Spurious detection of a high serum imipramine level due to coating of Vacutainer stopper.
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Blood Chemical Analysis↗
Biomedical subjects
P Dorian
Publications and source records attributed to P Dorian.
Evaluation of zopiclone physical dependence liability in normal volunteers.
The potential of zopiclone, a non-benzodiazepine sedative hypnotic, to induce physical dependence in normal human volunteers was investigated. 9 male subjects (age range 21-39 years) participated in a 56-day double-blind study with random assignment to initial treatment A or B: (A) zopiclone 7.5 mg p.o. nightly for 21 days followed by placebo for 7 days, and (B) placebo nightly for 21 days followed by placebo for 7 days. Heart rate, blood pressure, hand tremor and auditory-evoked EEG were repeatedly measured during the withdrawal periods. No differences in any of these variables between phases were found (beta = 0.90 for mean differences of 16% between phases). Subjects slept longer (mean 28 min, p less than 0.013) on zopiclone than on placebo. Symptoms of state anxiety were greater on days 2 and 4 after discontinuing zopiclone compared to all other withdrawal days (p less than 0.0021). The mean relative increase on days 2 and 4 was 30%. Sleep depth (self-rating scale) was no deeper on drug than on placebo, but during the withdrawal phases, sleep was less deep on days 2 and 4 of withdrawal from zopiclone compared to all other withdrawal days (p less than 0.0001). Subjects were unable to identify the pattern of drug administration on withdrawal, and none reported important symptoms. Discontinuation of zopiclone (7.5 mg for 21 days) is associated with detectable increase in state anxiety and lighter sleep on days 2 and 4 of withdrawal. Quantitatively, similar changes occur with other hypnotic drugs of relatively low dependence liability.
Adult↗
Influence of hepatic dysfunction on the pharmacokinetics of propafenone.
Hepatic metabolism is the primary process of elimination of propafenone. It therefore is important to understand the effect of altered liver function on the disposition and elimination kinetics of this drug. Patients with abnormal liver function probably will require treatment with propafenone for cardiac arrhythmias; an understanding of the relationship between liver function and the pharmacokinetics of propafenone will provide a rational basis for optimal dosage adjustments in these individuals. Our results demonstrate that both systemic clearance and bioavailability of propafenone are sensitive to variability in liver function. The bioavailability of propafenone is inversely related to the clearance of indocyanine green (ICG), whereas a direct relationship exists between systemic clearance of propafenone and ICG clearance. Comparisons of clinical parameters with the propafenone data yielded interesting results. An overall clinical grading of severity of liver disease based on the presence or absence of portal hypertension (i.e., varices and/or splenomegaly), prior encephalopathy, and ascites did not correlate well with propafenone results. However, albumin, total bilirubin, serum glutamic oxaloacetic transaminase (SGOT) concentrations and prothrombin time values correlated strongly with the overall results. No definite relationships with subjects' age; weight; and hemoglobin, alkaline phosphatase, lactic acid dehydrogenose, cholesterol, blood urea nitrogen, or creatinine levels were detected. These results demonstrate that moderate to severe liver disease significantly affects the absorption and disposition of propafenone. In patients with cirrhosis, and presumably other forms of hepatic dysfunction, careful adjustments of propafenone doses are needed to optimize therapy.
Administration, Oral↗
Panic disorder and the heart: a cardiology perspective.
Panic disorder is a common condition that includes symptoms that may masquerade as a primary cardiovascular disorder. In addition, many patients with cardiovascular disease may also have panic disorder. To date, no definitive pathophysiological mechanism for panic disorder has been found; however, there are several hypotheses in the literature. Patients with syndrome X, coronary artery disease and/or palpitations, in addition to panic disorder all present to cardiologists. However, many patients go undiagnosed and ultimately place large costs on the health care system as a result. Panic disorder is a treatable condition, and cardiologists could easily identify patients with panic disorder and initiate appropriate therapy and/or referral.
Cardiovascular Diseases↗
Nonpharmacological therapy for malignant ventricular arrhythmias: implantable defibrillator trials.
Implantable cardioverter-defibrillators (ICDs) are an important nonpharmacological option in the treatment of malignant ventricular arrhythmias. Technological advances in current devices permit nonthoracotomy implantation with transvenous lead systems using biphasic shocks. Decreasing device size has resulted in pectoral implantation. Battery longevity is still short in comparison with that of pacemakers. Lead failure rates as well as pacing thresholds are significantly higher than those for cardiac pacing lead systems. Other complications of ICD systems include infection, perforation, and thrombosis. The long-term performance of nonthoracotomy lead systems for ICD devices has now been extensively studied. Sudden death recurrence rates for these systems are less than 2% in 3 years and less than 5% at 5 years. Clinical trials with both monophasic and biphasic systems show a high degree of prevention of sudden death. Comparison of ICD outcome with that of drug therapy in three large retrospective studies and two small prospective randomized trials favors improved survival and sudden death prevention with device therapy. However, these studies need corroboration from large prospective trials. Two large prospective trials, CIDS and the AVID study, are now in progress to address this issue.
Amiodarone↗
Psychological resolution of a supraventricular tachycardia.
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Adult↗
Pharmacodynamic modeling of antiarrhythmic drug effects--application to 3-methoxy-O-demethyl encainide.
The pharmacodynamic characteristics of 3-methoxy-O-demethyl encainide (MODE) were studied in instrumented, chloralose-anesthetized dogs. The HIS Purkinje conduction times (HV) were utilized to assess drug effect. Two protocols were conducted; the first protocol involved multiple pairs of loading and maintenance infusions to achieve several steady-state plasma drug concentrations. The second protocol involved a single short infusion. The data from both protocols supported a linear concentration-effect relationship for the concentration range studied. The slopes and intercepts were similar for both data sets. The data from the second protocol were also analyzed to assess the temporal aspects of the pharmacodynamics of MODE. Data analysis indicated that there is significant hysteresis in the plasma concentration-effect relationship that is characterized by a first-order rate constant corresponding to a half-life (t1/2) of approximately 10 min. These study results also demonstrated the advantages of single-infusion protocols over multiple-infusion studies for evaluating the concentration-effect relationship of antiarrhythmic drugs.
Anilides↗
Poor adherence to placebo or amiodarone therapy predicts mortality: results from the CAMIAT study. Canadian Amiodarone Myocardial Infarction Arrhythmia Trial.
OBJECTIVE: This study examined the relationship between adherence, mortality, and psychosocial factors. METHODS: Subjects were 1141 patients participating in the Canadian Amiodarone Myocardial Infarction Arrhythmia Trial. Poor adherence to study medication (amiodarone or placebo), measured by pill count over 2 years, was defined as the lower 20th percentile of the pill count distribution. Predictors of adherence were also studied and included demographic and cardiac variables and, in a subset of participants (N = 671), measures of depression, distress, hostility, and social support. RESULTS: In survival analysis controlling for cardiac and demographic variables, poor adherence in the placebo and amiodarone groups was associated with an increased risk of sudden cardiac death (relative risk (RR) = 2.11, 95% confidence interval (CI) = 1.03-4.56, p < .05; and RR = 3.15, 95% CI = 1.34-7.44, p < .01, respectively), total cardiac mortality (RR = 2.04, 95% CI = 1.12-3.72, p < .02; and RR = 2.49, 95% CI = 1.32-4.72, p < .01, respectively), and all-cause mortality (RR = 2.25, 95% CI = 1.27-3.97, p < .001; and RR = 2.34, 95% CI = 1.32-4.17, p < .004, respectively). Logistic regression analysis identified two predictors of poor adherence to placebo: age > 70 years (odds ratio = 2.18, 95% CI = 1.11-4.29, p < .03) and social activities in the month before the index heart attack (odds ratio = 1.02, 95% CI = 1.00-1.04, p < .05). CONCLUSIONS: Poor adherence is associated with a greater risk of mortality. The relationship between adherence and social activities suggests a higher motivation to adhere to treatment in individuals more engaged in enjoyable activities.
Aged↗
Depression and risk of sudden cardiac death after acute myocardial infarction: testing for the confounding effects of fatigue.
OBJECTIVES: This study examined the impact of depressive symptoms and social support on 2-year sudden cardiac death (SCD) risk, controlling for fatigue symptoms. METHODS: Myocardial infarction (MI) patients (N = 671) participating in the Canadian Amiodarone Myocardial Infarction Arrhythmia Trial completed measures of depression, hostility, and social support. RESULTS: After controlling for significant biological predictors, psychosocial predictors of increased SCD risk in the survival analysis were greater social network contacts (RR = 1.04; 95% CI = 1.01-1.06; p < .007), lower social participation (RR = 0.98; 95% CI = 0.96-1.00; p < .05), and, in placebo-treated patients, elevated depressive symptoms (RR = 2.45; 95% CI = 1.14-5.35; p < .02). Fatigue was associated with SCD (RR = 1.31; 95% CI = 1.11-1.53; p < .001), and, when included in the model, diminished the influence of depression (RR = 1.73; 95% CI = 0.75-3.98; p = .20). When the cognitive-affective depressive symptoms were examined separately from somatic symptoms, there was a trend for an association between cognitive-affective symptoms and SCD in placebo-treated patients after controlling for fatigue (RR = 1.09; 95% CI = 0.99-1.19, p < .06). CONCLUSIONS: Symptoms of depression and fatigue overlap in patients with MI. The trend for the cognitive-affective symptoms of depression to be associated with SCD risk, even after controlling for dyspnea/fatigue, suggests that the association between depression and mortality after AMI cannot be entirely explained as a confound of cardiac-related fatigue. The independent contribution of social participation suggests a role of both depressive symptomatology and social factors in influencing mortality risk after MI.
Activities of Daily Living↗
The effect of sinus node depression on heart rate variability in humans using zatebradine, a selective bradycardic agent.
Zatebradine is a bradycardic agent with a selective effect on the pacemaker current in the sinus node. The effect of such drugs on heart rate variability is not known. Thirty-six patients without structural heart disease were randomly assigned to receive 10 mg of zatebradine i.v. (n = 24) or isotonic saline (n = 12). Heart rate variability (HRV) was recorded as power in the very low frequency (VLF, 0.003-0.040 Hz), low frequency (LF, 0.040-0.150 Hz), and high frequency (HF, 0.150-0.400 Hz) spectral bands as well as total power (TP, 0.003-0.400 Hz) during 5-min ECG acquisitions at baseline, 30, and 60 min following the start of the infusion. No change in heart rate variability was detected in the control group. Zatebradine significantly reduced heart rate variability at 60 min in all frequency bands: VLF (-12+/-4%, p<0.001), LF (-19+/-4%, p<0.001), and HF (-26+/-5%, p<0.001). The reduction in HRV following zatebradine is due to depression of sinus node response to all external stimuli and underscores the need for documentation of normal sinus node function in HRV research.
Adult↗
Isoproterenol antagonizes drug-induced prolongation of action potential duration in humans.
The effects of an isoproterenol infusion on the duration of the human right ventricular endocardial monophasic action potential at 90% repolarization were recorded in the absence and in the presence of an antiarrhythmic drug regimen containing class III effects in two similar groups of patients. The drugs used were amiodarone (N = 3, 300 +/- 50 mg), sotalol plus quinidine (N = 11, 156 +/- 13 mg sotalol, 1688 +/- 594 mg quinidine), and sotalol alone (N = 3, 300 +/- 20 mg). All patients had underlying coronary disease but no evidence of inducible ischemia. In the absence of antiarrhythmic drug, isoproterenol did not significantly change the relationship of action potential duration at 90% repolarization to cycle length; there was a linear decrease in action potential duration by 19.8% between a paced cycle length of 600 and 300 ms. Isoproterenol did not significantly shorten the action potential duration at any cycle length. However, isoproterenol decreased the ventricular effective refractory period at 400 ms drive from 240 +/- 5.0 to 225 +/- 6.0 ms (p < 0.05) accompanied by no change in the ratio of refractory period to steady-state action potential duration. In the presence of class III drug effects, the action potential duration was increased by an average of 9.2% at all paced cycle lengths longer than 300 ms (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Action Potentials↗