American journal of therapeutics
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Review
QT prolongation and fatal arrhythmias: a review of clinical implications and effects of drugs.
A long QT interval due to prolonged repolarization may be associated with a polymorphic ventricular tachycardia known as torsades de pointes. During marked prolongation of the action potential (long QT) early after depolarizations may occur, which when propagated may trigger an arrhythmia. The duration of QTc interval is the major determinant of the risk of drug-induced torsades. ⋯ Antiarrhythmics that block the potassium channel prolong the QT and increase the risk for torsades (amiodarone, sotalol, quinidine, procainamide, ibutilide, disopyramide). Additionally, some macrolide and fluoroquinolone antibiotics, antipsychotic and antidepressant drugs, serotonin agonists of the triptan class, cisapride, dolasetron and others have been reported to be associated with QT prolongation or cases of torsades. Drug-induced effects on the QT interval with the associated possibility of inducing fatal arrhythmias have become a new challenge for the practitioner, the drug development process and the regulatory agencies.
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Torsade de pointes is a malignant dysrhythmia that has been reported in a variety of clinical settings and associated with several pharmacologic agents. Patients with a prolonged QTc for heart rate are at higher risk for the development of this arrhythmia. We review the literature supporting the relationship of haloperidol to the development of this malignant dysrhythmia. Clinicians in the critical care setting should be aware of potentially lethal drug-induced ventricular tachydysrhythmias such as torsade de pointes.
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Fomepizole (Antizol) was recently approved by the US Food and Drug Administration for treatment of methanol poisoning. By inhibiting the hepatic enzyme alcohol dehydrogenase, it presents formation of toxic metabolites with far fewer consequences than traditional ethanol therapy. It appears that fomepizole will become standard therapy for methanol intoxication as it is for ethylene glycol poisoning.
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A number of pharmacologic and nonpharmacologic technologies are in current use to minimize perioperative homologous blood use. Clinical trials, many of them randomized controlled trials, have been done evaluating these approaches and have demonstrated their efficacy. However, data on safety has relied mostly on case reports, uncontrolled studies, and, for the pharmacologic agents, extrapolation from the nonsurgical setting. ⋯ DDAVP is low-risk, provided it is not overused, which can induce hyponatremia. Autologous predonation probably has similar risks as homologous blood with respect to transfusion errors and bacterial infection. As with most medical interventions, we must be vigilant to prevent human error.
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In recent years, significant progress has been made in our understanding of the pathophysiology behind obstructive airway diseases in general and asthma in particular; this knowledge, however, has not translated to major breakthroughs in the treatment of these disorders. Current therapeutic options are less than optimal and frequently are associated with systemic adverse effects. Recent studies indicate that endogenous purine nucleotides, adenosine 5'-triphosphate (ATP) in particular, could play a mechanistic role in obstructive airway diseases through their actions on multiple cell types relevant to these disorders, including mast cells, eosinophils, dendritic cells, and neurons. The pharmacologic modulation of ATP signal transduction in these cells represents an attractive new therapeutic target.