ABSTRACT
INTRODUCTION: For the past 40 years, methadone has been known to be an efficient treatment of substitution. Its use allowed a significant reduction in the mortality related to opioid addiction. Since 2001, many articles have reported some cases of syncope, wave burst arrhythmia, ventricular tachycardia due to prolonged QT interval and sudden death secondary to cardiac arrest, with a risk of prolongation of the QT interval above 440 ms (men) and 460 ms (women). Many explorations have helped in understanding the physiopathology by showing that opioids, including methadone, cause a blockage of the potassium channels of the gene HERG K+P. This event could slow the repolarisation and the atrioventricular cardiac synchronization and could induce ventricular arrhythmia. LITERATURE FINDINGS: Nearly 20 studies showed a prolonged QT interval secondary to methadone in patients exhibiting the following features: (1) patients with cardiac pathologies, notably bradycardia, congenital long QT interval, myocardial pathologies related to AIDS and electrolyte disturbances; (2) patients receiving concomitant treatment with substances known to prolong QT interval, such as psychoactive stimulants, narcoleptics, tricyclic antidepressants, antiarrhythmic agents, macrolids, quinolones, non diuretic hypokalemiants and certain corticoids; (3) patients receiving treatments that inhibit methadone's metabolism, particularly those that act on the cytochrome P450 3A4 such as SSRI, antifungal agents, some macrolids and some retroviral agents. Many recent studies, while evaluating the dose-dependent effect of methadone on the QT prolongation, showed a tendency to a prolonged QT when using higher doses of methadone. CONCLUSION: Screening for these risk factors should be carried out before prescribing methadone. EKG should not be systematically performed unless the conditions described above are present or if a higher dose of methadone is needed.
Subject(s)
Analgesics, Opioid/toxicity , Long QT Syndrome/chemically induced , Methadone/toxicity , Opiate Substitution Treatment/adverse effects , Opioid-Related Disorders/rehabilitation , Adult , Death, Sudden, Cardiac/etiology , Dose-Response Relationship, Drug , Drug Interactions , Drug Therapy, Combination , Electrocardiography/drug effects , Female , Humans , Hypokalemia/chemically induced , Hypokalemia/diagnosis , Long QT Syndrome/diagnosis , Male , Methadone/therapeutic use , Risk FactorsABSTRACT
UNLABELLED: From results of office and home measurements of blood pressure (BP), patients can be classified as "hypertensive (HT)", "normotensive (NT)", "office hypertensive (OH)" or "masked hypertensive (MH)" by crossing the classifications obtained from each method. It seems that 9 to 20% of patients could be MH with a prognosis close to HT (SHEAF study). OBJECTIVES: To test the hypothesis that at least one part of the prevalence of MH would be an artefact due to the difference between the methods of measurements (shygmomanometer vs semi-automatic device) and/or due to different definitions of office hypertension (OHT). To determine the impact of different definitions of OHT on the prevalence of MH. METHODS: During the course of a phase IV study, BP was measured with the same semi-automatic device (OMRON 705CP) both at doctor's office (3 measurements at 1-minute intervals) and at home, by the patient himself (3 measurements in the morning and in the evening at 1-minute intervals over the 7 days before the visit). Following definitions were used: Office HT: SBP > or =140 mmHg, DBP > or =90 mmHg, SBP > or =140 mmHg or DBP > or =90 mmHg; Home HT: SBP > or =135 mmHg, DBP> or =85 mmHg, SBP > or =135 mmHg or DBP > or =85 mmHg. Another definition of office HT was used SBP > or =135 mmHg, DBP > or =85 mmHg SBP > or =135 mmHg or DBP > or =85 mmHg. RESULTS: 575 patients were analysed. Results from the two methods of measurements are closed but significantly different (difference for SBP: 3.2 +/- 16.5 mmHg; p < 0.0001; difference for DBP: 1.4 +/- 10.3 mmHg; p = 0.002)
