Origin. - A feebly basic substance [C5H(CH3)3N4O2 + H1O], obtained from the dried leaves of Thea Sinensis (tea) L., or from the dried seeds of Coffea Arabica (coffee) L., and found also in other plants.

It may also be prepared synthetically from theobromine by the introduction of a third methyl group.

Description and Properties. - Fleecy masses of long, flexible, white crystals, having a silky luster, without odor and of a bitter taste; permanent in the air; soluble in 80 parts of water and 33 parts of alcohol.

Dose. - 2-5 grains (0.12-0.3 Gm.) [1 grain (0.065 Gm.), U. S. P.].

Official Preparations

Caffeina Citrata - Caffeina Citratae - Caffeine Citrate. - Description and Properties.A white powder, odorless, having a purely acid taste and an acid reaction. One part of citrated caffeine forms a clear, syrupy solution with about 3 parts of water.

Dose. - 2-5 grains (0.12-0.3 Gm.) [2 grains (0.125 Gm.), U. S. P.].

Caffeina Citrata Effervescens - Caffeinae Citratae Effervescentis - Effervescent Citrated Caffeine. - Dose, 1-4 drachms (4.0-16.0 Gm.) [60 grains (4 Gm.), U. S. P.].

Antagonists and Incompatibles. - Cerebral and cardiac depressants antagonize the action of caffeine.

Synergists. - Members of this group and the cerebral and motor excitants. The action of caffeine upon the digestive tract may be enhanced by the vegetable bitters.

Physiological Action. - Externally and Locally.- Caffeine possesses no very important local action, though freshly roasted coffee is slightly analgesic and deodorant - a property due to the empy-reumatic oils developed by roasting rather than to the caffeine which it contains.

Internally. - Digestive System. - In moderate amounts caffeine, like tea and coffee, stimulates the appetite, improving the digestion, and relieving the sense of plenitude in the stomach. All of them increase peristalsis and (particularly coffee) act as mild laxatives and slightly stimulate the secretion of bile.

Immoderate and continued dosage of caffeine or the excessive use of tea and coffee profoundly disturbs the digestive function, resulting in gastric catarrh, indigestion, hepatic congestion, constipation, and hemorrhoids. Tea, by reason of the high percentage of tannin contained, frequently causes constipation.

Circulatory System. - Medicinal doses of caffeine strengthen and quicken the heart's action. The rapidity of the heart's action is increased, shortening the diastolic period, the drug in this respect differing from digitalis; at the same time the arterial pressure is elevated.

The precise modus operandi of caffeine in its action upon the circulatory system is still a disputed question, some investigators claiming that its whole and only influence proceeds from a direct stimulation of the heart-muscle, while others consider its action to be upon the nervous system. In a sense both are true. There are direct muscle stimulation and vagus inhibition. In some instances the heart is rapid by a preponderance of the one, in other cases, slowed by the greater action of the second. Blood-pressure increase is due to both central and peripheral causes, the heart-muscle being stimulated and the arterioles contracted.

Nervous System. - The drug is a decided cerebral excitant, stimulating the mental function, occasioning wakefulness, and under large doses producing hallucinations and delirium.

Caffeine renders the reasoning and imaginative powers more acute, enabling the person to perform increased and prolonged mental work. Rarely, the ability to take in ideas is increased, and there is a heightened power of association of ideas.

On the medulla caffeine is a stimulant. The spinal cord reflexes are also rendered more responsive. Muscular endurance is increased by moderate amounts; large doses, on the other hand, occasion muscular trembling and weakness. In moderate amounts coffee possesses some aphrodisiac action. Excessive doses lessen the activity of the spinal reflex centers.

Respiration is both quickened and strengthened. It is one of the most reliable and least toxic of the direct respiratory stimulants.

Kidneys. - Caffeine and all of the xanthines are marked diuretics. They cause an increase in the fluids, both by reason of increased filtering by heightened tension in the glomeruli, and they are also direct kidney epithelium stimulants. At times caffeine diminishes urinary secretion by a strong vasomotor action. Theobromine (monomethyl xanthine) is a better diuretic. Both the liquid and solid parts are increased.

Temperature. - Under large doses of the drug the temperature is slightly elevated, the result of combined increase of heat-production and heat-dissipation. Toxic doses first raise, and then depress, temperature.

Eye.- Strong solutions of caffeine applied to the cornea act as a mild mydriatic and anesthetic. Hutchinson records a case of amblyopia produced by the drug.

Absorption and Elimination. - Caffeine is freely absorbed, and is readily broken down in the body - first, into lower methylated xanthines and then into urea.

Ordinarily caffeine lessens tissue-waste; the elimination of urea, however, is not uniform, being in some cases increased and in others diminished.

Untoward Action. - Caffeine occasionally causes marked cerebral congestion, insomnia, and embarrassment of respiration, while the untoward effects of an immoderate use of coffee are described by Guilliot (Nat. Disp., p. 363) as follows:

"The skin is pale or dusky, the expression is dull, and the features have the look of premature old age, and sometimes are slightly swollen. The flesh wastes, the eyes have a glassy look, the pupils are dilated, the lips and tongue are tremulous; the appetite is lost; there is insomnia or else disturbed sleep; dyspepsia accompanies constipation or diarrhea; neuralgia affects the stomach and other parts; headache and vertigo are common, and spasms or general convulsions may occur." According to the same writer, "habitual excess of coffee induces in men sexual apathy and impotence, and in women leucorrhea. Sometimes it produces pruritus ani aut vulvce."

Poisoning. - A case has been reported by Liell where 18 grains (1.16 Gm.) of citrated caffeine taken by a women were in an hour and a half accompanied by the following symptoms:

"Delirium, semi-consciousness, absence of headache, pulse 55 and irregular, cold extremities and general clammy perspiration, normal temperature (?), anesthesia, slight paresis of hands, feet, and tongue, and a reeling gait. Convulsions followed of a tetanoid character; the pupils were normal, the vision dim; some vomiting took place; there was abdominal colic, but no opening of the bowels; and urination was frequent and copious."

Treatment of Poisoning. - This should include the use of emetics and eliminants, together with diffusible stimulants and the application of external heat.

Therapeutics. - Externally and Locally. - Burning coffee in a room deodorizes the air.

Internally. - The chief value of caffeine is as a diuretic and cardiac stimulant, being peculiarly useful in cases of senile cardiopathies associated with nephritis, in which, from degeneration of the heart-muscle, digitalis is not well tolerated.

In some instances the primary effect of caffeine is to increase the pulse-rate; usually, however, if the remedy be adapted to the case, there is a secondary slowing of the heart's action. The drug is considered by some physicians to be superior to digitalis as a cardiac stimulant in valvular disease accompanied by fatty heart. It is an efficient remedy to counteract the cardiac depression in low fevers, and is a comparatively safe drug in myocarditis.

It is a remarkably efficacious remedy in cardiac and renal dropsy and to remove pleuritic effusion, etc.

Caffeine cannot displace digitalis as a heart tonic, but as diuretics the xanthin derivatives, caffeine and theobromine, are excellent. Theobromine is the better diuretic of the two. They both act as stimulants to the kidney epithelium, and contrasted with the saline diuretics, which increase the elimination of inorganic salts, the xanthine derivatives aid in the elimination of nitrogenous substances, notably urea and uric acid.

Its action upon the digestive system renders caffeine of great value as a stomachic tonic. Migraine, due either to gastric catarrh or nervousness, frequently yields to this drug.

Its value in the treatment of headaches may be enhanced by administering it together with antipyrine or sodium bromide.

Choleraic diarrhea, the result of nervous depression, is often markedly benefited by citrated caffeine. It has also been used with some success in the diarrhea of phthisis.

Sodiobenzoate of caffeine in doses of 5 to 10 grains (0.32-0.64 Gm.) is considered by Misrachi to be superior to ergot in postpartum hemorrhage. Caffeine possesses a considerable reputation as a remedy for asthma. Caffeine is invaluable in the treatment of shock, and in all poisoning associated with low blood-pressures and respiratory depression. It is a valuable stimulant in acute adynamia, particularly in typhoid fever.

It is a matter of frequent observation that strong coffee certainly modifies the effects of alcoholic intoxication. Hiccough is often relieved by coffee.

Caffeine or strong coffee has unquestionably proved valuable in the reduction of strangulated hernias after taxis has failed.

The medical uses of caffeine would be incomplete without mention of its extreme value in opium-poisoning. Here a salt of caffeine may be used hypodermically or a strong infusion of coffee given by the mouth or rectum.

Contraindications. - Ordinarily, caffeine is contraindicated in acute inflammations, particularly of the kidney.

Administration. - The alkaloid may be given by the stomach, but when hypodermic medication is desired caffeine is unavailable, a fresh salt for hypodermic use being properly employed, made by combining caffeine with salicylic acid, cinnamic acid, or sodium benzoate. The latter salt - sodio-benzoate of caffeine - is probably the most eligible and contains 45 per cent. of caffeine.

The citrated caffeine should be given in pills, capsules, or tablets; the effervescent citrate, in water.

A valerianate of caffeine is prepared which has been employed with success, it is asserted, in hysterical vomiting and whooping cough in doses of from 1/2 to 2 grains (0.03-0.12 Gm.).

Strong coffee serves as a most excellent substitute for the alkaloid, and may be given by the mouth or as an enema.

Meat Extracts. - These contain high percentages of xanthin or purin bases, creatin, creatinin, etc., in addition to mineral salts. It was at first assumed, by the manufacturer at least, that these beef extracts represented the concentrated essence of beef, and as such they were valuable food-products. Such, however, is not the case, and this class of bodies is best classed with the xanthin stimulants. Their action is on the heart and blood-vessels and they are active diuretics. They are not foods in any sense.