PREANESTHETIC MEDICATIOI1

BARBITURATES

GEORGE F. SEEMAN, D.D.S., NASHVILLE, TENN.

T HE barbituric acid hypnotics act directly on the ganglion cells of the cen- tral nervous system, primarily on the higher nerve centers. As is well known, hypnotics and anesthetics act more on some groups of cells than on others. It is also equally as well known that these substances have a special affinity for the lipoid constituents of the ganglion cells. We know these sub- stances are soluble in lipoids, and the extent to which t,his solubility exists has much to do with the rapidity with which t,hey accumulate in the ganglion cells and with the degree of their action.

Reviewing the chemical names of these hypnotics mill give you an idea of the manifold combinations which can be produced by starting with malonyl- urea (barbituric acid).

Barbital : ethyl-ethyl-barbituric acid. Phenobarbital (luminal) : phenyl-ethyl-barbituric acid. Allonal : allyl-isopropyl-barbituric acid. Dial : allyl-allyl-barbituric acid. Neonal : butyl-athyl-barbituric acid. Sodium amytal : sodium iso-amyl ethyl barbituric acid . Amytal : iso-amyl-ethyl barbituric acid. Ipral : calcium-et,hyl-iso-propyl-barbituric acid. 1. Only about 25 per cent of the barbital is decomposed in the system,

while the remaining 75 per cent is slowly eliminated during seven or eight days following the int,ake.

2. About 80 per cent, of luminal is decomposed, but this decomposit,ion proceeds very slowly for traces of the remaining 20 per cent are still present in the urine as late as the tent,h day after intake, which explains prolonged posth,ypnotic effect.

3. Sodium amytal is rapidly and completely destroyed in body. 4. More than 80 per cent of allonal is decomposed in the syst.em soon after

intake and the rest is eliminated in less than twenty-four hours. No trace of the drug can be found in the urine later t,han on the second day, even after larger doses. Thus, the decomposition and elimination of allyl-isopropyl- barbituric account for the relative absence of prolonged hypnotic effects when therapeutic doses have been given.

The advantage of ally]-isopropyl-barbituric acid for premeditative use to the induction of anesthesia may be summarized as follows :

1. Rapid action. 2. Greater hypnotic action. 3. Greater margin of safety. 4. Rapid elimination.

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1018 George P. Seemall

These combinations all act as hypnotics, but this does not imply that they are of equal clinical value. In considering their therapeutic usefulness, one must take into account not only their hypnotic ef6ciency but also their lia- bility to produce undesirable effects, which may be referred to as toxicity. This toxicity depends upon chemical structure, upon the amounts necessary to produce hypnotic action, upon the duration of such action, upon the rate oxidation and upon the rapidity of elimination. It is now an established fact that all these properties differ widely in these various barbituric com- binations.

Actual figures for minimum effective doses, minimum fatal doses and the so-called margins of safety of various barbituric acid derivatives are given by Nielsen, Higgins and Spruth in Journal of Pharmacology and Ex- perimental Therapeutics 26: 379, 1926. The ratios are calculated on the basis of on,e for barbital.

BARRITURIC ACID RATIO OF RATIO OF SAFETY DERIVATIVE EFFECTIVENESS TOXICITY MARGIN

Barbital Luminal Allonal

PANTOPON

Pantopon can be recommended with the utmost confidence because there have been hundreds of clinical reports, both here and abroad, attesting to the special advantage of pantopon over morphine in producing a smoother anesthesia.

As to the action of the alkaloids other than morphine, it should be noted that narcotilze stimulates the respiratory center and in this respect is an an- tagonist to morphine, while papaverine smooth muscle and in this respect, differs from morphine so that the effect of total opium is qualitatively dif- ferent from that of morphine alone. Dose IA grain.