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Treatment and Management of Cardiac Arrhythmia (for Professionals) Pharmacological therapyThe primary objective of pharmacological treatment of cardiac arrhythmias is to reach an effective and well-tolerated plasma drug concentration for as long as required without producing adverse effects. For a specific patient, one must consider the response of the patient and of the arrhythmia to the drug. Low drug concentrations can exert a therapeutic or toxic effect in some patients, while drug concentrations higher than the normal range may be needed and tolerated in others. Normally, because antiarrhythmic agents have a narrow toxic-therapeutic relationship, important complications of therapy can result from amounts of drug that only slightly exceed the amount necessary to produce beneficial effects; lesser concentrations are often subtherapeutic. It is obvious that careful dosing is essential to maintain adequate but nontoxic amounts of drug in the body, a task facilitated by understanding drug pharmacokinetics. One must make a quantitative assessment of drug dose-concentration factors, including drug absorption, distribution, metabolism and excretion. Alterations in the rate of any of these processes can account for significant changes in the drug's effect on the patient. Likewise, changes in the functional status of any of the organs alter dose requirements in a given patient. Most of the available antiarrhythmic drugs can be classified according to whether they exert blocking actions, predominantly on sodium, potassium or calcium channels, and whether they block beta-adrenoceptors. The actions of these drugs are quite complex and depend on tissue type, the degree of acute or chronic damage, heart rate, membrane potential, the ionic compositions of the extracellular milieu and other factors. Many drugs exhibit actions that belong in multiple categories, or operate indirectly, such as by altering hemodynamics, myocardial metabolism or automatic neural transmission. Some drugs have active metabolites that exert different effects from the parent compound. Not all drugs in the same class have identical effects, e.g., bretylium, sotalol and amiodarone are dramatically different, while some drugs in different classes have overlapping actions, e.g., class IA and IC drugs. In vitro studies on healthy fibers usually establish the properties of antiarrhythmic agents rather than their antiarrhythmic properties. Factors regulating the effects of antiarrhythmic drugs
This content is reviewed regularly. Last updated 12/04/08. |
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