Modulation of ethanol-induced central nervous system depression by ibuprofen.

We investigated the effect of pretreatment with a prostaglandin synthetase inhibitor, ibuprofen, on the pharmacokinetics and pharmacodynamics of ethanol in six fasting subjects. Ibuprofen caused a 10% decrease in the maximum rate of elimination of ethanol. Visual memory, which is a function primarily mediated by the right cerebral hemisphere, was measured by the Benton Visual Retention test and was more impaired during combined ibuprofen and ethanol dosing than during ethanol dosing alone (P = 0.05). The auditory-verbal memory of the subjects, which is primarily a function of the left cerebral hemisphere, was assessed by the Selective Reminding Test and showed decreased impairment during combined ibuprofen and ethanol dosing as compared with ethanol dosing alone (P = 0.04). The opposite effect of ibuprofen on ethanol-induced cognitive impairment as measured by two lateralized functions is consistent with the reports in tissue and animal models that central nervous system effects of ethanol may be mediated at least in part by prostaglandins.

Hemoglobin iron absorption kinetics in the iron-deficient dog.

In the absorption of Hb iron (HbFe), heme is separated from globin in the intestinal lumen and enters mucosal cells where Fe is split off and transported to blood. Previous studies indicated that this final step is the limiting one in absorption of HbFe in normal and Fe loaded animals but not in Fe-deficient animals. The present studies were designed to determine the limiting step in absorption of HbFe in Fe-deficient dogs. Varying Amounts of 59Fe labeled Hb were injected into closed duodenal loops in anesthetized dogs. Each step in the absorptive process was measured: intralumenal separation of the heme from Hb; mucosal uptake of heme; intramucosal splitting of Fe from heme; transport of Fe to blood. This process was characterized using a five compartment kinetic model. The resulting seven rate constants were determined to best describe the observed absorption data. Results show: 1) with increasing dose of 59HbFe, mucosal uptake of heme, Fe split from heme in mucosa, and Fe transported to blood all increase linearly. 2) Mucosal 59Fe-heme accumulates over the 3-hour period while 59Fe does not, indicating rapid transport of 59Fe split from heme. These results suggest that the rate limiting step in absorption of HbFe in Fe-deficient dogs is the splitting of Fe from heme in the mucosa.

Strychnine poisoning. Recovery from profound lactic acidosis, hyperthermia, and rhabdomyolysis.

Strychnine poisoning results in a predictable and treatable sequence of events involving blockade of the inhibitory neurotransmitter, extensor muscle spasms, seizures, and respiratory paralysis. These spasms may lead to hyperthermia, profound lactic acidosis, and rhabdomyolysis. Acidosis is primarily attributable to lactate, as indicated by the correlation between arterial pH and log of lactic acid concentration (r = -0.878). Interruption of the strychnine blockade is the primary therapy for strychnine poisoning. Phenobarbital in moderate doses should be the first intervention and anesthetic doses should be used if necessary. Suppression of convulsions will permit successful management of the complications of strychnine poisoning. Our patient survived, even though at one point he had a pH of 6.55, a lactate level of 32 mM/liter, a temperature of 43 degrees C, and rhabdomyolysis with an increased creatine phosphokinase level of 359,000 mU/ml (5,983 mumol/s/liter).

Use of hemodialysis in meprobamate overdosage.

A case of meprobamate overdosage successfully treated with hemodialysis is described. The patient was admitted 4 hours after an overdosage of meprobamate (30-40 g) deeply unconscious, hypotensive, in respiratory failure and with a serum meprobamate level of 50 mg/100 ml. Hemodialysis was instituted using a Gambro parallel flow dialyzer and a portable re-circulating dialyzate delivery system (Redy, CCi Life Systems). Meprobamate removal with hemodialysis was 672+/-167 mg/hr with a corresponding clearance of 61.97+/-9.9 ml/min. Drug removal with forced diuresis was 177+/-23.4 mg/hr. Metabolic degradation of the drug was approximately 482 mg/hr with a plasma disappearance rate of 5.2%/hr. No drug could be detected in the dialyzate fluid after its passage through the Redy re-circulating dialyzate system. Because of the rapidity of metabolic degradation of meprobamate, we feel that hemodialysis should be reserved for severe clinical intoxication and either compromised normal excretory routes or progressive clinical deterioration.

Submersion injury. Epidemiology, prevention, and management.

The epidemiology of injuries resulting from submersion in water and their prevention are reviewed and the management of submersion injury is detailed.

Poisonings.

While the three demonstration programs failed to document a major impact on prevention of poisoning, they do provide a rationale for selected strategies that may have wide application. Future efforts and successes in poison prevention will involve both the primary care physician and the poison center, using primary and passive interventions. The primary physician can be a source of information and counseling, while the poison center, having succeeded in secondary prevention, can expand its role into primary prevention.

Behavioral treatment of phobic avoidance in multiple chemical sensitivity.

The clinical ecology model of environmental illness, or multiple chemical sensitivity (MCS), and particularly the theoretical assumptions, diagnostic procedures, and therapeutic recommendations promulgated by clinical ecologists are reviewed. No scientific evidence is found for their claims. MCS is conceptualized, instead, as a phobic disorder explicable in terms of the two-factor model of avoidance. Three cases of MCS are discussed in light of this model, and a comprehensive behavioral treatment package that includes biofeedback-assisted in vivo desensitization and cognitive restructuring is proposed.

Fatal transcutaneous iron intoxication.

Accidental iron intoxication is one of the most serious and potentially fatal intoxications in young children. Occurrence in the adult population is rare and is usually associated with a suicide or homicide attempt. Heretofore, all reported cases have involved oral ingestion of ferrous and ferric salts of iron. In a case of fatal iron intoxication reported by Doolin and Drueck, in addition to swallowing a liquid form of ferrous chloride, the patient aspirated it and absorbed it through chemically burned and denuded areas of skin when he fell into a vat of saturated ferrous chloride at work. It is the purpose of this report to describe the first case of fatal iron intoxication in which the sole route of iron absorption was the burned skin. Clinical course of this patient paralleled that of acute oral iron intoxication with development of refractory acidosis, disseminated intravascular coagulation, respiratory and renal failure, and sepsis.

Toxicodynamic approach to management of the poisoned patient.

We recommend a toxicodynamic approach to the management of the poisoned patient. We define the period between ingestion and onset of toxic manifestations (clinical or laboratory) as the preclinical phase, during which the management of the patient necessarily depends solely on the history of ingestion and the predicted toxicity. In the toxic phase during which the patient shows clinical or laboratory evidence of toxicity, the history, clinical status (signs, symptoms, drug levels, laboratory parameters), and toxicodynamics should guide the therapy. In the resolution phase, when the patient shows clinical improvement and declining drug levels, treatment should be based on clinical status. Gastrointestinal decontamination is critical in the first two phases and may be of value during the resolution phase until the body drug burden declines to safe levels. We recommend an aggressive approach to gastrointestinal decontamination, especially in the preclinical phase. With a history of a potentially toxic ingestion of an absorbable drug, an observation period until passage of a charcoal-laden stool should be achieved before discharge of the patient.

Generalized convulsions as the presenting sign of amoxapine intoxication.

Two infants presented for medical evaluation with sudden onset of seizures or coma, without obvious cause. Suspicious circumstances led to toxicological screening analysis. Amoxapine, a recently released antidepressant, was found in the gastric contents of both children an undetermined time after the putative ingestion, but elevated serum concentrations were noted only in one. The pharmacokinetics are described. There were no obvious cardiotoxic or anticholinergic effects in these infants. Thus, they, like older children and adults, manifest mainly central nervous system toxicity rather than the cardiotoxicity and anticholinergic effects of overdose seen with tricyclic antidepressants.

A user-oriented information system for emergency medicine.

A user-oriented Emergency Medical Services Information System ( EMSIS ) has been developed in our medical center that can readily be established by any interested medical center. This minicomputer based system provides online registration of poison center calls, access to the Poisindex (C) data base, concise patient information sheets, access to EMS treatment protocols, assistance in the differential diagnosis of acute poisoning, dosage recommendations for drugs with a narrow therapeutic margin, and kinetic analysis of drug overdoses. Video terminals access EMSIS in the Emergency Department, pharmacy, outpatient medicine clinic, pediatric clinic, medicine wards, poison control center, and biomedical engineering. A PDP 11/70 with 256 Kb core and 48 ports running under RSTS /E V7 .0 supports an average of 20 simultaneous users.

Comparison of US population and live birth rates with poison exposures reported to the National Poison Data System (NPDS): children ages 0-5 years from 2000 to 2012.

BACKGROUND: Monitoring of poison control center data has provided an important public health surveillance tool. Previous work has identified the population with the greatest risk of poisoning as children of < 6 years. It follows that the size of the population at highest risk should be an important driver/factor of poison center volume. Therefore, one would expect population changes to be reflected in corresponding National Poison Data system (NPDS) call volume changes. We examined this relationship. METHOD: This was a retrospective comparison of young children's poison exposures reported to NPDS with changes in US population as reported by the US Census Bureau and by live birth counts in the United States. We examined the relation of population and live birth counts to NPDS exposures in children of 0-5 years and for the total (children of 0-5 years). RESULTS: There was a statistically significant relation between exposures and population for the three of the seven age groups (1-3 years old) and between exposures and live birth counts for the five of the seven age groups (1-4 years old and total (0-5)). The highest correlation was seen with the age groups of 2-year olds (r = 0.815; slope, 4.7373; 95% CI, 2.36-7.11) and 1-year olds (r = 0.785; slope, 4.878; 95% CI, 2.163-7.592). Live birth count was more closely related than population for all but the 1-year-old age groups. DISCUSSION: Our study reports a number of interesting findings including 1) live birth counts and population are closely associated with each other, 2) poison exposures in NPDS were more strongly associated with live birth counts than with population, 3) the population at greatest risk is the 1- and 2-year-old age groups and the strongest associations between exposures and population and exposures and live birth counts occurred in these two age groups, and 4) changes occurring in the live birth counts, both positive and negative, were reflected in annual changes reported in NPDS human exposures in children < 6 years. These results mean that population changes underlie 37%-66% of the changes in poison exposures and suggests that the population at risk should be considered in monitoring poisoning injuries in the future. CONCLUSION: These results provide a quantitative assessment of the age-based risk rates and changes over time for NPDS exposure in children who are 0-5 years old. With the decrease in live births noted over the last 4 years (2008, 2009, 2010, and estimated 2011), US poison centers may expect a similar decline in human exposures in children of 0-5 years. Our analysis adds additional support to the validity of this data set as a public health surveillance tool.

Consistency of dosing with a thermal aerosol generation system: in vitro and in vivo correlation.

Dosing consistency and reproducibility are presented for a novel pharmaceutical inhaler technology based on a thermal condensation process. Two different device platforms producing thermally generated aerosols have been created and used in clinical studies with a number of different drug compounds. Because this approach does not rely on energy from the user to disperse the aerosol particles, aerosol production is reliable, reproducible and virtually user independent following actuation. Pharmacokinetic data from multiple clinical studies show rapid absorption, dose proportionality, and concentration levels and variability similar to intravenous injection. In addition, products used in clinical trials show excellent subject consistency with the vast majority of devices delivering greater than 90% of the loaded dose and little drug exhaled.

The pharmacokinetics and bioavailability of prochlorperazine delivered as a thermally generated aerosol in a single breath to volunteers.

A thermally generated aerosol (TGA) system can effect reliable delivery of excipient-free drug to alveoli, resulting in rapid systemic drug absorption. We developed a pharmacokinetic model of prochlorperazine, administered by inhalation and as a rapid intravenous infusion, and we determined absolute TGA bioavailability in eight healthy volunteers in this institutional review board-approved, two-period crossover study. After the drug was administered as either a 5-s intravenous infusion or a TGA single-breath inhalation, blood was collected at various times for up to 24 h. Plasma prochlorperazine concentrations were measured using liquid chromatography-tandem mass spectrometry. Inhalation and rapid intravenous administration produced similar plasma prochlorperazine concentration profiles. Intravenous and inhalation pharmacokinetics were well characterized by a simultaneous two-compartment model with multiple absorption delays. Prochlorperazine pharmacokinetic parameters were similar to those reported for single intravenous doses. The geometric mean bioavailability after TGA delivery was 1.10. The administration of prochlorperazine by inhalation resulted in pharmacokinetics similar to that seen after intravenous administration, in terms of speed, extent, and consistency of absorption.

Multiple chemical sensitivities--syndrome and solution.

After describing two patients seen by the author, we define multiple chemical sensitivities and discuss the scope of the problem and the epidemiology. Although the incidence of multiple chemical sensitivities is not known, the demographics are similar to that of agoraphobia. The classical conditioning model is proposed as a useful description of multiple chemical sensitivities. The desensitization approach to the diagnosis and treatment is proposed. Results with three patients were encouraging and the approach seems worthy of further evaluation and refinement.

Capsicum and capsaicin--a review: case report of the use of hot peppers in child abuse.

Capsaicin, the active principle of hot peppers of the genus Capsicum, exhibits broad bioactivity. It targets neuronal structures which contain substance P, clinically seen as gastrointestinal and dermatologic irritation, bronchospasm and fibrinolysis. As a research tool, capsaicin profoundly alters neurologic anatomy and function. We review the toxicity of capsaicin and comment briefly on the use of hot peppers in child abuse.

Pharmacokinetics of antimicrobial agents.

The use of formulas or nomograms is not a substitute for or in conflict with measurement of drug levels. We are always obligated to use the best available strategy in choosing a loading and maintenance dose. We must likewise measure and use serum levels for drugs with a narrow therapeutic margin, drugs administered for a long duration of time, and when there is uncertainty about a drug's kinetics. (The classic example is a patient on an aminoglycoside for more than three days, elderly or in renal failure).