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)

Sotalol is a nonselective, water-soluble beta-adrenoceptor antagonist with no membrane-stabilizing activity or intrinsic sympathomimetic activity. Sotalol is, essentially, completely absorbed and is not metabolized. Consequently, bioavailability is close to 100%. Age and food have slight but unimportant effects on bioavailability. Cmax of sotalol is 2 to 3 hours with a t1/2 between 7 and 15 hours. Excretion of sotalol is primarily through the kidneys, with no metabolism by liver and no first-pass effect. Therefore, sotalol plasma levels and half-life are directly related to creatinine clearance and glomerular filtration rate. Appropriate dose adjustments must be made for patients with impaired renal function or increased renal blood flow, as in pregnancy. The beta-adrenoceptor antagonistic effects of sotalol are directly related to plasma levels, which, in turn, are directly related to dose. However, the beta-adrenoceptor antagonism t1/2 is longer than the sotalol plasma t1/2. As a consequence of its ability to prolong the action potential duration, sotalol also increases cardiac contractility in isolated ventricular, but not atrial, preparations by 20 to 40%. This positive inotropic effect is not blocked by beta or alpha blockade or reserpine pretreatment and seems to be related to sotalol's effects on cardiac ionic currents. Like the effects of sotalol on action potential duration, the positive inotropic effects are inversely proportional to rate. The hemodynamics of sotalol indicate a relative lack of direct cardiac depressant activity in both animals and humans. The typical hemodynamic effects of sotalol in normotensive humans, even with depressed myocardial function, are a reduction in heart rate with little or no change in blood pressure, a reduction in cardiac output with no change in stroke volume, and little or no change in pulmonary wedge pressure and left ventricular end-diastolic pressure or volume, and little or no change in ejection fraction either at rest or during exercise.
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PMID:Pharmacology, pharmacodynamics and pharmacokinetics of sotalol. 240 31

The efficacy, safety, and pharmacokinetic parameters of a 30-mg oral dose of cetamolol hydrochloride (Betacor), a new synthetic cardioselective beta-adrenoceptor antagonist, with intrinsic sympathomimetic activity, were evaluated by studying 32 hypertensive patients with normal renal function or different degrees of renal impairment. After administration of cetamolol, serial blood and urine sample collections, as well as vital sign determinations for the next 48 hours, were performed in all patients (with the exception of urine collection, which was not possible in hemodialysis patients). Results indicate that cetamolol's pharmacokinetic parameters are significantly changed in patients who have moderate or severe renal impairment. Specifically, as the severity of renal impairment increased, the maximum serum concentration (Cmax) and the area under the serum concentration-time curve (AUC) increased, whereas the renal clearance (CLR), urinary excretion, and total body clearance (CL) decreased. Additionally, significant direct or inverse correlations for AUC, CL, CLR, and urinary excretion with creatinine clearance (CLCR) were demonstrated. In the subjects with mild renal impairment, the trends toward changes in the cetamolol pharmacokinetic parameters were evident, though small and not statistically significant. Although anuric, patients on hemodialysis still retained the ability metabolically to clear cetamolol at a rate of about one-third of that found in normal subjects. Reductions in blood pressure and heart rate also were found to be greater and more prolonged as the severity of renal impairment increased. There were no adverse drug or toxic effects noted in any of the study patients. Based on these findings, dosing recommendations are suggested for patients who have compromised renal function because of the effects of renal function on the pharmacokinetics of cetamolol.
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PMID:Pharmacokinetics of cetamolol in hypertensive patients with normal and compromised renal function. 289 95

Vasodilator prostaglandins produced in the renal medulla have a role in blood pressure regulation, beyond modulation of sodium and water retention. Systemic vasodilation resulting from effects of renomedullary prostaglandins lowers systemic vascular resistance, and administration of NSAIDs elevates blood pressure in hypertensive patients treated with diuretics and/or beta blockers, in patients with myocardial infarction, and in patients taking sympathomimetic agents such as phenylpropanolamine. Aspirin, which appears in the urine as salicylic acid (which has no effect on cyclooxygenase) has not been implicated as a drug which attenuates blood pressure control. Similarly, sulindac, the active sulfide metabolite of which is not filtered, does not inhibit renal synthesis of prostaglandins, though given in doses sufficient to inhibit serum thromboxane and 6-keto PGF 1-alpha. In a double-blind complete crossover study of blood pressure and renal function in hypertensive patients controlled with timolol-hydrochlorothiazide, sulindac lowered blood pressure significantly, whereas naproxen and piroxicam significantly raised blood pressure, in the absence of any effect on GFR, plasma renin, weight, creatinine clearance, or urinary sodium. It is suggested that for arthritic patients with hypertension, the NSAIDs of choice are aspirin and sulindac.
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PMID:The arthritic patient with hypertension: selection of an NSAID. 354 Nov 67

The effects of long-term infusion of fenoterol (a beta 2-sympathomimetic drug) in combination with the calcium antagonist verapamil on water balance, the renin-angiotensin-aldosterone system and antidiuretic hormone during pregnancy were studied. Within two hours of the start of infusion, plasma renin and antidiuretic hormone levels were significantly increased, but plasma aldosterone was strongly decreased. There was a concomitant marked reduction of urinary, sodium, and potassium excretion and a decreased creatinine clearance. The long-lasting reduction of urinary excretion which resulted in an elevated water retention is apparently due to other unknown factors. Results are discussed with special regard to the relationship between water balance disturbances and pulmonary edema.
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PMID:The renin-angiotensin-aldosterone system, antidiuretic hormone levels and water balance under tocolytic therapy with Fenoterol and Verapamil. 610 79

Three pharmacokinetic studies of terbutaline slow-release (SR) tablets, 5 and 7.5 mg, were performed in healthy subjects. Four men and 4 women volunteered for each study. Bricanyl plain tablets were used as reference formulation. Both single- and multiple-dose treatments were performed. For repeated administration, SR tablets were given every 12 h. Plain tablets were given every 8 h in two studies and every 12 h in one. Steady-state bioavailability correlated with the amount dissolved in vitro (paddle method) in 6 h. Single-dose bioavailability was limited by the amount dissolved in 4 h. The difference may have a pharmacological explanation, in that repeated administration of a sympathomimetic drug is known to decrease gastro-intestinal motility. Tablets of both strengths with an intermediate dissolution rate were extensively tested. Plasma concentrations and the rates of urinary excretion of unchanged terbutaline were measured. Mean relative bioavailability compared with plain tablets was 76-77% with 7.5 mg SR tablets and 74-80% with those of 5 mg. Variation in bioavailability between and within subjects was the same or smaller with the SR tablets. They gave smoother plasma concentration profiles with delayed peaks and the same peak/trough concentration ratios as the plain tablets, despite less frequent dosing. However, objectively measured side-effects were not significantly reduced. Measurements after cessation of treatment gave terminal half-lives in plasma of 11.5-23.0 h which is considerably longer than reported in the literature. Renal clearance averaged 140 mL/min, similar to predicted creatinine clearance. From these studies it is concluded that the main advantage with the SR tablets is the twice-daily dosage regimen. This should increase compliance, facilitate combination therapy with prolonged-action formulations of other drugs and better maintain therapeutic levels during the whole night interval.
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PMID:Pharmacokinetics of terbutaline given in slow-release tablets. 658 73

In 20 healthy subjects hydro-saline depletion was achieved by a 4-day natriuretic treatment associated with hypo-saline diet. Dopamine (DA) was infused in subpressor dose (.1 microgram . kg-1 . min-1) during sustained hypotonic polyuria induced by 5% glucose infusion. Four 15-min clearance periods were performed. DA was infused during the 2nd and the 3rd period. The effective renal plasma flow (RPF) as well as the glomerular filtration rate (GFR) were calculated by PAH and creatinine clearances, respectively. In our experimental conditions DA produced: a) an increase in the abnormally isoosmotic sodium reabsorption as % of sodium distal load; b) a decrease in both sodium and osmolar clearance; c) an early increase in free water clearance. RPF and GFR decreased not significantly. The present results indicate that DA in hydro-saline depletion helps to preserve the extracellular fluid volume in minimizing the salt and water loss associated with hypotonic polyuria. These effects on sodium excretion may be related to sympathomimetic properties acquired by DA in this experimental condition.
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PMID:[Sympathomimetic component of dopamine renal action in water-saline depletion]. 744 90

Tertalolol is a noncardioselective beta-blocker, devoid of intrinsic sympathomimetic activity. Its renal vasodilating properties have been demonstrated both in animals and in man. The beta-blocking activity of tertatolol was assessed on the reduction of heart rate at submaximal exercise. The oral dose of 5 mg was optimal, leading to a significant reduction of diastolic blood pressure throughout 24 h. The efficacy was confirmed in mid- and long-term studies. In mid-term, randomized controlled studies, versus beta-blockers, the antihypertensive efficacy of tertatolol 5 mg was comparable to that of acebutolol 400 mg but of earlier onset, and comparable to that of atenolol 100 mg. Its efficacy was confirmed in 3 long-term studies. In the first study, tertatolol 5 mg alone or combined with a diuretic and, if necessary, dihydralazine, controlled 93.6% of patients (supine DBP < 90 mm Hg). 72.7% of patients were controlled with tertatolol alone, 16.4% with tertatolol plus diuretic, and 4.5% with tertatolol plus diuretic and dihydralazine. In a second study, 88.5% of patients were controlled, 56.3% with tertatolol alone and 32.2% with tertatolol plus diuretic. In the third study, 88.8% of patients were controlled after 1 year treatment, 66.1% with tertatolol alone and 22.7% with tertatolol plus diuretic. The overall clinical safety was excellent: only 6.6% of the 2,706 patients treated for 1 year withdrew from the study because of side effects. In patients followed for 1 year, side effects were rare, transient and mostly of mild severity. Biochemical surveillance did not show any adverse metabolic effects of tertatolol. Conversely, in two long-term studies, creatinine and cholesterol levels decreased significantly.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Overview of clinical safety and efficacy of tertatolol. 790 14

Fluid management and dosage regimens of drugs in preterm infants should be based on the glomerular filtration rate. The current methods to determine glomerular filtration rate are invasive, time-consuming, and expensive. In contrast, creatinine clearance can be easy obtained and quickly determined. The purpose of this study was to compare plasma creatinine on the third and seventh day of life in preterm newborn infants, to evaluate the influence of maternal creatinine, and to demonstrate creatinine clearance can be used as a reliable indicator of glomerular filtration rate. We developed a prospective study (1994) including 40 preterm newborns (gestational age < 37 weeks), average = 34 weeks; birth weight (average) = 1840 g, in the first week of life. Inclusion criteria consisted of: absence of renal and urinary tract anomalies; O2 saturation >/= 92%; adequate urine output (>1ml/kg/hr); normal blood pressure; absence of infections and no sympathomimetic amines in use. A blood sample was collected to determine plasma creatinine (enzymatic method) on the third and seventh day of life and creatinine clearance (CrCl) was obtained using the following equation: [formula: see text], k = 0.33 in preterm infant All plasma creatinine determinations showed normal values [third day: 0.78 mg/dl +/- 0.24 (mean +/- SD)and seventh day: 0.67 mg/dl +/- 0.31 - (p>0.05)]. Also all creatinine clearance at third and seventh day of life were normal [third day: 19.5 ml/min +/- 5.2 (mean +/- SD) and seventh day: 23.8 ml/min +/- 7.3 - (p>0,05)]. All preterm infants developed adequate renal function for their respective gestational age. In summary, our results indicate that, for clinical practice, the creatinine clearance, using newborn length, can be used to estimate glomerular filtration rate in preterm newborn infants.
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PMID:Relationship between plasma creatinine concentration and glomerular filtration in preterm newborn infants. 1077 19

Juxtaglomerular (JG) hyperplasia and tubular damage along with a decrease in the urine creatinine level induced by FK506 in rat kidney have already been reported in previous paper by us. In this paper, we document the relationship of FK506 nephrotoxicity to the change in the production of thromboxane (Tx) A2 and the lipid peroxidation of the cellular membrane in the rat kidney in order to clarify its morphogenesis. The urinary excretion of TxB2 increased with FK506 administration even on day 1 (P < 0.02). Histologically, OKY-046 (thromboxane synthetase inhibitor) decreased tubular damage, although JG hyperplasia was not eradicated, while biochemically the excretion of TxB2 decreased significantly (P < 0.02), and both the decrease in the urine creatinine level and the increase in the N-acetyl-beta,D-glucosaminidase (NAG) index were relatively smaller. Although the FK506-induced morphological and biochemical changes could not be prevented by the continuous administration of superoxide dismutase (SOD) 30,000 U/kg daily, the malondialdehyde content in renal tissue removed 1 h after FK506 administration had increased. These data suggest that FK506 nephrotoxicity is related to the change in the production of TxA2 and lipid peroxidation of the cellular membrane. However, other mechanisms such as the involvement of sympathomimetic effects of FK506 and other vasoconstrictive factors cannot be ruled out.
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PMID:New morphological changes induced by FK506 in a short period in the rat kidney and the effect of superoxide dismutase and OKY-046 on THEM: the relationship of FK506 nephrotoxicity to lipid peroxidation and change in production of thromboxane A2 in the kidney. 1462 78

Pseudoephedrine is a commonly used over-the-counter decongestant with sympathomimetic activity. We present the case of a previously healthy young man who had an acute myocardial infarction 45 minutes after ingesting the recommended dose of an over-the-counter cold remedy containing pseudoephedrine. Elevations of cardiac-specific creatinine kinase and cardiac troponin I confirmed the diagnosis. Cardiac catheterization 8 hours later revealed normal coronary arteries, suggesting a mechanism of vasospasm. Cardiac magnetic resonance imaging confirmed findings of regional myocardial infarction. This case highlights a potential danger of pseudoephedrine even when used by otherwise healthy individuals.
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PMID:Acute myocardial infarction after over-the-counter use of pseudoephedrine. 1567 80


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