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Antiarrhythmic drug therapy is the mainstay of treatment of patients with nearly every form of cardiac arrhythmia. An in-depth knowledge of the pharmacology of antiarrhythmic drugs, including their pharmacokinetics and pharmacodynamics, is essential to their successful and safe implementation.

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Pharmacokinetics describes the relationship between drug administration and plasma concentration. It is assumed that the plasma concentration reflects, in a general sense, myocardial concentrations and thus the availability of the drug at its site of action. The pharmacokinetics of antiarrhythmic drugs are variable and not predictable by drug classification or by knowledge of the drug's chemical structure.

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Absorption/Bioavailability

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Absorption describes the movement of orally administered drug from the gut lumen to the systemic circulation, and the efficiency of this absorption is defined as bioavailability. Those factors that influence passage of the drug through the gut wall into the portal circulation and through the liver will have an effect on drug bioavailability. Thus, diseases that affect bowel motility, bowel wall blood flow, gastric and bowel pH, and presystemic or "first-pass" hepatic clearance will, to some extent, influence the amount of drug that is available to the systemic circulation.

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A common way to extend interdosing intervals during treatment with drugs that have a relatively short plasma half-life is to formulate them into a sustained-release preparation. Changes in bowel pH and other conditions within the gut influence the amount of drug that is released from sustained-release preparations, which, in turn, has an effect on the amount of drug that is absorbed from the gastrointestinal tract. Drugs can also have altered absorption because of intraluminal binding by other substances, such as milk and antacids. Finally, the physiochemical properties of the drug itself can have an effect on absorption.

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Varying the salt of the drug can change solubility and thus its rate of absorption. Drug solubility is also determined by the pH of its medium. Weak bases are rapidly dissolved in acid medium. Antacids, by increasing gut pH, can slow the absorption of a weakly basic drug. In clinical situations, high intestinal pH, caused by such factors as bacterial overgrowth syndrome, can reduce the bioavailability of antiarrhythmic drugs. Thus, for patients with serious arrhythmias, especially those that are controlled by drugs that have a relatively narrow toxic-to-therapeutic ratio, reassessing plasma concentration or clinical efficacy during conditions of altered bowel physiology or pathology is relevant.

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Finally, many antiarrhythmic drugs have a food-fast effect; that is, the bioavailability of a drug may be changed several-fold in the presence of food or during fasting. A notable example is oral amiodarone, which is three times more bioavailable after a high-fat meal.1 For such drugs, providing the patient with specific information as to the timing of drug ingestion with relationship to meals is important to maintain a predictable and reproducible plasma concentration over the course of therapy.

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Generic antiarrhythmic drugs are approved by ...

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