Efficacy Of Labetalol Research Articles

The safety and efficacy of labetalol vs. methyldopa in treatment of pregnancy induced hypertension

The safety and efficacy of labetalol vs. methyldopa in treatment of pregnancy induced hypertension

Assessment and Efficacy of Labetalol and Methyldopa in Controlling Blood Pressure in Patients with Pregnancy Induced Hypertension (PIH)

Assessment and Efficacy of Labetalol and Methyldopa in Controlling Blood Pressure in Patients with Pregnancy Induced Hypertension (PIH)

Hypertensive Emergency: Parenteral Antihypertensives and Population Data.

Review parenteral therapeutic choices in treatment of hypertensive crises by mechanism of action and summarize recent literature on the management of hypertensive crises. Recent data have documented the safety and efficacy of labetalol and nicardipine in treatment of hypertensive crises as well as characterized the hypertensive emergency population to a much greater extent. Based on recent data, hypertensive emergencies are seen in 0.5% of all emergency room visits. Ischemic stroke and heart failure/pulmonary edema are the most common forms of organ damage seen in hypertensive emergencies. There are many therapeutic choices in treatment of hypertensive crises with varied mechanisms of action. Large randomized, controlled trial evidence is lacking in this therapeutic area; however, recent data have documented the safety and efficacy of labetalol and nicardipine.

Intra-Arterial Labetalol and Nitroglycerin in Preventing Radial Artery Spasm Following Transradial Angiography: A New Approach

Background: Radial artery spasm (RAS) resulted from decreasing blood flow and activation of vasomotor system leads to a decrease in artery diameter, perfusion and patency, and increase the risk of procedure failure. In this study, we investigated the effects of intra-arterial administration of nitroglycerin and labetalol on radial artery diameter, RAS, and pain intensity in patients undergoing diagnostic radial angiography. Methods: Sixty-four patients randomly enrolled into one of the nitroglycerin (150 μg) or labetalol (500 μg) groups. The radial artery size, and the incidence of RAS were measured before, immediately after puncture, and at the end of treatment. Pain intensity was evaluated using a visual-analog-scale (VAS) at the end of the procedure. Hemodynamic status before, and during the procedure was also recorded. Results: Labetalol causes a significantly larger increase in radial diameter than nitroglycerin immediately after intra-arterial injection (2.24±0.58 mm vs. 1.65±0.39 mm, P-value<0.001). The rate of RAS immediately after vasodilator administration in the labetalol group was 3.1% vs. 12.5% in the nitroglycerin group (P-value=0.355), but the overall incidence (immediately after administration+ at the end of procedure) did not show a statistically significant difference (53.125% vs 31.25% respectively, P-value=0.076). The VAS score did not show a significant difference between two groups (1.15±0.44 in nitroglycerin vs. 1.50±0.91, P-value=0.063). Conclusion: Labetalol increases radial artery diameter more than nitroglycerin. However, the efficacy of labetalol in terms of RAS incidence, and patients’ pain was similar to nitroglycerin. Therefore, intra-arterial labetalol could be considered as one of the therapeutic options in clinical practice in order to reduce RAS and procedure failure.

SUN-174 EFFICACY AND SAFETY OF INTRAVENOUS LABETALOL FOR HYPERTENSIVE CRISIS IN CHILDREN

Hypertensive crisis is uncommon in children. American Association of Pediatrics acknowledges the lack of robust evidence-based management guidelines for the same. Most data on the choice of drugs is extrapolated from adults and small case series in children. The objectives of this study were to determine the efficacy and safety of IV labetalol as a first-line agent or an add on drug compared to IV nitroprusside/nitroglycerine in the management of hypertensive crisis in children. A retrospective chart review of 56 consecutive children (age 1 month to ≤ 12 years) with hypertensive crisis admitted to pediatric intensive care unit (PICU) during a 10-year period (July 2009- 2019) was done. Data with respect to baseline demographics, clinical presentation, etiological workup, treatment details, and blood pressure (BP) trends were recorded. The choice of antihypertensive agents was left to the clinician's discretion. The proportion of patients, attaining target BP (95th percentile) in >12 to ≤ 48 hours after admission was taken as primary endpoint. The secondary endpoints were PICU needs, morbidity, and mortality. The median age of the children was 7 years (range 1-12). Hypertensive crisis comprised < 1 % of PICU admissions. Most crisis presented as hypertensive emergency (89%) and had renal etiology as the leading cause (61%). The proportion of children attaining the primary endpoint was significantly more in the group receiving labetalol (n=23) as compared to those not receiving labetalol (n=33) (62% vs. 29%, p < 0.0001). The proportion of children having precipitous fall in BP before 12 hours, leading to hypotension was similar in both treatment groups (13% vs 15%). The PICU needs for ventilation (0% vs 27%, p < 0.0001), renal replacement therapy (0% vs 9%, p = 0.003) and raised intracranial pressure (ICP) (0% vs 9%, p = 0.003) were significantly less in the labetalol group. The central nervous system (CNS) morbidity was also significantly reduced in the labetalol group (41% vs. 9%, p < 0.0001). One child compared to three died in the labetalol and non-labetalol group respectively (4.3% vs. 9%, p = 0.2). The data were also analyzed for practice variations between two periods of five years each (2009-2013 and 2014-2019). There latter cohort showed significantly more use of labetalol (74% for 2014-2019 vs. 26% for 2009-2013, p < 0.0001). Labetalol, when used alone or as an add on drug was more efficacious than IV nitroprusside/nitroglycerine in attaining the primary endpoint. There was a lesser need for ventilation and renal replacement therapy with labetalol. The CNS morbidity at discharge was also lesser. The propensity to hypotension was however similar in both groups. There is only one study looking at the safety and efficacy of labetalol in children with hypertensive crisis up to ≤ 24 months of age. Ours is the only study to the best of our knowledge in children up to 12 years of age. However, our study suffers from the inherent problems of a retrospective analysis. In conclusion, our study shows that labetalol is safe and efficacious in hypertensive crisis in children up to ≤ 12 years of age.

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Associations of polymorphisms of CYP2D6 and CYP2C9 with early onset severe pre-eclampsia and response to labetalol therapy.

Early onset preeclampsia (PPE) contributes to life-threatening maternal complications and fetal demise. Pharmacogenomics is a precision medicine, and metabolizing enzymes responsive to antihypertensive remains understudied. The aim of this study was to evaluate the associations of polymorphisms of cytochrome P450, family 2, subfamily D, polypeptide 6 (CYP2D6) and cytochrome P450, family 2, subfamily C, polypeptide 9 (CYP2C9) with PPE and the relationship among CYP2D6, CYP2C9 polymorphisms and response to labetalol therapy. Totally 105 gravidas diagnosed with PPE (case) and 103 healthy gravidas (control) were recruited between August 2013 and July 2016. Labetalol was given to control blood pressures (BP) with PPE. If labetalol administration alone did not exceed the mean dose and effectively controlled the BP, it would be considered to be valid (n = 75). Genotype and allele frequencies of CYP2C9 gene (rs1057910 and rs4918758) and CYP2D6 gene (rs1065852, rs28371725, rs35742686, and rs3892097) were analyzed by TaqMan PCR. Differences in the genotype and allele frequencies were compared between case-control groups, and the responsive and nonresponsive to labetalol in PPE. Out of six variants, only CC and CT genotypes of the CYP2D6 variants (rs28371725) in PPE were significantly higher than those in the control group [18.1% (19/105) vs 14.6% (15/103); 56.2% (59/105) vs 42.7% (44/103); χ2 = 6.707]. However, there were no differences in maternal age, diastolic pressure, BMI, BW, serum triglyceride, and creatinine were observed among women with CC, CT, or TT genotype of CYP2D6 gene rs28371725 in the experimental group (all P > 0.05). Compared with the gravidas with CT or TT genotype of CYP2D6 gene rs28371725, those with CC genotype had longer gestational age [(32.5 ± 2.1) vs (29.5 ± 1.8) and (29.8 ± 2.2)weeks] and higher plasma albumin [(27.2 ± 9.3) vs (20.3 ± 10.4) and (22.5 ± 7.4)g/L], but lower systolic pressure and 24h urine protein (LSD test, all P < 0.05). The G allele frequency in CYP2D6 gene rs1065852 nonresponsive to labetalol group was higher than that in responsive labetalol group [93.3% (56/60) vs 76.0% (114/150), χ2 = 8.351, P = 0.004]. The polymorphism of CYP2D6 gene rs28371725 may be associated with PPE, and the allele of G in CYP2D6 gene rs1065852 may be associated with the efficacy of labetalol in treatment of PPE.

Associations of polymorphisms of cytochrome P450 enzymes (CYP2D6 and CYP2C9) with early-onset severe pre-eclampsia and labetalol therapy

Objective To explore the associations of the genetic polymorphisms of cytochrome P450, family 2, subfamily D, polypeptide 6 (CYP2D6) and cytochrome P450, family 2, subfamily C, polypeptide 9 (CYP2C9) with early-onset severe pre-eclampsia and the efficacy of labetalol therapy. Methods Totally 105 gravidas diagnosed with early-onset severe pre-eclampsia (experimental group) and 103 healthy gravidas (control group) were recruited from Beijing Obstetrics and Gynecology Hospital between August 2013 and July 2016. Labetalol was given to control blood pressures in gravidas with early-onset severe pre-eclampsia. If labetalol administration alone did not exceed the mean dose (100 mg, one dose per eight hours) and effectively controlled the blood pressures, it would be considered to be valid (n=75), otherwise it would be viewed as an invalid treatment. Genotype and allele frequencies of CYP2C9 gene (rs1057910 and rs4918758) and CYP2D6 gene (rs1065852, rs28371725, rs35742686 and rs3892097) in the gravidas were analyzed by TaqMan probe polymerase chain reaction. Differences in the genotype and allele frequencies were compared between the experimental and control groups, and the valid and invalid labetalol treatment groups. Chi-square test, analysis of variance and LSD test were used as statistical methods. Results The gravidas in both experimental and control groups were AA genotype in CYP2C9 gene rs1057910, TT genotype in CYP2D6 gene rs35742686 and CC genotype in CYP2D6 gene rs3892097. Frequencies of CC and CT genotypes in CYP2D6 gene rs28371725 in the experimental group were higher than those in the control group [18.1% (19/105) vs 14.6% (15/103); 56.2% (59/105) vs 42.7% (44/103); χ2=6.707], and higher C allele frequency in CYP2D6 gene rs28371725 was also observed in the experimental group [46.2% (97/210) vs 35.9% (74/206), χ2=4.529] (all P 0.05). Compared with the gravidas with CT or TT genotype of CYP2D6 gene rs28371725, those with CC genotype had longer gestational age [(32.5±2.1) vs (29.5±1.8) and (29.8±2.2) weeks] and higher plasma albumin [(27.2±9.3) vs (20.3±10.4) and (22.5±7.4) g/L], but lower systolic pressure and 24 hours urine protein (LSD test, all P<0.05). The G allele frequency in CYP2D6 gene rs1065852 in invalid labetalol treatment group was higher than that in valid labetalol treatment group [93.3% (56/60) vs 76.0% (114/150), χ2=8.351, P=0.004]. Conclusions The polymorphism of CYP2D6 gene rs28371725 may be associated with early-onset severe pre-eclampsia, and the allele of G in CYP2D6 gene rs1065852 may be associated with the efficacy of labetalol in treatment of early-onset severe pre-eclampsia. Key words: Pre-eclampsia; Labetalol; CYP2D6; CYP2C9; Polymorphism, single nucleotide

The efficacy of labetalol vs dexmedetomidine for attenuation of hemodynamic stress response to laryngoscopy and endotracheal intubation

ObjectiveTo assess the effectiveness of labetalol vs dexmedetomidine for attenuation of hemodynamic stress response to laryngoscopy and endotracheal intubation. DesignProspective, randomized, controlled, observer-blinded study. SettingThis study was carried out in Tanta University Hospital. PatientsNinety patients of both sexes; American Society of Anesthesiologists physical status I and II; age range from 20 to 60 years; scheduled for elective surgery under general anesthesia. InterventionsPatients were divided into 3 groups (30 each). Group A received 1 μg/kg of dexmedetomidine as intravenous (IV) infusion, group B received labetalol 0.25mg/kg IV, and group C received 10mL saline IV. MeasurementsThe groups were compared for heart rate (HR), mean arterial pressure (MAP), and rate pressure product (RPP). Hemodynamic parameters were recorded during the preinduction; after induction; at intubation; and at 1, 3, 5, 10, and 15minutes. The primary outcomes were hemodynamic changes (HR, MBP, and RPP), and the secondary outcome was propofol dose requirement for induction of general anaesthesia. ResultsSignificant decrease (P < .05) in HR, MBP, and RPP in groups A and B in comparison with group C and in group A in comparison with group B. Just before intubation, there was a significant decrease (P < .05) in HR, MBP, and RPP in groups A and B in comparison with group C. In group C, there was a significant increase in HR, MBP, and RPP at all points when compared with the baseline. In group A, the mean propofol induction dose (mg) was statistically significantly low as compared with that in groups B and C. ConclusionDexmedetomidine attenuates the hemodynamic stress response to laryngoscopy and intubation more effectively compared with labetalol without any deleterious effects. Furthermore, dexmedetomidine decreases dose of propofol for induction of anesthesia as guided by bispectral index.

Comparison of labetalol versus enalapril as monotherapy in elderly patients with hypertension: Results of 24-hour ambulatory blood pressure monitoring

This study compared the safety and efficacy of labetalol and enalapril as antihypertensive therapy for elderly patients. A randomized, open-label, parallel controlled trial was conducted. After completing a 4-week placebo phase, 79 elderly (65 years or older) patients with an average standing diastolic blood pressure (BP) 95 mm Hg or above and 114 mm Hg or less were randomized to receive a 12-week course of either labetalol or enalapril in an open-label design. The patients' BP and heart rate were evaluated biweekly by trained observers unaware of the treatment status, and drug dosage was titrated (up to 400 mg twice a day of labetalol or 40 mg daily of enalapril) to achieve a standing diastolic BP of less than 90 mm Hg and a decrease of 10 mm Hg from baseline. Patients underwent 24-hour ambulatory BP monitoring (ABPM) at the end of the placebo phase and again after 8 weeks of active treatment. The treatment groups were comparable in their reduction of supine diastolic BP, with no significant differences between the two treatments. Labetalol demonstrated a significantly greater reduction (p less than 0.05) in standing diastolic BP at the end of the titration period compared to enalapril, but this difference was not significant by the end of the study period. Based on 24-hour ABPM readings, labetalol reduced mean 24-hour diastolic BP (p less than 0.05) and mean heart rate (p less than 0.05) more than enalapril. The labetalol-treated patients were significantly less often above their diastolic BP goal throughout the 24-hour ABPM period (p less than 0.01). The two treatments were equally well tolerated. The results indicate that labetalol and enalapril are equally effective in lowering supine diastolic BP in the elderly, but labetalol is more effective in lowering ambulatory BP and heart rate throughout the day.

Comparison of labetalol versus enalapril as monotherapy in elderly patients with hypertension: results of 24-hour ambulatory blood pressure monitoring

purpose: This study compared the safety and efficacy of labetalol and enalapril as antihypertensive therapy for elderly patients. patients and methods: A randomized, open-label, parallel controlled trial was conducted. After completing a 4-week placebo phase, 79 elderly (65 years or older) patients with an average standing diastolic blood pressure (BP) 95 mm Hg or above and 114 mm Hg or less were randomized to receive a 12-week course of either labetalol or enalapril in an open-label design. The patients' BP and heart rate were evaluated biweekly by trained observers unaware of the treatment status, and drug dosage was titrated (up to 400 mg twice a day of labetalol or 40 mg daily of enalapril) to achieve a standing diastolic BP of less than 90 mm Hg and a decrease of 10 mm Hg from baseline. Patients underwent 24hour ambulatory BP monitoring (ABPM) at the end of the placebo phase and again after 8 weeks of active treatment. results: The treatment groups were comparable in their reduction of supine diastolic BP, with no significant differences between the two treatments. Labetalol demonstrated a significantly greater reduction (p <0.05) in standing diastolic BP at the end of the titration period compared to enalapril, but this difference was not significant by the end of the study period. Based on 24-hour ABPM readings, labetalol reduced mean 24-hour diastolic BP (p <0.05) and mean heart rate (p <0.05) more than enalapril. The labetalol-treated patients were significantly less often above their diastolic BP goal throughout the 24-hour ABPM period (p <0.01). The two treatments were equally well tolerated. conclusions: The results indicate that labetalol and enalapril are equally effective in lowering supine diastolic BP in the elderly, but labetalol is more effective in lowering ambulatory BP and heart rate throughout the day.

Comparison of Labetalol and Hydrochlorothiazide in Elderly Patients with Hypertension Using 24‐Hour Ambulatory Blood Pressure Monitoring

The safety and efficacy of labetalol and hydrochlorothiazide (HCTZ) were compared in a group of 34 patients aged 65 years or older with mild to moderate essential hypertension. After a 4-week placebo run-in period, during which all previous antihypertensive medication was discontinued, patients were randomized to receive either labetalol (100 mg bid) or HCTZ (25 mg bid). The patients' blood pressure and heart rate were evaluated biweekly and drug dosage was titrated (up to 400 mg and 50 mg bid of labetalol and HCTZ, respectively) to achieve a standing diastolic blood pressure less than 90 mm Hg. Patients underwent 24-hour ambulatory blood pressure monitoring at the end of the placebo run-in period and again after the 6-week titration period. Both labetalol and HCTZ significantly (P less than .01) reduced standing systolic (-19.4 vs -27.7 mm Hg) and diastolic (-14.0 vs -15.2 mm Hg) blood pressures following 12 weeks of treatment. Both antihypertensives effectively controlled the 24-hour ambulatory blood pressure, however, the labetalol group experienced a significantly lower rate of rise in diastolic blood pressure (P = .02) and mean arterial pressure (P = .02) during the acceleration period (400-1200) compared to the HCTZ group. HCTZ caused significant decreases in serum potassium (P less than .01) and alkaline phosphatase (P less than .05) and increases in uric acid (P less than .01) and urea nitrogen (P = .07). These results indicate that labetalol may offer some unique advantages over thiazide diuretics that may be particularly important in the treatment of elderly patients with hypertension.

Pharmacokinetics, beta‐adrenoceptor blockade and anti‐hypertensive action of labetalol during chronic oral treatment

1 beta-Adrenoceptor blockade, plasma labetalol concentrations and anti-hypertensive actions were investigated at 2 hourly intervals during the interdose period of chronic oral therapy in six hypertensive patients. 2 beta-adrenoceptor blockade varied during the inter-dose period and was maximal 2 and 4 h after the oral dose (P < 0.05). 3 Systolic pressure rose during the interdose period (P < 0.05). A significant correlation was found between the degree of beta-adrenoceptor blockade and the change in systolic pressure at 2 h after the oral dose. 4 Efficacy of labetalol as a beta-adrenoceptor antagonist and anti-hypertensive drug was assessed 2 h after an oral dose during chronic eight hourly dosage in sixteen hypertensive patients. Pharmacokinetics of labetalol were studied in the same patients. 5 Peak plasma labetalol concentration occurred 2 h after the oral dose and subsequently the plasma concentration declined monoexponentially. 6 The steady state concentration (CSS) of labetalol was correlated significantly with the daily oral dose in mg kg-1, the mid point labetalol concentration (Cmax+Cmin) divided by 2 and the isoprenaline dose ratio-1 at 2 h after the oral dose. 7 No correlation was found between the antihypertensive effect and the CSS ng ml-1 labetalol or between the isoprenaline dose ratio-1 and the CSS labetalol ng ml-1.

COMPARISON OF LABETALOL, HYDRALLAZINE, AND PROPRANOLOL IN THE THERAPY OF MODERATE HYPERTENSION

The efficacy of labetalol, an alpha and beta adrenoceptor blocking drug, has been compared with that of placebo, of propranolol alone, of hydrallazine alone, and of hydrallazine plus propranolol in combination in a randomized double-blind, fixed-dose crossover trial. Labetalol (300 mg twice a day) was equally effective with propranolol (80 mg twice a day), and more effective than hydrallazine (50 mg twice a day) alone. The effect of labetalol was comparable with that of hydrallazine plus propranolol when the patient was standing, but less potent with the patient in the supine position. Side effects were few.

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.