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The β-adrenergic receptor antagonists, or β-blockers, are common medications used in the treatment of various cardiovascular, neurologic, endocrine, ophthalmologic, and psychiatric disorders. Because of their widespread availability, accidental and intentional toxicity is common. In 2008, the American Association of Poison Control Centers received reports of 21,282 exposures to β-blockers with six associated deaths.1 Among all the exposures to cardiovascular agents, β-blocker exposures were the leading cause of poison center calls and ranked among the top three in this class as a cause of severe toxicity and mortality.

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The β-adrenergic receptors are membrane glycoproteins present in various tissues. At least three β-adrenergic receptor subtypes have been characterized (Table 188-1). These receptors play a critical role in cardiovascular physiology by modulating cardiac activity and vascular tone.

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Table 188-1 Location and Activity of β-Adrenergic Receptors 
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During times of stress (i.e., catecholamine release), β-adrenergic receptor stimulation increases myocardial and vascular smooth muscle cell activity through a sequence of intracellular events (Figure 188-1).2,3

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Figure 188-1.
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Cardiac myocyte β-receptor and calcium signaling. Calcium plays a key role in intracellular signaling and myocyte contraction. Binding of a β agonist to the β1-adrenergic receptor (B1) on the cell surface activates the Gs protein. The Gs protein then activates adenylate cyclace (AC), which converts adenosine triphosphate (ATP) to cyclic adenosine monophosphate (cAMP). The increased cAMP activates protein kinase A (PKA). Activated PKA causes the L-type voltage-dependent calcium channel (L-VDCC) to open. Extracellular calcium (Ca2+) then enters the cell and binds to the ryanodine receptor (RyR) in the sarcoplasmic reticulum, causing an efflux of sequestered Ca2+ out of the sarcoplasmic reticulum into the cell. The released Ca2+ binds to troponin, which allows the myosin and actin interaction that causes contraction of the cardiac myocyte. Glucagon is a stress-reactive protein that independently activates adenylate cyclase. cAMP is metabolized by phosphodiesterase (PDE) into inactive adenosine 5′-monophosphate (5′AMP).

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The β-blockers modulate the activity of myocyte and vascular smooth muscle contraction by decreasing calcium entry into the cell.2,3 Therapeutically, β-blockade lessens the work performed by the diseased or injured myocardium. On the other hand, excessive β-blockade may lead to profound pump failure, with bradycardia, decreased contractility, and ...

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