An educational tool for the care of the hemodialysis patient admitted to an acute care hospital.

The goal of this article was to develop an educational tool for nurses working in an acute care hospital in the hope of improving quality of care for hemodialysis patients. In Canada, the prevalence of end stage renal disease is increasing by approximately 10% annually (Mendelssohn et al., 1999). Today, the hemodialysis patient is often older than previously, and may well have multiple comorbidities resulting in hospital admissions in a multitude of settings. Hemodialysis patients are not always admitted under the nephrology service due to lack of beds or medical necessity. For example, a hemodialysis patient with an acute myocardial infarction would be admitted to a cardiology unit, where the cardiology staff are better able to treat the patient's primary diagnosis. When patients are transferred among the various hospital units, effective communication of knowledge and expertise between nursing staff is essential for care of the hemodialysis patient to be seamless.

2-heterosubstituted-3-(4-methylsulfonyl)phenyl-5-trifluoromethyl pyridines as selective and orally active cyclooxygenase-2 inhibitors.

A series of novel 2-alkoxy, 2-thioalkoxy and 2-amino-3-(4-methylsulfonyl)phenylpyridines has been synthesized and shown to be highly potent and selective cyclooxygenase-2 (COX-2) inhibitors. Structure-activity relationship studies have demonstrated that central pyridine ring substituents play an important role in the COX-2 potency, selectivity vs the COX-1 enzyme, and oral activity.

Thioridazine lengthens repolarization of cardiac ventricular myocytes by blocking the delayed rectifier potassium current.

Proarrhythmia has been observed with the antipsychotic agent thioridazine (THIO). The mechanisms underlying these effects are unknown. The objectives of this study were 1) to characterize the effects of THIO on cardiac repolarization and 2) to determine whether lengthening of the Q-T interval could be explained by blocking major K+-repolarizing currents. Isolated, buffer-perfused guinea pig hearts (n = 32) were stimulated at various pacing cycle lengths (150-250 ms) and exposed to THIO at concentrations ranging from 300 nM to 3 microM. THIO increased monophasic action potential duration at 90% repolarization (MAPD90) in a concentration-dependent manner from 14.9 +/- 1.8 at 300 nM to 37.1 +/- 3.2 ms at 3 microM. Increase in MAPD90 was also reverse frequency-dependent; THIO (300 nM) increased MAPD90 by 14.9 +/- 1.8 ms at a pacing cycle length of 250 ms, but by only 7.7 +/- 1.2 ms at a pacing cycle length of 150 ms. Patch-clamp experiments demonstrated that THIO decreases the time-dependent outward K+ current elicited by short depolarizations (250 ms; IK250) in a concentration-dependent manner. Estimated IC50 for IK250, which mostly underlies IKr, was 1.25 microM. Time-dependent outward K+ current elicited in tsA201 cells expressing high levels of HERG protein was also decreased approximately 50% by 1.25 microM THIO. On the other hand, THIO was less potent (IC50 of 14 microM) to decrease time-dependent K+ current elicited by long pulses (5000 ms; IK5000). Under the latter conditions, IK5000 corresponds mainly to IKs. Thus, these results demonstrate block of K+ currents and lengthening of cardiac repolarization by THIO in a concentration-dependent manner. This may provide an explanation of Q-T prolongation observed in some patients treated with THIO.

Droperidol lengthens cardiac repolarization due to block of the rapid component of the delayed rectifier potassium current.

INTRODUCTION: Torsades de pointes have been observed during treatment with droperidol, a butyrophenone neuroleptic agent. Our objectives were (1) to characterize the effects of droperidol on cardiac repolarization and (2) to evaluate effects of droperidol on a major time-dependent outward potassium current involved in cardiac repolarization (I(K)r). METHODS AND RESULTS: Isolated, buffer-perfused guinea pig hearts (n = 32) were stimulated at different pacing cycle lengths (150 to 250 msec) and exposed to droperidol in concentrations ranging from 10 to 300 nmol/L. Droperidol increased monophasic action potential duration measured at 90% repolarization (MAPD90) in a concentration-dependent manner by 9.8+/-2.3 msec (7.3%+/-0.7%) at 10 nmol/L but by 32.7+/-3.6 msec (25.7%+/-2.2%) at 300 nmol/L (250-msec cycle length). Increase in MAPD90 also was reverse frequency dependent. As noted previously, droperidol 300 nmol/L increased MAPD90 by 32.7+/-3.6 msec (25.7%+/-2.2%) at a pacing cycle length of 250 msec but by only 14.1+/-1.3 msec (13.6%+/-2.3%) at a pacing cycle length of 150 msec. Patch clamp experiments performed in isolated guinea pig ventricular myocytes demonstrated that droperidol decreases the time-dependent outward K+ current elicited by short depolarizations (250 msec; I(K)250) in a concentration-dependent manner. Estimated IC50 for I(K)250, which mostly underlies I(K)r, was 28 nmol/L. Finally, HERG K+ current elicited in HEK293 cells expressing high levels of HERG protein was decreased 50% by droperidol 32.2 nmol/L. CONCLUSION: Potent block of I(K)r by droperidol is likely to underlie QT prolongation observed in patients treated at therapeutic plasma concentrations (10 to 400 nmol/L) of the drug.

2-Pyridinyl-3-(4-methylsulfonyl)phenylpyridines: selective and orally active cyclooxygenase-2 inhibitors.

A series of novel 2-pyridinyl-3-(4-methylsulfonyl)phenylpyridines has been synthesized and evaluated with respect to their ability to inhibit the isozymes of cyclooxygenase, COX-1, and COX-2. Optimum COX-2 activity is observed by introduction of a substituent at C5 of the central pyridine. 5- Chloro-3-(4-methylsulfonyl)phenyl-2-(2-methyl-5-pyridinyl)pyridine 33 was identified as the optimum compound in this series.