Pharmacologic, Pharmacokinetic, and Clinical Assessment of Illicitly Used γ-Hydroxybutyrate.

γ-Hydroxybutyrate (GHB) is a common drug of abuse and poses important health risks to users in the form of respiratory, cardiovascular, mental, or traumatic adverse events. GHB has non-dose-proportional effects and pharmacologic effects such as sedation and retrograde amnesia, which can incapacitate people targeted for assault. It has Krebs cycle metabolism, rapid clearance, relative hydrophilicity, and unique drug interactions. Promptly seeking medical attention during intentional or inadvertent overdose is critical to survival, as is prompt supportive care once medical personnel are alerted. People drugged before assault also need to promptly notify authorities because the period to detect the drug in the urine or blood is brief and the ultimate metabolites are carbon dioxide and water. After acute treatment has passed, withdrawal could be severe in chronic abusers that could harm the patient directly or drive them back into reuse.

The assessment and clinical implications of haloperidol acute-dose, steady-state, and withdrawal pharmacokinetics.

In order to evaluate comprehensively haloperidol pharmacokinetics under fixed-dose treatment conditions, psychiatric patients were studied after treatment with an acute dose, during maintenance therapy, and after withdrawal from haloperidol following steady-state conditions. After single doses, haloperidol appeared rapidly in serum, achieving peak concentration at a mean of 4.5 hours. The range of observed elimination half-life was broad, between 8.5 and 66.6 hours, with a mean of 19.5 hours. Under conditions of chronic dosing, serial measurements of steady-state serum concentration revealed intrapatient coefficients of variation between 2 and 72%. The mean for all patients was 26.4%. Body clearance decreased nonsignificantly, and elimination half-life increased significantly after chronic dosing compared with kinetic parameters determined after a single dose. The concentration of haloperidol in serum obtained at 8 hours after a single dose correlated most strongly (r = 0.73; p < 0.0001) with steady-state concentration resulting from chronic dosing. A value of 4 ng/ml or lower determined 8 hours after a single oral dose of 0.2 mg/kg identified patients who did not accumulate haloperidol during chronic dosing of 0.4 mg/kg per day above a presumed therapeutic range for haloperidol of 5 to 15 ng/ml. The implications of these data for the clinical use of haloperidol are discussed.

Alteration of thyroid hormone economy during alcohol withdrawal in alcoholics.

Alcohol and alcohol withdrawal may affect nutritional status in many different ways, including effects on thyroid activity. The influence of alcohol withdrawal on thyroid hormone economy was investigated by measurements of changes in the serum concentrations of thyroxine (T4), 3, 5, 3'-triiodothyronine (T3), 3, 5, 5'-triiodothyronine (reverse T3, rT3), and thyrotropin (TSH) in chronic alcoholics experiencing different degrees of alcohol abstinence. In addition, the serum concentrations of ethanol were measured at entrance. There was no significant correlation between the entrance serum ethanol levels, on the one hand, and those of T4, T3, rT3, or TSH, on the other. However, during severe ethanol abstinence (with or without delirium tremens), there was a significant increase in the serum levels of T4 and rT3, but not in those of T3 and TSH. These findings indicate that (severe) alcohol abstinence can interfere with thyroid hormone economy, either by enhancing thyroid hormone secretion or by reducing T4 and rT3 deiodination. It is an open question whether this represents a beneficial adaptation to the metabolic disturbance caused by alcohol intoxication and abstinence, or an additional derangement that warrants nutritional or other therapeutic measures.