Propranolol antiarrhythmic activity

An analog (ICI 46037) structurally similar to propranolol was shown to possess local anesthetic and antiarrhythmic activity similar to propranolol in the dog. No -blocking action and a lower level of myocardial depressant action was observed . Other analogs have been reported recently having antiarrhythmic activity similar to quinidine in potency. These include 1,5-dimorpholino-3-(l-naphthyl)pentane (DA-1686) 2-propyl amino-1-naphthylpropane (S-931) ethoxamine (BW 62-235) and xipranolol (BS-79770)28. 

Qass II antiarrhythmic drugs are beta-blockers that decrease SA and AV nodal activity, decrease the phase 4 slope, and prevent p, adrenocepter activation, thereby circumventing the normal increase in cAMP. Propranolol is nonselective acebutolol, metoprolol, and esmolol are selective. Their antiarrhythmic use is discussed. 

Answer E. Increased sympathetic activity is a major problem in hyperthyroidism and is best managed by use of beta blockers, which can offset cardiac stimulatory effects. Propranolol has an ancillary action in thyrotoxicosis in that it prevents conversion of T to Tj via its inhibition of 5 deiodinase. Amiodarone causes difficult-to-predict adverse effects on thyroid function and would not be appropriate in a patient with hyperthyroidism. Quinidine is a class lA antiarrhythmic, which is associated with tachycardia as a side effect. Digoxin is not ideal because of its complex actions on the heart, which include both inhibition and stimulation. 

The relationship between cardiac depressant, local anesthetic and 6-adrenergic blockade actions has evoked considerable interest. A common mechanism could be responsible for all actions. However, the separation of racemic alprenolol and propranolol into their optically active isomers resulted in only the levo isomers being potent 6-blockers while both isomers possessed local anesthetic and cardiac depressant actions . The separation of bunolol into its optical isomers resulted in a further separation of the actions of 6-blockers. Bunolol is devoid of significant antiarrhythmic and local anesthetic activities. Dextro-bunolol is inactive as a 6-blocker but did possess a cardio-depressant action equal to that of the leyo isomer. Thus, no correlation between local anesthetic, 6-blockade or toxic cardiac depression actions exist. Separate mechanisms for the three activities probably are involved. 

Local Anesthetic - Membrane Active Antiarrhythmics - Many established anti-arrhythmic agents have been found to possess local anesthetic activity which parallels their effectiveness against a variety of cardiac arrhyth-rnias. These agents include quinidine, procaine amide, lidocaine and propranolol. They appear to act by depressing impulse conduction and by restoring normal automaticity to the myocardium. 

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