Beta-blocking drugs toxicity

Greenblatt DJ, Koch-Weser J. Clinical toxicity of propranolol and practolol a report from the Boston Collaborative Drug Surveillance Program. Avery GS, editor. Cardiovascular Drugs. Vol 2. Beta-Adrenoceptor Blocking Drugs, Chapter VIII. Sydney Adis Press 1977 179. 

At this point, it is worth introducing stereoisomers. These are isomeric molecules that have the same molecular formula and hence the same sequence of bonded atoms. However, they differ in the three-dimensional orientation of their constituent atoms. For example, consider the example of the antiarrhythmic drug sotalol. Both d-sotalol and I-sotalol isomers affect 4, that influences cardiac repolarization, but only the I-isomer has beta-blocking effect. Another example is warfarin. The S-isomer is three to five times more potent than the R-isomer, and they are metabolized by different cytochrome pathways, an influence that contributes to variable response and toxicity between batches of the drug and ethnic populations. 

Additive sympathomimetic effects may develop when decongestants are administered with other sympathomimetic drug s (see Chap. 22). Use of the nasal decongestants with the MAOIs may cause hypertensive crisis. Use of a decongestant with beta-adrenergic blocking dragp may cause hypertension or bradycardia. When ephedrine is administered with theophylline, the patient is at increased risk for theophylline toxicity. 

The primary clinical effects observed in beta blocker toxicity are cardiovascular in nature. Direct cardiac effects include bradycardia (sinus, atrioventricular node, and ventricular), all degrees of atrioventricular block, bundle branch blocks, and asystole. Ventricular arrhythmias may occur secondary to bradycardia. Torsades de pointes has been associated with chronic toxicity from sotalol. Hypotension occurs and is due to decreased cardiac output and/or vasodilation. Central nervous system effects of these drugs including lethargy, coma, and seizures are secondary to the cardiovascular toxicities. Seizures and coma may be secondary to hypoglycemia. Bronchospasm can occur secondary to beta-2 blockade. Hypoglycemia and hyperkalemia can occur. 

Amiodarone, a special case Amiodarone is effective in most types of arrhythmias and is considered the most efficacious of all antiarrhythmic drugs. This may be because it has a broad spectrum it blocks sodium, calcium, and potassium channels and beta adrenoceptors. Because of its toxicities, however, amiodarone is usually reserved for use in arrhythmias that are resistant to other drugs. 

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