This section is from the book "Materia Medica: Pharmacology: Therapeutics Prescription Writing For Students and Practitioners", by Walter A. Bastedo. Also available from Amazon: Materia Medica: Pharmacology: Therapeutics: Prescription Writing for Students and Practitioners.
Chloralum hydratum, or hydrated chloral, CCl3Coh+H2O, is prepared by passing chlorine gas through absolute alcohol and precipitating by water. It occurs in the form of hygroscopic crystals with bitter, caustic taste and penetrating odor. It is freely soluble in water, alcohol, ether, chloroform, and the fixed and volatile oils, and liquefies when mixed with camphor, menthol, or thymol. In strongly alkaline liquids it is decomposed, chloroform being set free; but in a strength of carbonated alkali the same as that of the blood it remains unchanged. The dose is 15 grains (1 gm.). There are no preparations except the National Formulary liquid, chloral-camphor, made by mixing equal parts of chloral and camphor, and used externally as a counterirritant.
Applied to the skin it is counterirritant, producing reddening and warmth; there is slight local anesthesia from depression of the ends of the sensory nerves. If applied continuously in concentrated form, it will produce death of tissue, with sloughing and the formation of an ulcer. This is because of its contained chlorine, which gives it an especially destructive action upon protoplasm.
In hypnotic doses chloral hydrate fairly rapidly induces a mild but prolonged cerebral depression, accompanied by the phenomena of natural sleep. It is a very reliable hypnotic. The pulse and respiration are somewhat slowed, the pupil is in midcontraction, the Co2 of the blood is reduced as in sleep, and the patient may be fairly easily aroused by noises or pain or other sleep antagonists.
From therapeutic amounts there is no essential analgesia, so that pain is not abolished, and in animal experiments it is found that there must be profound narcosis before there is any perceptible diminution in the response to painful stimuli. The reflexes are somewhat depressed, but not enough by safe amounts to make the drug more than weakly antidotal to the convulsions of eclampsia, tetanus, and strychnine-poisoning. In dogs chloral is antidotal to strychnine, for dogs can take a much larger dose of chloral without dangerous depression. Pringard gave 0.25 gm. and Hopkins 1.5 gm. per kilo without death.
From poisonous doses there is profound stupor, diminished excitability of the motor areas of the brain, as shown in experiments with dogs, depressed pain sense, and diminished reflexes, so that there is more or less muscular relaxation. The patient passes through stages similar to those from chloroform, and may pass to a state of surgical anesthesia (coma), with abolition of consciousness and of the reflexes, but in imminent danger of collapse.
In the sleep produced by therapeutic doses the breathing is slowed as in ordinary sleep and the response to Co2 is normal; while from poisonous closes, through depression of the respiratory center and the failure of the circulation, the breathing becomes slow and shallow. Death takes place usually from failure of the respiration, but restoration by artificial respiration is impossible because of the feeble circulation.
The addition of chloral hydrate to the fluid used in perfusing an isolated heart induces a few strengthened beats, presumably from protoplasmic irritation, and then a slowing of the heart, with gradually weakening contraction in systole and increasing relaxation in diastole. The heart loses its tone and its contractility, and soon stops with the ventricles widely dilated in diastole. These effects are due to direct depression of the muscle.
On measuring the outflow of a perfused viscus or severed limb, the addition of a solution of chloral hydrate causes a momentary diminution of outflow, showing contraction of the arteries, but this is followed quickly and persistently by an increased outflow, so that the essential peripheral action is dilatation of the arteries. This is brought about by a direct depression of the arterial muscles. In the intact animal a large dose also depresses the vasoconstrictor center.
Chloral hydrate, therefore, in good-sized dose is a circulatory depressant, acting most strikingly to depress the heart muscle, but also to depress the vasoconstrictor center and the muscles of the arteries. The vagus center is also depressed, but in spite of this the heart is slowed from muscular weakening.
In the sleep from a single safe hypnotic dose it is observed that the slowing of the heart and the lowering of blood-pressure are not any greater than those in ordinary sleep., i.e., the circulatory depression is not manifest; while with only slightly larger than ordinary therapeutic doses the circulatory depression may supervene, so that the drug becomes distinctly dangerous. Archan-gelsky found that the blood of a dog in deep chloral sleep contained 0.03-0.05 per cent. of chloral hydrate, that at 0.056 per cent the arterial pressure had fallen to one-half, and at 0.07 per cent the breathing stopped. There are reports of death from only double the dose to which the patient or habitue had been accustomed. Hence the margin of safety with chloral is a narrow one.
When taken at regular intervals for a long period chloral tends to lessen the viscosity of the blood, to destroy the red and white blood-corpuscles, and to cause fatty degeneration in heart and arteries. Even small doses cause dilatation of the cutaneous arterioles, with flushing of the skin.