Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1323099 (sympathomimetic)
 2,957 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although many different beta blockers are now in clinical use, there is very little information concerning their relative efficacy, and it is still not clear what clinical importance should be attached to properties such as positive inotropic stimulation (intrinsic sympathomimetic activity or ISA) and membrane stabilizing action ("local anaesthetic effect" or "quinidine-like effect"). In this report we compare the ability of patients with angina to exercise on a bicycle ergometer while receiving a series of commonly used beta blockers, and attempt to determine the importance of ISA. The investigation is in four parts with the drugs given orally or intravenously: statistical analysis of the results was carried out using standard methods, both parametric and non-parametric (Friedmann analysis of variance, Wilcoxon matched pairs signed ranks test) by two independent statisticians. The relevant properties of drugs included in this paper are summarized in Table I. Laboratory reports using many different animal preparations may differ from this assessment under specific conditions, and the Table is intended only as a guide to the generally accepted properties of these drugs when used clinically. Results for sotalol are included for reference in the first part of this paper but the drug was withdrawn from clinical use and was not studied further.
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PMID:Comparative effects of beta adrenergic blocking drugs. 23 3

Sympathetic stimulation with epinephrine (EPI) combined with parasympathetic blockade with atropine was studied in 10 healthy volunteers premedicated with placebo or three different beta-adrenoceptor blockers: atenolol (62.5 micrograms/kg, beta 1-selective), propranolol (62.5 micrograms/kg, nonselective), and pindolol (7.5 micrograms/kg, nonselective with intrinsic sympathomimetic activity, ISA). EPI infusion (0.06 microgram/kg/min) after placebo increased heart rate (HR) and systolic blood pressure (SBP) and decreased diastolic BP (DBP). Pretreatment with atenolol reduced the HR increase, and caused similar changes in BP. In contrast, pretreatment with propranolol and pindolol decreased HR and increased BP. Combined EPI and atropine (15 micrograms/kg) after placebo increased HR by 40% without causing BP changes. Similar HR changes were observed after administration of all beta-adrenoceptor blockers, but whereas a marked pressor response was observed after propranolol and pindolol a blunted response was observed after atenolol. Propranolol and pindolol reduced myocardial oxygen demand estimated by the HR x BP product after EPI, but this response was abolished by atropine. Serum potassium decreased from 3.9 +/- 0.2 to 3.2 +/- 0.3 mM after EPi and atropine. This effect was less after atenolol, and potassium increased after premedication with propranolol and pindolol. Our results show that nonselective beta-adrenoceptor blockade has a favorable effect on potassium homeostasis and oxygen demand parameters during EPI infusion but causes a marked pressor response, contrary to a beta 1-selective agent, during combined sympathetic stimulation and parasympathetic blockade. They also highlight the importance of the vasodilator cholinergic system as a defense mechanism in such situations.
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PMID:Differential effect of selective beta 1 and nonselective beta-adrenoceptor blockade on epinephrine and atropine response in normal humans. 128 2

The authors summarize the principles of the therapeutic approach to the 5H syndrome [1. hyperinsulinism, 2. hyperglycaemia (NIDDM), 3. hyperlipoproteinaemia (obesity), 4. hypertension, 5. hirsutism], in particular its two components, i.e. NIDDM and arterial hypertension. The authors found that early treatment of hyperinsulinism, e.g. already in the stage of impaired glucose tolerance or NIDDM with oral antidiabetics, their disproportionate increase with regard to the blood sugar level and glycosylated haemoglobin without making "hygienic" provisions (radical weight reduction; increased physical activity to the maximum possible individual level; energy restricted diet in particular as regards carbohydrates and fat) does not prevent progression of the components of the 5H syndrome to the clinical stage. In treatment of arterial hypertension associated with 5H syndrome non-selective beta-blockers and thiazide diuretics are unsuitable because they worsen the HPLP and enhance insulin resistance. Suitable preparations are combinations of ACE-inhibitors, calcium antagonists, selective beta-blockers in particular with ISA and beta-blockers with a partial selective sympathomimetic activity (devalol and celiprolol). Hygienic provisions must be started in childhood, or when hyperinsulinism is detected.
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PMID:[How should we implement the basic principles of treatment of type 2 diabetes mellitus from the aspect of the hormono-metabolic syndrome X (5H)?]. 145 53

A double-blind multicentre study of 349 hypertensive patients was performed to compare the side-effects of the two beta-blockers atenolol (selective beta 1-blocker) and pindolol (beta 1- and beta 2-blocker with Intrinsic sympathomimetic activity (ISA] in equipotential doses (100 mg atenolol vs. 15 mg pindolol). Male and female patients aged 20-65 years with essential hypertension WHO stages I and II were included. Patients were examined 1 and 6 months after the start of treatment, and side-effects were recorded. The antihypertensive effect was similar for the two drugs. After 1 month there was significantly less bradycardia (P less than 0.01), cold hands and feet (P less than 0.05) and tiredness (P less than 0.02) in the pindolol group, and less sleep disturbance (P less than 0.02) in the atenolol group. After 6 months there was no significant difference in sleep disturbance, but the differences in the other side-effects remained significant.
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PMID:Comparison of the side-effects of pindolol and atenolol in the treatment of hypertension. 220 4

Bopindolol is a potent beta-adrenoceptor antagonist with mild intrinsic sympathomimetic activity that exhibits a long duration of action. The cardiac beta-adrenoceptor blockade produced by an oral dose of 1 mg bopindolol is of similar intensity as that seen after atenolol 100 mg p.o. or pindolol 10 mg p.o. Like other beta-adrenoceptor antagonists, bopindolol is effective in inhibiting resting and stimulated plasma renin activity. In contrast to compounds lacking ISA, bopindolol does not produce undesirable changes in plasma lipoprotein composition during chronic therapy. Its bioavailability after oral administration amounts to about 70%. In the studies reviewed, bopindolol was well tolerated even after an oral dose of 12 mg, which, as far as beta-adrenoceptor blockade is concerned, would be equivalent to a single oral dose of about 1.2 g of atenolol. The onset of action of bopindolol is relatively slow, a feature that to a certain extent might account for the good tolerance of the drug observed in experimental and therapeutic studies. The delayed onset of action of the drug has facilitated the elucidation of the relationship between plasma levels and pharmacological effects during the period immediately after oral administration. Analysis of the temporal relationship between drug plasma levels and beta-adrenoceptor blockade provides evidence suggesting that the cardiac beta adrenoceptors lie outside the plasma compartment.
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PMID:Clinical pharmacological studies with the long-acting beta-adrenoceptor blocking drug bopindolol. 243 11

Cicloprolol is a new cardioselective beta-blocking agent with partial agonist activity (intrinsic sympathomimetic activity, ISA). Its haemodynamic profile was compared with that of atenolol (cardioselective; no ISA) in a comparative dose-response study of 24 ischaemic patients with diminished cardiac reserve. Following a stable control period, equivalent intravenous (i.v.) beta-blocking boluses of atenolol (1, 1, 2, and 4 mg) or cicloprolol (0.025, 0.025, 0.05, and 0.1 mg/kg) were randomly administered and haemodynamics and left ventricular ejection fraction were determined at rest and during bicycle exercise. At rest, atenolol reduced heart rate (HR) and cardiac index; diastolic blood pressure (DBP), systemic vascular resistance index (SVRI), and pulmonary artery occluded pressure (PAOP) increased without change in mean arterial pressure (MAP). Cicloprolol increased left ventricular ejection fraction, reduced its end-diastolic volume, and tended to reduce filling pressure without change in other variables. During exercise, atenolol reduced ejection fraction and increased SVRI; in contrast, cicloprolol did not significantly alter these parameters. Attenuation of exercise tachycardia and cardiac index increase was similar after each agent. Thus, the cardiac performance assessed from left ventricular stroke index or ejection fraction/filling pressure relationships was less depressed after cicloprolol as compared with atenolol. The relevance of such haemodynamic differences to exercise ability or quality of life during sustained therapy warrants examination.
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PMID:Comparative effects of atenolol and cicloprolol on cardiac performance in coronary heart disease. 246 27

The response of two ophthalmic betablockers, Timolol (without ISA) and Pindolol (with marked ISA), on IOP and tonographic outflow facility was investigated in a single-blind clinical study on 20 patients with glaucoma or ocular hypertension. In two treatment groups, ten patients each, in a randomized order IOP and tonographic outflow facility measurements were performed before and 2 hrs after drug application. Timolol reduced IOP by 6.8 mm Hg and Pindolol eye drops by 4.5 mm Hg. Both topically applied betablockers did not influence tonographic facility of outflow. It is concluded that the intrinsic sympathomimetic activity of an ophthalmic betablocker has no effect on outflow facility of aqueous humor.
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PMID:The effect of betablockers with and without ISA on tonographic outflow facility. 266 49

The effect of pindolol (a beta-blocker with intrinsic sympathomimetic activity, ISA) on fasting plasma lipid profile in 30 hypertensive patients was compared with atenolol (without ISA) in a crossover single blind study. Both drugs lowered blood pressure. HDL-cholesterol increased significantly with pindolol (from 1.15 +/- 0.05 to 1.34 +/- 0.05 mmol/l at 12 weeks, P less than 0.001), but not with atenolol. VLDL-cholesterol increased with atenolol (from 0.57 +/- 0.09 to 0.86 +/- 0.14 mmol/l at 12 weeks, P less than 0.002), while there was no change with pindolol. These changes in lipoprotein profile suggest a more favourable effect of pindolol than of atenolol on lipid profile.
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PMID:Effect of pindolol versus atenolol on lipid profile in hypertensive patients. 275 53

The ideal sympathomimetic derivative should possess the positive inotropic and relaxing effects of catecholamines whilst remaining free of their side-effects. Theoretically, such properties could be present in beta 1-adrenoceptor partial agonists. Xamoterol (ICI 118,587, Corwin; ISA 43 p. 100) seems to be the most promising beta 1 partial agonist. The aim of the study was to determine if the beneficial effects of Xamoterol were maintained during long term administration. Xamoterol (200 mg twice dialy) was administered to 14 patients with anterior myocardial infarction and moderate heart failure (class II-III NYHA). After 3 months' therapy, left ventricular function improved as indicated by reduction in left ventricular (LV) end-diastolic pressure (23 +/- 5 to 16 +/- 5 mm Hg; P less than 0.0005), LV end-diastolic volume (153 to 140 ml/m2; P less than 0.05) and in LV end-systolic volume especially in 11 patients with a control end-systolic volume less than 100 ml/m2 (- 15 p. 100; P less than 0.05). LV inotropic state was also enhanced as indicated by 21 p. 100 increases in EMax, the maximal LV pressure/volume ratio (P less than 0.02) and 20 p. 100 increases in the ratio end-systolic stress/ end-systolic volume (P less than 0.02). Myocardial oxygen consumption was unchanged, global lactate extraction fraction increased from 20 +/- 18 to 33 +/- 14 p. 100 (P less than 0.05) and LV alanine release was reduced (-1.7 to -0.2 muMol/min; P less than 0.05). The rate of LV pressure fall accelerated from 57 to 52 ms (P less than 0.05) and the mean diastolic wall stress was reduced by 35 p. 100 (P less than 0.05), reflecting the improvement in LV relaxation and diastolic function. Thus, the beneficial effects of Xamoterol were maintained after prolonged therapy particularly in patients with class II-III heart failure; patients in class IV benefited less from this therapy. No tachyphylaxis or side-effects were observed.
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PMID:[Role of adrenergic beta receptor partial agonists in left ventricular failure of ischemic origin. Value of xamoterol (ICI 118,587, Corwin)]. 286 23

The effect of labetalol (alpha- and beta- adrenoceptor blocking agent) on the respiratory organs of guinea pig was investigated in vivo and in vitro. The asthmatic symptoms which were induced by inhalation of histamine were relieved by pretreatment with labetalol (1-5 mg/kg, i.p.) in most cases. Propranolol, on the contrary, aggravated distinctly the histamine-induced asthma, although phentolamine and diphenhydramine relieved the asthma. Experiments carried out in vitro showed that labetalol relaxed the tonus of isolated tracheal preparation, shifting the histamine dose-response curve to the right and downward. The down shifting by labetalol was dose-dependent and much more sensitive than that by papaverine, and it disappeared after pretreatment of propranolol. Thus, it was considered that labetalol exerted a relaxing action on the tracheal preparation by a beta 2-adrenoceptor partial agonist action (intrinsic sympathomimetic activity, ISA). Since labetalol in high concentration also shifted the histamine dose-response curve parallel to the right as seen with phentolamine or diphenhydramine, it was considered that labetalol exerted not only an alpha-blocking action but also an antihistaminic action.
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PMID:[A study on the mechanism of the antiasthmatic effect of labetalol on experimental histamine-induced asthma]. 287 45


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