Model-Informed Development of Sotalol Loading and Dose Escalation Employing an Intravenous Infusion.

Background: Sotalol is often employed to prevent recurrence of symptomatic atrial flutter/atrial fibrillation. Because sotalol can prolong the QT interval excessively causing ventricular arrhythmias, a 3-day in-hospital loading or dose escalation period is mandated with oral administration in the product label for patient safety. In patients with normal renal function, 3 days (five oral doses) are required to obtain steady state maximum sotalol concentration, which results in maximum QT prolongation.

Inhibition of Human Ether-A-Go-Go-Related Gene (hERG) Potassium Current by the Novel Sotalol Analogue, Soestalol.

The clinical utility of intravenous sotalol is limited due to an extended half-life combined with the potential to generate life-threatening arrhythmias. The authors developed a novel sotalol analogue, soestalol, with an ester linkage introduced to the molecule to shorten half-life. Their hypothesis was that soestalol, but not the acid metabolite, would inhibit the hERG potassium current.

What is New in Pharmacologic Therapy for Cardiac Resuscitation?

Antiarrhythmic therapy can be a critical component of cardiac resuscitation. Therapies in this area have seen little advance in the last decade. Bretylium, a very old drug, has been reintroduced for ventricular tachycardia/ventricular fibrillation (VT/VF) therapy.

Retrospective Evaluation on the Analgesic Activities of 2 Compounded Topical Creams and Voltaren Gel in Chronic Noncancer Pain.

Pharmacologic treatment of chronic pain is challenging. Oral therapy may require multiple medications; each has side effects, dose limitations, and limited efficacy. Compounded topical formulations have evolved as potential treatment options.

Evaluation of the Effects of Different Energy Drinks and Coffee on Endothelial Function.

Endothelial function plays an important role in circulatory physiology. There has been differing reports on the effect of energy drink on endothelial function. We set out to evaluate the effect of 3 energy drinks and coffee on endothelial function.

A Rapid Method to Evaluate Cardiac Repolarization Changes: The Effect of Two Coffee Strengths on the QT Interval.

Objectives: To assess the effect of coffee on ventricular repolarization as measured by an electrocardiogram.

Methods: Fifty-four healthy volunteers (34 males and 20 females, age 23 ± 5 years) received 1 cup of coffee (caffeine content 120 mg) and 11 participants received 2 cups. Blood pressure and heart rate were measured prior to coffee and every hour thereafter for 5 h.

Retrospective Study on the Analgesic Activity of a Topical (TT-CTAC) Cream in Patients With Diabetic Neuropathy and Other Chronic Pain Conditions.

Treatment of chronic pain in diabetic neuropathy or neuropathic pain of other origins is challenging. Compounded topical formulations have evolved as potential treatment options. The objective of this retrospective study was to evaluate the efficacy of a compounded topical cream (Transdermal Therapeutics).

Assessment of cardiovascular and noncardiovascular medical device recalls.

Medical device recalls have called attention to the device approval process in the United States. The premarket approval (PMA) process requires clinical trials to evaluate safety and effectiveness, whereas the expedited 510(k) process does not. The 510(k) process has been considered a source of increased recalls.

The clinical pharmacology of ethacrynic acid.

Ethacrynic acid (Edecrin) is a loop diuretic that produces a prompt and profound diuresis. The primary action of ethacrynic acid is the inhibition of the activity of the Na⁺-K⁺-2Cl⁻ symporter in the thick ascending limb of the loop of Henle. The onset of action is usually within 30 minutes after an oral dose and within 5 minutes after an intravenous injection.

Chiral cardiovascular drugs: an overview.

Stereochemistry in drug molecules is rapidly becoming an important aspect in drug research, design, and development. Recently, individual stereoisomers of drug molecules with asymmetric centers such as fexofenadine, cetirizine, verapamil, fluoxetine, levalbutarol, and amphetamine, for example, have been separated and developed as individual drugs. These stereoisomers have different therapeutic activity, and each isomer has contributed differently with respect to its formulation's pharmacologic activity, side effects, and toxicity.

Pharmacology and toxicology of a new aqueous formulation of intravenous amiodarone (Amio-Aqueous) compared with Cordarone IV.

Hypotension is the most frequent adverse event reported with intravenous amiodarone (Cordarone IV). The hypotension has been attributed to the vasoactive solvents of the formulation, polysorbate 80 and benzyl alcohol, both known to exhibit negative inotropy and hypotensive effect. A new aqueous formulation of intravenous amiodarone (Amio-Aqueous) does not contain vasoactive excipients and may be less toxic and cause less hypotension than Cordarone IV.

Enhancement of myocardial vulnerability by atrial fibrillation.

Certain groups are known to have an increased risk for sudden cardiac death. Epidemiologic studies have suggested that patients with atrial fibrillation may be at higher risk. The authors hypothesize that atrial fibrillation may increase myocardial vulnerability.

Effect of angiotensin-converting enzyme therapy on QT interval dispersion.

Patients with chronic heart failure (CHF) have an increased risk for sudden death. This increased risk has been associated with increased QT dispersion (QTd), a reflection of the heterogeneity in ventricular repolarization. Angiotensin-converting enzyme (ACE) inhibitors have been reported to decrease heart size as well as decreasing morbidity and mortality in moderate-to-severe CHF.

Influence of electrolyte abnormalities on interlead variability of ventricular repolarization times in 12-lead electrocardiography.

Increased QT dispersion (QT(d)) has been associated with increased risk for ventricular arrhythmias. Pathologic extracellular electrolyte concentrations may result in ventricular arrhythmias. The aim of this study was to evaluate the effect of electrolyte abnormalities on QT(d).