Hyperinsulinemic-euglycemic therapy for intoxication with calcium channel blockers

Conventional therapy for intoxication with calcium channel blockers consists of crystalloid solutions, calcium gluconate, glucagon and vasopressor agents. These therapies often fail to improve hemodynamic function in intoxicated patients. The pathophysologic mechanism proposed for intoxication with these agents, suggest hypoinsulinemia as the determinant factor. We will describe the case of a 77 years old man treated for an overdose of nifedipine and atenolol who arrived at our institution with hypotension and bradycardia. After conventional therapy failed to improve the patient's hemodynamic status, hyperinsulinemia and euglycemia contributed to the improvement of the patient's neurologic and hemodynamic condition. Thus, hyperinsulinemic-euglycemic therapy was of benefit in this patient with hemodynamic compromise secondary to intoxication with calcium channel blocker not responding to conventional therapy. We will review the mechanism of action of calcium channel blocker drugs as well as the clinical presentation and treatment options for calcium channel blocker intoxication.

Inhibition of acute and chronic inflammatory responses by the hydroxybenzoquinonic derivative rapanone.

Rapanone (2,5-dihydroxy-3-tridecyl-1,4-benzoquinone), a natural compound isolated from Myrsine guianensis growing in the Andean highlands of Colombia, was studied in different in vitro and in vivo models as a potential antioxidant and anti-inflammatory drug. Rapanone showed a mild anti-lipoperoxidative profile in rat liver microsomes and inhibited potently degranulation (IC(50) of 9.8 microM) and superoxide chemiluminescence (IC(50) of 3.0 microM) in human neutrophils. In addition, rapanone is a selective and potent human synovial PLA(2) inhibitor (IC(50) of 2.6 microM). In vivo experiments using the carrageenan paw oedema and the zymosan air pouch model in mice as well as the adjuvant arthritis model in rats have proved that rapanone is very efficient in controlling the inflammatory process by different administration routes.

Alterations in the reproduction of mice induced by rapanone.

Oral administration of rapanone to a group of female mice at doses of 60 and 120 mg/kg, reduced the percentage of pregnancies compared to control group, suggesting an anovulatory effect. Postcoital administration induced uterine alteration in both the first and second gestation periods. These results seem to indicate inhibition of trophoblast implantation in the first period, and an abortive effect and/or reabsorption in the second. Daily administration of rapanone to a group of male mice resulted in fertility alteration, which is attributed to an antispermatogenic effect. Rapanone did not show acute toxic effects at the doses tested in this research.

New pyridinium alkaloids from a marine sponge of the genus Spongia with a human phospholipase A(2) inhibitor profile.

Four new bioactive pyridinium alkaloids, named spongidines A-D (5-8), have been isolated from a Vanuatu sponge of the genus Spongia, together with known petrosaspongiolides D (1) and G (2). Compounds 3 and 4 are 21-hydroxy derivatives of petrosaspongiolides K and P. Structure elucidation was accomplished through extensive 2D NMR experiments (COSY, ROESY, HMBC, HMQC) and IR, UV, and FABMS data. All compounds significantly inhibited human synovial phospholipase A(2) (PLA(2)) at 10 microM, with an IC(50) value of 5.8 microM for compound 4, which is the most potent inhibitor, with a higher selectivity toward this enzyme than the reference inhibitor manoalide. Pyridinium alkaloids (5-8) mainly inhibited human synovial PLA(2). Compound 8, which contains a sulfonic acid group, is the most interesting inhibitor.