Critical Management of Severe Hypotension Caused by Amlodipine Toxicity Managed With Hyperinsulinemia/Euglycemia Therapy Supplemented With Calcium Gluconate, Intravenous Glucagon and Other Vasopressor Support: Review of Literature

Abstract

Calcium channel blocker (CCB ) overdose, whether intentional or accidental, is a common clinical scenario and can be very lethal. Conventional treatments for CCB overdose include intravenous (IV) fluids, calcium salts, dopamine, dobutamine, norepinephrine, phosphodiesterase inhibitors, and glucagon. However, the conventional therapies are unsuccessful in reversing the cardiovascular toxicity of CCB, so they commonly fail to improve the hemodynamic condition of the patient. Blockade of the L-type calcium channels that mediate the antihypertensive effect of CCBs also decreases the release of insulin from pancreatic β-islet cells and reduces glucose uptake by tissues (insulin resistance). By targeting this insulin-mediated pathway, hyperinsulinemia/euglycemia therapy (HIET) appears to have a distinct role, and its clinical potential is underrecognized in the management of severe CCB toxicity. We present a case of young man with amlodipine toxicity successfully managed with high dose of IV insulin therapy.

Emergency management of calcium channel blocker overdose

“…[11,13] They are lipophilic and have a higher affinity for cardiomyocytes than the dihydropyridine agents, where they reduce the influx of calcium during phase two of the action potential. [13][14][15][16] Because calcium is not able to enter the cell, excitation coupling in these cells cannot occur, resulting in reduced myocardial contractility. [15,16] Reduced binding of calcium to the calcium channels in the conducting system leads to slowing of sinoatrial and atrioventricular conduction, resulting in bradycardia.…”

“…[13][14][15][16] Because calcium is not able to enter the cell, excitation coupling in these cells cannot occur, resulting in reduced myocardial contractility. [15,16] Reduced binding of calcium to the calcium channels in the conducting system leads to slowing of sinoatrial and atrioventricular conduction, resulting in bradycardia. [15,16] The dihydropyridines preferentially affect vascular smooth muscle in the periphery at therapeutic dosages, thereby decreasing peripheral vascular resistance and reducing afterload and lowering blood pressure (BP).…”

“…[15,16] Reduced binding of calcium to the calcium channels in the conducting system leads to slowing of sinoatrial and atrioventricular conduction, resulting in bradycardia. [15,16] The dihydropyridines preferentially affect vascular smooth muscle in the periphery at therapeutic dosages, thereby decreasing peripheral vascular resistance and reducing afterload and lowering blood pressure (BP). [11,13] They are therefore excellent agents for the management of hypertension.…”

“…[17] They are highly protein bound and have a high volume of distribution, so are not amenable to removal by haemodialysis. [15,17]…”

“…In OD, non-dihydropyridines cause sinus bradycardia, atrioventricular blocks, hypotension and cardiogenic shock. [11,15,[17][18][19] In dihydropyridine OD, profound peripheral vasodilation produces…”