James R. Shipe

Relation between amiodarone and desethylamiodarone plasma concentrations and electrophysiologic effects, efficacy and toxicity

Because the value of monitoring amiodarone plasma concentrations remains undefined, this study was performed to evaluate its role during the management of patients receiving amiodarone. The early electrophysiologic effects of amiodarone were assessed in 40 consecutive patients with coronary artery disease and sustained ventricular tachycardia or fibrillation who underwent electrophysiologic studies and measurement of amiodarone plasma concentration before and 29 +/- 15 (mean +/- SD) days after initiation of therapy. Amiodarone and desethylamiodarone plasma levels did not correlate with changes in either sinus cycle length, QTc interval, ventricular effective refractory period, AH and HV intervals or ventricular tachycardia cycle length. Amiodarone and desethylamiodarone plasma concentrations and the effects of the drug on conduction intervals or right ventricular effective refractory periods were not related to suppression of arrhythmia induction by ventricular stimulation after 1 month of therapy. The relation between amiodarone plasma concentrations and both toxicity and efficacy during long-term therapy were prospectively assessed in a larger series of 114 consecutive patients with either symptomatic supraventricular or ventricular arrhythmias who were followed up on long-term amiodarone therapy for 26 +/- 15 months. Sixty-three patients (55%) had one or more adverse effects attributed to amiodarone. By life-table analysis, 40, 69 and 80% of patients had experienced an adverse reaction after 1, 2 and 3 years of therapy, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Human Xylazine Overdose: A Comparative Review with Clonidine, Phenothiazines, and Tricyclic Antidepressants

We report a case of horse tranquilizer (xylazine) overdose from oral ingestion in man, detail a gas-liquid chromatography/mass spectrometer method for xylazine assay in the blood and urine, and suggest the management of acute poisoning. We present a comparative review of some toxicological properties that xylazine shares with the pharmacologically related clonidine and with the structurally related phenothiazines and the tricyclic antidepressants.

The reversal of amiodarone-induced perioperative reduction in cardiac systolic reserve in dogs

There is controversy about the myocardial depressant effects of amiodarone in patients with decreased cardiac function undergoing surgery. Some surgeons believe that these effects complicate the discontinuation of cardiopulmonary bypass. Accordingly, the hemodynamic effects of amiodarone were evaluated in two groups of anesthetized mongrel dogs that had undergone a median sternotomy. A control group of 10 dogs and an amiodarone-treated group (15 mg/kg per day for 3 weeks) of 10 dogs were studied, and serum (0.26 to 1.09 micrograms/ml) and tissue (cardiac 2.97 to 11.60 micrograms/ml) levels of amiodarone were measured by liquid chromatography. Hemodynamic measurements were made at baseline and after administration of routine therapeutic intravenous doses of dobutamine (10 micrograms/kg per min), isoproterenol (0.06 micrograms/kg per min) and epinephrine (2 micrograms/min). The amiodarone-treated dogs had a smaller increase in cardiac output compared with baseline than did control dogs. For each drug when the amiodarone-treated group was compared with the control group, increases in cardiac output (liters/min) were: dobutamine, 1.32 +/- 0.24 versus 1.73 +/- 0.31; isoproterenol, 0.84 +/- 0.26 versus 1.43 +/- 0.28; epinephrine, 0.25 +/- 0.15 versus 0.44 +/- 0.53. Amiodarone-treated dogs were also given higher doses of drugs, dobutamine (50 micrograms/kg per min), isoproterenol (1.2 micrograms/kg per min) and epinephrine (20 micrograms/min). Increases in cardiac output were 1.24 +/- 0.24, 1.62 +/- 0.25 and 2.82 +/- 0.64, respectively. All cardiac outputs were significantly increased from the baseline values (p less than 0.05) except those measured in the amiodarone group receiving the lower dose of epinephrine. Thus, amiodarone-treated dogs have a relative reduction of perioperative cardiac systolic reserve.(ABSTRACT TRUNCATED AT 250 WORDS)

Polyamines as tumor markers.

(1981). Polyamines as Tumor Markers. CRC Critical Reviews in Clinical Laboratory Sciences: Vol. 16, No. 1, pp. 1-34.

Carbamazepine toxicity: comparison of measurement of drug levels by HPLC and emit and model of carbamazepine kinetics

A 23-month-old boy accidently ingested 2000 mg (148 mg/kg) of carbamazepine. The delayed onset of convulsions coincided with the peak serum level of total parent drug and an active metabolite (carbamazepine 10,11-epoxide). Comparisons of homogeneous enzyme multiplied immunoassay technique (EMIT) and high pressure liquid chromatography (HPLC) revealed that the EMIT slightly over-estimated plasma carbamazepine levels due to immunochemical cross reactivity with the epoxide metabolite. The peak plasma levels of the parent drug plus the active metabolite were more accurately determined by HPLC. These results emphasize the need to understand both the presence of active metabolites and characteristics of the assay being used in managing clinical intoxication with carbamazepine.

Acute electrophysiologic effects of bethanidine sulfate in patients with ventricular tachycardia or fibrillation

Ten patients with a history of ventricular tachycardia or ventricular fibrillation underwent electrophysiologic study with programmed stimulation before and 90 minutes after oral administration of bethanidine sulfate, 20 mg/kg. Mean plasma bethanidine concentration was 2.62 +/- 2.2 (+/- SD) micrograms/ml at the start of repeat testing. This dose of bethanidine produced no effect on sinus node function, atrioventricular conduction, or atrial or ventricular refractoriness. Ventricular tachycardia or fibrillation, inducible in all patients during the control study, could still be initiated by ventricular stimulation in 9 of 10 patients after bethanidine. Bethanidine suppressed the ability to initiate an arrhythmia in one patient with ventricular fibrillation during control stimulation. Orthostatic hypotension was seen in all patients despite pretreatment with the tricyclic antidepressant, protriptyline, 15 mg every 8 hours. The results suggest that bethanidine has few electrophysiologic effects and is of limited efficacy during electrophysiologic testing in patients with life-threatening ventricular arrhythmias.