Search

Preeclampsia is a pregnancy-specific disorder, and it is a leading cause of maternal and perinatal morbidity and mortality. The application of pharmacogenetics to antihypertensive agents and dose selection in women with preeclampsia is still in its infancy. No current prescribing guidelines from the clinical pharmacogenetics implementation consortium (CPIC) exist for preeclampsia. Although more studies on pharmacogenomics are underway, there is some evidence for the pharmacogenomics of preeclampsia therapies, considering both the pharmacokinetic (PK) and pharmacodynamic (PD) properties of drugs used in preeclampsia. It has been revealed that the CYP2D6*10 variant is significantly higher in women with preeclampsia who are non-responsive to labetalol compared to those who are in the responsive group. Various genetic variants of PD targets, i.e., NOS3, MMP9, MMP2, TIMP1, TIMP3, VEGF, and NAMPT, have been investigated to assess the responsiveness of antihypertensive therapies in preeclampsia management, and they indicated that certain genetic variants of MMP9, TIMP1, and NAMPT are more frequently observed in those who are non-responsive to anti-hypertensive therapies compared to those who are responsive. Further, gene-gene interactions have revealed that NAMPT, TIMP1, and MMP2 genotypes are associated with an increased risk of preeclampsia, and they are more frequently observed in the non-responsive subgroup of women with preeclampsia. The current evidence is not rigorous enough for clinical implementation; however, an institutional or regional-based retrospective analysis of audited data may help close the knowledge gap during the transitional period from a traditional approach (a "one-size-fits-all" strategy) to the pharmacogenomics of preeclampsia therapies., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Asymptomatic severe hypertension (also known as hypertensive urgency) is frequently encountered in the hospital. Previous evidence suggests that management with one-time doses of intravenous (IV) antihypertensives may increase adverse events. Despite this, single-dose treatment remains common in the emergency department and inpatient settings., Methods: This quality initiative was launched at New York City Health + Hospitals, the largest safety net hospital system in the United States. The initiative involved two changes to electronic orders for IV hydralazine and IV labetalol: a nonintrusive advisory statement within the order instructions and a mandatory requirement to document the indication for IV antihypertensive use., Results: This initiative took place from November 2021 to October 2022. Of the indications selected for IV antihypertensive orders, 60.7% were for hypertensive emergency, 15.3% were for patients who were strictly NPO, 21.2% were for other, and 2.8% selected more than one indication. For ED-only encounters, aggregate IV hydralazine and IV labetalol orders per 1,000 patient encounters were 2.53 preintervention and 1.55 postintervention (38.7% reduction, p < 0.001). For inpatient encounters, aggregate IV hydralazine and IV labetalol orders per 1,000 patient-days were 18.25 preintervention and 15.81 postintervention (13.4% reduction, p < 0.001). Similar trends were observed for individual orders of IV hydralazine and IV labetalol. There were significant reductions in 7 of the 11 hospitals in inpatient administration of aggregate IV hydralazine and labetalol orders per 1,000 patient-days., Conclusion: This quality improvement initiative successfully reduced unnecessary IV antihypertensive use in an 11-hospital safety net system., (Copyright © 2023 The Joint Commission. Published by Elsevier Inc. All rights reserved.)

Aim: To compare the blood pressure (BP) lowering effects of labetalol and nifedipine modified release (MR) in hypertensive pregnant women. We also investigated the effect on the heart rate (HR) and determined the proportion of time spent in target., Methods: This was an exploratory study. Women with chronic hypertension taking either labetalol or nifedipine were offered 24-h ambulatory blood pressure monitoring (ABPM). Sleep, wake and drug ingestion times were self-reported. An indirect response model was used to analyse the systolic BP (SBP), diastolic BP (DBP) and HR time-series; the effect of gestation and type of drug was evaluated., Results: Forty-eight women were recruited: 24 in each group. There was no difference in clinical characteristics. In women taking nifedipine there was a positive association between the dose of nifedipine and pre-dose BP p = .002, this was not present in the labetalol group. There was a difference between the drug effects on both the SBP and DBP time-series (p = .014). In comparison to labetalol, there was less variation in day time BP in those women prescribed nifedipine. Women on labetalol spent a larger proportion of time with their DBP below target (<80 mmHg). The HR dynamics were qualitatively different, a stimulatory effect was found with nifedipine compared to an inhibitory effect with labetalol., Conclusion: There are significant and important differences between the BP lowering effects of nifedipine and labetalol. A large randomised control trial is required to investigate the relationship between BP variability and time in target on pregnancy outcomes., (Copyright © 2018 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.)

Objective: To assess the efficacy of labetalol versus nitroglycerin for induction of controlled hypotension during sinus endoscopic surgery., Design: A prospective, double-blind and randomized study., Setting: Carried out in operating room in university hospital., Patients: 60 patients of both sexes, American Society of Anesthesiologists (ASA) physical status I and II, age range from 20 to 60years; scheduled for elective sinus endoscopic surgery under general anesthesia (GA)., Interventions: Patients were divided into two groups (30 each). NTG group received nitroglycerin infusion at a dose of 2-5μg/kg/min, LAB group received labetalol infusion at a dose of 0.5-2mg/min., Measurements: Surgical condition was assessed by surgeon using average category scale (ACS) of 0-5, a value of 2-3 being ideal. In both groups mean arterial blood pressure (MAP) was gradually reduced till the ideal ACS for assessment of surgical condition, the target of ACS was 2-3 or lower., Results: Both studied drugs achieved desired hypotension and improved visualization of surgical field by decreasing bleeding in the surgical site, but ideal surgical conditions were created at mild hypotension (MAP 70-75) in LAB group while same conditions were created at MAP of 65-69mmHg in NTG group. Mean heart rate (HR) was significantly higher in NTG group as compared to LAB group. Blood loss decreased significantly in LAB group., Conclusion: Both labetalol and NTG are effective and safe drugs for induction of controlled hypotension during sinus endoscopic surgery. While, labetalol was better as it offered optimum operative condition with mild decrease in blood pressure, decreased surgical bleeding and less tachycardia during the surgery., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: Labetalol is often used in severe preeclampsia (PE). Hypotension, bradycardia and hypoglycemia are feared neonatal side effects, but may also occur in (preterm) infants regardless of labetalol exposure. We analyzed the possible association between intrauterine labetalol exposure and such side effects., Study Design: From 1 January 2003 through 31 March 2008, all infants from mothers suffering severe PE admitted to one tertiary care center were included. Severe PE was defined according to the International Society for the Study of Hypertension in Pregnancy (ISSHP) criteria. Infants exposed to labetalol in utero (labetalol infants) were compared with infants, who were not exposed to labetalol (controls). Neonatal records were reviewed for hypotension (RR

Rapid lowering of blood pressure can precipitate or worsen ischemic strokes. This usually has been observed in the setting of profoundly lowered pressure and hypotension. We report on six patients in whom ischemic neurologic injury ensued or worsened after moderate reduction of blood pressure by pharmacological treatment. The 6 patients suffered new or worsened ischemic neurologic deficits after receiving oral or intravenous antihypertensive medications, mostly after relatively small doses. Mean arterial blood pressure in these patients was decreased by 25 +/- 7.7%, or 37 +/- 16 mm Hg (mean +/- SD) without resultant hypotension. These cases emphasize the potential hazards of moderate blood pressure reduction by antihypertensive medications in the setting of an acute ischemic stroke or transient ischemic attack (TIA), as well as rapidly treated hypertension even in those who have not yet manifested ischemic symptoms.

Objective: We sought to compare the efficacies of oral nifedipine and intravenous labetalol in the acute management of hypertensive emergencies of pregnancy., Study Design: We performed a randomized double-blind trial of oral nifedipine (10 mg) and intravenous labetalol (20 mg) in 50 peripartum patients with sustained systolic blood pressure of >/=170 mm Hg or diastolic blood pressure of >/=105 mm Hg. Both agents were repeated at sequentially escalating dosages every 20 minutes until a therapeutic goal of systolic blood pressure of <160 mm Hg and diastolic blood pressure of <100 mm Hg was achieved. Crossover occurred if the treatment goal was not achieved after 5 doses. Primary outcome was time to achievement of the therapeutic goal. Secondary outcome variables were agent failure, urinary output, and adverse effects. Data were analyzed by unpaired t test, Mann-Whitney U test, and analysis of variance for repeated measures., Results: The time to achieve the blood pressure goal was significantly shorter with nifedipine (mean +/- SD, 25 +/- 13.6 minutes) than with labetalol (43.6 +/- 25.4 minutes; P =.002). No patients required crossover therapy. Urine output was significantly increased (P <.001) at 1 hour after nifedipine dosing (99 +/- 99 mL) compared with labetalol (44.8 +/- 19.1 mL) and remained significantly increased at 2, 6, 12, 18, and 24 hours after initial administration. Adverse effects were infrequent. There were no differences in maternal age, gestational age, number of antepartum patients, or enrollment blood pressures between groups., Conclusions: Both oral nifedipine and intravenous labetalol are effective in the management of acute hypertensive emergencies of pregnancy; however, nifedipine controls hypertension more rapidly and is associated with a significant increase in urinary output.

Labetalol and hydrochlorothiazide (HCTZ) were compared for their efficacy in controlling hypertension of blacks in a prospective, double-blind study. Sixty-one adult patients with mild to moderate hypertension (standing diastolic blood pressure greater than or equal to 95 mm Hg and less than or equal to 114 mm Hg) were randomly selected to receive either labetalol 100 mg twice daily (n = 30) or HCTZ 25 mg twice daily (n = 31). The study was divided into two phases: a 4-week placebo run-in phase, during which all previous antihypertensive medication was discontinued, and a 12-week drug treatment phase. Labetalol and HCTZ doses were titrated to 400 mg twice and 50 mg twice daily, respectively, during the first 6 weeks of the drug treatment phase for those patients not achieving blood pressure control (standing diastolic blood pressure less than 90 mm Hg and a decrease of 10 mm Hg from baseline) on initial dosages. By the end of the 12 weeks of drug administration, patients on labetalol experienced a mean decrease of 10 mm Hg in standing diastolic blood pressure compared to a mean decrease of 10.1 mm Hg in patients on HCTZ. No differences were observed between the two treatment groups in reductions of either standing blood pressure or heart rate. While 19 of 30 patients on labetalol (63%) achieved blood pressure control at some point during the study with a mean daily dose of 568 mg, 18 of 31 (58%) HCTZ-treated patients achieved control with a mean daily dose of 72 mg.(ABSTRACT TRUNCATED AT 250 WORDS)

A 66-year-old hypertensive woman presented with epigastric and scapular pain on the basis of type 3 aortic dissection. Appropriate therapy with a combined alpha-adrenergic and beta-adrenergic antagonist agent prevented further ongoing dissection and amelioration of symptoms. On day 5, an episode of coronary vasospasm occurred presumably due to beta-blockade with unopposed alpha-adrenergic activity.

The efficacy and the clinical and biological safety of labetalol were assessed, in primary care, in an ambulatory hypertensive elderly population, with systolo-diastolic hypertension (mean 175 +/- 14/100 +/- 7 mmHg) monitored during a 6 month period by general practitioners. Two hundred and sixty six of the 309 patients recruited (86%) completed the study, with satisfactory compliance. Mean blood pressure reduction after six months treatment was 27.6/17.7 mmHg and 25.9/17.4 mmHg (p less than 0.001) supine and standing respectively; and 75 p. cent of the patients who tolerated the treatment had their blood pressure normalized (BP less than 160/95 mmHg) with monotherapy by labetalol, posology ranging from 100 to 200 mg b.i.d. in 9/10th of them. Maximal antihypertensive effect, almost obtained within 4 months of treatment, was equivalent in smokers and non smokers (blood pressure normalization 84% vs 74.4%, p = 0.29) and less in obese patients compared to non obese (68% vs 80%, p less than 0.05). Drug withdrawal rate for side effects was only 7.4 p. cent and clinical and biological tolerance to labetalol was satisfactory in most patients. This 6 month survey in primary care confirmed the efficacy of monotherapy by labetalol in elderly hypertensive patients, and good compliance to treatment with a drug well tolerated in this population.

A 64-yr-old asthmatic patient underwent a two-vessel aortocoronary vein grafting. Before surgery, the patient received cimetidine 400 mg and labetalol 650 mg. During the first 60 min of bypass, hypotension (40-45 mm Hg) was observed in spite of phenylephrine 14 mg. This initial hypotension was followed, during rewarming, by a slow increase in arterial pressure to 150 mm Hg. On cessation of bypass, bronchospasm was observed and was protracted. It is assumed that labetalol clearance and metabolism were reduced by cimetidine, that labetalol alpha-antagonism was responsible for the vasodilatation withstanding the phenylephrine, and that a combination of labetalol beta-antagonism and phenylephrine alpha-agonism initiated the bronchospasm. These observations indicate that, after labetalol therapy, higher doses of vasopressor agents such as phenylephrine may be necessary, but that such therapy may lead to bronchospasm in asthmatic patients.

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.

Elevated blood pressure can be lowered safely in the vast majority of patients by selecting the single drug most likely to be efficacious in that patient. Skillful management with full knowledge of drug pharmacology should provide the patient with the maximum opportunity to benefit from normalization of blood pressure while at the same time having little or no impact on quality of life.

The antihypertensive effect of labetalol was evaluated in 18 adult black patients with mild to moderate essential hypertension previously controlled with a combination of a diuretic and a beta blocker. After a 4-week washout period, standing blood pressure had increased from 138 +/- 2.2/85 +/- 1.5 mmHg, (mean +/- SEM) to 154 +/- 1.9/100 +/- 0.6 mmHg. Labetalol was then titrated to a maximum of 600 mg BID to obtain a standing diastolic blood pressure of less than or equal to 90 mmHg and/or a decrease of greater than or equal to 10 mmHg from baseline (end of washout period). By the end of the labetalol titration period, standing blood pressure had decreased to 140 +/- 2.0/84 +/- 1.5 (p less than 0.01). Following a 2-week maintenance period, standing blood pressure was 136 +/- 1.6/80 +/- 1.5 mmHg (NS vs. titration). Labetalol therapy was well tolerated and reduced diastolic blood pressure to less than or equal to 90 mmHg in 17 of 18 patients, 13 of whom required dosages less than or equal to 300 mg BID. The average reduction in standing heart rate while on labetalol was 4 bpm (p less than 0.01). Side effects were limited to skin rash in one patient and possible mild urinary retention in another. These data indicate that labetalol is an effective antihypertensive for black patients with mild to moderate essential hypertension.

Labetalol is a unique alpha- and beta-adrenergic-receptor blocking agent that has recently been approved for the treatment of hypertensive emergencies and urgencies. This agent lowers peripheral vascular resistance by vasodilatation with little or no effect on cardiac output. The method of administration of labetalol will be determined by the particular hypertensive emergency. Rapid reduction in blood pressure within 5 minutes follows the administration of a bolus injection of 1.0-2.0 mg/kg, whereas smaller minibolus injections of labetalol are associated with a more gradual reduction in blood pressure. Labetalol may also be administered by continuous incremental infusion for smooth control of blood pressure. The convenience and safety of labetalol makes this agent a valuable addition to our therapeutic armamentarium for the treatment of hypertensive urgencies or emergencies.

The antihypertensive effect of oral labetalol and propranolol were evaluated in 65 black and 75 white patients with mild to moderate hypertension (standing diastolic blood pressure (StDBP) of 90-115 mmHg) in a double-blind multicenter clinical trial. Following a 4-week placebo phase, labetalol (n = 70) or propranolol (n = 70) was randomly assigned. During a 5-week titration phase, labetalol could be increased from 100 mg BID to 600 mg BID to achieve a StDBP of less than 90 mmHg and a decrement of greater than or equal to 10 mmHg. Propranolol could be titrated from 40 to 240 mg BID. A 3-month maintenance phase was followed by an optional 8-month maintenance phase. Hydrochlorothiazide (HCTZ) could be added at any time during the maintenance phase. Supine and standing blood pressures were measured at each visit. Statistical analysis revealed significant (ANOVA, p less than 0.05) treatment by race effects. Therefore, the treatment groups were stratified retrospectively by race. This study demonstrated that labetalol is equally effective in white and black patients, whereas, propranolol is significantly (p less than 0.05) more effective in white than in black patients. Moreover, labetalol is significantly more effective than propranolol in lowering the standing systolic/diastolic blood pressure of black patients (p less than 0.02/p less than 0.001). These blood-pressure effects were accompanied by a significantly greater (p less than 0.04) reduction in heart rate with propranolol. Furthermore, significantly more (p less than 0.05) black patients treated with propranolol compared to those treated with labetalol required the addition of a diuretic for control of their blood pressure.

Urgent hypertension is defined by severe elevations of blood pressure without associated end-organ damage. The use of parenteral agents for this entity entails intensive monitoring and the potential for significant hemodynamic complications. Therefore, various oral regimens have been studied. Herein described are mechanisms of action, pharmacokinetics, clinical efficacy, and side effects of oral agents used in the treatment of urgent hypertension.

In a randomized study, labetalol-induced hypotension and nitroprusside-induced hypotension were compared in 20 patients (10 in each group) scheduled for major orthopedic procedures. Each patient was subjected to an identical anesthetic protocol and similar drug-induced reductions in mean arterial blood pressure (BP) (50 to 55 mmHg). Nitroprusside infusion was associated with a significant (p less than 0.05) increase in heart rate and cardiac output; rebound hypertension was observed in three patients after discontinuation of nitroprusside. Labetalol administration was not associated with any of these findings. Arterial PO2 decreased in both groups. It was concluded that labetalol offers advantages over nitroprusside.

Severe hypertension may be a difficult management issue, and it often requires therapy with multiple drugs at frequent dosing intervals. We report on the antihypertensive effects of the alpha-beta adrenergic blocking agent, labetalol, in combination with enalapril, a long-acting angiotensin-converting enzyme inhibitor, administered to 14 patients with severe hypertension (nine of whom had nephrosclerosis or renal artery stenosis) on other antihypertensive drug therapies. Blood pressure (BP), heart rate (HR), hematologic and blood chemistry values, and adverse side effects were monitored at 24 hours, 1 week, and 4 weeks of therapy. Rapid titration of the drugs was performed in the hospital in 10 patients; four were managed closely as outpatients. Following one month of combination therapy blood pressure decreased from 212 +/- 31/120 +/- 16 mm Hg at baseline to 155 +/- 19/86 +/- 12 mm Hg, and heart rate declined from 86 +/- 18 bpm to 70 +/- 16 bpm. Ten of the 14 patients (71%) maintained good BP control (BP less than 140/90 mm Hg) with no additional treatment. Serum potassium, creatinine, blood urea nitrogen concentrations, and hematologic parameters did not significantly change in 13 of 14 patients. Three patients developed symptomatic postural hypotension; in one patient this side effect resulted in discontinuation from the study. These data suggest that combination therapy with labetalol and enalapril is effective in lowering BP in patients with severe essential or renovascular hypertension. An additional advantage of this regimen is the twice-daily dosing interval, which may promote better long-term compliance.