The Anatomy of Pain
Therapeutic doses of barbiturates cause a decease in alveolar ventilation and a slight increase in alveolar carbon dioxide tension accompanied by a decrease in arterial oxygen saturation. As the dose is increased, the hypoxic stimulus to respiration is diminished, with the respiratory center ultimately becoming insensitive to carbon dioxide. Chronic use of the hypnotic drugs is associated with both psychological and physical dependence. Tolerance develops with chronic administration of barbiturates or nonbarbiturate hypnotics. Acute intoxication can, therefore, occur with only slight increases in dosage above the tolerance threshold. Many of the hypnotics, sedatives, and minor tranquilizers are known to influence the hepatic endoplasmic reticulum of the liver, with barbiturates having the most prominent effects. In general, the direction of the enzymatic response is both frequency- and dose-related. Chronic administration of barbiturates and other sedatives will result in enzymatic induction, whereas acute administration of large doses may cause an inhibition of enzymatic activity.