Beta Blocker and Calcium Channel Blocker Overdose

Proposed actions in cardiac muscle of calcium, epinephrine (EPI), glucagon, amrinone, and insulin in the treatment of β-blocker (BB) and calcium-channel blocker (CCB) toxicity: (a) Calcium enters open voltage-sensitive calcium channels to promote the release of calcium from the sarcoplasmic reticulum. The released calcium combines with troponin to cause muscle contraction via actin and myosin fi bers. (b) EPI binds to β-receptors (β) that are not occupied by a BB. Stimulation of the receptors, which are coupled to a G protein (G s ), brings about the activation of adenylate cyclase (AC). AC catalyzes the conversion of adenosine triphosphate (ATP) to cyclic adenosine monophosphate (cAMP), which activates protein kinase A (PKA), which promotes the opening of dormant calcium channels, enhances release of calcium from the sarcoplasmic reticulum, and facilitates release of calcium by troponin during diastole. Therapies that promote cAMP formation generally have transient eff ects in CCB overdose due to the myocyte running out of carbohydrates. (c) Glucagon bypasses β-receptors and acts directly on G s to stimulate conversion of ATP to cAMP. (d) Amrinone inhibits phosphodiesterase (PDE) to prevent the degradation of cAMP. (e) Insulin promotes the uptake and use of carbohydrates as an energy source. It also promotes antiinfl ammatory eff ects that may correct problems caused by ineffi cient energy production. The associated infl ux of potassium may also provide benefi t by prolonging repolarization and allowing calcium channels to remain open longer. Illustration by Marie Dauenheimer, CMI. Adapted, with permission, from reference 1. PMID: 16990629