Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Adrenergic blockers for beta-receptors were studied for inhibition of mitochrondrial CoQ10-enzymes. These enzymes are indispensable for the bioenegetics of the myocardium. Propranolol is frequently used to treat hypertension; in some patients, it depresses myocardial function as an adverse reaction. This side effect may be related to the inhibition by propranolol of CoQ10-enzymes of the myocardium. Timolol showed negligible inhibition of the CoQ10-enzyme, NADH-oxidase. Metoprolol was less inhibitory than propranolol. Five alprenolols showed inhibition which approached that of propranolol. The 1-isomer of alprenolol showed weak inhibition of another CoQ10-enzyme, succinoxidase, but the other beta-blockers were essentially non-inhibitory to this enzyme. The drug of choice is timolol, based on negligible inhibition of these bioenergetic enzymes of the heart, which correlates with its pharmacologically low cardiac depressant effects.
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PMID:Bioenergetics in clinical medicine XV. Inhibition of coenzyme Q10-enzymes by clinically used adrenergic blockers of beta-receptors. 1 92

Clinical drug trials have shown that pindolol, timolol and sotalol are effective hypotensive agents in Nigerians with mild to moderate hypertension (standing diastolic blood pressure below 120 mmHg). There was no significant difference between the three beta-blockers with respect to their antihypertensive effect irrespective of differences in their other pharmacological actions. There was also no correlation between the hypotensive effect of the drugs and the initial blood pressure. Timolol at 30 mg daily had an additive effect to the hypotensive action of binazine, a peripheral vasodilator. Increasing the dose of timolol to 60 mg daily did not produce further fall in the blood pressure. Pindolol at a dose of 30 mg per day also had an additive effect to the hypotensive action of the thiazide diuretics, methyldopa and debrisoquine. There was no significant difference between the hypotensive effect of sotalol and that of methyldopa. The three beta-blockers produced no side effects. This was considered to be a distinct advantage over most of the drugs currently available for treatment of hypertension in Nigeria.
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PMID:beta-Adrenoceptor blockers in the treatment of hypertension. 4 32

Timolol, 10 to 40 mg daily, given to 103 patients with uncomplicated arterial hypertension induced significant increments of serum potassium at all dose levels (p less than 0.05). The magnitude of the increments was dependent on daily timolol dosage. When hydrochlorothiazide and amiloride were added, serum potassium decreased (p less than 0.001), but a major determinant of the magnitude of the decrease was the dosage change of the timolol. Serum uric acid was influenced in a paradoxical way during timolol monotherapy; there was a rise in all 3 dosage groups (p less than 0.02) but the lowest group showed the largest increase and vice versa. On addition of hydrochlorothiazide and amiloride, there was a further increase in serum uric acid, the magnitude of which depended on the concomitant reduction in the dose of timolol, with reductions in dose causing a larger rise in serum uric acid and increments, a smaller rise. The increments of serum uric acid were greater in females than in males during both treatment periods. The results indicate that beta blockers induce dose-dependent rises in serum potassium and may counteract undesirable effects of diuretics on serum potassium. Beta blockers seem to have a paradoxical effect on serum uric acid and may aggravate the hyperuricemia induced by diuretics.
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PMID:Serum potassium and uric acid changes during treatment with timolol alone and in combination with a diuretic. 38 Aug 67

Timolol given on a twice-daily schedule has shown both antihypertensive effectiveness and plasma renin-suppressing action in eight patients with mild or moderate hypertension. However, the causal relationship between the drug plasma level, blood pressure fall, and change in plasma renin activity was not so clearly demonstrated in the present study. The disposition profiles of timolol at the steady state show an elimination half-life of 4.7 +/- 0.7 hours and a total plasma clearance of 225 +/- 21 ml/min. These values are found to be different from those of our previous observations obtained in normal individuals. Although the range of mean timolol concentrations at steady state varies to a certain extent among different patients, the dosage regimens for patients who will receive treatment for certain chronic disease states (e.g., arrythmias, obstructive cardiomyopathy, and angina pectoris, but not hypertension) in relation to plasma levels should be based on the disposition data obtained under steady state conditions. Bronchospasm developed in one of eight patients whose timolol level was found to be higher than the average of other patients given the same dosage.
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PMID:Clinical pharmacologic observations on timolol. II. Antihypertensive effect and kinetic disposition on twice-daily dosing in patients with mild or moderate hypertension. 72 49

The effect of beta-blocking agents on post-myocardial infarction patients with a history of hypertension or elevated blood pressure (BP) at baseline in two prospective placebo-controlled postinfarction studies using beta-adrenoceptor blocking agents (the Stockholm Metoprolol Trial and the Norwegian Timolol Study) is discussed. The results of both of these trials indicate that active beta-blockade reduces the incidence of nonfatal reinfarction, although the BP levels were similar in the two treatment groups. The differences in the efficacy of treatment in previous studies of hypertension are discussed. So far, none of the studies has shown a significant difference in mortality when different antihypertensive therapies have been compared in the same study. Some aspects of designing future trials comparing different treatment regimens in hypertension are discussed.
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PMID:Beta-blockade in ischemic heart disease and hypertension. 248 Nov 71

In a 24-week randomized, single-blind study Timolol (n = 63) and Enalapril (n = 57) proved to be potent and safe antihypertensive drugs. However, the effect on lipid metabolism was fundamentally different, despite the fact that the effect on total serum cholesterol did not significantly differ between the two groups. Enalapril had no adverse effect on any lipid fractions, while Timolol increased very low (VLDL) + low (LDL) density lipoprotein cholesterol by 7.6% (p less than 0.001) and total triglycerides by 34.5% (p less than 0.001), and decreased the favorable high density lipoprotein (HDL) cholesterol by 11.3% (p less than 0.001). Thus, the ratio HDL/VLDL + LDL cholesterol was reduced by 17.1% (p less than 0.001). Enalapril reduced uric acid by 3.4% (NS), while Timolol increased uric acid by 4.0% (p less than 0.05). The difference between the groups was statistically significant (p less than 0.01). The first steps in any attempt to solve the hypertension-coronary dilemma should be to take into consideration all pharmacologic effects of antihypertensive drugs.
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PMID:The effect of enalapril and timolol on blood lipids. A randomized multicenter hypertension study in general practice in Norway. 283 91

New England Deaconness Hospital rats harboring a transplantable pheochromocytoma exhibit plasma norepinephrine concentrations 20-fold higher than controls. A cardiomyopathy (CM) characterized by multifocal areas of interstitial and replacement fibrosis, mixed inflammatory infiltrates and contraction band necrosis is evident 35 to 45 days after tumor implantation. Using a morphological scoring system of 0 (no cardiac damage) to 3 (involvement of almost the complete ventricular cross-section sampled), a CM score of 1.8 +/- 0.1 was found in rats harboring pheochromocytoma, a significant increase over that in age- and sex-matched controls (0.4 +/- 0.1, P less than .001). The pheochromocytoma rats also had hypertension (systolic blood pressure = 182 +/- 4 vs. 131 +/- 2 mm Hg in controls, P less than .001). In an effort to prevent the CM, rats harboring pheochromocytoma were treated with either the beta receptor antagonist timolol, the alpha receptor antagonists phentolamine or phenoxybenzamine or the nonspecific vasodilator hydralazine. Hydralazine normalized systolic blood pressure (135 +/- 6 mm Hg), whereas timolol (144 +/- 5 mm Hg), phenoxybenzamine (166 +/- 5 mm Hg) or phentolamine (154 +/- 10 mm Hg) only moderately decreased blood pressure in rats harboring pheochromocytoma. Hydralazine had no effect on CM score (1.8 +/- 0.1). Timolol markedly attenuated the CM score (0.6 +/- 0.1), whereas the alpha adrenergic antagonists were not as effective (phenoxybenzamine CM score = 1.3 +/- 0.2; phentolamine CM score = 1.7 +/- 0.2). Furthermore, timolol prevented desensitization of beta adrenergic receptor-mediated contraction in the hearts of rats harboring pheochromocytoma.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of adrenergic receptor antagonists on cardiac morphological and functional alterations in rats harboring pheochromocytoma. 288 96

Beta-adrenergic blocking drugs are gaining acceptance as initial therapy for patients with mild to moderate hypertension. In a postmarketing surveillance study, 5,190 hypertensive patients received timolol maleate monotherapy and were evaluated by 1,355 physicians. A total of 1,057 patients did not complete the study: 28% of these patients experienced an adverse event. Mean systolic and diastolic blood pressure readings were reduced 20 and 13 mm Hg, respectively. Mean diastolic blood pressure was reduced 11% for patients with mild hypertension; larger mean reductions were noted for patients with moderate (17%) and severe hypertension (22%). The effect in black and elderly patients was less than in other groups. Although 22% of all patients experienced an adverse event, less than 2.2% of all patients experienced events related to beta-adrenergic blockade, ie, respiratory difficulty, heart failure, bradycardia, and cold extremities. Fatigue, dizziness, and nausea were the most frequently reported adverse events requiring discontinuation of therapy. Timolol monotherapy is a well-tolerated and effective treatment for a broad range of hypertensive patients.
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PMID:Clinical experience with timolol maleate monotherapy of hypertension. 396 44

All available beta-adrenergic blocking agents share the property of blocking beta 1 adrenoceptors, including those in the heart. They differ, however, in their ability to block beta 2 receptors (cardioselectivity), their membrane stabilizing action, intrinsic sympathomimetic activity and their pharmacokinetic properties. The strongest evidence for efficacy in secondary prevention has been obtained with timolol, metoprolol and propranolol. Timolol and propranolol block all beta-receptor-mediated responses and are therefore nonselective, whereas metoprolol is relatively cardioselective. Propranolol and metoprolol have membrane stabilizing action, but timolol does not; none of these agents show intrinsic sympathomimetic activity. Thus, no ancillary property is a requirement for efficacy. All of these agents may precipitate heart failure, but this problem has been exaggerated, and transient failure during the early course of myocardial infarction is no longer a contraindication to therapy. Cardioselective agents cause less bronchospasm, but this can still occur, especially with higher dosages. In addition, these agents probably cause somewhat less fatigue and result in less hypertension during hypoglycemia than nonselective agents. The availability of at least three effective agents allows for a choice of therapy to offer individual patients.
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PMID:Clinical pharmacology of the beta-blocking drugs: implications for the postinfarction patient. 613 42

Alcoholics during detoxification have elevated blood pressures which are related to the severity of their withdrawal symptoms. We studied the effect of a non-selective beta-blocker, timolol on symptoms, blood pressure and plasma levels of cortisol (PC), noradrenaline (NA), vasopressin (AVP) and renin activity (PRA) during alcohol withdrawal. Eighteen alcoholics, admitted for detoxification, were randomly allocated to timolol or placebo in a double blind trial. Alcohol withdrawal symptoms did not differ either before or after timolol or placebo but patients receiving timolol required less sedation with chlormethiazole. Systolic blood pressures (SBP) and pulse both fell significantly during detoxification in both groups, the change being greater with timolol. Plasma levels of cortisol, NA, AVP and PRA fell significantly, though only NA and PC correlated with initial SBP. Timolol had no effect on any of the biochemical parameters observed. The pressor response to alcohol withdrawal is reduced by beta-blockade and the height of the blood pressure is related to plasma NA and PC levels. Alcohol withdrawal hypertension is probably due to increased sympathetic activity.
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PMID:The effect of a non-selective lipophilic beta-blocker on the blood pressure and noradrenaline, vasopressin, cortisol and renin release during alcohol withdrawal. 637 39


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