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W A Watson

Publications and source records attributed to W A Watson.

At least 73 records · Page 4Linked to original sources

Activated charcoal and acetylcysteine absorption: issues in interpreting pharmacokinetic data.

Studies determining the effects of activated charcoal on drug absorption frequently use area under the plasma drug concentration versus time curve or drug and metabolite recovery in the urine as endpoints. The considerations in using these endpoints is presented using studies that have evaluated the effects of activated charcoal on acetylcysteine absorption. Acetylcysteine's pharmacokinetics, quantitation of plasma concentrations, and the lack of an identifiable pharmacokinetic-pharmacodynamic relationship all contribute to the difficulties in determining whether activated charcoal inhibits the oral absorption of acetylcysteine, or alters acetylcysteine's efficacy in treating acetaminophen overdoses. The results of these studies should be interpreted cautiously, with consideration of internal and external study validity.

Absorption↗

The emergency department treatment of dyspepsia with antacids and oral lidocaine.

The treatment of dyspepsia in the emergency department often consists of antacid in combination with viscous lidocaine, even though the specific etiology of the pain is frequently unknown. The efficacy of lidocaine as a component of symptomatic therapy was evaluated in a randomized, patient-blinded protocol. Patients presenting to the ED with dyspeptic symptoms were randomized to receive 30 mL of antacid (Mylanta II), or 30 mL of antacid plus 15 mL of 2% viscous lidocaine (GI cocktail). Patients recorded their pain score on an 11-cm linear analog scale prior to and 30 minutes after treatment. Seventy-six patients were enrolled; three were excluded from analysis due to incomplete data. Thirty-four patients were randomized to receive antacid and 39 to receive GI cocktail. Patients rated their baseline pain at 6.4 +/- 2.8 cm in the antacid group and 6.7 +/- 2.7 cm in the cocktail group (P greater than .50). Improvement in pain score with treatment was 0.9 +/- 2.9 cm in the antacid group compared with 4.0 +/- 3.4 cm in the GI cocktail group (P less than .0001). Assessment of pain relief using a five-point rating scale also indicated greater relief with GI cocktail therapy compared with antacid alone (P = .004). No adverse effects were noted with either treatment. We conclude that a single dose of antacid and viscous lidocaine provides a significantly greater degree of immediate pain relief than antacid alone in patients with dyspepsia.

Acute Disease↗

Clinically significant radiograph misinterpretations at an emergency medicine residency program.

Radiographic misinterpretation rates have been suggested as a quality assurance tool for assessing emergency departments and individual physicians, but have not been defined for emergency medicine residency programs. A study was conducted to define misinterpretation rates for an emergency medicine residency program, compare misinterpretation rates among various radiographic studies, and determine differences with respect to level of training. A total of 12,395 radiographic studies interpreted by emergency physicians during a consecutive 12-month period were entered into a computerized data base as part of our quality assurance program. The radiologist's interpretation was defined as correct. Clinical significance of all discrepancies was determined prospectively by ED faculty. Four hundred seventy-five (3.4%) total errors and 350 (2.8%) clinically significant errors were found. There was a difference in clinically significant misinterpretation rates among the seven most frequently obtained radiograph studies (P less than .0005, chi 2), accounted for by the 9% misinterpretation rates for facial films. No difference (P = .421) was noted among full-time, part-time, third-year, second-year, and "other" physicians. This finding is likely due to faculty review of residents' readings. Evaluation of misinterpretation rates as a quality assurance tool is necessary to determine the role of radiographic quality assurance in emergency medicine resident training. Educational activities should be directed toward radiographic studies with higher-than-average reported misinterpretation rates.

Diagnostic Errors↗

Clinical utility of a saliva alcohol dipstick estimate of serum ethanol concentrations in the emergency department.

Rapid determination of serum ethanol concentrations can be a useful adjunct in evaluating patients with decreased levels of consciousness. Previous reports suggest that saliva ethanol concentrations measured by a colorimetric saliva dipstick assay correlate well with serum ethanol concentrations and could be useful in the emergency department. We compared saliva dipstick assay results with concurrent serum ethanol measurements in 67 emergency department patients with altered mental status. Color changes of the stick are calibrated to reflect serum ethanol concentrations of negative (no color change), 4.3 mmol/L, 10.8 mmol/L, 21.7 mmol/L, and greater than or equal to 65.1 mmol/L. Emergency department staff were instructed to conduct the measurement according to the manufacturer's directions and round up equivocal results to the next highest concentration. Serum ethanol concentrations (mean +/- SD) grouped by dipstick results were: negative, 5.2 +/- 13.1 mmol/L; 4.3 mmol/L, 29.1 +/- 18.0 mmol/L; 10.8 mmol/L, 46.6 +/- 27.6 mmol/L; 21.7 mmol/L, 47.0 +/- 18.5 mmol/L; and 65.1 mmol/L, 62.4 +/- 24.2 mmol/L. There were 12 false-negative and 2 false-positive results. Correlation between dipstick results and serum ethanol concentrations was rho = 0.611 (p less than 0.0005). The lack of accuracy of the saliva dipstick measurements and the high number of false-negative results make it a poor choice for determining alcohol use in the emergency department patient.

Colorimetry↗

The safety of halobetasol 0.05% ointment in the treatment of psoriasis.

The effects on the hypothalamic-pituitary-adrenal axis of the ultra-high potency corticosteroid halobetasol in the treatment of psoriasis were evaluated in seven patients with extensive, long-standing plaque psoriasis. Each patient applied 3.5 g halobetasol 0.05% ointment in the morning and evening for 7 days. Morning plasma cortisol levels and 24-hour urinary excretion of 17-hydroxycorticosteroid were determined before and on the last 2 days of treatment; plasma cortisol levels were also determined 4 and 5 days after completion of therapy. Morning plasma cortisol concentrations did not decrease significantly during treatment, and no values were below the normal range. Mean 24-hour urinary 17-hydroxycorticosteroid excretion fell from 6.6 +/- 1.4 mg to 5.1 +/- 1.4 mg. Two patients had mild, localized pruritus and stinging with the initial ointment application. No other adverse cutaneous effects were observed. Halobetasol was also clinically efficacious over the 7 days of treatment, based on evaluation of pruritus, erythema, scaling, and plaque elevation. These results demonstrate no adverse effects of the drug on the hypothalamic-pituitary-adrenal axis at doses that are clinically effective in the management of plaque psoriasis.

17-Hydroxycorticosteroids↗

The effect of sucralfate pretreatment on the pharmacokinetics of ciprofloxacin.

Based on the results of our study of norfloxacin-sucralfate coadministration, we suspected that sucralfate would interact also with ciprofloxacin if the drugs were administered concurrently. Therefore, we decided to give a 1-g dose of sucralfate at 6 and 2 hours before a single 750-mg dose of ciprofloxacin and evaluate its effect on the bioavailability of ciprofloxacin. Twelve healthy, male volunteers received ciprofloxacin alone and with sucralfate pretreatment in a randomized, balanced, crossover design. Blood and urine samples were collected over 24 hours after ciprofloxacin administration, and drug concentrations were assayed by high-performance liquid chromatography. When sucralfate was given at 6 and 2 hours before ciprofloxacin, an average 30% decrease in ciprofloxacin's bioavailability was noted (p less than 0.05). Four of the 12 subjects, however, had decreases in the agent's area under the curve of more than 50% with sucralfate pretreatment. The results of this study suggest that ciprofloxacin and sucralfate should not be administered concurrently until a dosing interval is found that will avoid this potential interaction.

Adult↗

Magnesium toxicity secondary to catharsis during management of theophylline poisoning.

Multiple doses of oral activated charcoal are used increasingly to promote elimination of toxins that have already reached the bloodstream; this is often referred to as gastrointestinal dialysis. Cathartics usually are used in conjunction to hasten transit of the charcoal-adsorbed toxin. In the present case, a regimen of activated charcoal and magnesium citrate was used to treat a patient with theophylline poisoning. It was effective in lowering the patient's serum theophylline concentration but produced an elevated magnesium level associated with decreased responsiveness, confusion, and diminished deep tendon reflexes. Magnesium citrate may not be the optimal cathartic for use in gastrointestinal dialysis, at least in selected patients. Sorbitol has been shown to produce a more rapid catharsis without disturbing magnesium serum concentrations. Therefore, the use of sorbitol in place of magnesium citrate, at least in selected patients, may be preferred.

Aged↗

Large surface area activated charcoal and the inhibition of aspirin absorption.

Activated charcoal's adsorptive capacity, and therefore potential efficacy, is generally related to its surface area. In our study, the efficacy of two activated charcoal preparations, Actidose-Aqua 1,500 m2/g and Super Char, 3,000 m2/g, were compared on the basis of their ability to inhibit aspirin absorption. Twelve healthy male subjects fasted for eight hours before and four hours after a 20 mg/kg oral dose of aspirin. One hour after aspirin dosing, each subject received either no charcoal, 25 g Actidose-Aqua, or 25 g Super Char in a randomized crossover design. Each aspirin dose was separated from the previous dose by at least seven days. Total urine volumes were collected over 12-hour intervals, beginning 12 hours before the aspirin dose and continuing for 72 hours after dosing. Urine salicylate concentration was measured with a colorimetric assay. The fraction of aspirin dose recovered in the urine was 0.96 +/- 0.13, 0.78 +/- 0.18, and 0.50 +/- 0.20 for the control, Actidose-Aqua, and Super Char treatment phases, respectively. In vitro, Super Char was found to bind more salicylic acid than Actidose-Aqua at pH 8.1. We conclude that both activated charcoal preparations significantly reduced the gastrointestinal absorption of aspirin (P less than .05) and that Super Char was significantly more effective than Actidose-Aqua in reducing the gastrointestinal absorption of aspirin (P less than .01).

Absorption↗

Effects of aluminum and magnesium antacids and ranitidine on the absorption of ciprofloxacin.

The effect of an antacid (Maalox) and ranitidine administration on the absorption of ciprofloxacin was evaluated in healthy male volunteers who were enrolled in three separate studies. Each study was designed at a three- or four-period crossover and included the administration of 750 mg ciprofloxacin alone as a control treatment. Treatments that were evaluated included the administration of ciprofloxacin 5 to 10 minutes, 2 hours, 4 hours, and 6 hours after a single 30 ml dose of antacid; the administration of antacid 2 hours after ciprofloxacin was given; and the administration of ciprofloxacin 2 hours after a 200 mg ranitidine tablet. Administration of antacid within 4 hours before ciprofloxacin dose resulted in a significant decrease in ciprofloxacin absorption (p less than 0.05). Percentages of relative bioavailability compared with control values were 15.1%, 23.2%, and 70% for the 5 to 10 minute, 2 hour, and 4 hour antacid pretreatments, respectively. Administration of antacid 6 hours before or 2 hours after the ciprofloxacin dose did not affect absorption. Ranitidine did not alter ciprofloxacin absorption. Antacids that contain magnesium and aluminum salts may reduce the absorption of ciprofloxacin. The extent of this interaction appears to increase as the time between administration of the two drugs decreases. Ranitidine is suggested as an alternative to antacids for patients receiving treatment with ciprofloxacin.

Adult↗

Effects of magnesium citrate and clidinium bromide on the excretion of activated charcoal in normal subjects.

The efficacy of cathartics in shortening the gastrointestinal transit time of activate charcoal (AC) in the presence of drugs that alter gastrointestinal motility has not been determined. We evaluated the effects of magnesium citrate (MC) on the excretion of activated charcoal in healthy volunteers alone and with concurrent administration of the anticholinergic drug clidinium bromide. Forty subjects were randomized to clidinium bromide 5 mg or placebo capsule (PC), followed by activated charcoal 15 g and magnesium citrate or a placebo liquid (PL). The onset and duration of excretion of activated charcoal were noted. Mean onset times for activated charcoal were: group I (CB, MC) 4.5 +/- 2.1 h; group II (CB, PL) 17.0 +/- 10.0 h; group III (PC, MC) 6.3 +/- 5.8 h; and group IV (PC, PL) 20.6 +/- 8.4 h. The onset of excretion of activated charcoal was statistically different in both magnesium citrate groups as compared with the placebo liquid groups. The duration of activated charcoal in the stool was similar among the groups. The addition of clidinium bromide did not appear to affect gastrointestinal transit time. These results support previous studies of the effects of cathartics on the excretion of activated charcoal, and suggest that cathartic efficacy is not inhibited by anticholinergic drugs when used in therapeutic doses.

Adult↗

Thiopental-sparing properties of butorphanol/diazepam for induction of anesthesia in ambulatory gynecologic surgery.

Butorphanol/diazepam was compared with thiopental for induction of anesthesia, and the thiopental-sparing effects of butorphanol/diazepam determined. One hundred women, American Society of Anesthesiology physical status class I, undergoing ambulatory, elective termination of pregnancy were randomized to receive either butorphanol 2 mg plus diazepam 10 mg, or thiopental, until loss of the lid reflex occurred. The butorphanol/diazepam group received supplemental thiopental as necessary to attain adequate induction of anesthesia. The combination of butorphanol and diazepam significantly reduced the thiopental dose required to produce loss of the lid reflex, from 4.2 +/- 0.8 to 0.8 +/- 0.6 mg/kg (p less than 0.005), with 22 percent of the patients not requiring supplemental thiopental. The intraoperative course and anesthetic requirements were similar between the two groups. Lower recovery room rating scale values upon arrival at the recovery room were attributed to significantly higher weight-normalized doses of butorphanol (p = 0.004) and diazepam (p = 0.005). The duration of the recovery room stay was 68.8 +/- 24.9 min for the control group, and 80.8 +/- 29.0 min for the butorphanol/diazepam-treated patients (p = 0.026). There were no clinically significant differences in anesthesia or postanesthesia recovery. The combination of butorphanol and diazepam has a significant thiopental-sparing effect, and is a useful induction technique for short, ambulatory surgical procedures.

Abortion, Induced↗

Zinc phosphide ingestion: a case report and review.

We present the case of a patient who attempted suicide by ingestion of the rodenticide zinc phosphide. Zinc phosphide manifests its immediate toxicity through production of phosphine gas. Signs and symptoms of toxicity include nausea, vomiting, dyspnea, and changes in mental status; immediate death results from pulmonary edema. Delayed effects are secondary to the absorption of phosphide, affecting primarily the liver, heart and kidneys. Delayed deaths are related to a direct cardiotoxicity. Treatment is mainly symptomatic and supportive; aggressive airway management and circulatory support are critical to a successful outcome.

Adult↗

Kidney function during naproxen therapy in patients at risk for renal insufficiency.

The effects of naproxen on renal function in 34 patients with minimally elevated serum creatinine (Scr) or subnormal creatinine clearance (Ccr) were evaluated in a parallel-design study. All patients received open-label naproxen 375 mg twice daily for 2 weeks (phase I); patients were then randomly assigned to receive naproxen 750 mg twice daily (n = 26) or to continue naproxen 375 mg twice daily (n = 8) double-blind for an additional 2 weeks (phase II). Renal function was assessed by Scr, Ccr, and BUN measurements at baseline and at the end of each treatment phase. Neither treatment group had a clinically meaningful change in median laboratory values between baseline and the end of phase I, or between baseline and the end of phase II. During the first 2 weeks of treatment with naproxen 375 mg twice daily, there was no change in Scr. At the time of the first Scr measurement following the increase in naproxen dose to 750 mg twice daily, 13 of 26 patients had Scr levels of 1.1 mg/dL or higher, but four days later, only three patients had Scr levels of 1.1 mg/dL or higher, suggesting that a transient increase in Scr may accompany dosage increase. Chronic administration of naproxen 375 mg twice daily in patients at risk for renal insufficiency based on laboratory evidence of renal impairment was not associated with further deterioration in renal function. An increase in dosage to 750 mg twice daily in such patients appeared to be associated with only small, transient changes in laboratory measures of renal function.

Adult↗

Unpredictable anaphylactic reaction to protamine sulfate.

Anaphylactic reactions to protamine administration often can be predicted by the presence of patient risk factors. In the case described, an anaphylactic reaction to protamine occurred in a patient without identifiable risk factors. A history of prior protamine exposure, fish allergy, or vasectomy suggests patients may be at greater risk for anaphylactic response to protamine; however, patients can develop anaphylaxis in the absence of such factors.

Anaphylaxis↗