Temperature

On account of diminished activity there is lessened production of heat, and on account of the dilatation of the cutaneous vessels there is increased dissipation of heat, so chloral tends to lower temperature. It is not, however, employed as an antipyretic. A subnormal temperature is seen in poisoning.

Elimination

When warmed with strong alkalies in a test-tube chloral readily liberates chloroform, yet in a solution of sodium carbonate of the strength in the blood it does not decompose at the temperature of the body; and it does not liberate chloroform in the blood, for none has been found either in the blood or in the breath (Hammarsten, etc.). Instead of this the chloral, which is trichloraldehyd, becomes trichlorethyl-alcohol, and combines with glycuronic acid to form the non-toxic uro-chloralic acid (trichlorethyl-glycuronic acid). This is excreted slightly by the stomach, but mostly by the kidneys. A small amount of chloral may be excreted unchanged. In the urine, urochloralic acid is said to give a reaction with Fehling's solution similar to that of glucose, but in a large number of tests of the urine from patients taking from 10 to 120 grains of chloral hydrate a day the writer was unable to get a single reduction of the Fehling's, except after boiling for a minute or two. The reducing substance is readily distinguished from dextrose, as it turns the plane of polarized light to the left and does not ferment with yeast.

Metabolism

Chloral hydrate, chloroform, and other chlorine-containing bodies of the methane group are marked protoplasm poisons; and after chloral there is evidence of increased protein destruction, with the appearance in the urine of increased nitrogen, phosphorus, and sulphur, the destructive products being less completely oxidized than normally. The effects are much less pronounced than from chloroform. There is a slight tendency to fatty degeneration in the liver, heart, and arteries, especially in chronic chloral takers.

In a study of the effects on metabolism J. G. Hopkins (1911) gave dogs as much as 1.5 gm. per kilo as the daily dose, enough to produce profound narcosis and anesthesia. He found no areas of necrosis and only occasional very slight fatty changes in the liver, of the type produced by chloroform, and no changes at all in the kidneys.

Uterus

Chloral is said to promote relaxation of the cervix in the first stage of labor, without very greatly lessening the normal uterine contractions.

Untoward Effects

Occasionally, owing to idiosyncrasy, a hypnotic dose results in excitement and headache instead of sleep; or in a skin rash of the types of erythema, urticaria, purpura, and bullae; or in temporary gastro-intestinal disturbances.

Toxicology

Acute Poisoning

The condition is one of profound narcosis, with diminution or abolition of the reflexes, muscular relaxation, and early and marked respiratory and circulatory depression. It may be distinguished from morphine poisoning by the absence of very slow respiration and by the circulatory depression, the muscular relaxation, the marked diminution or abolition of the reflexes, and the pupil in midcon-traction. The many cases reported of collapse from very little above the hypnotic dose show that the drug is a dangerous one. Death has resulted from 1 dram (4 gm.) given at one dose, though 2 or 3 drams (8-12 gm.) have been taken in twenty-four hours without apparent toxic effects. Amounts of 720 grains (45 gm.) in forty-two hours (Geis), and 640 grains (41 gm.) in three days (Rogers), have been recovered from. The treatment is that for collapse and central depression, the preferred drugs being caffeine, atropine, strychnine, and camphor. Artificial respiration, oxygen, and other measures may be employed. Excretion may be promoted by saline infusion or abundant alkali-water therapy. The greatest care is necessary to avoid exertion on the part of the patient, as this tends to precipitate heart failure.

Chronic Poisoning Or Chloralism

The chloral habit is not uncommon, especially among neurotic persons and brain-workers, The pronounced habitue becomes thin and anemic, has gastric disturbances, loss of appetite, constipation, mental depression, lack of energy, weakened will power, and various nervous symptoms. Skin eruptions may appear, and there is a possibility of fatty degeneration of heart, arteries, liver, and kidneys. The treatment is to withdraw the drug slowly, to administer alkalies in large quantity, to give wholesome food, especially carbohydrates, and to place the patient in hygienic conditions of living.

Tolerance is but slowly established, and the nightly dose may not require increasing for a long time.

Therapeutics

Externally, chloral-camphor is employed as a counterirritant and local analgesic in muscular and neuralgic pains and toothache.

Systemically

1. As a hypnotic - in fever, in various forms of delirium, or in conditions of nervousness or restlessness from overwork or excesses, e. g., alcoholic or sexual. It is a powerful and reliable sleep-producer in dose of 10 to 30 grains (0.7-2 gm.). The beginning dose should not ordinarily exceed this.

2. As a circulatory depressant - in cases with high arterial tension, as in chronic nephritis or arteriosclerosis. Its action may be due to its effect upon the viscosity of the blood, but it is probably of very little real use. Dose, 5 to 10 grains (0.3-0.7 gm.) three or four times a day.

3. In obstetrics, when the first stage is prolonged, a dose of 30 grains (2 gm.), by mouth or rectum, may give the patient rest and promote relaxation of the cervix.

Chloral has some employment as a motor depressant in certain spasmodic conditions, such as whooping-cough, chorea, spasmodic asthma, tetanus, eclampsia, and strychnine-poisoning, but for an effect in these cases larger than safe doses are required. It is of no value to check pain.

Cautions Or Contraindications

1. Failure or threatened failure of the circulation.

2. Depressed states of the respiration, as in pneumonia and uremia.

3. Acute nephritis.

4. Acute gastritis and conditions of stomach irritation.

Administration

In aqueous solution, well diluted, often with the addition of bromides. It should never be given with alcohol (whisky, elixirs, etc.), as the chloral alcoholate formed is rapidly depressing to the cerebrum and medulla and constitutes the notorious "knock-out drops."

Butyl chloral hydrate is sometimes employed for trifacial neuralgia in dose of 5 grains (0.3 gm.).

Chloralformamidum (chloralamide) (CCl3Coh.Hconh2) is a crystalline compound of chloral and formamide (Hconh2), which splits into its components in the blood. Its hypnotic action, therefore, results from chloral, but the formamide is believed to render it less depressing to the heart and vasoconstrictor center. In spite of the formamide, however, the chloral set free has its usual metabolic effects. Chloralamide is soluble in 18.7 parts of water and 1.3 of alcohol. Heated with water to 6o° C. (1400 F.), it is separated into its components. The dose for mild hypnosis is 15 to 30 grains, administered in capsule, cachet, or powder, or in hot whisky. An elixir is on the market. It does not form knock-out drops.

Chloretone, Chlor-Butanol, Or Chloroform-Acetone, Ccl3c

(Ch3)2.OH, is a compound of acetone and chloroform. It is a white powder, soluble in hot water, alcohol, glycerin, and the fixed and volatile oils. It is somewhat antiseptic, and is used as a preservative in solutions of adrenaline and other unstable bodies.

Its solutions are not absorbed by the unbroken skin, but are absorbed by mucous membranes and raw surfaces, and are locally somewhat anesthetic, depressing the ends of the sensory nerves. On this account it may be used in solution or powder as an antiseptic, analgesic application to ulcers, as of the leg or stomach, or in tuberculous laryngitis or in a decayed tooth. In seasickness it acts both locally in the stomach, to lessen nausea and vomiting, and as a central sedative. Systemically it depresses the cerebrum, producing quiet and sleep. But it is a much less powerful hypnotic than chloral, and is said to be not without danger in the larger doses. It has been recommended for its narcotic value as a preliminary to ether anesthesia. Dose, 15 grains (1 gm.).

In the laboratory it is employed to anesthetize small animals, such as rabbits, but a systemic effect sufficient to abolish pain cannot be elicited in man without danger.