Assessment and reporting of clinical pharmacology information in drug labeling.
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Drug Administration Schedule↗
Biomedical subjects
D A Spyker
Publications and source records attributed to D A Spyker.
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.
Adult↗
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.
Adult↗
Screening for disulfiram-induced liver test dysfunction in an inpatient alcoholism program.
The objective of this study was to report the frequency of disulfiram-related elevations of four commonly used hepatic screening chemistries using a retrospective record review design. An inpatient alcoholism program was selected for the setting. Patients who had initial laboratory values within the normal range started daily supervised doses of disulfiram, then underwent follow-up testing after 2 and 4 weeks on the drug. The study population consisted of 108 patients receiving disulfiram and 27 patients who did not receive disulfiram (controls). The four screening serum chemistries performed were aspartate aminotransferase (SGOT), alanine aminotransferase (SGPT), alkaline phosphatase, and gamma-glutamyl transferase. Twenty-seven (25%) of the 108 patients who were taking 250 mg of disulfiram a day for 2 to 4 weeks had disulfiram-related elevations in alanine aminotransferase above the upper limit of normal, as opposed to one elevation in 27 patients (4%) for whom disulfiram was not prescribed. In the 108 patients (with initially normal serum chemistries) who were prescribed disulfiram, 32 were discontinued from the drug at 2 weeks and an additional 11 were discontinued from the drug at 4 weeks because of one or more abnormal serum chemistries. Alanine aminotransferase was the most specific and sensitive indicator of the four screening chemistries performed.
Adult↗
What's in a name?--Regional Toxicology Treatment Centers.
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Humans↗
Massive strychnine intoxication: serial blood levels in a fatal case.
A fatal case of strychnine intoxication is reported. The patient expired despite early aggressive management and prevention of metabolic complications. Serial blood levels are reported. In contrast to a previous report describing first order elimination kinetics, our data suggest that strychnine follows Michaelis-Menton elimination kinetics. The case illustrates the rapid, dramatic course of severe strychnine ingestions. A review of the toxicokinetics, mechanism of action and treatment of strychnine intoxication follows.
Autopsy↗
Massive overdoses with sustained-release lithium carbonate preparations: pharmacokinetic model based on two case studies.
Clinically significant delayed absorption after lithium overdose has been reported previously without adequate explanation. We have studied two patients after they took massive intentional lithium overdoses. The first patient presented shortly after ingesting 74 g of lithium carbonate. Pharmacokinetic analysis with a multicompartmental model of 29 serum lithium concentrations during 300 h (including hemodialysis) established absorption and elimination kinetics. Lithium absorption was both slow (peak concentration 33 h after the initial overdose) and delayed (a second peak occurred at 148 h, 30 h after initiation of oral tube feedings). The delayed absorption of a large fraction of lithium implicated a gastrointestinal drug reservoir. Study of the pharmacokinetics in a second patient, who ingested 98 g of lithium carbonate, provided additional evidence of an endogenous reservoir. This patient's medical management was guided by experience gained from the initial case. Appropriate management for a predicted endogenous drug reservoir may have shortened intensive care and hospitalization. In treating overdoses of sustained-release drug preparations, clinically significant delayed absorption triggered by enteral fluids must be considered as a contributor to delayed absorption.
Adult↗
Enhanced clearance of vancomycin by hemodialysis in a child.
Clearance of vancomycin by hemodialysis has previously been reported to be negligible. We describe a child undergoing chronic hemodialysis using a hollow fiber dialyzer with cellulose acetate membrane. When the patient was treated with intravenous vancomycin for staphylococcal bacteremia, the serum vancomycin half-life was found to decrease by more than 90% during each course of hemodialysis. We conclude that, contrary to prevailing opinion, vancomycin can be rapidly cleared by hemodialysis in the small pediatric patient, and that the dosage should be adjusted accordingly.
Child↗
Comparison of equal-weight oral dosages of verapamil hydrochloride and diltiazem hydrochloride in patients with mild to moderate hypertension.
The clinical efficacy, safety, and tolerability of oral verapamil and diltiazem, at total daily dosages of equal weight, were evaluated in a placebo-controlled, double-blind crossover study. Thirty-six ambulatory patients with chronic, stable, mild to moderate hypertension (supine diastolic blood pressure of 94-116 mm Hg) received a dosage of either verapamil or diltiazem 80 mg t.i.d. as the hydrochloride salt for one week after an antihypertensive-drug washout period. Each then received 120 mg of the same drug t.i.d. for one week. After another two-week washout period, the patients were crossed over to the other drug. Each patient had a 12-lead electrocardiogram and measurement of supine and standing blood pressure weekly. In the 32 patients completing the study, low-dose verapamil reduced supine diastolic blood pressure (DBP) from a mean of 101.5 +/- 5.2 to 95.3 +/- 9.5 mm Hg; high dose verapamil reduced DBP to 90.9 +/- 7.4 mm Hg. Standing DBP was reduced to a similar degree. Diltiazem showed an almost identical effect: Supine DBP was reduced from a mean of 101.7 +/- 5.3 to 94.0 +/- 10.1 mm Hg with the low dose and to 91.0 +/- 8.6 mm Hg with the high dose, with similar effects on standing DBP. The high dose of both drugs significantly increased the QTc interval, and both doses of diltiazem significantly increased the PR interval compared with baseline. Both drugs exhibited consistent efficacy with minimal adverse effects. The electrophysiologic safety profile of verapamil was superior to that of diltiazem.
Aged↗
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.
Animals↗
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.
Adult↗
Serum osmolal gap and ethanol concentration: a simple and accurate formula.
The estimation of serum ethanol concentration by measurement of serum osmolality has been re-evaluated. A formula for calculation of serum osmolality was first validated in 193 patients who had not ingested ethanol. The mean difference between measured and calculated osmolality ("osmolal gap") was 1.5 mOsm/Kg +/- 5.3 mOsm/Kg (1 S.D.). In 37 sera from 35 patients who had ingested ethanol, the osmolal gap was highly correlated with measured serum ethanol (r = 0.994). The serum ethanol (mmol/L) was related to osmolal gap (mOsm/Kg) by the formula: Ethanol = 0.83 X osmolal gap. The factor 0.83 indicated that the behavior of ethanol in serum did not conform to that expected from ideal solutions. This equation accurately predicted serum ethanol in 32 additional samples (r = 0.988). We propose that the formula above be used in place of those that have been previously proposed. The previous formulas involved unwarranted assumptions of ideality and had not been experimentally derived from studies of ethanol in serum.
Ethanol↗
Neurobehavioral sequelae of subcutaneous injection with metallic mercury.
A 19 year old, white male, with nine years of education, attempted suicide by injection of metallic mercury (Hg) into the left forearm. CT scan findings suggesting mercury infiltration of the brain and results from urinalysis indicated clinically high levels of Hg excretion. Premorbid cognitive history was essentially normal, yet comprehensive neuropsychological assessment revealed significant impairment of higher cortical functioning beyond those expected of a moderately to severely disturbed psychiatric patient. Neuropsychological test results appear to offer a more sensitive, quantitative assessment of heavy metal toxicity.
Abdomen↗
Acute amoxicillin nephrotoxicity following an overdose.
A 3 year old boy developed acute renal failure following an ingestion of 574 mg/kg of amoxicillin. Accidental ingestions of oral penicillins occur commonly, and are usually considered completely nontoxic. Based on this case, however, the possibility of adverse effects following large oral doses of penicillin-type antibiotics, mediated by allergic hypersensitivity or direct toxicity, should be considered.
Acute Kidney Injury↗
Activated charcoal in oral ethanol absorption: lack of effect in humans.
Activated charcoal has been recommended for use in poisonings by ethanol, other toxic alcohols and glycols, but it has been avoided with therapeutic use of oral ethanol. Six healthy young adults drank a dose of ethanol designed to give a peak concentration of 125 mg/dl on two different days after overnight fasting. Each individual drank the same dose on both occasions; but on one of these days, the subjects drank an aqueous slurry of 60 g of superactive charcoal prior to ethanol ingestion. We compared the pharmacokinetic profile of ethanol with and without activated charcoal treatment. The fraction of ethanol absorbed was similar on both protocols. The mean peak ethanol concentration after pretreatment with activated charcoal was 8% greater than ethanol alone (p = 0.08). Thus oral activated charcoal does not significantly impair ethanol absorption and can be used in patients requiring oral ethanol. Our results do not support the use of activated charcoal in overdose of ethanol alone. Extending our results to poisonings by other toxic alcohols and glycols, the use of activated charcoal to reduce their absorption deserves evaluation.
Absorption↗
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.
Carbamazepine↗
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.
Adolescent↗
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.
Adolescent↗