10 to 40 mg 3 times daily. Patients with angina were treated in 9 double-blind, crossover design studies: 4 of these were placebo-controlled; 3 were comparison studies with beta blockers; 2 were comparisons with nifedipine. Treadmill exercise tests were the major measure of efficacy. Results of these studies showed consistent, statistically significant improvement in exercise tolerance and time to onset of angina, and clinical improvement in patients with chronic stable angina. The effective dosages of nicardipine were 30 or 40 mg 3 times daily. A placebo-controlled study demonstrated remarkable efficacy in patients with vasospastic angina. No deaths or serious adverse reactions were attributed to nicardipine during clinical trials. The most common side effects reported were flushing, palpitations, headache and pedal edema. These appeared to be due to the drug's pharmacologic property of vasodilatation.
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PMID:An overview of the safety and efficacy of nicardipine in clinical trials. 330 Feb 39

The clinical use of calcium antagonist drugs in coronary artery disease preceded knowledge of the mechanism of their action. Basic research into their pharmacological actions and development of a wide range of compounds which block calcium entry into cells enabled clinicians to greatly expand the indications for their use. Thus the calcium antagonists were rediscovered and found to be potent anti-anginal drugs when used in adequate dosage for effort related angina. Knowledge of their potent relaxing action on vascular smooth muscle led to their use in coronary artery spasm. The exact trigger mechanism/s for spasm and the reason for enhanced vascular reactivity remain unclear, perhaps explaining the failure of specific antagonist therapy. Calcium antagonists acting nonspecifically inhibit both induced and spontaneous attacks of vasospastic angina. They may favourably influence the prognosis and are now drugs of first choice for this condition. The vasodilator action of these drugs has most recently been utilized to treat hypertension, with efficacy confirmed in many controlled trials. Unlike other vasodilators, the calcium antagonists reduce blood pressure without salt and water retention, and with mild or no stimulation of renin, aldosterone, or sympathetic nervous overactivity, and without postural effects. This spectrum of action makes them ideal therapeutic agents, and current guidelines are changing to include calcium antagonists as first or second line therapy.
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PMID:Calcium antagonist drugs in the treatment of coronary spasm, effort angina and hypertension. 330 67

From among 899 consecutive patients who underwent their first coronary arteriography, we selected 147 pts with vasospastic angina (VA) and 356 pts with classic angina (CA) and divided them into three different age groups: -49 years old, 50 to 59, and 60-. In these 899 pts, incidences of VA showed no increase with aging. Prevalence of coronary risk factors in CA, such as diabetes, hypercholesterolemia, hypertension, and obesity, was higher than in VA, although prevalence of smoking in CA was lower than in VA. In VA, we found an age-related increase in the incidence of smoking only, in contrast to the other four risk factors. The VA showed no age-related increase in the incidence of complication of fixed coronary stenosis. These findings suggest that aging and atherosclerosis might not play a major role in pathogenesis of VA, although the mere presence of atherosclerosis irrespective of its severity could interact with local susceptibility to spasm, leading to coronary vasospasm.
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PMID:Age-related changes of clinical features and prevalences of coronary risk factors in Japanese patients with vasospastic angina. 394 Jul 72

The use of voltage clamps in cardiac muscle has permitted the separation of two inward depolarizing membrane currents. The first is the fast sodium current, with rapid kinetics of activation and inactivation, which is blocked by local anesthetics. The second is the slow current carried largely by calcium ions, having slow kinetics with a long time constant of inactivation. Agents which selectively block this current are called Ca antagonists. Such agents are heterogeneous structurally; they also block calcium currents in smooth muscle and therefore produce coronary as well as peripheral vasodilatation. The most significant agents are verapamil, gallopamil, nifedipine, diltiazem and tiapamil. They have a varying spectrum of pharmacological effects with respect to changes they produce on heart rate, afterload, preload, contractility, coronary flow and on the AV node. A similar spectrum of therapeutic effects is apparent in different clinical disorders, in particular vasospastic angina, stable and unstable angina, cardiac arrhythmias, hypertension, hypertrophic cardiomyopathy and possibly other disorders. Indeed, the full range of clinical disorders which may respond to calcium antagonists is still not fully delineated and may well be at least as extensive as that for beta-adrenoceptor blocking drugs. The advent of calcium antagonists in the last decade represents one of the most significant advances in cardiovascular therapeutics.
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PMID:An overview of slow channel blocking drugs: pharmacological basis for therapeutic applications. 629 28

Coronary artery calcification (CAC) was easily demonstrated by plain CT-scan. The aim of this study was to clarify the clinical significance of CAC in cardiovascular diseases. The subjects were 90 patients with ischemic heart disease (30 myocardial infarction, 50 exertional angina pectoris and 10 variant form of angina pectoris; 46 males and 44 females, 68 +/- 10 y/o) and 50 patients without ischemic heart diseases (30 hypertension, 10 arrhythmia, 3 valvular disease, 2 cardiomyopathy, 2 congenital heart disease and 3 others; 25 males and 25 females 65 +/- 9 y/o). CAC and calcification of thoracic aorta were evaluated by plain CT-scan (1 second scan time and 5 mm slice). The relationship between CAC and other clinical features (age, sex, hypertension, diabetes mellitus, hyperlipidemia, smoking, resting ECG, exercise stress ECG, aortic calcification and optic fundi) were studied. CAC were seen more frequently in patients with ischemic heart disease (63%), old age (67%), aortic calcification (70%) and positive exercise testing (64%). On the other hand, CAC were rare in variant angina (30%). In younger patients (under 70 y/o), CAC were seen more frequently in diabetic patients. But, in older patients, CAC were frequently in those with hyperlipidemia. These results suggested that CAC was associated with not only systemic arteriosclerosis, but also ischemic heart disease, except vasospastic angina. The prognostic value of CAC would be studied later.
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PMID:Clinical significance of coronary artery calcification. 779 Jul 45

Improved understanding of the pathogenesis of symptomatic and silent myocardial ischemia has led to important advances in the prevention and treatment of these syndromes. For example, recognition of the role of platelets in the atherogenic process and of thrombosis in acute myocardial ischemia has led to extensive use of aspirin and thrombolytic therapy, with resultant decreases in mortality. Both nitrates and beta-adrenergic blockers effectively alleviate myocardial ischemia. However, long-term nitrate use is limited by the occurrence of tolerance. beta blockers have been shown to decrease subsequent cardiovascular events in patients with acute myocardial infarction; however, adverse effects are often associated with their use. Calcium antagonists have been shown to be effective in the treatment of stable and vasospastic angina. In patients with coronary artery disease and symptoms resulting from either fixed obstruction or vasospasm, these agents decrease the frequency of angina episodes. The 3 types of calcium antagonists currently available--phenylalkylamine, benzothiazepine, and dihydropyridine derivatives--while chemically a heterogeneous group, share the common property of decreasing depolarization of smooth muscle, albeit to varying degrees. Nonetheless, other characteristics, including varying electrophysiologic effects, distinguish these groups. The novel calcium antagonist amlodipine is effective and well tolerated as an antianginal agent, and offers the advantage of once-daily dosing. Calcium antagonists appear to be well tolerated in patients with concomitant conditions such as diabetes and are effective in commonly coexistent cardiovascular disorders such as hypertension.
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PMID:Emerging options in the management of myocardial ischemia. 790 91

The chemistry, pharmacology, pharmacokinetics, efficacy, and adverse effects of amlodipine are reviewed. Amlodipine belongs to the dihydropyridine subclass of calcium antagonists. Amlodipine is a potent peripheral and coronary vasodilator with high selectivity for vascular smooth muscle and minimal effect on myocardial contractility or cardiac conduction. Absorption after oral administration is slow, and the duration of action is long, with a half-life of 36-45 hours. Amlodipine has FDA-approved labeling for use in the treatment of hypertension, chronic stable angina, and vasospastic angina. The agent is also indicated for use in hypertensive or anginal patients who also have congestive heart failure due to systolic dysfunction (New York Heart Association classes II and III). Clinical trials suggest that effective 24-hour control of hypertension and angina is provided by once-daily administration of amlodipine 5-10 mg alone or in combination with other drugs. No clinically important drug interactions have been observed to date. Amlodipine has not shown any unfavorable effects on serum glucose or lipid levels. The most common adverse effect is peripheral edema. Amlodipine is effective and well tolerated when given alone or in combination with other drugs for the treatment of hypertension and angina. Amlodipine may offer advantages over verapamil, diltiazem, and nifedipine in patients with hypertension or angina with associated congestive heart failure due to systolic dysfunction.
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PMID:Amlodipine: a new calcium antagonist. 813 60

The outcome of patients presenting with spasm of normal or subnormal coronary arteries is only known in small series of patients at medium-term. The authors reviewed the outcome of 277 successive patients over an average period of 86 +/- 43 months (12 to 174 months). There were 206 men and 71 women with a mean age of 54 +/- 9 years. Coronary angiography was performed in all cases and did not show any stenosis greater than 50%. Spasm was documented during coronary angiography in 157 cases (57%) by a positive Methergin test after coronary angiography in 113 cases (41%) and by an ECG recording of Prinzmetal angina in 7 cases (2.5%). Nearly all patients (264: 95%) were treated by calcium antagonists. At the end of follow-up, there were: 35 lost to follow-up (12.6%), 20 deaths (7.2%) of which 10 were cardiac (3.6%), 18 myocardial infarctions (6.5%): 11 had repeat coronary angiography which showed one or more new significant (> 70%) coronary lesions in all cases; 109 patients had persistence of chest pain (39%). The severity of symptoms in 52 cases (over one attack of chest pain per month) led to repeat coronary angiography which showed significant coronary disease in 19 cases; 95 patients (34%) were asymptomatic. A multivariate statistical analysis showed hypertension or subnormal appearances on the initial coronary angiography to be significant predictive factors for new coronary events (death, myocardial infarction or angina requiring repeat coronary angiography). The authors conclude that coronary spasm of angiographically normal or subnormal arteries is only well controlled at long-term in 39% of patients not lost to follow-up and is responsible for death or myocardial infarction in 11.6% of cases (nearly 1.5% per year).
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PMID:[Spasm of normal or irregular coronary arteries. Long-term outcome of 277 patients]. 872 61

There are a number of cardiovascular conditions in which calcium channel antagonists (CCAs) are accepted as first-line therapy, including Prinzmetal's angina and Raynaud's phenomenon. The real issue is whether symptomatic relief of angina or effective reduction of blood pressure (BP) is matched by a good safety record. In effort angina, verapamil is as safe as metoprolol, and nifedipine (tablet form) is as safe as atenolol. In unstable angina, intravenous diltiazem is better than intravenous nitroglycerin; there are no similar data on beta-blockade. Short-acting nifedipine is contraindicated in unstable angina. There is no place for CCAs in acute phase myocardial infarction and short-acting nifedipine is contraindicated. In the post-MI phase, two specific groups of patients benefit from diltiazem or verapamil: (1) those who had non-Q-wave infarcts and (2) those who are hypertensive. The DAVIT studies argue for the safety and efficacy of verapamil but do not allow comparisons with standard beta-blocker therapy. In the treatment of hypertension, the recommendation often made that a low-dose diuretic should be first-line therapy holds for the elderly with systolic hypertension but is not based on prospective studies in the case of younger patients. High-dose diuretics may have adverse effects, as reported in two case-controlled studies. Prospective outcome data favoring beta-blocker monotherapy as first-line therapy are limited, especially in the elderly, while case-control studies suggest an increased incidence of cardiac death in those treated by beta-blockers. CCAs may be the preferred first-line antihypertensive treatment for those groups in whom low-dose diuretics are unlikely to work as monotherapy.
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PMID:Calcium channel antagonists should be among the first-line drugs in the management of cardiovascular disease. 892 59

We investigated the role of the insertion (I)/deletion(D) polymorphism in the angiotensin I converting enzyme (ACE) gene in the cardiovascular diseases. First, we studied 520 patients who had undergone coronary angiography: including 220 patients with acute myocardial infarction, 98 patients with effort angina pectoris (> 75% stenosis), 83 patients with vasospastic angina and 119 controls with normal coronary artery. There was no difference in the frequency of ACE gene I/D allele or genotype II, ID and DD among the four groups. Second, we studied the correlation between ACE gene I/D polymorphism and the clinical characteristics in patients with essential hypertension. The distribution of I/D allele and genotype were similar in 140 essential hypertensives and 83 normal controls. In patients with DD genotype, age at onset of hypertension was lower and left ventricular mass index was greater than those in patients with ID and II, although blood pressure levels and the severity of damage to other organs-were similar in the three groups. Further, 66 patients with essential hypertension were classified into 35 salt-sensitive and 31 salt-resistant patients according to changes in mean blood pressure during a week of low salt diet followed by a week of high salt diet. The frequency of I allele was significantly higher in the salt-sensitive group than in the salt-resistant group. In conclusion, ACE gene I/D polymorphism is not associated with coronary artery diseases. In patients with essential hypertension, the D allele was associated with early onset and left ventricular hypertrophy, while I allele was associated with salt sensitivity.
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PMID:[Evaluation of angiotensin I converting enzyme gene polymorphism in patients with essential hypertension and coronary artery disease]. 912 Sep 94


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