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Both calcium channel blockers (CCBs) and β blockers (BBs) are associated with fatal substance exposures within the United States. Cases of overdose with these agents have the potential to be both complex and difficult to manage. A variety of pharmacologic treatment options are available for clinicians to use to help mitigate harm from these poisonings. Hyperinsulinemic‐euglycemic therapy (HIET) was once regarded as a last‐ditch effort to treat patients in highly refractory cases. In recent years, this therapy has become a routine therapy in the treatment of CCB/BB overdose. This article provides a literature review regarding HIET in cases of overdose with CCB and BB agents. Relevant literature articles from 1997–2018 were identified and reviewed using the PubMed and Embase databases. The following search terms were used to identify potential articles: "hyperinsulinemic‐euglycemic therapy," "overdose," "calcium channel blocker," "beta blocker," and "insulin." Articles published in the English language were included in this review. A manual search of reference lists was also conducted. Much of the literature is limited to case reports, series, retrospective chart reviews, and small prospective studies. The success rate observed in published case series ranged from 80.4–100%. Regular insulin is most commonly dosed at an initial bolus of 1 unit/kg followed by a regular insulin infusion of 0.5–1 unit/kg/hour. Euglycemia is often maintained using intravenous fluids containing dextrose. Hyperinsulinemic‐euglycemic therapy exhibited a promising safety profile, provided close monitoring is conducted. More research is needed to determine optimal strategies for maintaining euglycemia, ideal monitoring parameters, and consistent efficacy goals. [ABSTRACT FROM AUTHOR]

Cocaine abuse is associated with cardiovascular complications that include chest pain and myocardial infarction. Traditional therapy for these conditions includes a β-adrenergic antagonist. However, guidelines released in 2008 recommended against this treatment option because of the prevailing theory that cocaine will potentiate vasospasm secondary to unopposed α-adrenergic effects. Subsequently, further evidence and updated guidelines have become available, debunking this claim. Current literature is limited but suggests that β-adrenergic antagonists are harmful. Although case reports support a detrimental effect of β-adrenergic antagonists, the anecdotal data are inconsistent, and the conclusions from case studies are overruled by larger studies. The pharmacology, pathophysiology, and literature on the use of β-adrenergic antagonists in association with cocaine are reviewed. Future studies that focus on outcomes and different pharmacologic profiles of β-adrenergic antagonists are needed. [ABSTRACT FROM AUTHOR]

Rational use of phosphodiesterase inhibitors represents an ongoing controversy in contemporary pharmacotherapy for heart failure. In randomized clinical trials, phosphodiesterase inhibitors increased cardiac output at the expense of worsening the rates of sudden cardiac death and cardiovascular mortality. Preliminary findings from ongoing clinical and preclinical investigations of phosphodiesterase activity suggest that combined use of phosphodiesterase inhibitors with β-adrenergic antagonists may prevent these adverse outcomes. Compartmentation of cyclic adenosine 3',5'- monophosphate signaling may prove critical in determining myocardial response to combination therapy. [ABSTRACT FROM AUTHOR]

The role of β-blockers in uncomplicated hypertension has been challenged recently. Compared with other antihypertensives, β-blockers are less effective for preventing cardiovascular events in patients with uncomplicated hypertension. Moreover, a recent meta-analysis of placebo-controlled clinical trials concluded that atenolol is not more efficacious than placebo for preventing cardiovascular events in patients with hypertension. Although these agents lower blood pressure measured conventionally over the brachial artery with a blood pressure cuff, they do not exert a commensurate effect on blood pressure in the central aorta. Central aortic blood pressure and aortic augmentation index are strong predictors of left ventricular hypertrophy, an independent risk factor for cardiovascular events. Emerging data are illuminating the antihypertensive paradox whereby antihypertensive agents may elicit discordant effects on central and peripheral blood pressure and hemodynamics. Vasodilatory antihypertensives, such as renin-angiotensin-aldosterone system inhibitors and calcium channel blockers, elicit reductions in central aortic blood pressure equal to or greater than that in the brachial artery. Conversely, β-blockers lower central aortic blood pressure to a lesser degree even when blood pressure measured by sphygmomanometry is reduced substantially. Given the strong relationship between central aortic blood pressure and target organ damage, the effectiveness of β-blockers may be overestimated in practice on the basis of conventional blood pressure measurements alone. Differences in central and peripheral blood pressure may account for the lack of cardiovascular protection afforded by [B-blockers in clinical trials and could account for a portion of the apparent "benefit beyond blood pressure" reduction with other classes of antihypertensive agents. Future studies should aim to better clarify the role of central aortic blood pressure in the treatment of hypertension. In the meantime, the effects of antihypertensive drugs on blood pressure "beyond the brachial blood pressure cuff" should be considered when prescribing antihypertensive agents for a patient. [ABSTRACT FROM AUTHOR]

Study Objective. To determine whether β-blocker dose influences cardiac collagen turnover and the effects of spironolactone on cardiac collagen turnover in patients with heart failure. Design. Prospective clinical study. Setting. Two heart failure centers. Patients. Eighty-eight spironolactone-naive patients with heart failure who were taking β-blockers. Intervention. In a subset of 29 patients, spironolactone was started at 12.5 mg/day, with the dosage titrated to 25 mg/day if tolerated. Measurements and Main Results. Venous blood samples were collected from each patient. Serum procollagen type I and type III aminoterminal peptides (PINP and PIIINP) were determined by radioimmunoassay and compared between the 25 patients receiving low doses (< 50% of recommended target dose) and the 63 patients receiving high doses (< 50% of recommended target dose) of β-blockers. Patients receiving low-dose β-blockers had higher mean ± SD PIIINP concentrations (6.6 ± 3.5 vs 4.9 ± 2.6 µg/L, p=0.03) and tended to have higher PINP concentrations (74.0 ± 44.1 vs 57.1 ± 28.6 µg/L, p=0.10) compared with those receiving high doses. A repeat blood sample was collected from the 29 patients who received spironolactone after 6 months of therapy. Changes in procollagen peptides also were compared in this subset between low-dose (9 patients) and highdose (20 patients) β-blocker groups. Low β-blocker doses were associated with greater reductions in concentrations of PINP (median [intraquartile range] -14.3 µg/L [-9.8 to -19.3 µg/L] vs -2.5 µg/L [5.9 to -9.8 µg/L], p=0.02) and PIIINP (-1.4 µg/L [-0.9 to -2.4 lag/L] vs 0.1 lag/L [0.9 to -1.3 µg/L], p=0.045) with spironolactone therapy than high β-blocker doses. In addition, 100% of the patients in this subset taking 10w-dose β-blockers versus only 35% taking higher doses had reductions in both markers of cardiac fibrosis, Conclusion, Spironolactone may benefit patients with heart failure who cannot tolerate upward titration of 13-blocker dosages, its effects on cardiac remodeling. [ABSTRACT FROM AUTHOR]

Study Objective. To determine the rates of hospitalizations and emergency department (ED) visits during cardioselective and nonselective β-blocker therapy in patients with asthma and/or chronic obstructive pulmonary disease (COPD). Design. Retrospective, observational cohort study. Data Source. Electronic medical records database. Patients. A total of 11,592 adult patients with asthma and/or COPD, identified from August 1, 1997-December 31, 2005, who were taking β-blockers for at least 30 days or had never received a β-blocker (controls). Measurements and Main Results. Of these patients, 3062 were taking cardioselective and 690 nonselective β-blockers; 7840 were controls. The primary end point for the β-blocker groups was the rate of hospitalizations and ED visits/patient-year of β-blocker therapy relative to the control group. In patients with asthma with or without concomitant COPD, cardioselective β-blockers were associated with a relative risk of 0.89 (95% confidence interval [CI] 0.53-1.50) for hospitalizations and 1.40 (95% CI 1.20-1.62) for ED visits compared with controls. Nonselective β-blockers were associated with a relative risk of 2.47 (95% CI 1.37-4.48) for hospitalizations and 1.21 (95% CI 0.91-1.62) for ED visits. In patients with COPD only, cardioselective β-blockers were associated with a relative risk of 0.64 (95% CI 0.43-0.96) for hospitalizations and 1.19 (95% CI 1.02-1.39) for ED visits. Nonselective β-blockers were associated with a relative risk of 1.02 (95% CI 0.52-2.02) for hospitalizations and 0.51 (95% CI 0.33-0.80) for ED visits. Conclusion. In patients with asthma with or without COPD, both cardioselective and nonselective β-blocker use increased hospitalizations and ED visits compared with controls. Thus, these patients should receive β-blocker therapy only if their cardiac risk exceeds their pulmonary risk and if they have concomitant cardiac disease for which β-blockers decrease mortality, such as previous acute myocardial infarction or chronic heart failure. In patients with COPD only, cardioselective β-blockers slightly increased the risk of ED visits but reduced the risk of hospitalizations. Nonselective β-blocker therapy in these patients reduced the rate of ED visits and total visits. These findings suggest a larger safety margin with β-blocker therapy in patients with COPD only than in those with asthma with or without COPD. [ABSTRACT FROM AUTHOR]

Treatment with β-blockers is recommended to achieve and maintain adequate blood pressure control in patients with hypertension, and these agents have been shown to decrease cardiovascular risk factors in patients with both hypertension and type 2 diabetes mellitus. However, β-blocker therapy also may worsen glycemic and lipidemic control and may lead to microalbuminuria. A recent study showed a better metabolic profile with carvedilol than with metoprolol in patients with both type 2 diabetes and hypertension in the presence of renin-angiotensin system blockade. This beneficial effect on metabolic components has been proposed as attributable to carvedilol's α-blocking effects or antioxidant properties. In this article, the pathophysiology of hypertension and type 2 diabetes and the association between them are reviewed, the pharmacologic properties of carvedilol are discussed, and clinical studies in the literature comparing carvedilol with selective β-blockers in patients with both type 2 diabetes and hypertension are identified and evaluated. This information should be useful to practitioners when selecting the optimum β-blocker for treating hypertension in patients with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Study Objective. To explore reasons for discrepancies between findings from case reports and those from a meta-analysis of randomized controlled trials regarding the association between β-adrenergic blockers and depression. Design. Systematic review. Data Source. PubMed/MEDLINE database. Measurements and Main Results. We reviewed 24 published case reports showing an association between β-blockers and depression and eight randomized controlled trials included in a recta-analysis of the adverse effects of these drugs. We abstracted the β-blocker taken, patients' age and sex, diagnoses, history of depression, type of depressive symptoms reported, and method and timing of the assessment of depression. Naranjo criteria were used to evaluate the strength of evidence from each case report for a possible association between β-blockers and depression. Twelve case reports had a Naranjo score of 5 or more (suggesting a likely causal relationship), nine of which involved propranolol. In all nine, depression began soon after treatment, and in four, the patient had a history of depression. Three randomized controlled trials assessed propranolol. Depression rates in the control groups of these studies differed substantially from each other (0-40%, p<0.0001). In only one randomized controlled trial did investigators assess depression systematically; they evaluated depression after 1 year of treatment and eliminated patients who had previously been prescribed an antidepressant. Conclusion. A criterion standard to assess the true relationship between β-blockers and depression is lacking. Factors such as the lack of systematic assessment of depression, the timing of assessments, and the selection of patients may have reduced the ability of researchers in the randomized controlled trials to detect depression as an adverse effect. Evidence from case reports should be carefully considered when relevant randomized controlled trials have not been adequately designed to detect adverse effects. [ABSTRACT FROM AUTHOR]