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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The chief site of action of the calcium antagonist drugs is the slow calcium channel in two tissues: the atrioventricular node and vascular smooth muscle. The exact mode whereby these agents work is still unknown, but recently studies with radioligands suggest that the binding site for the dihydropyridines such as nifedipine is different from the site for the verapamil group (including diltiazem). In some way these agents 'close' or 'block' the calcium channels. Verapamil and diltiazem are active against the calcium channel of the atrioventricular node which nifedipine in clinical doses is not; in contrast, nifedipine is more active on peripheral vascular arterial muscle, presumably inhibiting the calcium channel more strongly. An intracellular site of action of these agents on calmodulin in vascular smooth muscle cannot be excluded. Clinically, the chief calcium antagonists (verapamil, nifedipine, diltiazem) constitute a powerful group of cardioactive agents with a spectrum of therapeutic actions rather similar to beta-adrenoceptor blockade, being effective in angina of effort and rest, and hypertension. Critical differences are dependent on the individual properties of the calcium antagonists. Thus only verapamil and diltiazem are effective in inhibiting the AV node while the dihydropyridines such as nifedipine are only vasodilators in clinical doses. As a group, calcium antagonists cause vascular dilation and do not cause bronchial constriction, in contrast to the beta-adrenoceptor blocking agents. In many patients these diverse properties allow safe combination of calcium antagonists and beta-adrenoceptor blockers if due care is observed.
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PMID:Calcium antagonists. Mechanisms, therapeutic indications and reservations: a review. 632 68

The pharmacokinetics, clinical efficacy, and adverse effects of three calcium-channel blocking agents--verapamil, nifedipine, and diltiazem--are reviewed. Verapamil, nifedipine, and diltiazem are absorbed well after oral dosing, but absolute bioavailability of each is reduced substantially by a first-pass effect. Each drug is metabolized extensively (verapamil and diltiazem to moderately active metabolites) by the liver. A substantial percentage of each drug is bound to plasma proteins, but the binding is of clinical importance only for nifedipine (92--98% protein bound). Intravenous verapamil has become the agent of first choice for treatment of acute paroxysmal supraventricular tachycardia (PSVT); use of chronic oral verapamil therapy for prophylaxis remains controversial. Verapamil and diltiazem have been evaluated with mixed results for atrial flutter and fibrillation. For treatment of myocardial ischemia, calcium-channel blockers may be of some value (possibly in combination with nitrates of B blockers). All three agents have been studied in patients with exertional angina with good results. Calcium-channel blockers appear to be equal with nitrates for treatment of variant angina. Patients with hypertropic cardiomyopathy have been treated with verapamil and nifedipine with promising results. Nifedipine has been effective for treatment of essential hypertension. Adverse effects of calcium-channel blockers have been relatively minor or infrequent. Diltiazem overall has the best side-effect profile, with adverse effects causing discontinuation of therapy in about 2--10% of patients; verapamil in intermediate (8--10%) and nifedipine the worst (17%) in this respect. The most common side effects generally are fatigue, headache, dizziness, skin rash, and peripheral edema. While they generally should be reserved for patients in whom more conventional therapy has failed (except those with PSVT), calcium-channel blockers appear to have a valid role as reserve agents for exertional and variant angina, cardiomyopathy, and hypertension.
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PMID:Update on calcium-channel blocking agents. 635 66

The role of calcium in the cardiovascular system, and the pharmacology, pharmacokinetics, and studies evaluating the clinical use of three calcium-channel blocking agents--verapamil hydrochloride, nifedipine, and diltiazem hydrochloride--are reviewed. Inhibition of calcium conductance and alteration of calcium availability cause profound changes in: slow inward current of the cardiac action potential, myocardial contractility and metabolism, blood pressure regulation, and smooth-muscle activity. Calcium-channel blocking agents affect the movement of calcium through these channels in smooth and cardiac muscle; the specific agents in this class differ markedly in their inhibitory effects. Verapamil hydrochloride is useful intravenously for treating supraventricular rhythm disturbances. It is absorbed well when taken orally, but there is an extensive first-pass effect, so that about 20% enters the systemic circulation. The incidence of side effects in patients receiving verapamil is 9-10%; about 1% require discontinuation of therapy. Verapamil is contraindicated in patients with sinus-node disease, unstable atrioventricular block, and shock. Nifedipine has proven useful for hypertension, coronary-artery spasm, and exertional angina; it has little negative inotropic effect. Approximately 90% of an oral dose is absorbed, and 65-70% reaches the systemic circulation after first-pass metabolism. Protein binding of nifedipine ranges from 92 to 98%. Side effects of nifedipine, usually associated with the peripheral vasodilatory action, occur in approximately 15% of patients, requiring discontinuance in 2-5%. Diltiazem hydrochloride has been shown effective in the treatment of coronary-artery spasm; limited studies indicate it may be useful in treating exertional angina, hypertension, and possibly arrhythmias. Diltiazem's oral bioavailability is good (90% reaches systemic circulation), but there is significant interindividual variability between administered dose and resulting plasma concentration. Geriatric patients have delayed absorption and reduced clearance of diltiazem given in sustained-release tablets. Studies of diltiazem are limited at this time. The exact role of calcium-channel blocking agents has not yet been elucidated. However, their ability to influence the calcium channel greatly expands the therapeutic armamentarium for cardiovascular disease and other disorders.
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PMID:Calcium-channel blocking agents. 676 59

Digoxin remains a very useful agent for chronic atrial fibrillation or for the ectopic beats associated with heart failure. But when rapid control of the ventricular rate is required to arrhythmias such as atrial fibrillation, atrial flutter, or paroxysmal atrial tachycardia, a slow infusion of verapamil is the agent of choice. In general, verapamil may be added to digoxin or given intravenously while a digoxin effect is awaited, unless there is digitalis toxicity. In digitalis toxicity, lignocaine remains the agent of choice for ventricular arrhythmias, and is given in the same doses as for acute myocardial infarction; phenytoin is used for digitalis-arrhythmias with A-V block. Verapamil may be infused very cautiously for digitalis-induced supraventricular tachyarrhythmias. The use of oral agents such as quinidine, disopyramide and mexilitene for chronic prophylaxis of ventricular ectopic beats is of doubtful effectiveness, unless the ectopic activity is symptomatic. Serious ventricular arrhythmias may be induced by quinidine and disopyramide. Beta-blockade is especially useful for ectopic beats associated with anxiety, or when arrhythmias are associated with angina of effort or hypertension. As always, major contraindications to the use of beta-blockade include cardiomegaly, heart failure or asthma.
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PMID:Anti-arrhythmic agents in ischemic heart disease: supraventricular arrhythmias, digitalis toxicity and chronic stable ventricular ectopic beats. 708 6

The role of systemic arterial hypertension as a possible trigger of myocardial ischemia during angina at rest was studied in 13 consecutive patients who also had a history of exertional angina. Significant (greater than or equal to 70%) stenosis of at least one major vessel was present in each of the 10 patients in whom coronary arteriography was carried out. After documentation of the electrocardiographic and arterial blood pressure changes during two or more episodes of resting angina, i.v. methoxamine was infused under continuous monitoring of the ECG, arterial blood pressure and pulmonary artery diastolic pressure. The heart rate was maintained either spontaneously or by atrial pacing to levels similar to those during angina at rest. Despite increases in arterial blood pressure and the double product (systolic blood pressure x heart rate) to levels higher than those during spontaneous angina in all patients, no chest pain or electrocardiographic changes occurred in nine patients. In the other four patients, however, angina supervened. Three of these four patients, but only one of the remaining nine, had a borderline or elevated pulmonary artery diastolic pressure at rest. We conclude that in a considerable number of patients with "nonvariant" resting angina, acute increases in arterial blood pressure during the spontaneous attacks are not likely to be the cause of myocardial ischemia. Nevertheless, in some of these patients, increases in resting pulmonary artery diastolic pressure may favor the development of ischemia during afterload augmentation.
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PMID:Acute arterial hypertension during spontaneous angina in patients with fixed coronary stenosis and exertional angina: an associated rather than a triggering phenomenon. 723 26

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

While studying the functional activity of poly- and mononuclear leucocytes in 75 patients with various clinical types of ischemic heart disease (angina of effort, angina decubitus, arrhythmias, cardiac insufficiency at the background of atherosclerotic cardiosclerosis and atherosclerotic hypertension), decline in the functional activity of the phagocytizing cells has been revealed, this being considered to be a pathogenetic prerequisite for atherosclerosis progression.
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PMID:[The functional activity of the poly- and mononuclear leukocytes in patients with different clinical forms of ischemic heart disease]. 783 69

Recent findings about the effects of biorhythms on cardiovascular disorders are reviewed, and their implications for drug therapy are discussed. The chronobiological approach to physiology evaluates time-dependent changes in biological functions and considers those changes to be multifactorial. Characterization of disease states with this approach allows more accurate determination of the times when patients are at highest risk and therefore in greatest need of preventive measures; it also provides a mechanism for designing optimal drug regimens. There is evidence of circadian variations in the occurrence of myocardial ischemia, acute myocardial infarction, ventricular tachycardia, and sudden cardiac death. Many cardiovascular disorders occur with greatest frequency between 0600 and 1200 in the general population. Blood pressure, too, follows a distinct circadian pattern. Factors affecting circadian variations in cardiovascular disorders include physiological determinants, such as heart rate, catecholamine release, and platelet aggregation--which themselves vary cyclically--and exogenous factors, such as mental stress, anxiety, and physical activity. In chronotherapy, circadian variations in disease states and in the pharmacodynamic properties of drugs are exploited to improve prevention and treatment. Conditions in which research suggests a chronotherapeutic approach may be advantageous include thromboembolism, hypertension, stable exertional angina, variant angina, sustained ventricular tachycardia, and acute myocardial infarction. Information on circadian patterns in the occurrence of many cardiovascular disorders is enabling clinicians to tailor treatment in ways that may lead to improved patient outcomes.
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PMID:Biorhythms and chronotherapy in cardiovascular disease. 784 20

Diltiazem hydrochloride in a once-daily capsule formulation (DCD) has recently been approved in the United States for the treatment of mild to moderate hypertension and chronic stable angina pectoris. This trial evaluated the dose response of DCD in patients with chronic stable angina pectoris. In a multicenter, randomized, double-blind, parallel-design trial, the effects and tolerability of once-daily therapy with placebo or DCD (60, 120, 240, 360, or 480 mg) were evaluated 24 hours after dosing, following 3 weeks of therapy in 227 patients with reproducible stable exertional angina pectoris. A significant linear dose trend (p = 0.004) was present across the 6 treatment groups for the primary end point--time to exercise termination at 24 hours after dosing--using a standard Bruce treadmill exercise test. A significant linear dose trend was also seen for time to 1 mm ST-segment depression at 24 hours after dosing. Similar effects on exercise parameters were also seen at 4 hours after dosing. A linear dose trend (p = 0.04) was noted relative to the overall anginal attacks during daily activities and for anginal attacks during exercise (p = 0.02). Overall frequency of treatment-related adverse effects was dose-related and occurred in 24.4% and 17.5% of patients treated with DCD and placebo, respectively. At a dose up to 240 mg/day, improvement in exercise tolerance was achieved without an associated increase in the rate of treatment-related adverse events compared with placebo.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Dose-response evaluation of once-daily therapy with a new formulation of diltiazem for stable angina pectoris. Diltiazem CD Study Group. 801 16

Coexisting medical conditions often complicate the selection of antihypertensive drugs. Felodipine, a new vascular-selective calcium antagonist with demonstrated antihypertensive efficacy, has not been found to alter lipid profiles in hypertensive patients. Studies in additional patient populations have yielded insights into the effects of the drug on other diseases that may coexist with hypertension. In individuals with stable angina pectoris or congestive heart failure, acute administration of felodipine reduces systemic vascular resistance and increases cardiac output and total coronary blood flow; myocardial contractility is not depressed at doses that produce a clinically significant reduction in vascular resistance. In patients with coronary stenoses, the drug increases vessel diameter in the vicinity of obstructive lesions. Single-dose and long-term studies in patients with exertional angina have found that felodipine reduces anginal frequency and improves exercise tolerance. In patients with congestive heart failure, chronic dosing with felodipine produces a persistent reduction in vascular resistance and an increase in cardiac output, both at rest and during exercise. Symptomatic improvement and increased exercise tolerance have been noted in some studies. In patients with Raynaud's phenomenon, felodipine has been associated with a dose-dependent improvement in symptomatology. Among individuals with exercise-induced bronchospasm, the drug has no effect on resting bronchial tone and may exert some positive effects during exercise. In hypertensive patients with Type II diabetes, felodipine has not been found to raise glucose levels significantly. The data obtained thus far suggest that felodipine is safe for use in hypertensive patients with a variety of concomitant diseases.
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PMID:Treatment of hypertension with felodipine in patients with concomitant diseases. 845 9


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