Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Labetalol is a unique antihypertensive agent which is a competitive peripheral antagonist at both alpha- and beta-adrenoceptor sites. Clinically, it possesses about one fourth of the beta-adrenoceptor blocking activity of propranolol and one half of the alpha-adrenoceptor blocking activity of phentolamine with a beta- to alpha-blocking ratio of approximately 7:1. Nowadays, the clinical profile of labetalol is clearly defined. Perorally, it has often been used in the treatment of mild, moderate and severe hypertension and intravenously in the management of hypertensive emergencies. It offers many advantages over beta-blockers with no prominent side-effects. Hemodynamically, labetalol reduces blood pressure, heart rate and, first of all, peripheral resistance with almost no change in resting cardiac output or stroke volume. Labetalol appears to be useful particularly in patients whose blood pressure is not adequately controlled by beta-blockers alone or combined with a diuretic, but sometimes at the expense of postural hypotensive side-effects. It has proved to be safe in patients with coronary artery disease or after acute myocardial infarction and in pregnant patients, but in phaechromocytoma further clinical experience is needed. In induced hypotension during anesthesia and surgery no invasive blood pressure measurements are needed. The most frequent adverse effects include fatigue, postural hypotension, headache and gastrointestinal complaints. On the whole, labetalol expands the armamentarium of the practising physician in the treatment of hypertension of different origin.
 ...
PMID:Current status of labetalol, the first alpha- and beta-blocking agent. 286 49

The side-effect profile of labetalol was assessed in 34 patients with mild to moderate essential hypertension who had previously experienced side effects during beta-blocker therapy. The most frequently reported beta-blocker side effects were fatigue, impotence, cold extremities, and depression. After discontinuing their previous beta-blocker for 4 weeks, labetalol was titrated (100-400 mg b.i.d.) to achieve blood pressure control. Twenty-seven of 34 patients did not have a recurrence of a beta-blocker related side effect while receiving labetalol. The most common new side effect with labetalol was dizziness (3 patients). As judged by the attending physician and the patient, labetalol was better tolerated than conventional beta-blocker therapy in 30 of 34 patients (88%). Twenty-four of 34 patients (71%) preferred labetalol over previous therapy. Labetalol controlled blood pressure in 30 of 34 patients (88%). At equal antihypertensive doses, some side effects common to beta-blockers are seen less frequently with labetalol.
 ...
PMID:Comparative tolerability of labetalol versus propranolol, atenolol, pindolol, metoprolol, and nadolol. 287 65

The purpose of this study was to investigate the efficacy and safety of labetalol, an alpha and beta-adrenergic receptor blocking agent in 32 patients aged from 72 to 97 years (mean = 85 years) with blood pressure (B.P.) greater than or equal to 160/95 mmHg. This study was carried out in a double-blind, randomized, placebo-controlled design. After 6 weeks of treatment with labetalol (mean dose = 235 +/- 47.5 mg/day), the systolic pressure was lowered from 187 +/- 24 to 145 +/- 28 mmHg (p less than 0.001) and the diastolic pressure from 98 +/- 10 to 82 +/- 9 mmHg (p less than 0.001). Likewise, in the placebo group, both systolic and diastolic pressures were significantly reduced but the changes were significantly greater in the labetalol group, -33 +/- 26 versus -13 +/- 20 mmHg and -14 +/- 10 versus -8 +/- 14 mmHg respectively. Labetalol achieved B.P. control (160/95 mmHg) in 64% of the treated patients, compared to 40% in the placebo group. Two patients on labetalol discontinued their treatment due to side-effects (one bradycardia and one cutaneous reaction) compared with one patient on placebo (cardiac failure). Two other cases in the labetalol group had side-effects (one fatigue and one dizziness) which prevented increasing the treatment as necessary.
 ...
PMID:[Arterial hypertension in the elderly. Double-blind study versus placebo of the efficacy and tolerability of an alpha-beta blocker: labetalol]. 382 57

Labetalol is a combined alpha- and beta-adrenoceptor blocking agent for oral and intravenous use in the treatment of hypertension. It is a nonselective antagonist at beta-adrenoceptors and a competitive antagonist of postsynaptic alpha 1-adrenoceptors. Labetalol is more potent at beta that at alpha 1 adrenoceptors in man; the ratio of beta-alpha antagonism is 3:1 after oral and 6.9:1 after intravenous administration. Labetalol is readily absorbed in man after oral administration, but the drug, which is lipid soluble, undergoes considerable hepatic first-pass metabolism and has an absolute bioavailability of approximately 25%. There are no active metabolites, and the elimination half-life of the drug is approximately 6 hours. Unlike conventional beta-adrenoceptor blocking drugs without intrinsic sympathomimetic activity, labetalol, when given acutely, produces a decrease in peripheral vascular resistance and blood pressure with little alteration in heart rate or cardiac output. However, like conventional beta-blockers, labetalol may influence the renin-angiotensin-aldosterone system and respiratory function. Clinical studies have shown that the antihypertensive efficacy of labetalol is superior to placebo and to diuretic therapy and is at least comparable to that of conventional beta-blockers, methyldopa, clonidine and various adrenergic neuronal blockers. Labetalol administered alone or with a diuretic is often effective when other antihypertensive regimens have failed. Studies have shown that labetalol is effective in the treatment of essential hypertension, renal hypertension, pheochromocytoma, pregnancy hypertension and hypertensive emergencies. In addition, preliminary studies indicate that labetalol may be of value in the management of ischemic heart disease. The most troublesome side effect of labetalol therapy is posture-related dizziness. Other reported side effects of the drug include gastrointestinal disturbances, tiredness, headache, scalp tingling, skin rashes, urinary retention and impotence. Side effects related to the beta-adrenoceptor blocking effect of labetalol, including asthma, heart failure and Raynaud's phenomenon, have been reported in rare instances.
 ...
PMID:Labetalol: a review of its pharmacology, pharmacokinetics, clinical uses and adverse effects. 631 May 29

Labetalol is a competitive antagonist of alpha 1-, beta 1-, and beta 2-adrenergic receptors. The hemodynamic effects of the drug include reduced blood pressure, heart rate, and peripheral resistance, with little change in resting cardiac output or stroke volume. In open trials and controlled studies, labetalol was an effective antihypertensive. Labetalol compared favorably with beta-blockers alone or in combination with vasodilators, for the treatment of hypertension. Reductions in heart rate are less pronounced with labetalol as compared with propranolol. Labetalol produces rapid reductions in blood pressure when administered intravenously for severe hypertension. The most frequent adverse reactions to the drug include fatigue, postural symptoms, headache, and gastrointestinal complaints. Labetalol may prove advantageous when vasodilation in addition to beta-blockade is desired, or for selected patients experiencing adverse effects attributable to beta-blockade. Until the clinical profile of labetalol is better defined, the use of the drug should be limited.
 ...
PMID:Labetalol. 635 58

The antihypertensive effects of oral labetalol, a new alpha- and beta-adrenergic blocking agent, and metoprolol, a relatively beta1 selective adrenergic blocker, were evaluated in 91 patients with mild to moderate hypertension (standing diastolic blood pressure of 90 to 115 mm Hg) in a double-blind parallel group multicenter clinical trial. The effects of the two drugs on plasma lipids and lipoprotein fractions were also assessed. Following a four-week placebo phase, 44 patients were randomized to receive labetalol and 47 metoprolol. During a four-week titration phase, the labetalol dose was increased from 100 mg twice daily to a maximum of 600 mg twice daily to achieve a standing diastolic blood pressure of 90 mm Hg that was decreased by 10 mm Hg or more. Metoprolol was titrated from 50 mg to 200 mg twice daily. An eight-week maintenance period followed during which hydrochlorothiazide could be added. At the end of the maintenance phase, the doses of labetalol and metoprolol were tapered over a two to four day period after which patients received a placebo for one week. Blood pressure in the supine and standing position was measured at each visit. Labetalol and metoprolol both significantly (p less than 0.01) lowered the supine and standing blood pressure from baseline with no significant difference found between the two treatment groups. Both drugs lowered the heart rate; however, the rate-lowering effect was significantly greater with metoprolol (p less than 0.01). There were no significant effects of either drug on plasma lipids or lipoprotein fractions. Fatigue was the most frequently reported complaint with both drugs. Dizziness, dyspepsia, and nausea were more common with labetalol; bradycardia was more common with metoprolol. There was no blood pressure "overshoot" after withdrawing drug treatment; however, a heart rate "overshoot" was seen after metoprolol was tapered off and stopped. Labetalol is as safe and effective as metoprolol in the treatment of patients with mild to moderate hypertension.
 ...
PMID:Multiclinic comparison of labetalol to metoprolol in treatment of mild to moderate systemic hypertension. 635

The long-term efficacy and safety of labetalol, an antihypertensive agent with combined beta- and alpha-blocking activity, were evaluated alone (number = 193) and in combination with a diuretic (number = 144) in an open-label multicenter trial of 337 hypertensive patients aged 21 to 75 years, including initially 205 (61 percent) men and 219 (65 percent) Caucasians. There were 219 (65 percent) mild, 85 (25 percent) moderate, and 33 (10 percent) severe hypertensive patients. Labetalol (100 to 1,200 mg twice a day) alone or in combination with a diuretic reduced the mean standing blood pressure by 13/11 and 25/16 mm Hg to 135/88 and 130/91 mm Hg, respectively (p less than 0.01), and supine blood pressure by 6/7 and 18/13 mm Hg to 141/86 and 138/90 mm Hg (p less than 0.01), respectively. Blood pressure reductions observed at one month were maintained after one year; 206 (62 percent) patients had 10 mm Hg or greater reductions and 184 (56 percent) patients were maintained at diastolic blood pressures less than 90 mm Hg. Most frequently reported drug-related side effects included fatigue (14 percent), dizziness (12 percent), nausea (11 percent), nasal stuffiness (8 percent), headache (4 percent), and male sexual dysfunction (14 percent). Side effects were generally of mild to moderate intensity and often transient. In addition, in 27 (8 percent) patients reversible asymptomatic transaminase elevations to greater than twice normal developed at some time during the study. In 13 (4 percent) patients these alterations resolved during continued labetalol therapy, but in five (2 percent) patients these marked elevations led to discontinuation of the drug. A total of 32 (9.5 percent) patients were terminated prematurely due to side effects (most commonly genitourinary or gastrointestinal) possibly attributable to the drug. These findings indicate that labetalol with or without a diuretic is a potentially effective, safe, and relatively well-tolerated long-term antihypertensive therapy.
 ...
PMID:Multicenter clinical evaluation of long-term efficacy and safety of labetalol in treatment of hypertension. 635 1

Labetalol, a new alpha- and beta-adrenergic blocking agent, was administered to 57 patients with essential hypertension whose standing diastolic blood pressure was 105 to 120 mm Hg after three and four weeks of placebo therapy and greater than 90 mm Hg after three to four weeks of therapy with hydrochlorothiazide, 25 mg twice a day. Patients were then randomly assigned on a double-blind basis to receive either labetalol, 100 mg twice a day, or placebo combined with hydrochlorothiazide. Thereafter, the dose of labetalol was titrated weekly in both groups to a maximum of 400 mg twice a day to achieve a standing diastolic blood pressure of less than 90 mm Hg that was also decreased from the hydrochlorothiazide baseline by 10 mm Hg or more (therapeutic goal). Labetalol was abruptly discontinued after four weeks of treatment and patients were given hydrochlorothiazide alone for two additional weeks. After one week of labetalol therapy, 100 mg twice a day (added to hydrochlorothiazide), there was a significantly greater reduction in supine systolic/diastolic blood pressure (6/5 mm Hg, p less than 0.04/less than 0.03) and standing blood pressure (9/7 mm Hg, p less than 0.01/less than 0.01) than with placebo therapy (3/0.5 and 3/1 mm Hg, respectively). The blood pressure reduction in the labetalol-treated group was associated with a 4 and 5 beats per minute reduction in the supine and standing heart rates, respectively. The median labetalol dose required to achieve the standing diastolic blood pressure goal was 400 mg twice a day. After four weeks of labetalol treatment, the mean reduction in blood pressure from the hydrochlorothiazide baseline was 12/13 mm Hg (p less than 0.01/0.01) in the standing position and 8/8 mm Hg (p less than 0.01/0.01) in the supine position. These blood pressure reductions were accompanied by a mean reduction in heart rate of 7 beats per minute. The most frequently reported complaints other than thiazide-induced nocturia included dizziness, fatigue, nausea, rash, and/or pruritus. Most of these complaints were reported at a similar incidence while patients were receiving placebo or hydrochlorothiazide alone as when receiving labetalol with hydrochlorothiazide. After abrupt withdrawal of labetalol, no evidence of rebound hypertension was observed. Labetalol is a safe and effective step II drug when added to hydrochlorothiazide for the treatment of patients with moderate to moderately severe hypertension.
 ...
PMID:Step II treatment with labetalol for essential hypertension. 635 2

Thirty-two patients with primary hypertension were studied in a double-blind cross-over comparison between the cardioselective beta 1-blocking agent atenolol and the combined alpha- and beta-blocking agent labetalol. The doses used were atenolol 50--150 mg twice daily and labetalol 200--600 mg twice daily. Both drugs effectively reduced blood pressure and heart rate. Dose increments every second week resulted in a higher proportion of patients with normal blood pressure (les than or equal to 150/90 mm Hg) with both drugs. Labetalol was somewhat more effective in lowering upright blood pressure while atenolol caused a more pronounced heart-rate reduction. Both agents decreased plasma renin activity and urinary aldosterone excretion. Scalp tingling on labetalol (2 patients) and cold fingers with atenolol (1 patient) caused withdrawal of the drugs. Cold fingers were reported in another four patients during treatment with atenolol and in one when on labetalol. Tiredness and postural symptoms were more common during intake of labetalol.
 ...
PMID:Antihypertensive and metabolic effects of increasing doses of atenolol and labetalol. A comparative study in primary hypertension. 676 Jun 79

The antihypertensive effect of labetalol (L) was compared with that of clonidine (C) in a randomized cross-over study in 17 hypertensive outpatients on bendrofluazide (B). After treatment for two weeks with B(5 mg qd), either L (100 mg tid) or C (0.1 mg tid) was given and their doses were titrated at 2-weekly visits until normotension was achieve, or intolerable side-effects occurred. The treatment with B and L or C was than continued in a cross-over fashion for two 6-week periods, with 3 week diuretic washouts and subsequent dose-titration periods between the treatment periods. At the end of B, the supine blood pressure (BP) was 156/101, and at the end of B + L and B + C it was 136/91 (p less than 0.001) and 137/91 (p less than 0.0001), respectively, pooling the data from both periods. At the end of B the standing BP was 155/115, and at the end of B + L and B + C 134/100 (p less than 0.001) and 139/106 (p less than 0.0001), respectively. The mean daily doses required were L 476 mg and C 0.335 mg. On a weight basis, labetalol had about 1/1400 of the potency of clonidine. 12 patients complained of tiredness and dry mouth on clonidine and 2 patients of unsteadiness on labetalol. Labetalol caused a psoriasiform rash on the hands in one patient and limb weakness in one patient.
 ...
PMID:Comparison of labetalol and clonidine in hypertension. 707 40


1