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

The role of hepatic drug-metabolizing enzyme activity for plasma propranolol and sotalol levels was investigated in 68 patients with hypertension or angina pectoris by comparing elimination rate with antipyrine kinetics and cytochrome P-450 content in the liver. All subjects were resistant to or had hepatotoxic reaction to previous treatment. Plasma antipyrine clearance and cytochrome P-450 content in biopsies were related to propranolol elimination from plasma, the best fit being obtained with the clearance values. Sotalol plasma clearance was not related to any indirect or direct reflector of the hepatic drug-metabolizing enzyme system. The results demonstrate that plasma clearance of the short-acting beta blocker, propranolol, depends on the activity of hepatic drug-metabolizing enzyme system and indicates a trial with a drug such as sotalol which is not dependent on liver metabolizing capacity.
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PMID:Plasma clearance of propranolol and sotalol and hepatic drug-metabolizing enzyme activity. 45 85

Plasma concentrations and the effect of sotalol, a beta blocker, on arterial blood pressure and other haemodynamic variables (determined by echocardiography) were measured in 15 patients with arterial hypertension of different severity, after acute administration and during long-term treatment for 3 to 16 months. Sotalol absorption was relatively constant, the correlation coefficient between plasma concentrations and administered dose being r=0.67. The biological half-life was about eight hours, The effects of the drug on blood pressure, heart rate and other haemodynamic variables were small after acute administration. But in ten patients blood pressure returned to normal during chronic treatment with sotalol alone, while in five others it was necessary to combine sotalol with a diuretic and dihydralazine. These results show that sotalol is suitable for long-term treatment of arterial hypertension.
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PMID:[Treatment of arterial hypertension with sotalol, a beta-blocker (author's transl)]. 84 11

The beta-adrenergic antagonist propranolol, administered subcutaneously to conscious adrenalectomized rats made hypertensive by exogenous glucocorticoids, has been shown to induce acutely a marked fall in blood pressure and heart rate. These animals almost completely lacked circulating epinephrine. Because both changes were closely related, it was suggested that in this model of hypertension propranolol acts via a central mechanism. To test this hypothesis, we now administered sotalol (300 micrograms) intracerebroventricularly to unanesthetized adrenalectomized rats with glucocorticoid-induced hypertension (this hydrophilic beta-blocking agent does not cross the blood-brain barrier). The same experiments were also performed in sham-operated glucocorticoid-hypertensive rats. On the day of the study, there was no significant difference between adrenalectomized and sham-operated groups of rats in intraarterial pressure and heart rate. Sotalol increased blood pressure and significantly slowed heart rate during the 60-min observation period, both in adrenalectomized and sham-operated rats. Sotalol's vehicle had no blood pressure effect and caused a transient heart rate acceleration in rats with, as well as without, circulating epinephrine. These results therefore suggest that the previously observed enhanced effect of peripherally administered propranolol in the absence of detectable circulating epinephrine, in this model, is not mediated centrally.
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PMID:Blood pressure and heart rate response to central beta-blockade in conscious rats with glucocorticoid-induced hypertension. 258 Jan 31

251 untreated patients with mild to moderate hypertension were included in a multicenter study aimed 1) to detect arrhythmias (24-H Holter recording) and 2) to assess the efficacy of sotalol on blood pressure and possible arrhythmias. Patients with coronary heart disease or previously documented arrhythmias were excluded. Atrial arrhythmias such as premature beats, fibrillation, flutter and paroxysmal atrial tachycardia were detected in 16% of patients. Monomorphic ventricular premature contractions (VPCs) (Lown I and II) were detected in 41% of patients and polymorphic VPCs or duplets/triplets (Lown III and IV) in 14%. A correlation seems to exist between the level of hypertensive cardiopathy, judged on electrocardiographic data (Tarazi classification), age of patients and severity of arrhythmias. Sotalol was administered during 2 months at a mean dose of 160 mg per day. The treatment was effective on blood pressure and arrhythmias (82% improvement of severe VPCs) and the drug was well tolerated. It was difficult to conclude if these good results are due to the betablocking properties or specific class II antiarrhythmic effects of sotalol or to the combined activity.
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PMID:[Cardiac arrhythmia in moderate arterial hypertension. Epidemiologic survey of 251 cases. Effect of sotalol]. 264 67

Sotalol is a beta-adrenoceptor blocking agent devoid of intrinsic sympathomimetic activity, membrane stabilising actions and cardioselectivity. It lengthens repolarisation and the effective refractory period in all cardiac tissues independently of its antiadrenergic properties. Combining Class II and Class III antiarrhythmic properties, sotalol can be given either intravenously or orally and its pharmacokinetic properties permit long dosing (once or twice daily) intervals. Controlled and uncontrolled studies have established the efficacy of sotalol in mild-to-moderate essential hypertension and in angina of effort. Sotalol reduces anginal frequency and glyceryl trinitrate (nitroglycerin) consumption and increases exercise capacity during treadmill stress tests. In addition, although there is evidence that the drug reduces reinfarction rate in survivors of acute infarction, the data for reduction in sudden death rates in these patients are not as compelling as for other beta-blockers. However, comparative and additional long term studies are required before an accurate assessment of the use of sotalol in these disorders can be made. When used in the treatment of mild-to-moderate hypertension sotalol is more effective than placebo and comparable to other beta-blockers in reducing elevated blood pressures. In addition, a synergistic antihypertensive response is achieved when sotalol is combined with hydrochlorothiazide. Still, additional well-controlled comparative studies are required before the value of sotalol relative to other drug treatment regimens in the management of hypertension can be made. In preliminary studies sotalol appeared effective in most forms of supraventricular tachyarrhythmias with its effects being similar to those of other beta-blockers. However, preliminary data indicate that sotalol is likely to be more effective than than conventional beta-blockers in converting atrial flutter and fibrillation to sinus rhythm and maintaining stability post-conversion. Sotalol also appears to be a promising agent in the control of ventricular arrhythmias. In suppressing premature ventricular contractions it is at least as effective as procainamide. In ventricular tachycardia and fibrillation, intravenous sotalol (1.5 mg/kg), prevents reinduction by programmed electrical stimulation in 40 to 50% of cases if double stimuli are used. Both prevention of reinducible arrhythmia and the suppression of spontaneous arrhythmias on Holter recordings are predictive of a long term favourable clinical outcome. In patients with reduced ejection fractions, sotalol depresses ventricular function less than conventional beta-blockers.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Sotalol. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use. 331 21

An assessment was made of the efficacy of Sotalol, a beta1 selective beta blocker, in the management of essential arterial hypertension. A single 160 mg dose per diem was administered per os to 34 patients over a period of 14 weeks. Arterial pressure and heart rate were checked periodically. In addition, SAP, DAP and heart rate were evaluated before and during the third week of treatment in 8 subjects under maximum ergometric test conditions. Excellent tolerance was observed. Under basal conditions, all subjects displayed good reduction of SAP and DAP. This was highly significant. During exercise, it was less evident, and the results were only significant for low work loads. It is nevertheless felt that the simple dose protocol of the drug, its good tolerance and its effectiveness under basal conditions suggest that more extensive ergometric studies should be conducted.
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PMID:[Hypotensive effect of sotalol under basic conditions and during exercise. Clinical cases]. 665 6

Broad-breasted white male turkeys develop hypertension, tachycardia and aortic arteriosclerosis spontaneously by approximately 5 weeks of age. When fed B-aminopropionitrile (BAPN), aortic tensile strengths are lowered, and a high percentage of the turkeys die from aortic dissecting aneurysms. There are essentially no deaths from aneurysms when either dl-propranolol or reserpine is fed in concert with BAPN; practolol and soltalol partially protect the BAPN-fed turkey from lethal aneurysms while hydralazine and phenelzine sulphate potentiate mortality from aneurysms. Dl-propranolol decreases and reserpine increases dP/dtmax and both drugs lower arterial pressure and heart rate when fed with BAPN. Such diets also decrease the ultrastructural disarray of collagenous and elastic fibres in the media of the abdominal aorta that occurs from the feeding of BAPN and thereby raise aortic tensile strength. Sotalol and practolol when fed to BAPN-fed turkeys lower blood pressure and dP/dtmax, but neither drug affects aortic tensile strength and both counteract the deleterious effect of BAPN on the ultrastructure of collagenous and elastic fibres to a minor degree. Phenelzine sulphate does not affect arterial pressure while hydralazine reduces arterial pressure; both drugs decrease aortic tensile strength and increase the ultrastructural disruption of aortic elastin and collagen in the BAPN turkey. The results suggest that dl-propranolol, reserpine, phenelzine sulphate, and hydralazine have an action on aortic tissue and indicate the usefulness of the BAPN-fed turkey as a model for identifying potential drug effects on aortic elastin and collagen.
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PMID:The B-aminopropionitrile-fed turkey: a model for detecting potential drug action on arterial tissue. 685 Jul 14

There were studied 31 patients 20 of them sanes and 11 with sustained systemic arterial hypertension to whom it was administered propranolol and sotalol in different periods. By means of phonomechanocardiographic study it was observed that the contractile heart function didn't present alterations in the sane patients, with the administration of the two drugs. Sotalol produced significative changes with depression of contractility in hypertense patients, even though there were no alterations of the "pump" function. It is probably on account that hypertensive cardiopathy per se has a minor functional myocardiac reserve and the negative inotropic effect is made evident with greater clearness. The fall of the elevation velocity of radial pulse (EVRP) in the two groups, suggests the increase of vascular resistances by the peripheric beta blockade.
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PMID:[Effects of sotalol on ventricular function]. 741 69

Sotalol, a beta-adrenoceptor blocking drug, was administered to 12 hypertensive pregnant women. The concentration of the drug was assayed in samples of maternal plasma, amniotic fluid and mixed umbilical cord plasma at delivery and, in five mothers who elected to breast feed, in paired samples of maternal plasma and breast milk. Sotalol reduced blood pressure effectively at a mean daily dose of 433.1 +/- 54.1 mg but crossed the placental barrier. The mean maternal: fetal plasma concentration ratio was 1:1.05 and the mean amniotic fluid concentration was 7.0 +/- 2.7 microgram/ml. Delivery occurred at mean gestational age of 37.7 +/- 0.7 weeks; 12 infants were liveborn with a mean weight of 2.8 +/- 0.1 kg and eight of them had no significant neonatal problems. Of the other four, two died from severe congenital anomalies, one had perinatal asphyxia and one mild transient hypoglycaemia. High sotalol concentrations were found in breast milk (mean plasma: milk ratio was 1:5.4) raising the possibility of pharmacological effect in the newborn infant. The results suggest that sotalol adequately controls blood pressure in hypertension complicating pregnancy but because, unlike results from the pregnant ewe, it crosses the human placental barrier it offers no apparent advantages over other beta-adrenoceptor antagonists.
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PMID:Sotalol as a hypotensive agent in pregnancy. 742 41

beta-Blockers have been in clinical use for 30 years, and have an accepted role in (among others) the treatment of high blood pressure, the secondary prevention of myocardial infarction and the treatment of arrhythmias. Their place in the treatment of heart failure is currently under investigation. The drugs available in the 1970s and early 1980s were subjected to intense investigation. A new generation of beta-blockers, including some such as carvedilol and bucindolol, with vasodilating properties, is now appearing. As yet these later agents have not been the subject of large clinical trials. Clinical practice involves the treatment of individual patients with defined dosages of particular drugs. It is, therefore, not acceptable to base practice on theories derived from the clinical pharmacology of a particular drug, on the results of small trials or on a meta-analysis of results from a number of trials that were individually inadequate. Clinical practice must follow the results of large-scale trials in defined populations. The major trials in hypertension, myocardial infarction, arrhythmias and heart failure provide the best evidence for the use of individual beta-blockers in each of these clinical situations. In patients with high blood pressure, beta-blockers do not seem to have any particular advantage over other hypotensive agents. In myocardial infarction, relatively late use of a beta-blocker undoubtedly reduces fatality, though the value of early treatment is less clear. beta-Blockers are not powerful antiarrhythmics, but they do appear to prevent sudden death. Their possible role in heart failure is perhaps the most interesting current field of beta-blocker research. There are very few comparative studies of beta-blockers, and it is difficult to make precise recommendations. None of the new generation of beta-blockers has yet been used in a trial that is large enough trial for any of them to be accepted for routine use in preference to older drugs. The use of individual beta-blockers, as with any drug, should follow the results of clinical trials. Propranolol and atenolol have been studied most intensely in hypertension. For secondary prevention of myocardial infarction, the evidence is best for timolol. Sotalol is probably the best antiarrhythmic among the beta-blockers. Whether any individual beta-blocker is best for heart failure remains to be seen.
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PMID:Choosing the right beta-blocker. A guide to selection. 752 29


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