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Biomedical subjects

Brian F McBride

Publications and source records attributed to Brian F McBride.

16 recordsLinked to original sources
PubMed2006

Ranolazine in the management of chronic stable angina.

PURPOSE: A review of the pharmacology, pharmacokinetics, clinical trials, safety, and efficacy of ranolazine is presented. SUMMARY: Ranolazine has recently been approved as adjunctive treatment for chronic stable angina (CSA). Data suggest that ranolazine exerts its antiischemic effect through antagonism of the late sodium current and other cardiac ion channels. Peak plasma levels of ranolazine have been observed two to five hours following repeated dosing and are unaffected by food. In placebo-controlled and active-controlled clinical trials conducted with ranolazine, ranolazine has been effective in the treatment of patients with CSA. One trial demonstrated that monotherapy with extended-release ranolazine was effective against angina and ischemia in patients with CSA. Ranolazine improved exercise duration and time to onset of angina. In a trial in which ranolazine was given in combination with atenolol, diltiazem, or amlodipine, ranolazine produced clinically significant improvement in exercise duration and reduced the incidence of anginal attacks compared with placebo. Another trial demonstrated that extended-release ranolazine 1000 mg given twice daily reduced mean weekly angina episodes in patients with chronic angina. Ranolazine is generally well tolerated. In clinical trials, adverse effects were seen more in the ranolazine groups than in the placebo groups. CONCLUSION: Despite a lack of mortality data, ranolazine has demonstrated its efficacy and safety, either as monotherapy or in combination with other antianginal agents, in the management of CSA. Patients who fail optimal therapy with standard-of-care antianginal agents are the best candidates for treatment with ranolazine.

Acetanilides↗
PubMed2006

An evaluation of the impact of oral magnesium lactate on the corrected QT interval of patients receiving sotalol or dofetilide to prevent atrial or ventricular tachyarrhythmia recurrence.

BACKGROUND: Intravenous magnesium reduces the QTc interval of patients receiving ibutilide. Whether oral magnesium can reduce the QTc interval associated with oral sotalol and dofetilide is not known. This study was undertaken to evaluate the impact of oral magnesium on the QTc interval and whether an inherent intracellular magnesium deficiency exists among patients with arrhythmias. METHODS: Participants receiving sotalol or dofetilide for atrial or ventricular arrhythmias were randomized to receive magnesium l-lactate (504 mg elemental magnesium daily, Niche Pharmaceuticals, Roanoke, TX) or placebo for 48 hours. A 12-lead electrocardiogram (ECG) was obtained at baseline, 3 hours, and 51 hours after dosing to correspond to the Tmax after oral ingestion. The QTc interval was measured from the ECGs and compared between groups. Intracellular magnesium concentrations were determined by energy-dispersive x-ray analysis at baseline and 51 hours after dosing (Intracellular Diagnostics, Inc., Foster City, CA). RESULTS: The QTc interval reductions from baseline were greater in the magnesium group than placebo at 3 and 51 hours (P = 0.015 and P < 0.001, respectively). Sixty-three percent of patients (regardless of experimental group) had baseline intracellular magnesium concentrations below the normal reference range of 33.9-41.9 mEq/IU, with an average level of 32.6 +/- 2.2 mEq/IU. CONCLUSIONS: Oral magnesium l-lactate raises intracellular magnesium concentrations and lowers the QTc interval of patients receiving sotalol or dofetilide.

Administration, Oral↗
PubMed2005

Hemodynamic impact of an ephedra-free multicomponent weight-loss supplement.

PURPOSE: The effect of Metabolife Ephedra-Free on blood pressure (BP) and hemodynamics was studied. METHODS: Healthy volunteers were randomly assigned to take a single dose of Metabolife Ephedra-Free or matching placebo and then crossed over to the opposite treatment after a seven-day washout period. BP was measured at baseline and one, three, and five hours after administration. Cardiac index, systemic vascular resistance index (SVRI), and total thoracic fluid content were determined in a subgroup of subjects. RESULTS: Twenty patients (mean +/- S.D. age, 24.8 +/- 1.9 years) completed the study. No significant differences in systolic or diastolic BP were found between the Metabolife Ephedra-Free and placebo groups. In the subgroup (n = 8), SVRI was higher (but not significantly so) in the Metabolife Ephedra-Free group than in the placebo group at one hour (2162.5 +/- 421.1 versus 1934.6 +/- 344.2 dyn x sec x cm(-5) x m(2)); the difference was significant at five hours (1981.6 +/- 293.3 versus 1765.1 +/- 340.3 dyn x sec x cm(-5) x m(2)). CONCLUSION: Single doses of Metabolife Ephedra-Free did not affect BP in healthy young volunteers. SVRI did not exceed the normal range but was elevated at five hours compared with SVRI in placebo recipients.

Adult↗
PubMed2005

The impact of catecholamines on defibrillation threshold in patients with implanted cardioverter defibrillators.

OBJECTIVES: To determine the effect of physiologic catecholamine concentrations on the defibrillation threshold (DFT) in patients with implanted cardioverter defibrillators. BACKGROUND: DFT is the minimum energy delivered by an implanted cardioverter defibrillator that successfully converts ventricular fibrillation. DFT testing is performed under conscious sedation. Since activities of daily living enhance sympathetic tone substantially over these nadir levels, it is important to explore the impact of catecholamines on DFT. METHODS: In this double-blind study, we determined DFT by the step-down method. Patients (n = 50) were stratified by beta-blocker use and then randomized to a 7-minute infusion of epinephrine, norepinephrine, or placebo. After study infusion, DFT testing was repeated. Changes in DFT with different study medications were compared. Subgroup analyses of the effects of catecholamines on DFT, based on beta-blocker use, were also performed. RESULTS: Norepinephrine reduced DFT from baseline measurements by 22.6% (P = 0.008). Neither epinephrine nor placebo impacted DFT (P = 0.999, P = 0.317, respectively). In the subgroup analyses, DFT was reduced with norepinephrine regardless of beta-blocker use, while epinephrine reduced DFT among those receiving beta-blockers. No change in DFT was observed in either of the placebo subgroups. CONCLUSIONS: Elevation of plasma norepinephrine concentrations reduces the DFT, while elevations in epinephrine had no effect. Norepinephrine seems to reduce DFT regardless of beta-blocker therapy but epinephrine's effects are beta-blocker dependent.

Adrenergic beta-Antagonists↗
PubMed2005

The impact of catecholamines in patients with or without beta-blockers on the ventricular fibrillation cycle length and ventricular fibrillation cycle length variability.

OBJECTIVES: To evaluate the impact of epinephrine, norepinephrine, or placebo on the ventricular fibrillation cycle length (VFCL) and the variability of VFCL (cvVFCL) measurements in implantable cardioverter defibrillator (ICD) patients with or without beta-blockers. METHODS: Forty-three patients scheduled for their 6-week post-ICD placement noninvasive electrophysiologic study were included in the study at the Arrhythmia Procedure Laboratory at Hartford Hospital, Hartford, CT. This randomized, double-blind, placebo-controlled evaluation was approved by the Hartford Hospital Institutional Review Board. RESULTS: After 2 seconds of continuous VF, 7 consecutive VFCLs were measured from the ICD device recording printout using a 0.5 mm scale ruler under magnification at baseline and after the infusion of catecholamines (epinephrine or norepinephrine at 2 mcg/min) or matching placebo at steady state. The average VFCL and the cvVFCL were determined for each study phase. Subgroup analysis based on chronic beta-blocker use was performed. No between-group differences were noted for epinephrine, norepinephrine, or placebo group for baseline (P=0.538) or postinfusion VFCL (P=0.749) or for baseline (P=0.561) or postinfusion cvVFCL (P=0.623) Regardless of catecholamine group randomization, longer pre- and postinfusion VFCL were noted in those receiving beta-blockers (P=0.157, P=0.019) but no differences in cvVFCL were noted (P=0.216, P=0.474) versus those without beta-blockers, respectively. CONCLUSION: Moderately dosed epinephrine or norepinephrine does not affect either VFCL or the variability of VFCL after short duration of ventricular fibrillation. Chronic cardioselective beta-blockade prolongs VFCL without any impact on coefficient of variation of VFCL.

Adrenergic alpha-Agonists↗
PubMed2005

Critical differences among beta-adrenoreceptor antagonists in myocardial failure: debating the MERIT of COMET.

In the United States, carvedilol and metoprolol (tartrate or succinate) are the most commonly employed beta-adrenoreceptor antagonists for the treatment of heart failure. However, use of these agents in patients with heart failure remains extremely low despite overwhelming evidence of their beneficial short- and long-term effects. Because the myocardial pathophysiology associated with heart failure involves not only beta-1 adrenoreceptors but also beta-2 and alpha-1 adrenoreceptors, this indicates a more complex disease process that may require pan-receptor antagonism to provide optimal clinical benefit. Relative to metoprolol (tartrate or succinate), carvedilol represents an extremely complex molecular entity that not only possesses the ability to antagonize all of the principle adrenoreceptors involved in heart failure but also reduces oxidative stress and provides an antiarrhythmic benefit independent of beta-adrenoreceptor antagonism. Taken together, an interesting pharmacologic premise for the superiority of carvedilol relative to metoprolol (tartrate) may exist, but the lack of clinical trials comparing an optimal dose of either extended-release metoprolol (ie, succinate) or immediate-release metoprolol (ie, tartrate) to carvedilol limits the clinical application of the pharmacologic differences between the agents.

Adrenergic beta-Antagonists↗
PubMed2005

A preliminary assessment of the critical differences between novel oral anticoagulants currently in development.

Chronic anticoagulation represents a clinical conundrum for the health care community that balances unquestionable morbidity and mortality benefits against interindividual variability, leading to drug interactions, adverse events, and thromoembolic events related to underdosing. Despite the growing data regarding the appropriate use and dosing of agents used for chronic anticoagulation, use in clinical practice remains low, thus leading to a theoretical reduction in the risk-to-benefit ratio in the clinical setting relative to that reported in the literature. Oral anticoagulants currently in development represent a heterogeneous group of compounds that are specific for the final common pathway in the coagulation cascade and show indications toward a reduced drug interaction profile, reduced interpatient variation in pharmacokinetic parameters, and morbidity and mortality benefits that might be similar to currently available treatment modalities. This review highlights the critical differences among oral anticoagulants in development and places their role in the context of the benefits and limitations of currently available anticoagulants.

Administration, Oral↗
PubMed2005

Electrocardiographic effects of an Ephedra-Free, multicomponent weight-loss supplement in healthy volunteers.

STUDY OBJECTIVE: Metabolife 356, an ephedra-containing weight-loss product, substantially increases the corrected QT (QTc) interval. Metabolife Ephedra Free, a similar supplement, contains caffeine and extracts of green tea, garcinia cambogia, and yerba mate. Its electrocardiographic (ECG) effects are not known. Therefore, we sought to determine the effect of this supplement on the QTc interval. DESIGN: Randomized, double-blind, placebo-controlled, crossover study. SETTING: University of Connecticut, Storrs Campus. SUBJECTS: Twenty healthy volunteers. Intervention. A single capsule containing half the normal recommended dose of Metabolife Ephedra Free or matching placebo was administered in crossover fashion, with a 7-day washout period between treatments. MEASUREMENTS AND MAIN RESULTS: Baseline and three postdose ECG measurements were obtained, and QTc intervals were measured over a 5-hour study period. No significant differences in the QTc interval or other ECG variables were observed between the Metabolife Ephedra Free and placebo groups. CONCLUSION: At half the recommended single dose, Metabolife Ephedra Free does not affect the QTc interval or other ECG variables over 5 hours. Dose-response studies and studies of longer duration should be conducted.

Adult↗
PubMed2004

Electrocardiographic and hemodynamic effects of a multicomponent dietary supplement containing ephedra and caffeine: a randomized controlled trial.

CONTEXT: Metabolife 356, a multicomponent dietary supplement containing ephedra and caffeine (DSEC) in addition to several other components, is the top-selling dietary weight loss supplement. Given its common use, anecdotal reports of cardiovascular and cerebrovascular adverse events, and paucity of safety data, further research with this DSEC was warranted. OBJECTIVE: To determine the impact of the DSEC on corrected QT (QTc) interval duration and systolic blood pressure (SBP). DESIGN: Randomized, double-blind, placebo-controlled, crossover study conducted from January to May 2003. SETTING AND PARTICIPANTS: Fifteen healthy volunteers (mean [SD] age, 26.7 [2.52] years; weight, 72.7 [14.93] kg), 6 (40%) of whom were women, recruited from the University of Connecticut, Storrs campus. INTERVENTION: A single dose of the DSEC (containing 19 ingredients including ephedra [12 mg] and caffeine [40 mg]) or matching placebo were administered in a crossover fashion with a 7-day washout period between treatments. MAIN OUTCOME MEASURES: Maximal QTc interval and SBP assessed at 1, 3, and 5 hours after dosing for the DSEC relative to placebo. RESULTS: Individuals receiving the DSEC had a longer maximal QTc interval (mean [SD], 419.4 [11.8] vs 396.1 [15.7] milliseconds; P<.001) and higher SBP (mean [SD], 123.5 [10.98] vs 118.93 [9.62] mm Hg; P =.009) compared with placebo. Participants who received the DSEC were more likely to experience a QTc interval increase of at least 30 milliseconds vs placebo (8 individuals [53.3%] vs 1 individual [6.7%]; relative risk, 2.67 [95% confidence interval, 1.40-5.10]). There were no significant sex-related differences. CONCLUSIONS: The ephedra- and caffeine-containing dietary supplement Metabolife 356 increased the mean maximal QTc interval and SBP. Since the actual ingredient or ingredients in Metabolife 356 responsible for these findings are not known, patients should be instructed to avoid this and similar dietary supplements until more information is known about their safety.

Adult↗
PubMed2004

Inappropriate implantable cardioverter defibrillator discharge following consumption of a dietary weight loss supplement.

This report describes the clinical course of a 40-year-old female who experienced repetitive ICD firing after consuming Metabolife 356, a multicomponent dietary weight loss supplement. Following the initiation of Metabolife 356, the patient experienced four shocks over a 3 day period with two 30 J shocks being delivered sequentially. Interrogation of the device revealed atrial tachycardia with 1:1 AV conduction at a rate of 240 beats/min. Metabolife 356 was discontinued and the dosage of sotalol was increased to 120 mg twice daily without recurrence of ICD discharge.

Adult↗
PubMed2004

Anemia management in heart failure: a thick review of thin data.

Heart failure is defined as the inability of the heart to pump blood at an amount sufficient to meet the metabolic needs of the body. In heart failure, the inability to meet the body's metabolic needs is based on hemodynamic derangement and suboptimal oxygen-carrying capacity of the blood itself. Current pharmacologic therapy attempts to improve survival and reduce symptomatology by optimizing hemodynamics to increase oxygen delivery, but does not address oxygen-carrying capacity. Unfortunately, there is a high prevalence of anemia in patients with heart failure, which compromises oxygen-carrying capacity, is an independent predictor of mortality, and may be caused in part by pharmacologic agents that confer morbidity and mortality benefits in this population. Recombinant human erythropoietin supplementation improves the functional capacity of the failing myocardium, reverses and antagonizes the detrimental remodeling induced by autoimmune activity, and may reduce mortality and morbidity among patients receiving maximal pharmacologic therapy for heart failure. However, limited clinical data prohibit widespread recommendations for its use in patients with heart failure.

Anemia↗
PubMed2003

Levosimendan: implications for clinicians.

Levosimendan is a novel calcium sensitizing agent in development for the treatment of acute and chronic heart failure. The agent increases myocardial force without increasing myocyte calcium concentrations, thus reducing the possibility for myocardial necrosis. In addition, the agent also causes vasodilation of coronary and peripheral vessels to improve coronary blood flow and reduce afterload. The short half-life is a benefit for intravenous administration but could be problematic for the drug's use in chronic heart failure. The risk of the development of arrhythmias from levosimendan appears small secondary to an increase in the QTc interval of 15 msec but needs to be evaluated in light of the ability of levosimendan to open adenosine triphosphate (ATP)-sensitive potassium channels. In addition, the agent has not been studied in patients with additional risks for torsades de pointes. Levosimendan has been shown to have beneficial survival effects in several populations; its use improves patient outcomes relative to the standard of care and has the potential to reduce hospital costs associated with heart failure.

Calcium↗
PubMed2003

Nicardipine to control neonatal hypertension during extracorporeal membrane oxygen support.

OBJECTIVE: To describe the clinical course of a newborn (gestational age 38 wk, 6 d) administered intravenous nicardipine to control hypertension while on extracorporeal membrane oxygen (ECMO) support. SETTING: Urban, university teaching hospital. CASE SUMMARY: A 1-day-old male neonate presenting with a left congenital diaphragmatic hernia developed a sustained elevation in blood pressure following a change of ECMO tubing. After several unsuccessful treatment regimens, nicardipine was started at a rate of 0.5 micro g/kg/min and aggressively titrated to 1.5 micro g/kg/min. Nicardipine produced a sustained antihypertensive effect that was noticed 8 hours after the start of the infusion. The infusion was continued through postoperative day 2. Following a second circuit change, nicardipine was discontinued and sodium nitroprusside therapy was started. Treatment with nitroprusside failed to lower the blood pressure. DISCUSSION: Nicardipine is an effective antihypertensive agent for neonates receiving ECMO therapy. However, the expanded volume of distribution caused by the ECMO circuit may result in a reduced serum concentration and a reduced antihypertensive effect. CONCLUSIONS: We recommend a conservative initial dose of nicardipine of 0.5 micro g/kg/min that is aggressively titrated to reduce blood pressure effectively in neonates receiving ECMO therapy.

Antihypertensive Agents↗
PubMed2003

Acute decompensated heart failure: a contemporary approach to pharmacotherapeutic management.

Hospital admissions for acute decompensated heart failure (ADHF) have increased precipitously during the past few decades and are projected to continue to increase in the future. To optimize patient outcomes and reduce the costs associated with this disorder, evidenced-based pharmacotherapy is essential. Continuous infusions of loop diuretic therapy rather than bolus dosing may enhance efficacy and reduce the extent of diuretic resistance. Nesiritide is a pharmacologically novel preload and afterload reducer but based on clinical trial evidence should be reserved for those unable to take or with resistance to intravenous nitrate therapy. Catecholamine- and phosphodiesterase-based inotropic therapies are efficacious, but the increased risk of arrhythmogenesis and the potential for negative survival effects limit their use. The experimental agent levosimendan is a positive inotropic agent but does not increase myocyte calcium concentrations as do catecholamines or phosphodiesterase inhibitors. Clinical trial evidence demonstrates a positive survival benefit for levosimendan versus dobutamine.

Acute Disease↗