Experimental evidence implicates altered calcium and potassium homeostasis as a contributing mechanism of toxicity.2 PHARMACOLOGY AND PHARMACOKINETICS
Many b blockers are available. They differ slightly in pharmacologic ( Xab.!e 169:1) and pharmacokinetic (T§bJ.e...169:2) properties. Pharmacologic differences among drugs influence expression of toxicity. Highly lipid-soluble agents penetrate the blood-brain barrier to a greater extent than do water-soluble b blockers, resulting in more central nervous system toxicity. Propranolol, acebutolol, labetolol, oxprenolol, and pindolol inhibit myocardial sodium channels, making these drugs potentially more cardiotoxic. Several b blockers have partial agonist activity, and thus weak stimulation of the b receptor occurs concurrently with blockade. Thus, partial agonist activity may have a protective effect in overdose. Labetolol has the potential to cause profound hypotension due to combined a 1- and b-receptor antagonism.
TABLE 169-2 b-Blocker Pharmacologic
Clinically relevant pharmacokinetic characteristics include drug formulation (regular versus sustained release), rate of drug absorption, lipid solubility, and volume of distribution (Vd). Absorption of normal-release b blockers occurs rapidly, with peak effect in 1 to 4 h. For this reason, toxic symptoms begin soon after ingestion. The high degree of protein binding, the large Vd, and lipid solubility predict that extracorporeal drug removal will not be useful for most b blockers. Hemodialysis may be beneficial for atenolol, nadolol, and sotalol because these agents have lower protein binding, are hydrophilic, and have Vds similar to that of water.
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