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Biomedical subjects

M D Allen

Publications and source records attributed to M D Allen.

At least 19 recordsLinked to original sources
PubMed1979

Lorazepam kinetics in the elderly.

Lorazepam is a 3-hydroxy-1,4-benzodiazepine derivative biotransformed by glucuronide conjugation, followed by urinary excretion of the glucuronide metabolite. The kinetic properties of single 1.5- to 3.0-mg doses of intravenous lorazepam were assessed in 15 healthy elderly subjects, 60 to 84 yr of age, and in 15 healthy young subjects, 19 to 38 yr of age. Volumes of distribution for lorazepam in the elderly group (mean, 0.99 1/kg), were slightly but significantly smaller than in the young group (1.11 1/kg), suggesting less extensive drug distribution in the elderly. Values of elimination half-life (t1/2beta) in the elderly (15.9 hr) did not differ significantly from those in the young group (14.1 hr), but total clearance in the elderly (0.77 ml/min/kg) was 22% less (p less than 0.05) than in the young subjects (0.99 ml/min/kg). Age differences in lorazepam clearance were partly explained by more frequent cigarette smoking in the young subjects. Gender had no apparent relationship to kinetics. The rate and completeness of absorption of intramuscular (IM) and oral loraxepam was assessed in 10 of the elderly subjects. Deltoid IM injection and oral administration of tablets in the fasting state led to rapid absorption of lorazepam into the systemic circulation. Peak plasma lorazepam concentrations were always reached within 2.5 hr, and values of absorption half-life (t1/2a) did not exceed 45 min. Absorption of IM and oral lorazepam was 80% to 100% complete. Thus, the aging process is associated with small changes in the kinetics of lorazepam. IM and oral administration of lorazepam in elderly persons, as in the case of young individuals, leads to rapid and nearly complete absorption into the systemic circulation.

Absorption↗
PubMed1979

Single- and multiple-dose kinetics of estazolam, a triazolo benzodiazepine.

The pharmacokinetic properties of estazolam, a triazolo benzodiazepine hypnotic agent, were assessed in a series of healthy volunteers following single and multiple doses. After single oral doses of 2--16 mg, peak plasma concentrations were reached within 6 h. Values of elimination half-life ranged from 8.3--31.2 h (mean 17.0 h) and did not vary significantly with dose. During 3 weeks of therapy, steady-state plasma concentrations increased approximately in proportion to increasing doses. and accumulation was essentially complete within 3 days of each dose change. The mean observed accumulation ratio was 1.84, which was slightly larger than the predicted ratio of 1.53. Exposure to multiple-dose estazolam therapy had no significant influence on the kinetics of a single dose of antipyrine, suggesting that estazolam neither stimulates nor inhibits enzyme activity in humans. Thus the accumulation and elimination kinetics of estazolam can be classified as intermediate to those of the short-acting (such as oxazepam) and the long-acting (such as diazepam) benzodiazepine derivatives.

Adult↗
PubMed1979

Comparison of the aerodynamic size distribution of chain-like aggregates measured with a cascade impactor and a spiral centrifuge.

Several authors have suggested that chain-like aggregates fragment in the jets of cascade impactors and that the impactor consequently underestimates the median aerodynamic diameter and overestimates the geometric standard deviation (GSD). The aerodynamic size distribution of (Pu0.14U0.86)02.2 aggregates were measured simultaneously with two Mercer cascade impactors and a LAPS spiral centrifuge to investigate this problem. Although the median aerodynamic diameters were generally in good agreement, the impactor consistently measured higher values for the GSD than did the spiral centrifuge. Based on experiments in which losses in the centrifuge inlet were measured, it was concluded that the centrifuge had measured the aerodynamic size distribution more accurately than the impactor. Interception of chain-like aggregates on the first few impactor stages may have been the primary reason for the disparity between the impactor and centrifuge measurements.

Aerosols↗
PubMed1979

Self-poisoning with over-the-counter hypnotics.

Over-the-counter (OTC) hypnotic preparations (such as Sominex, Nytol, and Sleep Eze) were implicated in 21 of the 773 admissions to Massachusetts General Hospital due to psychotropic drug overdosage between 1962 and 1975. Ten of the 21 cases had manifestations of central anticholinergic toxicity ("atropine-like psychosis"), such as hallucinations, delirium, and confusion. However, all patients recovered rapidly and without sequelae. Specific therapy (i.e., physostigmine) was rarely required. Thus OTC hypnotic overdosage commonly produces "toxic psychosis." Fortunately, intoxication is usually of short duration and relatively benign.

Adolescent↗
PubMed1979

Correlates of outcome following acute glutethimide overdosage.

Potential predictors of outcome following acute glutethimide overdosage were assessed in 63 patients hospitalized with this diagnosis at a large urban medical center between 1962 and 1975. Their mean age was 34 years (range, 15 to 84 years) and 62% were female. Assisted ventilation was required in 59% of cases, and 32% developed hypotension. Six patients died, including all three aged 60 years or older. Multiple regression analysis confirmed that age was the major identifiable determinant of survival, regardless of other factors. Among identifiable determinants of coma grade, glutethimide dose, glutethimide plasma concentration, and coingestion of barbiturates were the most important. An ingested dose of 10 g or more, or a plasma concentration exceeding 30 microgram/ml, was almost always associated with deep coma. However, a relatively small ingested dose or a low plasma level by no means ruled out development of serious intoxication, particularly in those patients who also ingested barbiturates. Thus elderly individuals are at high risk for fatal outcome following glutethimide overdosage and should receive priority for intensive care and monitoring. Glutethimide dose, plasma concentration, and history of coingestion of barbiturates are of value in predicting development of deep coma. These items of information should be obtained on admission whenever possible.

Adolescent↗
PubMed1978

Rapid recovery from massive diazepam overdose.

Two patients were hospitalized in moderately deep coma after ingestion of large doses of diazepam (500 and 2,000 mg) with suicidal intent. Neither patient experienced important complications; both recovered fully and were discharged within 48 hours. Concentrations of diazepam and its three pharmacologically active metabolites (desmethyldiazepam, temazepam, and oxazepam) were determined in multiple samples drawn during and after hospitalization. High concentrations of all four compounds were present in early samples, then declined slowly during the next one to two weeks. Rapid clinical recovery after diazepam overdose is not attributable to rapid elimination of active compounds from the body, but more likely to adaptation or tolerance to their depressant effects.

Adult↗
PubMed1978

Intramuscular injection-site complications.

Among 26,294 hospitalized medical patients monitored by the Boston Collaborative Drug Surveillance Program, 46% received at least one intramuscular (IM) injection. Drugs for which IM injection was the route of administration in more than 80% of all exposures included penicillin G procaine, mercurial diuretics, cyanocobalamin, streptomycin sulfate, colistimethate sodium, meperidine hydrochloride, cephaloridine, scopolamine hydrobromide, kanamycin sulfate, and iron dextran injection. Local complications of IM injection were reported in a total of only 48 patients (0.4% of all IM recipients). Local complications were most commonly associated with IM injection of cephalothin sodium. Clinically important local complications are uncommonly associated with IM injections in general. However, certain drugs, eg, cephalothin, produce injection-site complications with relatively high frequency; the clinical role of IM injection of such drugs should be reevaluated.

Abscess↗
PubMed1978

Impaired absorption of desmethyldiazepam from clorazepate by magnesium aluminum hydroxide.

Ten healthy volunteers ingested single 15-mg doses of clorazepate dipotassium (CZP) with 60 ml of water, or with 60 ml of magnesium aluminum hydroxide (Maalox), on two occasions in a randomized, two-way crossover study. Plasma concentrations of desmethyldiazepam (DMDZ) were determined in multiple samples drawn during 48 hr after each dose. Mean kinetic variables for DMDZ in CZP-water and CZP-magnesium aluminum hydroxide treatment conditions, respectively, were: peak measured concentration, 273 and 188 ng/ml (p 0.001); time of peak concentration, 1.8 and 2.8 hr after dose (p less than 0.01); apparent absorption half-life, 14.8 and 30.7 min (p less than 0.02); area under the 48-hr plasma concentration curve, 6,028 and 5,433 ng/ml X hr (p less than 0.02). Self-rated sensations of feedling "spacey," "thinking slowed down," and of generalized sedation, were reported with both treatment conditions, but these subjective effects occurred earlier and were more profound when CZP was taken with water as opposed to magnesium aluminum hydroxide. Thus administration of single doses of CZP with usual doses of a commonly prescribed antacid reduces the rate and extent of appearance in blood of DMDZ (the compound responsible for clinical activity) and attenuates self-rated clinical effects.

Adult↗
PubMed1978

Toxicity of nitrazepam in the elderly: a report from the Boston Collaborative Drug Surveillance Program.

1 To assess the potential hazards of nitrazepam therapy of insomnia in the elderly, adverse reactions to nitrazepam were studied in 2111 hospitalized medical patients who received the drug. 2 Manifestations of unwanted central nervous system (CNS) depression (such as drowsiness or 'hangover') were reported in 49 nitrazepam recipients (2.3%), and signs of unwanted CNS stimulation (such as nightmares, insomnia, agitation, etc.) in 15 (0.7%). None of the adverse reactions were considered serious. 3 Physician-rated clinical efficacy of nitrazepam was not related to dose, but the frequency of both types of adverse reactions increased significantly at higher daily doses. CNS depression also was significantly more frequent in the elderly, being reported in 11% of those aged 80 years or older, whereas the frequency of CNS stimulation was not correlated with age. 4 The effect of age on the reported rate of unwanted CNS depression was most striking at high doses. Among patients aged 80 years or over whose daily dose averaged 10 mg or more, 55% experienced unwanted CNS depression attributed to nitrazepam. 5 Low doses of nitrazepam are safe for elderly individuals, but the elderly are readily susceptible to excessive CNS depression at high doses. The findings suggest that there is little reason to exceed 5mg doses of nitrazepam for most patients, particularly those who are elderly.

Aged↗
PubMed1977

Toxicity of high-dose flurazepam in the elderly.

To assess the potential hazards of flurazepam (Dalmane) therapy of insomnia in the elderly, the relation of dosage and patient age to the frequency of flurazepam-attributed adverse reactions was studied in 2,542 hospitalized medical patients. Adverse reactions, predominantly unwanted residual drowsiness, were reported in 78 flurazepam recipients (3.1%). None of the adverse reactions were serious. The frequency of reported toxicity increased with average daily dose, ranging from 1.3% among those receiving less than 15 mg/day to 12.3% at doses of 30 mg/day or more (p less than 0.001). Toxicity increased with age, progressively from 1.9% among those under 60 to 7.1% among those 80 or over (p less than 0.001). Unwanted effects of high-dose flurazepam were observed much more commonly in the elderly. Only 2.0% of those 70 years of age or older experienced adverse reactions at doses under 15 mg/day, as opposed to 39.0% at 30 mg or more per day. Low doses of flurazepam appear to be safe for elderly individuals, but they are susceptible to unwanted central nervous system depression at high doses.

Adult↗
PubMed1977

Acute overdosage with benzodiazepine derivatives.

A total of 773 admissions to Massachusetts General Hospital between 1962 and 1975 were due to acute overdosage with one or more psychotropic drugs. Benzodiazepine overdosage, particularly with diazepam, increased relative to other psychotropic drugs over the years. Only 12 admissions were due to benzodiazepine overdosage alone, and none of these patients were seriously ill or had significant complications. Multiple drugs were ingested in the other 87 cases, and the frequency and severity of complications among these individuals depended upon the type and quantity of other nonbenzodiazepines taken. For example, 21 of 31 patients who ingested benzodiazepines together with barbiturates experienced severe central nervous system (CNS) depression, and 14 of 31 required assisted ventilation. However, the frequency of such complications was nearly identical in a group of patients who ingested barbiturates alone. This report and a review of the literature suggest that serious intoxication following overdosage with a benzodiazepine derivative alone is unusual. Ingestion of benzodiazepines together with other drugs appears to be considerably more common than benzodiazepine overdosage alone as a cause of intoxication. The severity of intoxication in such cases of multiple drug ingestion probably depends largely on the type and quantity of nonbenzodiazepines.

Adolescent↗