Clinical pharmacology of hypnotics and sedatives

Abstract

If there is any tendency to become complacent about the adequacy of knowledge in a given area, a review of the subject usually serves to dispel this attitude. Although there exists a formidable body of knowledge on the pharmacology of the hypnotics and sedatives, that which remains unknown is even more formidable. Many of the experiments which have yielded information on the pharmacodynamics and disposition of these drugs in laboratory animals do not have their counterparts in human studies. In such instances, only a logical guess can be made in an effort to bridge this gap. The known effects of the barbiturates, bromides, paraldehyde, chloral hydrate, and newer hypnotics and sedatives in man are presented and an attempt is made to compare these with findings in other species. Where data of a critical nature with respect to the human pharmacology of these drugs are lacking, the fundamental features of their actions on other animals are presented. In addition to the more classic aspects of their pharmacodynamics, the more significant alterations in behavior produced by these agents are summarized. Studies dealing with their pharmacology in both the normal and pathologic states and in therapeutic and toxic dosages are outlined. Finally, the disposition of these compounds in the body is considered, inasmuch as this aspect of their pharmacology may have important bearing on the responses elicited by them in the organism.

Circulatory Effects of Succinylcholine in Man

“…dnacsthsia.-Anaesthesia induced by short-acting barbiturates (e. g. Enibomal, which was used in the present investigation) or by N,O brings about significant circulatory changes; some of them show close similarity to some of the SCh circulatory effects, and differentiation between these two factors may therefore sometimes be difficult. The more important of such circulatory changes are: active vasodilatation and increased blood flow, especially in the limbs (24, 31, 106, 117, 132, 168, 210a, 232, 242, 249-251, 254, 273, 287)-also observed as increased haemorrhage or oozing of blood (6,106,109,183,227,251,299)-and cardiac arrhythmia (169,172,182,254,300), the latter probably due to a vagal-stimulatory effect of anaesthesia (14,72,55,89,101,214). Other circulatory reactions observed during general anaesthesia are, however, qualitatively different from those caused by SCh, in particular, tqchycardia (50,172,231,266) and the commonly reported decrease in arterial blood pressure (79,117,119,133,168,172,254), in cardiac output (50,87,160,168,210,232,254) and in the contractile force of the heart (45,149,16...…”

Hypnotic drugs

“…An 'ultra-short acting' barbiturate such as hexobarbital (Sombulex, Cyclonal) probably has the most prompt onset of action while a 'long-acting' barbiturate such as phenobarbital may require several hours to produce maximal effect (Sharpless, 1965a). The reasons for the variability of pharmacodynamic (and thus biochemical) behaviour among the various hypnotic agents is beyond the scope of this review (see Shideman, 1961;Sharpless, 1965a, b).…”

“…To be truly addicted to a hypnotic agent, that is physiologically dependent, one must take large doses over a long period of time (Shideman, 1961). The large dose requirement distinguishes the hypnotics from the opiates.…”

“…Among such interacting compounds are alcohol, calcium salts, tranquilizers, mephenesin (Myanesin, Tolserol), and thiamine (Shideman, 1961). The exact physiological and biochemical nature and causes of these interactions are not understood.…”