RESUMEN
The clinical practice of pharmaceutical medicine includes contributions from physicians, pharmacists, nurse practitioners, and physician assistants. Drug safety considerations are of considerable importance. This article discusses drug-induced proarrhythmia, with a specific focus on Torsade de Pointes (Torsade), a polymorphic ventricular tachycardia that typically occurs in self-limiting bursts that can lead to dizziness, palpitations, syncope, and seizures, but on rare occasions can progress to ventricular fibrillation and sudden cardiac death. A dedicated clinical pharmacology study conducted during a drug's clinical development program has assessed its propensity to induce Torsade using prolongation of the QT interval as seen on the surface electrocardiogram (ECG) as a biomarker. Identification of QT-interval prolongation does not necessarily prevent a drug from receiving marketing approval if its overall benefit-risk balance is favorable, but, if approved, a warning is placed in its Prescribing Information. This article explains why drugs can have a proarrhythmic propensity and concludes with a case presentation.
Asunto(s)
Arritmias Cardíacas/etiología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/complicaciones , Arritmias Cardíacas/fisiopatología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/fisiopatología , Electrocardiografía/métodos , Humanos , Síndrome de QT Prolongado/etiología , Síndrome de QT Prolongado/fisiopatología , Torsades de Pointes/etiología , Torsades de Pointes/fisiopatologíaRESUMEN
PURPOSE: To describe initial antihypertensive management relative to important aspects of JNC7 hypertension guidelines, to identify predictors of receiving JNC7 discordant therapy, and to determine the association between receiving JNC7-concordant antihypertensive treatment and achieving blood pressure (BP) control. This study focused on aspects of the JNC7 guidelines which are consistent with other guidelines that have been published since JNC7. METHODS: EMR data from eleven multi-specialty medical groups in the US were retrospectively collected between 2008-2011. The study cohort included incident hypertensive patients who received an antihypertensive prescription during the 6-month follow-up period. Patients with existing hypertension were excluded. JNC7-concordance of the prescribed antihypertensive regimen was evaluated. Using multivariable logistic regression, we determined the association between JNC7-concordance and achieving BP control. Additionally, we determined predictors of receiving JNC7-discordant treatment. RESULTS: 14,910 incident hypertensive patients who were treated with an antihypertensive during the 6-month follow-up period were included. Overall, 79.4% patients were prescribed antihypertensive therapy concordant with JNC7; however among patients with stage 2 hypertension, the concordance was found to be 50%. BP control was achieved by 64.1% and 48.5% of patients who received JNC7-concordant and JNC7-discordant therapy, respectively. The overall adjusted odds ratio (95% CI) for BP control and JNC7-concordance was 1.53 (1.40, 1.68). The association was attenuated for cohort members with diabetes, chronic kidney disease (CKD), and stage 2 hypertension. Predictors of receiving JNC7-discordant therapy were congestive heart failure, CKD, and diabetes. CONCLUSION: JNC7-concordance is high overall, but drops substantially when JNC7 recommendations are more demanding (e.g., among patients with stage 2 hypertension and/or CKD, CHF, diabetes). Overall, patients who are prescribed an antihypertensive regimen that is JNC7-concordant are more likely to achieve BP control.