Faculty Bibliography

BACKGROUND: The purpose of this trial was to compare the pharmacokinetics of the two available acetaminophen dosage forms in simulated human overdose. METHODS: Ten healthy volunteers received acetaminophen, 75 mg/kg orally, either as the regular release or extended relief formulation in a random, crossover fashion. Blood samples were analyzed using a TDx assay and a best fit correlation of data points was determined by PCNONLIN. RESULTS: The area under the curves for extended relief acetaminophen and regular release acetaminophen were 426 mg h/L and 432 mg h/L, respectively (p = 0.768). The mean half times for extended relief acetaminophen and regular release acetaminophen were 4.02 h and 2.56 h, respectively (p < 0.001). The mean maximum serum acetaminophen concentrations were 62.6 mg/L (414.4 mmol/L:) and 94.3 mg/L (624.3 mmol/L) for extended relief acetaminophen and regular release acetaminophen, respectively (p < 0.001) and the mean time to maximum serum acetaminophen concentrations were 0.87 h and 0.75 h for extended relief acetaminophen and regular release acetaminophen, respectively (p = 0.508). CONCLUSIONS: Although the formulations appear to have equal bioavailability, their half-lives and peak concentrations were significantly different. Further study is required to determine whether these differences affect the assessment and management of poisoned patients

BACKGROUND: Many authors currently recommend infusing the adult dose (1 g) of pralidoxime over a 15-30 minute period. When administered in this manner, computer simulations predict that plasma pralidoxime concentrations will fall below 4 mg/L as early as one and one half hours after administration. The objective of this study was to assess whether a loading dose followed by a continuous infusion would maintain therapeutic levels longer than the traditional short infusion regimen of pralidoxime if the same total dose was administered. METHODS: Utilizing a randomized, crossover design, healthy volunteers were administered either 16 mg/kg of pralidoxime intravenous over 30 minutes or 4 mg/kg of pralidoxime intravenous over 15 minutes followed by 3.2 mg/kg/h for 3.75 h (for a total dose of 16 mg/kg). Pralidoxime levels were obtained at 0, 10, 20, 30, 60, 120, 180, 240, 300, and 390 minutes and patients were observed for vital sign changes and adverse effects. RESULTS: Seven subjects completed both arms of the study. One subject's data were excluded from pharmacokinetic analysis due to aberrant plasma pralidoxime analysis. The loading dose followed by the continuous infusion maintained therapeutic levels for 257.3 +/- 50.5 minutes whereas the short infusion maintained therapeutic levels for 118.1 +/- 52.1 (p < 0.001). Adverse effects were encountered during the short infusion regimen which did not occur during the continuous infusion. Dizziness or blurred vision occurred in all subjects during the short infusion regimen. Additionally, statistically significant increases in diastolic blood pressure occurred during the short infusion regimen. CONCLUSIONS: The results of this study indicate that a loading dose followed by a continuous infusion of pralidoxime maintains therapeutic concentrations for a longer period of time than the currently recommended short infusion regimen in healthy volunteers

OBJECTIVE: To review the adverse effects and risks of deferoxamine for the treatment of iron poisoning. METHODS: A literature search of deferoxamine induced adverse effects was used to identify pertinent articles. The references of these articles served as the source of other references not previously identified. RESULTS: Deferoxamine is a relatively safe antidote for iron intoxication, but adverse effects have been recognized with increased usage, particularly with prolonged intravenous dosing. This paper focuses on deferoxamine induced cardiovascular, pulmonary, ocular and auditory toxicity as well as its potential to increase the risk of infection. Information on iron's toxicology and toxicokinetics and deferoxamine's pharmacology and pharmacokinetics are reviewed. With this background information a hypothesis is generated to maximize deferoxamine benefit while minimizing deferoxamine induced pulmonary toxicity. The hypothesis is based upon a stoichiometric approach to maximal chelation during the first 24 h following iron ingestion. CONCLUSION: Deferoxamine is a relatively safe antidote for iron poisoning but the potential for pulmonary and cardiovascular toxicity should be respected. Studies defining maximum regimens over defined periods of time will allow a more logical utilization of deferoxamine, optimizing benefit and minimizing risk

Beta-adrenergic agonists and theophylline are both capable of producing tremor, agitation, tachycardia, metabolic acidosis, hypokalemia, hyperglycemia, cardiac arrhythmias, and seizures. However, theophylline preparations, especially in the sustained-release formulations, are associated with a much higher incidence of morbidity and mortality secondary to status epilepticus and cardiovascular collapse. Overdoses of sustained-release preparations place patients at exceedingly high risk. This article describes the differentiation of the patient with acute and chronic theophylline overdoses and the implications for management of both clinical states

STUDY OBJECTIVES: To determine the availability and use of premixed activated charcoal in sorbitol preparations during multiple-dose activated charcoal therapy in the emergency department. DESIGN AND SETTING: A prospective telephone survey of all 911 receiving hospitals within the catchment area of one poison center. TYPE OF PARTICIPANTS: Hospital pharmacy supervisors and ED charge nurses. INTERVENTION: Hospital pharmacy supervisors were surveyed about the available preparations of activated charcoal on their hospital's formulary, and ED charge nurses in these same hospitals were surveyed about the prevalence of sorbitol use in multiple-dose activated charcoal regimens. MEASUREMENTS AND MAIN RESULTS: Eleven hospitals (16%) stocked only activated charcoal in sorbitol preparations. Twenty-one hospitals (31%) had both activated charcoal in sorbitol preparations and activated charcoal without sorbitol preparations, and 35 hospitals (52%) had only activated charcoal without sorbitol preparations. Repeat dosing of sorbitol during multiple-dose activated charcoal therapy occurred in 33 of 67 (49%) of the EDs surveyed. CONCLUSION: Sorbitol dosing is often repeated with activated charcoal during multiple-dose activated charcoal therapy in the ED because of the ready availability (and sometimes exclusive availability) of premixed activated charcoal in sorbitol preparations

A study was designed to define the osmol gap in patients whose serum ethanol concentrations are known, to reevaluate several accepted equations for calculating osmolarity, and to apply the results to the theoretical clinical scenario of a toxic alcohol ingestion. The design for the study used consecutive, prospective enrollment of all patients presenting to a large inner city hospital who clinically required determination of their serum ethanol and electrolytes. Three hundred and twenty one consecutive adult patients were enrolled in the study, sixteen were excluded from the final analysis. A stepwise multiple linear regression analysis was performed to determine the best coefficients for sodium, blood urea nitrogen, and ethanol from the data set. Osmolarity was then calculated using these coefficients and traditional models. The osmol gap (measured osmolality minus calculated osmolarity [2*Na + BUN/2.8 + Glu/18 + Etoh/4.6]) was -2 +/- 6 mOsm. Although different equations produced different osmol gaps (ranging from -5 to + 15 mOsm) the standard deviations and correlation coefficients were similar. Large variations exist in the range of osmol gaps. Absolute values are very dependent on the equations used to calculate osmolarity. Because of the larger range of values, small osmol gaps should not be used to eliminate the possibility of toxic alcohol ingestion