BARBITURATES

Barbiturates are cyclic ureides (the condensation products of urea with carboxylic acids) derived from malonic acid. They are most widely used as sedative or hypnotic drugs, and some are introduced intravenously for the production of light general anaesthesia. Based on the old name barbituric acid for malonylurea the parent compound of the group, they are called barbiturates. Structurally they are derivatives of hexahydropyrimidine. Barbituric acid is prepared by condensing urea with the acid chloride of malonic acid or with ethyl malonate in the presence of sodium ethoxide.

If thiourea is used in place of urea in the condensation, thiobarbiturates are formed which contain sulphur atom attached to the C-2 position. Employment of N-methylurea in this reaction yields l-methybarbiturates. For the preparation of substituted barbituric acids, dialkyl malonic ester is prepared .

All the barbiturates are colourless, crystalline solids which are not very soluble in water. They form sodium salts which are soluble in water. The barbiturates, though having much lower dissociation constants, are also acidic in character. Alkaline solutions of barbiturates give precipitates of copper complexes with copper sulphate in aqueous pyridine.

Both hydrogen atoms in position 5 of barbituric acid must be replaced for maximal activity. Increasing the length of an alkyl chain in the 5-position enhances the potency up to 5 or 6 carbon atoms. Beyond 6 carbons, depressant action decreases and convulsant action, may be observed. Branched, cyclic or unsaturated chains in the 5-position generally produce a lesser duration of action than that of normal saturated chains. Compounds with alkyl groups in the l or 3 position may have a shorter onset and duration of action. Replacement of oxygen by sulphur on the 2-carbon shortens the onset and duration of action. Thiobarbiturates are much more lipid soluble in the unionized form than are the corresponding oxygen analogs. Therefore, rapid onset and short duration of action are observed with thiobarbiturates.

Uses

The barbiturates are used as sedative and hypnotics. They are also applied to suppress a variety of convulsions with origins in the central nervous system, including those from tetanus, meningitis, cholera, epilepsy, eclampsia, insulin Overdosage and poisoning by Strychnine and similar drugs. They are also employed to produce anaesthesia. In combination with morphine and scopolamine, the barbiturates are used in producing obstetric amnesia.

Adverse Effect

The adverse effects of barbiturates include inconvenience, extreme depression, excitement or even mania. Some persons are hypersensitive in which skin lesions such as edema or scarletinal-like rashes are formed. The respiration and the circulation are depressed slightly by anaesthetic doses. Relatively large doses may cause prolonged coma, fall in blood pressure and paralysis of the respiratory centre. Habituation to the barbiturates is common. Abrupt withdrawal of the drug from an addicted person results in delirium, convulsions, insomnia, nausea, cramps, vomiting, Orthostatic hypotension, visual and auditory hallucination.