Disease relevance of glutethimide

• Column hemoperfusion with Amberlite XAD-4 resin was simpler and more effective than any known method of removing barbiturates and glutethimide from the blood of patients with drug overdoses [1].
• The authors describes a patient who presented catatonialike symptoms and dyskinesias associated with glutethimide discontinuance and antihistamine use [2].
• Severe hypocalcemia associated with chronic glutethimide addiction: a case report [3].
• The present case also indicates that, in the absence of cerebral ischemia or hypoxemia secondary to cardiopulmonary depression, complete clinical recovery from glutethimide-induced coma is possible no matter how severe the presenting neurologic and EEG signs [4].
• Controlled trials of glutethimide to compare its efficacy with that of other medications used in the treatment of action tremor are indicated [5].

Psychiatry related information on glutethimide

• Catatonia associated with glutethimide withdrawal [6].
• Recent reports suggest that adding a secondary hormonal therapy such as amino- glutethimide, ketoconazole or steroidal hormones may enhance the response rate and prolong response time to the antiandrogen withdrawal syndrome [7].
• 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 [8].
• Neonatal withdrawal symptoms associated with glutethimide (Doriden) addiction in the mother during pregnancy [9].

High impact information on glutethimide

• Letter: Activity of glutethimide metabolite in human beings [10].
• We performed experiments in primary chick embryo liver cells with tin-, zinc- and copper-chelated porphyrins to assess their effects on activities of delta-aminolevulinate synthase induced by prior treatment of cells with glutethimide and ferric nitrilotriacetate [11].
• Glutethimide and 4-OH glutethimide: pharmacokinetics and effect on performance in man [12].
• For glutethimide, breast feeding would appear to be safe for the infant when a single dose is taken occasionally [13].
• A method for quantifying the amount of haem oxygenase protein was developed with use of slot-blots and laser densitometry; linearity was observed from 0 to 5 ng of haem oxygenase protein per slot, and the method was applied to sonicated cultured chick-embryo liver cells treated with Cd2+ (0.3 mM) or iron plus glutethimide [14].

Chemical compound and disease context of glutethimide

• We evaluated blood concentrations of three nonbarbiturate sedative-hypnotics in 19 nonfatal (NF) and five fatal (F) intoxications which were "pure" (i.e. which involved only one drug each): glutethimide, 4 (NF), 3 (F); meprobamate, 9 (NF), 1 (F); and methyprylon, 6 (NF), 1 (F) [15].
• 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) [8].
• The administration of 250mg glutethimide daily for one week resulted in significant enhancement of antipyrine metabolism in 4 patients with compensated cirrhosis and 5 patients with features of hepatic failure as well as 7 control subjects without liver disease [16].
• Toxicity of alpha-phenyl-gamma-butyrolactone, a metabolite of glutethimide in human urine [17].

Biological context of glutethimide

• The bioavailability of glutethimide is higher in smokers, but this has not been associated with greater efficacy [18].
• Descriptive epidemiology of mortality in New Jersey due to combinations of codeine and glutethimide [19].
• A review of records of the Toxicology Laboratory of the New Jersey State Medical Examiner's Office yielded a total of 36 deaths attributable to overdose of "hits," an oral combination of codeine and glutethimide, during 1980-1981 [19].
• The features of hepatic enzyme induction with glutethimide in man [20].
• Investigation of the stereoselective in vitro biotransformation of glutethimide by high-performance liquid chromatography and capillary electrophoresis [21].

Anatomical context of glutethimide

• The immunochemical data showed that chick-embryo hepatocytes in culture retain the inducibility of glutethimide- and methylcholanthrene-induced isoenzymes of P-450 that are inducible in the liver of the chicken embryo [22].
• Rabbit antiserum against the 50 kDa protein inhibited benzphetamine demethylase activity in hepatic microsomes (microsomal fractions) from glutethimide-treated chick embryo [22].
• Relative uptake at equilibrium into adipose tissue slices increased from 6 to 87% in the following sequence: phenazone, morphine less than pentobarbital less than glutethimide, phenylbutazone less than thiopental, methadone less than chlorpromazine, imipramine [23].
• Comparisons of GLC and mass spectral data to a compound isolated from the body fluids of glutethimide overdose victims conclusively identified a new 3-methoxy-4-hydroxyphenyl metabolite of glutethimide in humans [24].
• The formation of labeled pregnenolone after incubation of brain mitochondria with [4-14C]cholesterol has been obtained, and this formation was inhibited by glutethimide, a specific inhibitor of cytochrome P-450scc [25].

Associations of glutethimide with other chemical compounds

• In this study, using a combination of immunological and enzymatic characterizations, we compared the forms of cytochrome P-450 induced by ethanol and glutethimide in primary cultures of chicken embryo hepatocytes [26].
• 4,6-Dioxoheptanoic acid, an inhibitor of heme synthesis, blocked the induction of HO caused by glutethimide and FeNTA, but did not decrease the induction of HO by TMH-ferrocene [27].
• This work shows that, in cultured chick embryo liver cells, synergistic induction of heme oxygenase by iron, added with the phenobarbital-like drug, glutethimide was heme-dependent [28].
• 1 The efficacy and safety of temazepam 30 mg, compared with glutethimide 500 mg and placebo, were evaluated in double-blind conditions in a 4-day study in 75 outpatients with a history of insomnia [29].
• Simultaneous determination of glutethimide, methyprylon, and methaqualone in serum by gas liquid chromatography [30].

Gene context of glutethimide

• CYP1A5 mRNA was expressed basally in chick embryo liver and was highly inducible by the Ah receptor ligands, 3-methylcholanthrene, beta-naphthoflavone, and 3,4,3', 4'-tetrachlorobiphenyl (TCB), but not by the phenobarbital analog, glutethimide [31].
• However, B[a]P significantly altered basal CYP2H1 mRNA expression in liver, a tissue in which this gene is highly inducible by glutethimide, and had no effect on basal CYP2H1 mRNA expression in lung, a tissue in which this gene is not drug-inducible [32].
• We found that the mRNAs for ALA synthase and PB1 P-450 were rapidly and simultaneously induced by the porphyrinogenic drugs glutethimide and 2-propyl-2-isopropylacetamide [33].
• Mechanism of synergistic induction of hepatic heme oxygenase by glutethimide and iron: studies in cultured chick embryo liver cells [28].
• Synergistic induction of delta-aminolevulinate synthase by glutethimide and iron: relationship to the synergistic induction of heme oxygenase [34].

Analytical, diagnostic and therapeutic context of glutethimide

• After ingestion of 75 gm of glutethimide, one patient received hemoperfusion on three successive days for nine, ten, and eight hours, respectively [1].
• The cyclic and, sometimes, unilateral nature of the clinical findings previously reported in glutethimide coma was confirmed and seen to be reflected in the EEG [4].
• Enantioseparation of glutethimide and its 5-OH-metabolite in capillary electrophoresis and study of selector-selectand interactions using one-dimensional rotating frame nuclear Overhauser and exchange spectroscopy [35].
• Glutethimide interfered with radioimmunoassay of barbiturate, producing false positives [36].
• 3 A 'modified' form of the 2 h breath test calculated from the area under the breath specific activity curve detected the increase in demethylation following glutethimide [37].

References