Epinephrine, more familiarly known by the proprietary name adrenaline, is an animal alkaloid or leukomain obtained from the medullary portion of the suprarenal glands, chiefly of cattle, sheep, and pigs. So far as we know, it is the same as the normal internal secretion of the gland in man. Its formula is NH.C6H3(OH)2.Choh.Ch2ch3, and it is a distant relative of the vasoconstricting principle of ergot, tyramine. It has the properties of an alkaloid, hence forms salts, is precipitated by alkalies, tannic acid, etc., and is destroyed by long contact with alkalies. In the dried glands it is present to the extent of about 1 per cent.

It is marketed under several trade names, adrenaline, supra-capsulin, suprarenalin, etc., in a solution purporting to have a strength of 1 part of the chloride in 1000. This solution is not decomposed by a moment's boiling, so it may be sterilized by heat. By prolonged boiling it is quite changed. On long standing, or if diluted, it deteriorates, slowly changing to a reddish color and eventually precipitating. When a precipitate is present, the solution should be discarded. It keeps better when it contains a slight excess of hydrochloric acid. Tablets of the hydrochloride, the pure alkaloid, and the tartrate are also obtainable. A synthetic substitute, suprarenin, or dioxyphenyl-ethanol-methylamine hydrochloride, has about half the strength (Schultz).

The dried suprarenal glands of the sheep and ox, freed from fat, and cleaned, dried, and powdered, are official under the title Suprarenalum siccum. This dried gland is about six times as strong as the fresh gland, and is used either in tablet form or in a mixture with water. The latter must be freshly prepared, as it does not keep.

Preparations And Doses

The dose varies according to the method of administration and the effect desired.

Dried Suprarenal Gland

Dose, 4 grains (0.25 gm.) by mouth.

Solution of epinephrine hydrochloride, 1: 1000, used hypoder-matically in asthma, urticaria, etc., 15 minims (1 c.c.); used intravenously, 2 minims (0.12 c.c.); or in shock, 30 minims (2 c.c.) added to saline and very slowly administered. Jane way has administered over 1 dram (4 c.c.) intravenously in a little more than an hour.

On testing the blood-pressure-raising power of the several commercial preparations as compared with pure-solutions of epinephrine, Schultz, Hunt, and others found them to be of variable efficiency and poor keeping quality.

Pharmacology

General Action

Epinephrine is a stimulant of sympathetic nerve-endings or their myoneural junctions. As Langley puts it, "the effects of epinephrine upon any tissue are such as follow excitation of the sympathetic nerve which supplies the tissue." The effects, so far as muscular activity is concerned, depend upon the degree of contraction already existing. Thus, with greatly relaxed arteries, the proportional response is greater than with arteries in normal contraction; and with contracted bronchi the relaxation is greater than in normal bronchi. Hence a dose which will constrict relaxed arteries may not affect the bronchi; and a dose which will relax contracted bronchi may not constrict normal arteries.

Skin And Mucous Membranes

It has no effect on the unbroken skin, but when applied to cuts, open wounds, ulcers, or any mucous membranes which can be reached (namely, those of the conjunctiva, lacrimal duct, nose, throat, mouth, esophagus, stomach, rectum vagina, urethra, and bladder), it penetrates sufficiently to stimulate the vasoconstrictor nerve-endings of the arterioles at the site of application. The result is a local contraction of the arterioles; and this is so marked that the blood is almost shut off from the part, the tissues shrink and appear blanched from comparative bloodlessness, and any moderate hemorrhage is checked. This local contraction of the arterioles is greater and more prompt than from any other drug in use. It follows almost instantly the application of the epinephrine and lasts from fifteen minutes to one or two hours. Repeated applications will continue to keep the arterioles contracted for an indefinite length of time.

But besides vasoconstriction, epinephrine has also a vasodilator action, so that when the application of the drug is stopped and the vasoconstriction wears off, the arterioles not only relax again, as usual after constriction, but may dilate away beyond the normal - in fact, may completely lose their tone, so that there may be a late return in marked degree of the condition which the epinephrine was intended to relieve, viz., the hemorrhage, or the congestion, or the relaxed mucous membrane. Cannon and Lyman (1913) bring forward some evidence against this dilator effect being due to stimulation of the vasodilator nerves. In the coronary arteries, the dilator effect alone is observed, and this is the effect on other arteries after the adrenaline solution is boiled for a length of time (Lieb).

Absorption depends upon the method of administration - 1. Applied to mucous membranes, or given by mouth, the drug regularly has no systemic effect, or almost none. Possibly by constricting the arteries it prevents its own absorption. It is reported that an aqueous extract of two pounds of fresh suprarenal capsules has been swallowed without apparent ill effect. Osborne and some others claim that it is slowly absorbed from the mouth, though not from the stomach, while some have found that such large doses as 1/2 ounce (15 c.c.) of the 1: 1000 epinephrine solution in the stomach have resulted in the characteristic effects on the circulation. A few cases also are reported of marked systemic effects from its application to the conjunctiva, the nose, and the urethra. But, as a rule, no systemic effect at all is obtained from the drug when it is given by mouth or applied to mucous membranes, and it seems to be rapidly destroyed at the point of entrance into tissues before it gets into the circulation. Pilcher has shown that the submucous injection in the nose is very rapidly absorbed and may produce dangerous effects.