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

The coexistence of the syndromes of essential hypertension and coronary artery disease (CAD) poses a major but common therapeutic challenge. High blood pressure is one of the most potent risk factors for the early development of CAD. Conversely, the presence of CAD significantly worsens the predictive prognosis associated with high blood pressure. Moreover, metabolic risk factors for the acceleration of both syndromes are similar, particularly with regard to abnormalities of the blood lipid profile, carbohydrate intolerance, and obesity. It is clinically crucial, therefore, to direct drug therapy not only at the immediate alleviation of the symptoms and signs of each syndrome but also to control the cardiac and vascular risk factors common to both syndromes. Carvedilol is a third-generation vasodilating beta-adrenoceptor antagonist with advantageous ancillary pharmacologic properties for the treatment of the patient with high blood pressure complicated by CAD. The immediate advantages of the drug in the treatment of both syndromes are distinct. In the patient with high blood pressure, carvedilol controls the pressure throughout the 24 h of the day and suppresses the increase associated with exercise. In the patient with CAD, the drug is efficacious in relieving anginal pain and electrocardiographic signs of myocardial ischemia. By reducing blood pressure and heart rate and retarding their increases during exercise, the drug exhibits a potent ability to reduce left ventricular work, wall stress, myocardial oxygen consumption, and left ventricular myocardial ischemia. In the patient in whom both syndromes coexist, carvedilol affords a remedy for both.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hypertension and coronary artery disease: a therapeutic challenge. 172 78

In an open clinical study, the efficacy and safety of carvedilol was investigated in 26 severely hypertensive patients controlled inadequately on a diuretic [diastolic blood pressure (DBP) greater than 120 mm Hg at first visit and greater than 110 mm Hg following more than 1 week administration of a diuretic]. Following diuretic treatment all patients were initially administered 5 mg of carvedilol once daily. The dose was gradually increased to 10 mg and 20 mg until DBP was reduced below 100 mm Hg or until it was reduced by at least 10 mm Hg. Antihypertensive activity of carvedilol (5 mg) was sufficient in only three cases, but after 4 weeks (inpatients) or 8 weeks (outpatients) administration of carvedilol (10 mg or 20 mg), DBP/systolic blood pressure was significantly reduced from 176 +/- 6/117 +/- 3 to 145 +/- 3/94 +/- 2 mm Hg (p less than 0.001) in all patients. Overall, a sufficient antihypertensive effect was observed in 80% of the patients. Heart rate was significantly decreased from 76 +/- 2 to 67 +/- 2 beats/min, but no patient experienced bradycardia. Carvedilol was generally well tolerated. These findings suggest that 10-20 mg of carvedilol once daily, in combination with a diuretic, is an effective and safe treatment for patients with severe hypertension.
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PMID:Clinical efficacy of carvedilol in severe hypertension. 172 83

Several so-called multiple-action compounds have been developed, such as medroxalol (alpha and beta blockade, and beta-2 stimulation), celiprolol (alpha-2 and beta-1 blockade, and beta-2 stimulation) and carvedilol (beta blockade and vasodilatation) for the treatment of patients with arterial hypertension and with coronary heart disease. Carvedilol exerts relatively uniform peripheral effects, i.e. a reduction of both systolic and diastolic blood pressure at rest and during exercise, and a decrease in the resting and exercise heart rate. Blood pressure fall due to carvedilol may be induced by its vasodilating effect, as documented by measurements of forearm blood flow and peripheral vascular resistance. Moreover, renal hemodynamics does not seem to be significantly altered by carvedilol. Carvedilol may also produce an improvement of the LV contractile status in patients with CHD and impaired LV function, mainly due to afterload reduction, in addition to its antianginal effect, which is due mainly to the beta-blocking properties of this substance. From the studies mentioned it may be concluded that carvedilol is a useful and promising drug for treating patients with both arterial hypertension and with coronary artery disease.
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PMID:Hemodynamic profile of carvedilol. 197 96

Carvedilol [25 mg once daily] (o.d.) was compared to atenolol (50 mg o.d.) as an adjunct to pre-existing hydrochlorothiazide (HCTZ) monotherapy in patients with mild to moderate hypertension [diastolic blood pressure (DBP), 100-115 mm Hg]. After a placebo run-in phase of 2 weeks, 131 patients received 25 mg HCTZ o.d. for 4 weeks. In all, 122 patients were transferred to the double-blind phase, in which 25 mg carvedilol or 50 mg atenolol was randomly added to HCTZ. After an additional 6 weeks of treatment, 112 patients were evaluable for efficacy (C/HCTZ group, n = 54; A/HCTZ group, n = 58). Blood pressure was measured and the heart rate was counted before medication, at 2-week intervals throughout the trial, and 2 h after medication on the 1st and the last day of the combination treatment period. Serum lipids were measured in addition to routine laboratory variables. A therapeutic response was defined as a reduction in supine and standing diastolic blood pressure to values of less than 90 mm Hg. In a relatively low number of patients (6 of 131), a response as defined above was achieved with HCTZ alone. This may be accounted for by the fact that patients were required to have a diastolic blood pressure of at least 100 mg Hg and by the relatively short period of monotherapy. The two groups of patients receiving different combination treatments were well matched for demographic data and blood pressure values before the adjunct was added. In both groups there was a marked additional blood pressure decrease on the initiation of combined treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Efficacy and safety of carvedilol in comparison with atenolol in hypertensive patients pretreated with hydrochlorothiazide. 197 6

Carvedilol and nitrendipine were given for 12 weeks in a double-blind study to 81 elderly patients (greater than or equal to 60 years) with essential hypertension. The effects on blood pressure were measured (Riva Rocci) before medication and after 2 h with the patient in a lying and standing position after 4 weeks of placebo therapy as well as after 4, 8 and 12 weeks of treatment. Carvedilol (25 mg/o.d.) reduced blood pressure measured in the supine and erect position very successfully, similar to the reduction achieved with nitrendipine (20 mg/o.d.), without influencing the pulse rate. Both substances were well tolerated. Carvedilol is an alternative substance for lowering high blood pressure in elderly hypertensive patients.
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PMID:Blood-pressure-lowering effect of carvedilol vs nitrendipine in geriatric hypertensives. 197 10

Carvedilol is a new beta-receptor blocking and vasodilating drug that is presently undergoing clinical trials in hypertension and coronary heart disease. In this article, the pharmacodynamic properties of carvedilol are compared with those of standard drugs. The beta-blocking activity was characterized in isolated organs and in conscious rats, rabbits, and dogs. For the beta 1-blockade in guinea pig atria, the pA10 values were 7.44 +/- 0.16 for carvedilol and 6.77 +/- 0.08 for propranolol. Carvedilol is a noncardioselective beta-blocker. The i.v. doses that inhibited the tachycardia by 50% induced by 1 microgram/kg isoprenaline were 62 micrograms/kg in dogs, 138 micrograms/kg in rabbits and 841 micrograms/kg in rats. In rabbits carvedilol was slightly more active and in rats less active than propranolol. In all models, carvedilol was much more active than labetalol or prizidilol. In contrast to propranolol, carvedilol relaxed rat aortic strips. A dose-dependent decrease in arterial blood pressure was seen in different in vivo models. The total peripheral and coronary resistance were decreased in conscious dogs. The doses required for both beta-blockade and decrease in blood pressure were in the same range. The drug was also active after oral administration. There is no hint for development of tolerance.
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PMID:Pharmacological profile of carvedilol as a beta-blocking agent with vasodilating and hypotensive properties. 243 99

Carvedilol (BM 14190) is a new potent and well-tolerated beta-adrenoceptor antagonist with vasodilating properties. Acute clinical studies have confirmed its efficacy as an antihypertensive agent. The present double-blind, randomized, metoprolol-controlled, long-term study reports the therapeutic results of carvedilol in essential hypertensive patients. Compared with placebo, carvedilol significantly reduces blood pressure after oral administration of 50 mg on a single and twice daily regimen. The antihypertensive effect was acute in onset, comparable in supine and standing position, and exercise-induced hypertension and tachycardia were significantly reduced. Indirect automatic 24 h blood pressure monitoring reliably confirmed clinic blood pressure and demonstrated a good antihypertensive effect of carvedilol after a single oral administration throughout daily activities and sleeping periods.
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PMID:Circadian antihypertensive profile of carvedilol (BM 14190). 245 57

In a randomized double-blind study, oral doses of 50 mg carvedilol were compared to 40 mg propranolol in 16 male patients with coronary heart disease (12 without significant stenosis after percutaneous transluminal coronary angioplasty) at rest, during and after exercise, and before and 80 min after drug application. Systemic and pulmonary pressures, heart rate, cardiac index, and lower limb blood flow were measured, and systemic and pulmonary resistances calculated. Carvedilol does not lead, as the classical beta-blocker propranolol does, to an increase in systemic or pulmonary resistance, nor to a decrease in cardiac output, or to an increase of the pulmonary capillary wedge pressure during exercise. In contrast to propranolol, the postexercise lower limb blood flow has increased significantly. The differences in action between the two beta-blockers can be explained by the vasodilating properties of carvedilol. Due to these acute effects, carvedilol may be of advantage compared to propranolol in the treatment of peripheral occlusive artery disease, hypertension, and coronary vasospasm.
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PMID:Acute hemodynamic effects of the vasodilating and beta-blocking agent carvedilol in comparison to propranolol. 245 62

In the treatment of hypertension, drugs with different mechanisms of action are frequently combined. The rationale for this procedure is that lowering blood pressure via one mechanism often leads to the activating of processes that tend to increase blood pressure. Thus, during antihypertensive treatment with vasodilating agents, reflex stimulation of the heart occurs with increase of cardiac output. By this, the blood pressure lowering effect of the vasodilator is antagonized. Combination of several drugs may complicate therapy because of differences in the onset and the duration of action. Sometimes, there are pharmacokinetic drug interactions. By combining several blood pressure lowering mechanisms in one drug molecule, one tries to prevent these difficulties. There are now several drugs with a dual mode of action available for the treatment of hypertension. Labetalol combines alpha- and beta-receptor blocking activities. Meanwhile, there is ample experience with the use of this drug in the treatment of hypertensive patients. Labetalol can be used for acute decrease of blood pressure in hypertensive emergencies. Most often, the drug is given for chronic treatment of hypertension. The overall incidence of side effects from labetalol compares favorably with that from other drugs. In addition to side effects caused by beta-blockade, the use of labetalol may result in postural hypotension due to the alpha-receptor blocking activity. Carvedilol is a new compound that combines beta-receptor blockade and vasodilation in one molecule. The drug can be used to acutely and chronically reduce blood pressure. Carvedilol is now undergoing clinical investigation. The same is true for celiprolol, a beta 1-receptor blocking agent with alpha 2-receptor blocking activity.
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PMID:Antihypertensive compounds with combined actions. 245 63

Carvedilol is a new substance displaying beta-sympatholytic and vasodilating activities in the same dose range. Data obtained from a considerable number of animal experiments show that the beta-blocking properties of carvedilol resemble those of propranolol. However, in contrast to propranolol the arterial blood pressure decreases dose dependently after single doses of carvedilol due to a reduced total peripheral resistance. The vasodilating activity of carvedilol can be demonstrated in a variety of experimental models. According to the present state of knowledge neither alpha-blockade, nor Ca antagonism, serotonin antagonism, prostaglandin-mediated vasorelaxation, or endothelial-derived relaxing factor (EDRF)-dependent activity are responsible for the antihypertensive effect. Thus, although the mechanism of vasodilation has still not been completely clarified, a postreceptor mechanism seems likely. The acute vasodilating properties in humans have been shown as a dose-dependent increase of the finger pulse amplitude in healthy subjects after both intravenous and oral administration, and as a decrease of the regional resistances and an increase of regional blood flow. The pharmacokinetics of carvedilol are dose linear and peak concentrations are reached within 1-1.5 h after oral administration. The elimination half-life after single oral doses varies from 6-7 h. The renal clearance of 4 ml/min is negligible in comparison with the total body clearance of 590 ml/min. Therefore, the absolute bioavailability of 24% indicates some degree of first-pass extraction. The highly lipophilic drug is extensively distributed to the tissues, as shown by the distribution volume of 132 l. In patients with hypertension, single doses of carvedilol (25-50 mg) decrease systolic and diastolic blood pressure for more than 10 h, whereas heart rate is only slightly decreased. In hypertensive patients treated from 7 days up to 1 year, carvedilol proved to be an effective and safe antihypertensive drug. In contrast to conventional beta-blockers, the reduced vascular resistance, in particular of the renal circulation, observed after both acute and chronic administration of carvedilol, indicated the useful hemodynamic profile of this compound. In addition, patients not sufficiently controlled with conventional beta-blockers responded promptly to carvedilol. At the same time left ventricular performance is not depressed. In a 1-year open clinical trial with hypertensives WHO I and II, the responder rate was about 85% with carvedilol as monotherapy.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:A new molecule with vasodilating and beta-adrenoceptor blocking properties. 245 64


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