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At least 19 recordsLinked to original sources

PubMed1979

Labetalol in controlled hypotension: administration of labetalol when adequate hypotension is difficult to achieve.

A study of controlled hypotension was undertaken in 50 major surgical patients using labetalol, a drug with both alpha- and beta-adrenoceptor blocking activity. The patients were such that difficulty in achieving controlled hypotension could be anticipated: the young, the anxious and those for whom halothane was contraindicated. The administration of labetalol quickly induced hypotension which was controlled easily and was rapidly antagonized.

Adolescent↗

PubMed1976

A review of the animal pharmacology of labetalol, a combined alpha- and beta-adrenoceptor-blocking drug.

1 The animal pharmacology of labetalol, a drug that blocks both alpha- and beta-adrenoreceptors, is reviewed. 2 In isolated tissues the blockade by labetalol of both alpha- and beta-adrenoreceptors satisfied accepted critera for competitive antagonism. In contrast phentolamine was a competitive antagonist at alpha-adrenoreceptors only, and propranolol a competitive antagonist at beta-adrenoreceptors only. Labetalol was 6-10 times less potent than phentolamine in blocking alpha-adrenoreceptors and 1.5-3 times less potent than propranolol in blocking beta-adrenoreceptors. Labetalol itself was 4-8 times more potent at beta- than at alpha-adrenoreceptors. 3 In anaesthetized dogs labetalol given intravenously blocked vasopressor responses to phenylephrine positive chronotropic, vasodepressor and bronchodilator response to isoprenaline. Phentolamine blocked the effect of phenylephrine only, and propranolol the effects of isoprenaline only. Labetalol was about 7 times less potent than phentolamine in blocking alpha-adrenoreceptors, about 4 times less potent than propranolol in blocking cardiac beta1-adrenoreceptors, and 11-17 times less potent than propranolol in blocking vascular and bronchial beta2-adrenoceptors. This difference in the relative potency of labetalol arises because propranolol is a slightly more potent antagonist at beta2- than at beta1-adrenoreceptors. Labetaol itself was about 16 times more potent at cardiac beta1- than at vascular alpha-adrenoreceptors. In conscious dogs labetaol given orally blocked vasopressor responses to phenylephrine and positive chonotropic responses to isoprenaline. 4 In anesthetized dogs and pithed rats labetaol blocked alpha- or beta-adrenoreceptor-mediated responses to sympathetic nerve stimulation and intravenously administered phenylephrine or isoprenaline to approximately the same extent. 5 Labetalol does not possess partial agonist (intrinsic sympathomimetic) activity at cardiac beta1-adrenoreceptors. 6 The blocking action of labetalol both in vivo was shown to be specific for alpha- and beta-adrenoreceptors. 7 The haemodynamic effects of labetalol are attributable to its adrenoreceptor-blocking actions. The observed responses vary from one experiment situation to another depending on the balance of autonomic influences. For example, in barbitone-anaesthetized dogs, in which sympathetic tone predominates, both labetalol and propranolol reduced heart rate, contractility, output and work--effects which are attributable to beta-adrenoreceptor blockade. Labetalol differed from propranolol in decreasing rather than increasing total peripheral resistance and in causing larger falls in blood pressure at equipotent beta-adrenoreceptor-blocking doses. These differences are probably attributable to peripheral vasodilatation resulting from the vascular alpha-adrenoreceptor-blocking action of labetalol...

Adrenergic alpha-Antagonists↗

PubMed1976

Pharmacological effects of labetalol in man.

1 The pharmacological effects of labetalol have been studied in normal healthy subjects. The results of these studies are reviewed. 2 In the evaluation of the beta-adrenoreceptor-blocking effects of labetalol various indices of beta-adrenoceptor blockade in man were used. Labetalol administered orally and intravenously competitively antagonized the effects of isoprenaline on heart rate and diastolic blood pressure. The beta-adrenoceptor blockade induced was regarded as 'non-selective'. In addition, labetalol produced dose-related inhibitory effects on exercise-induced increases in heart rate any systolic blood pressure and similar dose-related inhibitory effects on the tachycardia induced by valsalva's manoeuvre. Labetalol had only a modest inhibitory effect on the tachycardia induced by tilting since blood pressure was reduced on a dose-related basis. 3 Labetalol was a specific competitive antagonist of the alpha-adrenoceptor agonist effects of systemically administered phenylephrine and locally infused noradrenaline. In addition, oral and intravenous administration of labetalol reduced systolic and diastolic blood pressure in the supine, standing and sitting positions. 4 The onset and duration of the alpha- and beta-antagonist effects of oral labetalol did not seem to be dissociated in time and there was a close correlation between the change in plasma concentration and pharmacological effects. 5 In comparative studies with propranolol, similar beta-antagonist effects were observed but propranolol was 4-6 times more potent weight for weight. Precise comparison, however, was complicated by the combined alpha- and beta -effects of labetalol, especially as the predominant effect of labetalol in normotensive subjects was to reduce blood pressure; whereas the predominant effect of propranolol was to reduce heart rate. In addition propranolol had inhibitory effects on ventilatory function in normal subjects, whereas labetalol in equivalent beta-adrenoreceptor-blocking doses did not. 6 From the details of the studies reviewed it was concluded that in man labetalol possesses combined alpha- and beta-adrenoreceptor antagonist properties.

Adrenergic alpha-Antagonists↗

PubMed1977

Pharmacological basis for antihypertensive effects of intravenous labetalol.

Labetalol 1-5 mg/kg administered intravenously to normal subjects in the supine position produced an immediate mean fall in systolic (16%) and diastolic (25%) blood pressure with a concomitant increase in heart rate (12%). After graded exercise, intravenous labetalol inhibited increases in heart rate and blood pressure. Isoprenaline log dose response curves of increase in heart rate and reduction in diastolic pressure after intravenous labetalol shifted to the right in a parallel manner compared with pre-labetalol response curves suggestive of competitive antagonism at beta-adrenoceptor sites. Similarly, phenylephrine dose response curves of increase in systolic pressure before and after intravenous labetalol were suggestive of competitive antagonism at alpha-adrenoceptor sites. The ratio of relative potency alpha: beta adrenoceptor antagonism after intravenous labetalol was approximately 1:7, whereas in the same subjects after oral labetalol the ratio was approximately 1:3 as previously reported. Using the inhibition of isoprenaline tachycardia to estimate the potency of the beta-adrenoceptor antagonism of labetalol relative to that of propranolol the potency ratio was 1:6. However, using inhibition of Valsalva tachycardia as the index, the estimated ratio was approximately 1:3. Estimates of relative potency using inhibition of tilt tachycardia were complicated by the additional effects upon blood pressure after labetalol not seen after propranolol. Labetalol produced adrenoceptor blockade at both alpha and beta sites in man sufficient to explain its therapeutic antihypertensive effect.

Adrenergic alpha-Antagonists↗

PubMed1978

Release of noradrenaline by labetalol in the rat anococcygeus muscle.

The effects of labetalol on the accumulation and spontaneous release of (--)-[3H]noradrenaline, and on contractile responses to exogenously applied (--)-noradrenaline were studied in the isolated anococcygeus muscle of the rat. 1. Labetalol (3 x 10(-7)--10(-4)M) inhibited the accumulation of (--)-[3H]noradrenaline. 2. Labetalol (10(-6)--10(-4)M) and guanethidine (6 x 10(-6) M) increased the spontaneous release of [3H] following incubation of the muscle with (--)-[3H]noradrenaline. Nortriptyline (10(-6) M) had no effect on the spontaneous release of [3H], antagonised the increased release of [3H] produced by 6 x 10(-6) M guanethidine but not that observed with 10(-5) M labetalol. Labetalol (5 x 10(-6) M) markedly increased the loss of tritiated deminated metabolites with little change in the loss of (--)-[3H]noradrenaline. 3. Labetalol (10(-7)--10(-5)M), alone or in the presence of 10(-6) M nortriptyline, had no effect on contractile responses to (--)-noradrenaline. 4. Following pretreatment with 6-hydroxydopamine (10(-3)M for 3 h) to deplete endogenous noradrenaline stores, labetalol (10(-7)--10(-5) M) inhibited responses to exogenously applied (--)-noradrenaline. 5. These results suggest that, in the rat anococcygeus muscle, labetalol is a noradrenaline releasing agent and an alpha-adrenoceptor antogonist.

Animals↗

PubMed1979

Alpha- and beta-adrenoceptor blocking properties of labetalol in renin release.

The effect of labetalol, an alpha- and beta-adrenergic receptor blocking antihypertensive, on plasma renin activity (PRA) and the hemodynamics of healthy volunteers at rest and during an ergometric exercise test was studied. Oral doses of 200 and 400 mg labetalol were tested against a placebo in a crossover manner. The labetalol plasma concentrations were determined. Systolic and diastolic blood pressures in the supine position decreased after 400 mg labetalol as did the response of the heart rate to exercise. The lower dose decreased the resting heart rate, but had no effect on the heart rate during exercise. The ergometric exercise induced an increase in PRA which was partly inhibited after 200 mg labetalol in a manner similar to that induced by beta-blockers in our earlier studies. After 400 mg labetalol PRA was already increased at one hour at sitting rest and this higher basal level was maintained for four hours. After this higher dose of labetalol the reaction of PRA to exercise was not significantly inhibited. In renin release the vasodilating alpha-blockade thus dominated the beta-blocking property of labetalol at the dose which decreased the blood pressure.

Adrenergic alpha-Antagonists↗

PubMed1978

Effect of labetalol on plasma noradrenaline and adrenaline in hypertensive man.

Injection i.v. of labetalol, a new adrenergic alpha- and beta-blocking agent, decreased arterial blood pressure in 9 hypertensive subjects resting in the supine position, when standing and during supine exercise. Heart rate after labetalol was unchanged in the resting supine position, and it fell in the latter two conditions. Plasma noradrenaline concentration was higher after labetalol in all three experiments as compared to a control study. Plasma adrenaline after labetalol was increased only in the standing position, when the highest plasma noradrenaline concentrations were observed. Blood glucose concentration tended to increase after labetalol, but the difference was not statistically significant. The changes in plasma noradrenaline and blood glucose after labetalol mimic findings observed after alpha-adrenergic receptor blockade. The beta-adrenergic receptor blocking property of labetalol is responsible for the reduced heart rate and it is likely to contribute to the higher plasma noradrenaline concentration observed when standing and during supine exercise.

Adult↗

PubMedDate not supplied

Effects of labetalol on plasma renin, aldosterone, and catecholamines in hypertensive patients.

We studied the effects of labetalol, an alpha- and beta-adrenoceptor antagonist, on maximum exercise heart rate and on plasma renin, aldosterone, noradrenaline, and adrenaline levels at rest and during exercise in hypertensive patients. The dose of labetalol was doubled weekly from 0.3 to 2.4 g per day. The maximum exercise heart rate fell significantly during labetalol treatment, and there was a significant correlation between exercise tachycardia and the dosage of labetalol. Plasma renin activity and aldosterone concentration at rest decreased during treatment with labetalol. The exercise-induced increase in plasma renin activity was reduced by labetalol. Labetalol did not cause any significant changes in plasma noradrenaline and adrenaline at rest or during exercise.

Adult↗

PubMed1979

A comparison of the effects of labetalol, bendrofluazide and their combination in hypertension.

1 Bendrofluazide (10 mg/day) or labetalol (300 mg and 600 mg/day) produced significant reductions in lying, standing, and post-exercise blood pressure in ten hypertensives. 2 Active treatments were approximately equivalent in anti-hypertensive effect. However, comparing lying and standing determinations, labetalol (600 mg/day) produced significantly greater additional postural falls in systolic blood pressure than during placebo or bendrofluazide treatment. 3 Systolic blood pressure rose after exercise during placebo or bendrofluazide treatment. However, on labetalol, mean changes in systolic blood pressure after exercise were negative and significantly different from those seen on placebo. 4 Greater reductions in lying and post-exercise systolic blood pressure were produced by combination treatment than by either individual drug. Additional postural and exercise-related falls in systolic blood pressure tended to be smaller with combination treatment than during treatment with labetalol alone. 5 Labetalol significantly reduced lying, standing, or post-exercise heart rate by comparison with placebo or bendrofluazide. 6 Labetalol significantly reduced lying, standing, or post-exercise heart rate by comparison with placebo or bendrofluazide. 6 Labetalol moderately reduced plasma renin activity, whereas bendrofluazide caused marked elevation. The effect of bendrofluazide predominated during combination treatment.

Adult↗

PubMed1977

The effects of labetalol (AH 5158) on adrenergic transmission in the cat spleen.

1. The competitive alpha- and beta-adrenoceptor blocking agent labetalol, in concentrations up to 10(-4) M, produced dose-dependent increases in transmitter overflow from the isolated blood perfused spleen of the cat following nerve stimulation at 10 and 30 Hz. 2. At concentrations above 10(-4) M labetol produced a pronounced decrease in transmitter overflow. 3. Labetalol (1.5 X 10(-4) M) increased the recovery of 3H label in the venous blood following the close-arterial infusion of [3H]-(-)-noradrenaline indicating that the drug inhibits uptake of the amine. 4. Both labetalol (3.8 X 10(-5) M) and piperoxan (7.4 X 10(-6) M) produced parallel shifts to the right of the dose-response curves to noradrenaline and oxymetazoline in isolated strips of cat splenic capsule. In this preparation both drugs acted as competitive postsynaptic alpha-adrenoceptor blocking agents. 5. Labetalol (3.3 X 10(-5) M) increased the transmitter overflow following stimulation of the splenic nerves with 200 impulses at 10 Hz. The overflow could be further increased by subsequent addition of piperoxan (7.2 X 10(-6 M). Piperoxan (5.7 X 10(-6) M) alone produced a marked increase in transmitter overflow which could be further increased by subsequent addition of desmethylimipramine (DMI; 3.2 X 10(-5) M). Cocaine (1.5 X 10(-5) M) or DMI (5.4 X 10(-5 M) produced a small increase in transmitter overflow which was not further increased by addition of labetalol (2.8 X 10(-5) M). 6. Labetalol produced a biphasic effect on the responses of the isolated blood perfused spleen of the cat to nerve stimulation. With low doses (up to 10(-4) M) vascular responses were potentiated and with high doses (greater than 10(-4) M) inhibited. The potentiation was related to uptake blockade and the inhibition to decreased transmitter overflow and postsynaptic alpha-adrenoceptor blockade. 7. Labetalol appears to act as a postsynaptic alpha-adrenoceptor antagonist in the isolated blood perfused spleen of the cat with little effect on presynaptic alpha-adrenoceptors. The moderate elevation of transmitter overflow by the drug is related to the inhibitory effect of the drug on neuronal uptake rather than on presynaptic alpha-adrenoceptors.

Animals↗

PubMed1978

Hypotensive and vascular effects of labetalol in the normotensive rat and dog.

A new antihypertensive agent, labetalol, has potent hypotensive effects in the anesthetized rat and dog when given intravenously and also in the unanesthetized beagle when given orally. Labetalol slightly increased renal blood flow of the anesthetized dog while decreasing blood pressure. Labetalol slightly increased blood flow of canine femoral artery under constant pressure perfusion. However as compared with hydralazine, labetalol seems to have no marked vasodilatatory effect which accounts for its hypotensive effect. Pharmacologically, labetalol possessed both alpha- and beta-blocking activities, though weaker than phentolamine and propranolol respectively. Another specific action of labetalol was that it has stronger beta-blocking action on beta1 receptor (heart rate response) than on beta2 receptor (blood pressure response). Like several other beta-blockers, labetalol seems to block neuronal uptake of noradrenaline.

Adrenergic alpha-Antagonists↗

PubMed1979

Labetalol in severe and resistant hypertension.

1 The efficacy of labetalol in the treatment of severe hypertension (diastolic greater than or equal to 115 mm Hg) was studied retrospectively. Ten patients were followed for more than 6 months. At 6 months, eight were well controlled and the mean dose in those was 975 mg daily. Four of these were receiving labetalol alone; two were on labetalol and diuretic only. 2 Three patients were resistant to doses of 1600, 1800 and 2400 mg daily respectively; two of these were controlled with increased doses of vasodilator drugs. In two cases labetalol had produced large falls in the standing BP while not influencing the supine BP. 3 Three other resistant patients were seen, of whom one merely required an increase in dose to 2200 mg daily and the addition of a diuretic. Both the others were elderly, had severe vascular disease, and suffered disabling postural hypotension on a dose of labetalol which did not influence the supine BP. 4 Labetalol can control severe hypertension. There remain patients whose supine BP is not influenced by a dose of labetalol which produces marked postural hypotension.

Adult↗

PubMed1976

Controlled comparison of labetalol and propranolol in the management of severe hypertension.

1 Labetalol, a new hypotensive drug combining alpha- and beta-adrenoreceptor antagonist properties, has been compared with propranolol in the treatment of severe hypertension (blood pressure 190/115-249/139 mmHg) in a double-blind trial lasting 14 weeks. Additional diuretic therapy was given to both groups of patients. 2 Both drugs caused an effective reduction in blood pressure, bbut labetalol caused a greater fall in pressure in the standing position and after exercise. Two groups of nine patients have each completed the trial so far. Group average pressures for the last 3 weeks of treatment were: for labetalol 137/87 supine, 121/84 standing, and 117/78 mmHg after exercise; and for propranolol, 138/87 supine, 132/93 standing, and 133/94 mmHg after exercise. 3 Group average heart rates were lower in all three positions for those patients treated with propranolol compared with labetalol. 4 The average final dose ratio for labetalol: propranolol was 1.44:1 (w/w). 5 Labetalol initially induced a number of side-effects, predominantly related to alpha-adrenoreceptor blockade, which disappeared by the end of the trial. 6 Labetalol, in conjunction with diuretic therapy, was at least as effective as propranolol in lowering blood pressure in patients with severe hypertension.

Adult↗

PubMed1978

Concurrent antagonism of isoproterenol and norepinephrine after labetalol.

Labetalol reduces blood pressure in normotensive and hypertensive subjects. The effects of a therapeutic dose of intravenous labetalol upon the cardiovascular responses to intravenous isoproterenol and norepinephrine in 6 normotensive subjects were studied in order to investigate the drug's mode of action. Before labetalol, intravenous isoproterenol increased heart rate and reduced diastolic blood pressure in a dose-dependant manner; likewise, intravenous norepinephrine increased both systolic and diastolic pressure. The order of administration of these agonists was randomized between the subjects before and after labetalol. Following labetalol (1.5 mg/kg intravenously) the effects of isoproterenol were antagonized such that cumulative log-dose response curves of mean isoproterenol-induced increases in heart rate and reductions in diastolic pressure were shifted to the right in a parallel manner to approximately the same extent. At the same time, the mean norepinephrine-induced increases in systolic and diastolic blood pressure were also antagonized in a competitive manner. These responses were compared with others in the same subjects under the same conditions and it was concluded that the antihypertensive effect of labetalol is explained by concurrent blockade of alpha-and beta-adrenoceptors.

Adult↗

PubMed1979

Effect of increasing doses of labetalol on blood pressure, plasma renin activity and aldosterone in hypertensive patients.

1. Four different doses of labetalol (150, 300, 600 and 900 mg/day) were given for 1 week to each of four groups of patients with essential hypertension (six patients for each group). 2. Labetalol decreased mean blood pressure and heart rate to the same extent on the first and the seventh days of treatment. Only standing blood pressure showed a dose-dependent inhibition both in the supine and upright position. 3. Labetalol exerted a net inhibitory effect on plasma renin activity, which was related to basal renin values and was already maximal at the lowest doses. This effect was well maintained in the supine position. This effect was well maintained in the supine position, although during standing it tended to be less evident with increasing doses. 4. Urinary aldosterone was decreased in a dose-dependent fashion and its changes were largely independent fashion and its changes were largely independent of plasma renin activity. 5. Neither basal values nor changes of renin and aldosterone were related to the hypotensive effect of labetalol. 6. During labetalol treatment urinary sodium excretion fell for 2-3 days and then returned to basal values. The retentive effect of labetalol on sodium was directly related to the decrease of blood pressure, and the successive sodium escape might be explained either by the observed increase of plasma volume (indirectly measured by packed cell volume) or by aldosterone inhibition.

Adult↗

PubMed1979

A controlled trial of labetalol (Trandate), propranolol and placebo in the management of mild to moderate hypertension.

1. Labetalol, a new drug combining alpha-and beta-adrenoceptor blocking properties, has been compared with placebo in a double-blind crossover study of a group of patients with mild to moderate essential hypertension (blood pressure 150/100 to 189/114 mmHg). 2. Labetalol and propranolol lowered blood pressure satisfactorily in the supine position, but labetalol reduced blood pressure more in the erect posture and following exercise and induced less bradycardia. Thus alpha- as well as beta-adrenoceptor blocking actions appear to contribute to blood pressure reduction. 3. Side effects attributable to labetalol were few. The effective dose ratio labetalol: propranolol was 2.5:1 (w/w). 4. Labetalol, a new form of hypotensive agent, merits further controlled assessment of its usefulness in relation to existing drugs.

Adult↗

PubMed1978

Interference with fluorimetric assay of catecholamine by labetalol.

Influence of labetalol and 5-(1-hydroxy-2-aminoethyl)salicylamide (SA), a part of the chemical structure of labetalol, on the fluorimetric assay of catecholamine (CA) was studied. Both labetalol and SA have a weak but significant fluorescence which is indistinguishable from that of CA with peaks of excitation/emission wavelengths at 410/490. It is thus concluded that an apparent increase in urinary CA observed in patients receiving labetalol is caused by the contamination of labetalol and/or its metabolite, and that the evaluation of urinary CA in hypertensive patients must be done prior to the use of labetalol to avoid any confusion in diagnosis of pheochromocytoma.

Drug Interactions↗

PubMed1978

Labetalol in the treatment of hypertensive renal patients.

The efficacy of labetalol in lowering blood pressure was assessed in 18 patients with chronic renal failure and hypertension. Before the start of labetalol therapy, all patients were receiving combined antihypertensive therapy, the most common being a beta-blocker and hydrallazine. Over the period of about four weeks labetalol was substituted for the prior therapy. 51Cr edetic acid (EDTA) estimations of glomerular filtration rate were performed before labetalol therapy, and then again after one and six months. Before the therapy with labetalol, 12 of the 18 patients had supine diastolic blood pressures of 100 mm Hg or more. At six months, 14 patients remained in the trial and, of these, only four had a supine diastolic blood pressure of 100 mm Hg or more. In the supine position there was a significant reduction of systolic, but not of diastolic, blood pressure. However, in the erect position there was a significant reduction both in systolic and in diastolic blood presure. Pulse rate did not vary significantly. Few side effects were encountered, transient postural dizziness being the most common side effect. Labetalol seems to be an effective substitute for the beta-blocker plus hydrallazine therapy. However, it is not as potent as minoxidil.

Adrenergic beta-Antagonists↗