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Description

Abstract Valproic acid (VPA) is used to treat seizure and bipolar disorders as well as for migraine prophylaxis.Acute overdoses can present with CNS depression and in severe cases cerebral edema and herniation can occur.Recovery can be prolonged as overdose peak plasma levels can be delayed up to 7 h.In addition, some VPA preparations are specifically designed for delayed absorption.In addition, in supratherapeutic dosing, enzymatic metabolism becomes saturated and the rate of clearance reaches a plateau.Even with therapeutic dosing, VPA may cause problems.Via multiple mechanisms, VPA inhibits the urea cycle and can lead to hyperammonemia which can also cause CNS depression and confusion.This may or may not occur in conjunction with a transaminitis.As a corollary, transaminitis may occur without elevated ammonia levels but this should prompt treatment nonetheless (discussed below) as further hepatic dysfunction and hyperammonemia could ensue

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They can be used to elucidate disease mechanisms and predict the effects of candidate compounds by focusing on the electrophysiology, cellular signaling, metabolism, and contraction mechanisms of CMs