British journal of clinical pharmacology
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Br J Clin Pharmacol · Aug 2010
Risk of digoxin intoxication in heart failure patients exposed to digoxin-diuretic interactions: a population-based study.
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT * Increased frequency of electrolyte abnormalities and cardiac arrhythmias among patients exposed to digoxin-diuretic interactions has been well-documented in numerous descriptive studies. * Nonetheless, a clear causal relationship has not been established in these studies. WHAT THIS STUDY ADDS * The risks of digoxin intoxication associated with use of digoxin in combination with any diuretic use, types of diuretics, combinations of diuretics, and individual diuretics were quantified using a population-based nested case-control study design. * The combined therapy of digoxin with any diuretic is associated with a 3.08-fold increase in the risk of digoxin intoxication. * Regarding diuretic class, the risk carried by loop diuretics is greater than that of thiazides or potassium-sparing diuretics, and the risk varies with different combinations of diuretic classes and individual diuretics. AIMS To quantify the digoxin intoxication risk associated with exposure to digoxin-diuretic interactions, and evaluate whether the risk varies by diuretic type, individually or in combination. ⋯ CONCLUSIONS This study provided empirical evidence that digoxin-diuretic interactions increased the risk of hospitalization for digoxin intoxication in HF patients. The risk was particularly high for concomitant use of digoxin with a combination of loop diuretics, thiazide and potassium-sparing diuretics. The combined use of digoxin and diuretics should be avoided if possible.
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Br J Clin Pharmacol · Jul 2010
Randomized Controlled TrialEltrombopag does not affect cardiac repolarization: results from a definitive QTc study in healthy subjects.
Some non-anti-arrhythmic drugs delay cardiac repolarization, which can be measured as an increase in the QT interval. Delays in cardiac repolarization create an electrophysiological environment that favours the development of cardiac arrhythmias, which may lead to torsade de pointes, which can be fatal. As part of the clinical development of eltrombopag, a thorough QT(c) study was conducted to evaluate the effects of eltrombopag on cardiac repolarization at both therapeutic and supratherapeutic doses and to characterize the relationship between plasma eltrombopag concentrations and change in QT(c). ⋯ No clinically significant QT(c) prolongation was observed for eltrombopag at therapeutic and supratherapeutic doses.
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Br J Clin Pharmacol · Jul 2010
Randomized Controlled Trial Comparative StudyPharmacokinetics, pharmacodynamics, safety and tolerability of multiple ascending doses of ticagrelor in healthy volunteers.
The antiplatelet agent clopidogrel is currently the recommended treatment for acute coronary syndrome (ACS). Inhibition of platelet aggregation (IPA) with clopidogrel is insufficient, which increases the risk for recurrent ischaemic events. Therefore, there is a need for antiplatelet agents with improved IPA. Ticagrelor (AZD6140) is a new antiplatelet agent in clinical development for reduction of thrombotic events in patients with ACS. ⋯ Multiple dosing provided predictable pharmacokinetics of ticagrelor and its metabolite over the dose range of 50-600 mg once daily and 50-300 mg twice daily with C(max) and AUC(0,t) increasing approximately dose-proportionally. Greater and more consistent IPA with ticagrelor at doses > or = 100 mg twice daily and > or = 300 mg once daily were observed than with clopidogrel. Ticagrelor at doses up to 600 mg day(-1) was well tolerated.
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Br J Clin Pharmacol · Jul 2010
Teaching of clinical pharmacology and therapeutics in UK medical schools: current status in 2009.
Junior doctors feel poorly prepared by their training in Clinical Pharmacology and Therapeutics and commonly make prescribing errors. Since 1993 the General Medical Council's guidance on undergraduate medical education 'Tomorrow's Doctors' has emphasized the integration of Clinical Pharmacology and Therapeutics teaching within the medical curriculum. With the publication of a new version of Tomorrow's Doctors in 2009, medical schools will be further revising their Clinical Pharmacology and Therapeutics teaching. ⋯ CPT teaching in UK medical schools is very diverse. Most schools do not assess the performance of their graduates as prescribers and there is a lack of evidence that many of the teaching approaches employed are suitable for the development of prescribing skills. It is vital that developments in CPT teaching are driven by validated, real-world assessments of the prescribing skills of medical students and newly qualified doctors.
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Br J Clin Pharmacol · Apr 2010
Randomized Controlled TrialNo cardiac effects of therapeutic and supratherapeutic doses of rupatadine: results from a 'thorough QT/QTc study' performed according to ICH guidelines.
To evaluate the effects of therapeutic and supratherapeutic doses of rupatadine on cardiac repolarization in line with a 'thorough QT/QTc study' protocol performed according to International Conference on Harmonization guidelines. ⋯ This 'thorough QT/QTc study' confirmed previous experience with rupatadine and demonstrated that it had no proarrhythmic potential and raised no concerns regarding its cardiac safety.