BARBITURATES

The raw material for this group of strong sedatives, barbituric acid, which itself does not affect the CNS, was synthesized as early as 1863, and barbital was introduced around the turn of the century under the brand name Veronal as a sedative. It was widely used at first, but its medical use has now been drastically reduced since the introduction of the benzodiazepines, and is confined to a few specific situations. The main reason is that these substances not only produce strong physical dependence and a high level of tolerance, but also have a very limited therapeutic range. Overdoses with fatal consequences are far from unusual, especially because the therapeutic range declines as tolerance increases. The withdrawal syndromes, unlike that of opiates, can assume critical forms, especially because of the occurrence of seizures. Acute intoxication results in coma, and chronic intoxication can cause damage to the liver and delirium.

Barbiturates affect the GABA receptors and thereby bring about a general inhibition of the activity of the CNS, especially that part of the brain stem which governs the rhythm of waking and sleeping. By inhibiting activating stimuli, they induce sleep. The only activating stimuli which are not inhibited by barbiturates are pain stimuli.

Chronic barbiturate users often display irritability and aggressiveness, as well as lethargy, confusion and lack of emotional control (crying). They also display neurological phenomena such as nystagmus, dysarthria and cerebellar ataxia.

As in the case of other inhibitors (Rohypnol), enforced staying awake after taking barbiturates can produce a paradoxical intoxication, an effect that is also relatively common among the aged and patients with organic disturbances of the CNS.

Barbiturate use leads to an increase in the activity in the liver of the cytochrome P450, leading to a reduction in the breakdown of other exogenous and endogenous substances (incl. steroids), while stimulating other enzyme systems, so that some drugs have a reduced effect (incl. chlorpromazine, griseofulvin and coumarines). As a result, disturbances of the endocrine balance regularly occur among chronic barbiturate users and there is a risk of negative interaction with other drugs.

Other sedatives

Besides barbiturates, a number of sedatives have been developed, such as Glutethimide (brand name: Doriden), 'a nonbarbiturate sedative without any sideeffects', according to the manufacturer. Nevertheless, cases of persistent addiction to this drug have been described, including not only the same phenomena as in chronic barbiturate use, but above all loss of weight because of the extreme loss of appetite. Another of these drugs is methaqualone (brand names: Mandrax, Revonal, Isonox), which also affects the metabolism of other drugs and is therefore dangerous in combinations.