This section is from the book "A Text-Book Of Materia Medica, Pharmacology And Therapeutics", by George F. Butler. Also available from Amazon: A text-book of materia medica, pharmacology and therapeutics.
In the present work care has been taken to designate the proper pronunciation of the names of drugs and their preparations common to Materia Medica and Therapeutics. The simplest and most efficient method appears to be that herein followed - namely, to indicate accent and quantity by a single sign; for example: Alcohol (nom.) - Alcoholis (gen.), in which the A is short in the nominative and the accent upon the first syllable, while in the genitive the 0 is short and the accent is long upon the third syllable.
In nearly all cases the genitive, as used in prescription-writing, and the English equivalent, are given. When the accusative, not genitive, is adopted, the usage is marked by "(ace.)"; as, Pilulas, Pilulas (ace), etc.
A large number of compounds which are derived from members of the marsh-gas series are employed in medicine as depressants of the nervous system, acting more particularly on the higher cortical structures. They are here considered in one general group because of their close similarity in pharmacological action and in therapeutic efficiency. While the fundamental action of these derivatives is on nervous structures, it not infrequently happens that other effects - such as the action of alcohol on the heart, of chloral on muscular tissues, etc. - are of great therapeutic service. Such a consideration brings again into prominence the difficulties of therapeutic classification.
The bodies here under discussion are very numerous. They are derived from various members of the series, and include hydrocarbons, alcohols, ethers, aldehydes, ketones, esters, acids, halogen substitution compounds and their derivatives.
The simplest members of the paraffine group of this series are pentane, C5H12, hexane, C6H14, both of which are distilled from petroleum, coming off between 6o-8o C, (140-176o F.). Their mixture constitutes the well-known petroleum ether, or naptha, used so extensively in some anesthetic mixtures; Gasolin, or benzin, coming off at higher temperature, 8oo-120 C. (176-280 F.), containing heptanes, C7H16; octanes, C8H18, has also been used as a general anesthetic.
Of the olefines, or unsaturated hydrocarbons, amylene, C5H10, and acetylene, C2H1, have been used as general anesthetics. They have not proved satisfactory.
The hydroxyl compounds of the saturated hydrocarbons, the alcohols, constitute highly important members of the group. The simplest methyl alcohol, CH3OH, is widely used in the arts as a solvent, and is frequently drunk as an intoxicant - often with disastrous effects, as will be pointed out; ethyl alcohol, C2H5OH, the next member of the group, is one of the most ancient of remedies and perhaps the most widely used known drug. Its importance in dietetics, in therapeutics, and in toxicology is far-reaching. The higher alcohols, propyl, C3H7OH, butyl, C4H9OH, and amyl, C5H11 OH, are frequently found in ordinary alcoholic drinks, and, as fusel oil, constitute important poisonous principles.
Amylene hydrate, dimethyl ethyl carbinol, (CH3)2(C2H5)COH, is a hypnotic of this same series.
The oxides of the hydrocarbons, ethers, are represented chiefly by ether, diethyl oxide, (C2H5)2O, the most widely employed general anesthetic. The aether of the Pharmacopoeia contains a small percentage of alcohol, but a new synthetic ether has been introduced commercially and is under investigation. Methylal, methylene dimethyl ether, CH3OCH1OCH3, and acetal, diethyl acetal, C2H5OCHCH3OC2H5, have also been introduced, as anesthetic and hypnotic respectively. A few compound ethers, esters, compounds of an alcohol (or phenol) with an acid are of importance. Most of these bodies by the interposition of the acid molecule are weaker than the ethers of analogous structure. The action of many is unknown. Thus methyl formate (CH3OCOH) is a constant constituent in crude wood-alcohol and may be one of the factors in its toxic action. Ethyl formate (C2H5OCOH) is extensively used in the manufacture of artificial rum and arrack. Amyl acetate (C5H11OCOCH3) and the allied ethyl butyrate and iso-amyl iso-valerate are widely employed as artificial flavors, pears, pineapple and apples, respectively. Most of the fruit essences are mixtures of these and allied esters.
The addition of alcohol to the nitrous acid radical forms the ester, amyl nitrite (CH11ONO), so widely employed as a vasodilator. In this preparation, however, the NO ions play an important part. The esters formed with carbamic acid, urethane, ethyl carbamic ether, (C2H5)CO(NH1), ((OC2H5)CO(NH1)), and hedonal ((C2H5)CO(NH1)), ((OC2H5)CO(NH1)), a similar ester with amyl alcohol, have wide applicability as reliable hypnotics. Veronal, diethyl malonyl urea, (C(C2H5)2CO(CONH1)2), is a recent valuable addition to this series.
A number of important aldehydes are used: Paraldehyde (C2H4O)3 is one of the oldest, while within comparatively recent years several sulphur aldehydes have been introduced; sulphonal (CH3)2C(SO2)2(C2H5)2, trional (CH3)(C2H5)C(SO2)2(C2H5)2, and tetronal (C2H5)2C(SO2)2(C2H5)2 are the most important of these. Sulphonal is the mildest, trional stronger; tetronal is considered almost dangerous.
A number of halogen derivatives have been formed and are valuable. The addition of chlorine, bromine, or iodine to the hydrocarbons have resulted in chloroform, CHC13, bromoform, CHBr3, and iodoform, CHI3, the first in wide use as an anesthetic; bromoform as an antispasmodic (still under trial), and iodoform, a valuable antiseptic, showing its alcoholic relationships only in certain forms of poisoning. In these halogen compounds the Cl, Br, and I ions modify or entirely change the action of the hydrocarbon nucleus. In the case of all of the chlorine synthetics a certain poisoning of the heart muscle seems to accompany the combination. Ethyl compounds are ethyl chloride, C2H5C1, a useful general, as well as local, anesthetic, and the closely related ethylene and ethylidine compounds (CH1C1 - CH1C1) and (CH3CHC12), symmetrical and unsymmetrical ethane derivatives, are unsafe. Methylene chloride, CH1C12 has also been used as a general anesthetic. Aldehyde combinations with chlorine are: chloral, CCl3COH, trichloralde-hyde, or more properly chloral hydrate (chloral + water); butyl or croton chloral (trichlor butyl-aldehyde + water), ((C3H4C13)-CO + H1O); chloralose (chloral + glucose); chloretone(chloral + acetone) (CCl3(CH3)2OH); chloralamide (chloral formamide), (CCl3CHOHCONH1); ural, (CCl3COH) + (OO2H5)CO(NH1), a combination of chloral and urethane; somnal, ural in which another ethyl replaces the OH in chloral. This by no means exhausts the list of these alcohols and their derivatives. Synthetic chemists continue their kaleidoscopic manipulations, and undoubtedly many more useful members of this class will be introduced. The great necessity in the chloral series has been to devise combinations that would have a more agreeable taste than chloral, and further, compounds that would not possess cardiac-depressing effects. For the greater part it would seem that only with the weakest of these had this been accomplished. Efforts have further been directed to the obtaining of a chloral derivative in combination with an analgesic. Hypnal, a combination of chloral and antipyrine, was such, but it does not seem to have met with favor.
The physiological action of all of the compounds shows a marked qualitative resemblance. With the advance in the series, from lower to higher, until insolubility or non-absorbability militate, they show an increasing quantitative reaction, and from the chemical composition alone a fairly accurate estimate may be made of the grade of this increase in the physiological action. Naturally with the introduction of other active radicals, both qualitative and quantitative variations are introduced.
It has been thought that the action of this group of bodies depends in large part on their special affinity for certain classes of compounds as found in both plants and animals. Disregarding the evidences derived from anesthetization of the leaves of the sensitive Mimosa, etc., the studies of Meyer and Overton seem to represent the best interpretations of the cause of action of these bodies. They have elaborated and confirmed in great detail the belief that it is because of the affinity that these bodies have for lipoids, or fatty substances, that their physiological activities are what they are, and because of the great abundance of these lipoid substances, cholesterin, lecithin, etc., in the nervous structures, there is, as it were, a localized action in these organs, and in a few others rich in fat, the liver (cirrhosis) etc. The ganglion cells of the central nervous system are particularly rich in lipoid substances, and hence their great affinity for this group of substances. The further evidence of Mann Vas, Nissl, and others seems to lend some histological foundation to the hypothesis.
It is upon the nervous structures, then, that these bodies act, and the effect is one of gradual poisoning. As may be pointed out later, certain clinical symptoms accompanying the use of members of this series may seem to show irritation and exaltation of function, but even these signs of stimulation are capable of being interpreted in line with the general hypothesis of primary and persistent nerve-cell depression.
The grade of activity of these substances would seem to depend upon the relationship of the affinity of these bodies for water and for oily substances, and physicochemical methods have introduced a series of criteria by which their toxicity, for lower animals at least, might be measured. Thus methyl alcohol is freely soluble in water and dissolves in oil (olive oil being the oil usually used) with great difficulty. Hence its ability freely to enter into the protoplasm is limited, and its toxic action may be inferred to be slight. Amyl alcohol is less freely soluble in water and readily soluble in oils, its coefficient is higher and its toxic power much greater.
Overton has constructed a table showing the results of a series of experiments on plants and lower animals relative to this point.