Assessment of thyrotoxicity using in vitro cell culture systems.

The potential thyrotoxic effect of SK&F 93479 (an H2-receptor antagonist), aminoglutethimide (AG) and glutethimide were studied by examining their effects on 125iodide uptake and organification (incorporation into thyroglobulin) in cultured thyroid cells from the pig and rat. These effects were compared with those of positive controls (3-isobutyl-1-methylxanthine (IBMX), methimazole (MTI), propylthiouracil (PTU) and NaClO4). SK&F 93479 had no effect on 125I uptake in rat FRTL-5 cells or on 125I uptake and organification in porcine thyroid cells. In contrast, MTI, PTU and NaClO4 all depressed 125I uptake and organification and IBMX potentiated 125I uptake. It is concluded, therefore, that SK&F 93479 does not increase 125I uptake in rats in vivo by a direct action on the thyroidal iodide trapping mechanism. AG, but not glutethimide, depressed 125I organification by cultured porcine thyrocytes without affecting uptake. These results suggest that AG is thyrotoxic in rats and man probably as a result of its ability to inhibit iodide organification in thyroid cells.

Deaths as a result of a combination of codeine and glutethimide.

Toxicological findings are described in 16 medical examiner cases directly related to the combination of codeine and glutethimide. The cases described represent a six-month period, July through December 1982, showing the epidemic rate of abuse of this drug combination, most prominent in the Newark, NJ area since the late 1970s. Concentrations of codeine and glutethimide, measured by gas liquid chromatography (GLC), in the blood averaged 0.62 and 4.07 mg/L, respectively. Similarly determined urine concentrations averaged 38.06 and 12.68 mg/L, respectively. Specific concentrations of each drug in most cases were in the high therapeutic range, suggesting a possible toxic synergistic effect.

Blood concentrations and clinical findings in nonfatal and fatal intoxications involving glutethimide and codeine.

Blood concentrations and clinical findings were evaluated in twenty-six nonfatal and twelve fatal intoxications involving the combination of glutethimide and codeine ("loads"). The mean glutethimide concentration was 10 +/- 5 mg/L for nonfatal cases (range 2-18 mg/L) and 13.9 +/- 6.6 mg/L for fatal cases (range 4.6-26.4 mg/L). The mean codeine concentration for fatal intoxications was 1.21 +/- 1.17 mg/L (range 0.13-4.32 mg/L). Codeine concentrations were not measured in cases of nonfatal intoxication. Nine nonfatal cases required hospitalization on a medical ward (mean length of stay 3 +/- 3 days). Depressed level of consciousness was the most common abnormal physical finding (24 cases); 18 patients were lethargic but arousable with nonpainful stimulation and 6 patients with serum glutethimide concentrations of 10 mg/L or greater were comatose. The level of consciousness showed statistically significant correlation with the glutethimide concentration (P less than 0.01). Twenty-four nonfatal intoxications involved at least one other drug in addition to glutethimide and codeine (salicylates in 12 and acetaminophen in 4), while only 7 fatal cases involved at least one additional drug (acetaminophen and diazepam in 3 each). The finding of glutethimide should prompt a search for codeine and vice versa, especially when the presence of either does not in and of itself explain the clinical condition of the patient.