Barbiturates metabolites

Barbiturate metabolites are more heavily colored by the mercury(I) nitrate reagent (exception allobarbital), while unaltered barbiturates react more sensitively to the mercury(II)-diphenylcarbazone reagent (q.v.) [1]. 

While barbiturate metabolites are more intensely minred by the Tnermry(T) nitrate... 

Qualitative and Quantitative Investigation of Barbiturate Metabolites by GC-MS and High-Resolution Mass Spectrometry... 

Bromocresol green (3.8...5.4) aliphatic carboxylic acids[103,187 — 204] triiodobenzoic acid [205], derivatives of barbituric acid [206] amphetamine derivatives [207, 208] phenazones, morazone [209] alkaloids [91, 209] nephopam [210] phenyramidol metabolites [211] diethylalkylacetamide derivatives [212] zipeprol (Mirsol) [213] thalidomide and hydrolysis products [214] cyclohexylamine derivatives [215] herbicide residues [216]... 

Barbiturates and their metabolites always appear as red-violet chromatogram zones on a white background with this variant of the reagent [6]. 

The answer is d. (Katzung, pp 411, 1029.) An increased incidence of spina bifida may occur with the use of valproic acid during pregnancy Cardiovascular, orofacial, and digital abnormalities may also occur. The main issue with the use of phenobarbital or primidone (metabolite is phe-nobarbital) for the fetus is neonatal dependence on barbiturates. 

Zolpidem, chemically unrelated to benzodiazepines or barbiturates, acts selectively at the y-aminobutyric acidA (GABAA)-receptor and has minimal anxiolytic and no muscle relaxant or anticonvulsant effects. It is comparable in effectiveness to benzodiazepine hypnotics, and it has little effect on sleep stages. Its duration is approximately 6 to 8 hours, and it is metabolized to inactive metabolites. Common side effects are drowsiness, amnesia, dizziness, headache, and GI complaints. Rebound effects when discontinued and tolerance with prolonged use are minimal, but theoretical concerns about abuse exist. It appears to have minimal effects on next-day psychomotor performance. The usual dose is 10 mg (5 mg in the elderly or those with liver impairment), which can be increased up to 20 mg nightly. Cases of psychotic reactions and sleep-eating have been reported. 

However, metabolic cleavage represents only a very minor pathway for barbiturates, and it has been questioned whether the ring-opened products are really metabolites or artifacts resulting from workup procedures. The most important metabolic pathway for barbiturates is oxidation of the 5-substituent. 

Primidone is an other second line barbiturate used orally to control tonic-clonic and partial seizures. It is a pro-drug as it is metabolized to phenobarbital and phenylethylmalonamide (PEMA), however both the parent compound as well as the metabolites have anti seizure activity. Its use is more difficult to monitor and adverse effects occur even more frequently than with phenobarbital. 

Majewska MD, Harrison NL, Schwartz RD, Barker JL, Paul SM (1986) Steroid hormone metabolites are barbiturate-like modulators of the GABA receptor. Science 232 1004-1007... 

B arbitur ates are metabolized in the liver via hydroxylation and glucuronide conjugation. Short-acting barbiturates are excreted in the urine as metabolites for about one to four days, while long-acting barbiturates are excreted for two to three weeks. 

The rates of oral absorption of sedative-hypnotics differ depending on a number of factors, including lipophilicity. For example, the absorption of triazolam is extremely rapid, and that of diazepam and the active metabolite of clorazepate is more rapid than other commonly used benzodiazepines. Clorazepate, a prodrug, is converted to its active form, desmethyldiazepam (nordiazepam), by acid hydrolysis in the stomach. Most of the barbiturates and other older sedative-hypnotics, as well as the newer hypnotics (eszopiclone, zaleplon, zolpidem), are absorbed rapidly into the blood following oral administration. 

The half-lives of many benzodiazepines and barbiturates increase by 50-150% between ages 30 and 70. Much of this change occurs during the decade from 60 to 70. For some of the benzodiazepines, both the parent molecule and its metabolites (produced in the liver) are pharmacologically active (see Chapter 22). The age-related decline in renal... 

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