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Biomedical subjects

H G Giles

Publications and source records attributed to H G Giles.

12 recordsLinked to original sources
PubMed1992

Alcohol and deaths in police custody.

We examined the involvement of alcohol consumption, chronic alcohol abuse or dependence, the soundness of the police determination of alcohol-related intoxication, and the importance of other drugs in deaths in police custody in a survey of the cases reported to the Chief Coroner of Ontario during the past 10 years. The data suggest no mismanagement by the police. At least 86% of the fatalities were associated with recent alcohol consumption or chronic alcohol abuse/dependence. Use of drugs other than alcohol was far less common. Promoting use and further development of simple tests to estimate blood alcohol concentration, chronic alcohol problems, and suicide risk, before incarceration takes place, may save lives.

Adult↗
PubMed1979

Chlordiazepoxide and oxazepam disposition in cirrhosis.

When disease impairs clearance of drugs, multiple-dose therapy may result in cumulation. The disposition of chlordiazepoxide (CDX), 50 mg infused intravenously over 10 min, was studied in 14 normal subjects and in 11 patients with biopsy-proven cirrhosis. In the normal subjects, mean (+/- SE) kinetic parameters were: t 1/2 beta, 10.0 (+/- 0.9) hr; Vd, 0.38 (+/- 0.04) l/kg; clearance, 0.54 (+/- 0.13) ml/min/kg. Clearance of total drug correlated inversely with serum albumin concentration in normal subjects (r = -0.63). Values in cirrhotic patients were: t 1/2 beta, 34.9 (+/- 8.7) hr; Vd, 0.34 (+/- 0.024) 1/kg; and clearance, 0.185 (+/- 0.34) ml/min/kg. Desmethylchlordiazepoxide (DMCDX), the major metabolite of CDX, appeared in blood of cirrhotic patients less rapidly than in normal subjects. Severity of liver disease did not indicate the impairment of CDX clearance. In 5 of the same cirrhotic patients, mean t 1/2 beta for oxazepam (7.1 +/- 1.0 hr) was 27% longer than in control subjects (5.6 +/- 0.7 hr); the difference is not significant. On kinetic grounds oxazepam may be preferable to chlordiazepoxide in cirrhotic patients since its elimination kinetics are not greatly altered in cirrhosis.

Adult↗
PubMed1979

High-performance liquid chromatographic determination of plasma propylthiouracil.

A reversed-phase high-performance liquid chromatographic analysis was developed for propylthiouracil in plasma (1 ml). After protein precipitation with acetonitrile, the solution was diluted with water and injected into a liquid chromatograph equipped with C-18 and C-8 columns in series. The peak area was linear over the 0.25-10-mg/liter range, and the recovery was 101 +/- 4.5%. This assay has the advantages of specificity, simplicity, and speed over previously published methods and requires smaller sample volumes. None of 19 drugs tested interfered with the assay.

Chromatography, High Pressure Liquid↗
PubMed1979

Use of the overturn end point in goldfish to measure the interaction of diazepam and ethanol and the effects of the binding of diazepam to bovine serum albumin.

Over the ranges 2.8 X 10(-5) to 8.78 X 10(-5) M diazepam and 4.85 X 10(-2) to 1.22 X 10(-1) M ethanol, addition of the effects of these agents on the overturn end point in goldfish was observed. The addition of bovine serum albumin (1.56 X 10(-5) M) to aqueous solutions of diazepam modifies the diazepam effect by reducing the "free" drug concentrations.

Animals↗
PubMed1978

Influence of age and previous use of diazepam dosage required for endoscopy.

In 19 patients (10 men and 9 women) a 22-fold variation was observed in the intravenous dose of diazepam necessary as preparation for endoscopy (median dose, 20 mg; range, 5 to 110 mg). Analysis of plasma samples for diazepam and N-desmethyldiazepam revealed that the clinical response did not relate to the rate or character of initial drug distribution. There was a high correlation (r = 0.96) between the dose and the plasma concentration 10 minutes after administration. Users of diazepam displayed tolerance to its pharmacologic effects, requiring a significantly larger (P less than 0.05) dose than nonusers (median doses, 35.0 mg and 14.5 mg respectively). Older patients required less than younger patients (r = -0.54, P less than 0.05). The variation between individuals in the dose of diazepam required as preparation for endoscopy cannot be explained by variation in drug disposition but instead reflects previous diazepam use, age and probably differences in sensitivity at the site or sites of drug action.

Adult↗
PubMed1978

Interaction of disulfiram with benzodiazepines.

The disposition of chlordiazepoxide (50 mg, intravenously), diazepam (0.143 mg/kg, orally), and oxazepam (0.429 mg/kg, orally) were studied in normal and alcoholic men before and after chronic disulfiram administration. Decreases in the plasma clearance of chlordiazepoxide (54%, p less than 0.05), diazepam (41%, p less than 0.05), and their active N-desmethyl metabolites were observed. Oxazepam has no important active metabolites and its net disposition is minimally altered by disulfiram. Oxazepam disposition is unaffected by age and liver disease. These considerations together with that of the short half-life of oxazepam (median, 6.1 hr) suggest that oxazepam may be the drug of choice if benzodiazepine therapy is used for patients taking disulfiram.

Adult↗
PubMed1978

Binding of drugs to ion-exchange resins in simulated gastric fluid.

The binding of 13 frequently abused drugs to two ion-exchange resins was studied in simulated gastric fluid. The results were compared with those previously obtained with activated charcoal as the adsorbent. The ion-exchange resins adsorbed the drugs more slowly than activated charcoal, and the binding capacities of the resins were inferior. These ion-exchange resins are unlikely to be very useful in removing drugs from the stomach.

Adsorption↗
PubMed1977

Diazepam actions and plasma concentrations following ethanol ingestion.

In eight normal volunteers, the combination of ethanol (0.5 g/kg) and diazepam (10 mg) administered orally produced a greater decrease in motor performance on a pursuit rotor than diazepam alone. The pharmacologic effect of diazepam was enhanced by 73% and this potentiation was associated with significantly greater diazepam concentrations (p less than 0.01) than after diazepam alone. The failure to observe any increase in the concentrations of the principal metabolite, N-desmethyl diazepam, during the period of enhanced pharmacologic effect precludes any change in the demethylating metabolic process as being responsible. The data suggest (0.10 greater than p greater than 0.05) a trend to a smaller volume of distribution of diazepam when ethanol is administered prior to diazepam ingestion. The subjects showed acute tolerance to the effects of diazepam. Lower plasma concentrations on the ascending side of the plasma diazepam concentration versus time profile were linked with the same pharmacologic responses associated with a greater drug concentration on the descending portion, of the same curve.

Adolescent↗
PubMed1976

Markers for detection of supplementation in narcotic programs--deuterium-labeled methadone.

Specific deuterium labeling of methadone and use of gas chromatography-mass spectroscopy technique permits rapid and quanitative determination of the ratio of the labeled to unlabeled drug in body fluids. A trideuertiomethadone (methadone-d3) was shown to have exactly the same analgesic activity and toxicity in mice as methadone. The rates of absorption, distribution, and excretion of methadone-d3 and methadone were identical in rats. These observations suggest that methadone-d3 may be used as an in vivo marker for monitoring methadone intake of patients, and thus may improve the effectiveness of methadone treatment programs.

Animals↗