Plasma protein binding of phencyclidine.

In healthy male subjects (n = 12) phencyclidine (PCP) free fraction was 22.0 +/- 2.8 % (mean +/- SD).

Difficulties in assessing adverse drug reactions in clinical trials.

1. The discovery of an adverse drug reaction (ADR) depends on: the relative frequencies of the drug-related and non-drug events; the mechanism of drug-induced toxicity; the number of patients exposed to the drug; and the methods used for detecting toxicity. Clinical trials are usually short-term studies conducted in a few hundred patients before marketing a drug.

Development of optimal treatment tactics for alcohol withdrawal. I. Assessment and effectiveness of supportive care.

The relative roles of supportive care and pharmacotherapy in the treatment of alcohol withdrawal are not established. A reliable and validated withdrawal severity assessment scale (Clinical Institute Withdrawal Assessment for Alcohol, CIWA-A) was developed to assess initially and then follow the clinical course of 38 hospitalized chronic alcoholics requiring hospitalization for withdrawal but without serious concurrent medical or surgical problems. Supportive care, consisting of standardized half-hourly patient assessment (CIWA-A) and nursing care, was used as the initial treatment for all patients.

Disposition of intravenous propylthiouracil.

Propylthiouracil was administered to 10 healty, male volunteers by a short intravenous infusion. Plasma and urinary drug concentrations were determined by a specific high-performance liquid chromatography assay, and protein binding was determined by equilibrium dialysis. After infusion, the plasma concentrations declined biexponentially, and the following median parameters (and ranges) were determined: clearance 273.

Treatment of acetaminophen poisoning.

Acetaminophen is an analgesic that is frequently used in Canada, and the occurrence of overdoses with this drug seems to be increasing. The most serious complication of acetaminophen overdose is hepatic failure. Because of pathophysiologic effects of acetaminophen poisoning and the mechanisms of its toxic effects are now better understood, a rational approach to treatment is possible.

Effect of short- and long-term alcohol use on phenytoin kinetics in chronic alcoholics.

Phenytoin kinetics during long-term alcohol use and withdrawal were studied in 11 male alcoholics with a history of withdrawal seizures and no evidence of chronic liver disease. Ethanol, 20% v/v, was given for 6 days after admission to maintain the blood alcohol level between 500 and 800 mg/l and phenytoin suspension, 150 mg, was given orally or intravenously (on three occasions) every 12 hr for 20 days. The mean (+/- SD) total phenytoin clearance in 9 of 11 subjects was 0.

Barbiturate and hypnosedative withdrawal by a multiple oral phenobarbital loading dose technique.

Although intravenous phenobarbital loading is effective in barbiturate withdrawal, controlled infusions of a drug are inconvenient. To develop a practical and more widely applicable method, oral loading doses of phenobarbital were given to 21 barbiturate addicts, whose estimated mean daily intake of barbiturates was 1 gm (range 0.5 to 4 gm).

Further studies on plasma proteins, lipids, and dye- and drug-binding in a child with analbuminemia.

A previously reported patient with analbuminemia was re-investigated after 4 1/2 years, at age 6. The serum albumin concentration was 150 mg/L by radioimmunoassay. Most of the observed increase in total plasma protein over the 4 1/2 years was attributable to gamma-globulin.

Phencyclidine ingestion: drug abuse and psychosis.

Phencyclidine (PCP) is a popular illicit drug often misrepresented as some other hallucinogenic substance and distributed in widely varying dosage forms and strengths. Users of hallucinogenic drugs may present with unintentional PCP overdoses. Toxicological laboratory analyses are essential to establish the diagnosis.

Acute and chronic drug abuse emergencies in Metropolitan Toronto.

From 3,548 drug overdose or abuse cases presenting at 21 Metropolitan Toronto hospitals' Emergency departments, data concerning demographic and medical characteristics, investigative and management procedures, drug analysis services, and disposition of patients were collected. Of the 3,548 cases, 2,723 (77%) were acute overdose and 816 (23%) were drug abuse. Drug overdose was more common than drug abuse for both sexes, but was more characteristic of females.

Methadone binding to orosomucoid (alpha 1-acid glycoprotein): determinant of free fraction in plasma.

The distribution of basic drugs in blood differs qualitatively from that of acidic drugs. The binding of racemic, d-methadone, and l-methadone to human plasma and isolated protein fractions was studied by equilibrium dialysis at 37 degrees. In plasma samples from 29 healthy subjects free fraction of dl-methadone was (mean% +/- SD) 10.

Intravenous diazepam and oral ethanol interaction.

The mechanism of the interaction between ethanol and diazepam is not known. Six healthy male subjects (aged 21 to 32 yr) were randomly assigned in a balanced crossover study to each of two treatments, 28 days apart: (1) diazepam 10 mg intravenously over 20 min, preceded by 60 min with ethanol 0.7 gm/kg (diluted to 20% v/v) orally over 15 min and followed for 8 hr by ethanol 0.

Variability in heparin effect on serum drug binding.

Heparinized saline was given to seven men and one woman, aged 21 to 42 yr, after a 14-hr fasting period and 2 hr after breakfast; blood was collected in nonoheparinized tubes. Diazepam (D alpha) and warfarin (W alpha) free fractions were determined in serum by equilibrium dialysis to which radiolabeled drug was added. After 50 U heparin (Harris LO14) intravenously, the maximum effect on D alpha, W alpha, and free fatty acids (FFA) developed in 5 min and lasted 20 to 30 min.

Propranolol and chlordiazepoxide effects on cardiac arrhythmias during alcohol withdrawal.

The pattern of cardiac arrhythmias and their treatment, by propranolol and chlordiazepoxide, during the first 48 hr of alcohol withdrawal has been studied. Prior to treatment, the incidence of serious and life-threatening arrhythmias was found to be very low and uncorrelated with most biochemical parameters. Propranolol treatment, while efficacious in controlling arrhythmias, was limited due to its association with hallucinations.

Alcohol use by patients admitted to hospital emergency rooms for treatment of drug overdose and misuse.

Persons admitted to hospital emergency rooms for treatment of drug misuse with concomitant alcohol use were generally found to be heavy drinkers.

Dependence liability of two antidiarrheals, nufenoxole and loperamide.

We compared the dependence liabilities of therapeutic doses of nufenoxole and loperamide. Ten subjects received 10 mg nufenoxole every 12 hr for 10 days, and 9 others received 4 mg loperamide every 12 hr for 10 days. On the eighth day of drug a sensitive single-blind intravenous naloxone challenge was used to assess dependence liability.