Biomedical subjects

John C Somberg

Publications and source records attributed to John C Somberg.

18 recordsLinked to original sources

PubMed2002

Differential effect of glyburide (glibenclamide) and metformin on QT dispersion: a potential adenosine triphosphate sensitive K+ channel effect.

Glyburide (glibenclamide) is a specific blocker of the adenosine triphosphate (ATP) sensitive potassium (K+) channel. It has been reported to result in prolongation of the QT interval. QT interval dispersion (QTd) is a potentially sensitive marker for increased risk of arrhythmia and sudden cardiac death. The aim of the present study was to evaluate the effect of glyburide on QTd and compare it with that of metformin, a hypoglycemic agent that does not block the adenosine triphosphate sensitive K+ channel. Thirty patients with type 2 diabetes were randomized to glyburide and metformin groups. A 12-lead electrocardiogram was obtained before and at 2 months after being on glyburide or metformin. Therapy with QT and QTd were measured and QT corrected for rate (QTc). There was no significant difference between the glyburide and metformin groups in age (62 +/- 9 vs 59 +/- 10 years), baseline RR interval (819 +/- 86 vs 753 +/- 100 ms), QT (387 +/- 28 vs 383 +/- 27 ms), and QTc (433 +/- 25 vs 444 +/- 15 ms). Glyburide was associated with a significant increase in QTc (433 +/- 24 to 467 +/- 24 ms, p <0.001), QTd (24 +/- 16 to 60 +/- 22 ms, p <0.001), and QTc dispersion (QTcd) (35 +/- 18 to 68 +/- 21 ms, p <0.001). In contrast, metformin was associated with a decrease in QTc (444 +/- 15 to 432 +/- 15 ms, p <0.01) and did not affect QTd (14 +/- 5 to 12 +/- 6 ms, p = NS) and QTcd (23 +/- 9 to 22 +/- 10 ms, p = NS). Glyburide, unlike metformin, causes an increase in QT dispersion. Increased dispersion may be a factor underlying an increased risk of arrhythmias and sudden cardiac death.

Administration, Oral↗

PubMed2002

Hemodynamic and surface electrocardiographic effects of a new aqueous formulation of intravenous amiodarone.

Intravenous amiodarone is an effective antiarrhythmic agent. However, the standard formulation (Cordarone IV) frequently causes hypotension. Hemodynamic studies have attributed this adverse effect to the solvents employed. A newly developed aqueous formulation (Amio-Aqueous) lacks solvents and thus may not causes hypotension. This study evaluated the hemodynamic effects in a cardiac catheterization laboratory. Two boluses of 150-mg aqueous amiodarone were administered via a peripheral vein to 32 hemodynamically stable patients who underwent cardiac catheterization. Boluses were administered initially over 2 to 5 minutes and in the last 9 patients over 2 minutes. Hemodynamic evaluation was performed and 12-lead electrocardiograms were obtained at baseline, immediately after each bolus, and following 30 minutes of observation. No patient developed hypotension. There were no significant changes in systolic and diastolic blood pressure (BP) following the boluses. Compared with baseline, heart rate (HR) significantly decreased 5 minutes after the second bolus (73 +/- 12 vs 67 +/- 11 beats/min, p <0.05). Mean arterial BP increased (90 +/- 14 vs 100 +/- 16 mm Hg, p <0.05) and dp/dt decreased (1,599 +/- 645 vs 1,294 +/- 531 mm Hg/s p <0.05), whereas the PR, QT, and JT intervals increased (174 +/- 30 vs 182 +/- 33; 402 +/- 32 vs 424 +/- 35; 317 +/- 37 vs 336 +/- 32 ms, p <0.05, respectively) by the end of the 30-minute observation period. Amio-Aqueous possesses pharmacodynamic effects that have been attributed to amiodarone, whereas it lacks the hypotensive effect of the standard intravenous amiodarone formulation. Amio-Aqueous appears to be a safer alternative to Cordarone IV when rapid administration is indicated.

Adult↗

PubMed2002

Intravenous lidocaine versus intravenous amiodarone (in a new aqueous formulation) for incessant ventricular tachycardia.

The effectiveness of intravenous amiodarone for the treatment of incessant (shock resistant) ventricular tachycardia (VT) has not been established. This study evaluated the efficacy of a water-soluble amiodarone preparation or lidocaine for the treatment of shock-resistant VT. The trial was a double-blinded parallel design. Patients were randomized to receive up to 2 boluses of either 150 mg intravenous amiodarone or 2 boluses of 100 mg lidocaine followed by a 24-hour infusion. If the first assigned medication failed to terminate VT, the patient was crossed over to the alternative therapy. Twenty-nine patients were randomized to the study (18 received amiodarone and 11 received lidocaine). There were no significant differences between groups with regard to baseline characteristics. Immediate VT termination was achieved in 14 patients (78%) with amiodarone versus 3 patients (27%) on lidocaine (p <0.05). After 1 hour, 12 patients (67%) on amiodarone and 1 patient (9%) on lidocaine were alive and free of VT (p <0.01). Amiodarone had a 33% drug failure rate, whereas there was a 91% drug failure rate for lidocaine. The 24-hour survival was 39% on amiodarone and 9% on lidocaine (p <0.01). Drug-related hypotension with aqueous amiodarone was less frequent than with lidocaine. This study found that amiodarone is more effective than lidocaine in the treatment of shock-resistant VT.

Aged↗

PubMed2002

Usefulness of QT dispersion as an electrocardiographically derived index.

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Arrhythmias, Cardiac↗

PubMedDate not supplied

Bioterrorism 2002.

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Biological Warfare↗

PubMedDate not supplied

Rapid determination of partition coefficients between n-octanol/water for cardiovascular therapies.

The lipid solubility of a pharmaceutical may greatly influence its tissue activity. To evaluate lipid solubility of a group of cardiovascular agents a procedure to determine partition coefficients in n-octanol/water for a series of cardiovascular compounds was described. Ultraviolet absorbance measurements were used to assess partitioning between the two liquid phases of these compounds. In this study, sotalol was found to be the most hydrophilic (n-octanol/water ratio of 0.33) and fosinopril-sodium was the most lipophilic (ratio of 6.19). This is a versatile method permitting the evaluation of lipophilicity and, thus, parameters governing the events leading to pharmacologic actions such as gastrointestinal dissolution, absorption, and bioavailability. These observations can be related to a drug series, composed of several compounds having structural similarities or minor variations. The lipid solubility of a compound can markedly alter its side-effects profile, especially because lipophilic drugs enter the central nervous system with facility. Additionally, lipophilic agents may enter target tissue with greater ease than nonlipophilic compounds and thus possess local intracellular effects in addition to a macro systemic action.

1-Octanol↗

PubMedDate not supplied