Definition. - The cleaned, dried, and powdered suprarenal glands of the sheep or ox, freed from fat.

Description. - A light, yellowish, amorphous powder, having a slight characteristic odor; partially soluble in water. 1 part of the dried glands represents approximately 6 parts of fresh glands. Aqueous extracts of the glands rapidly deteriorate on keeping and should, therefore, be freshly prepared.

Dose. - Average dose: 4 grains (0.250 Gm. = 250 milligrammes), U. S. P.

Researches by Abel and Crawford first demonstrated the presence of an active principle. This they extracted in an impure form and termed it epinephrine. Takamine, by a different process, also extracted the principle and applied the name adrenalin.

In commerce the principle is sold under the names of adrenalin, suprarenin, suprarenalin, adnephrin, epinephrine, epirenan, hemisine, etc. Probably few of the bodies are pure.

Epinephrine is a nitrogenous body. Its structure is not definitely known, but it is thought to resemble the pyrrhol derivatives, particularly skatol.

Epinephrine itself as first isolated by Abel and Crawford is so unstable that it has not been possible to give it a satisfactory description. Its salts, sulphates, and hydrochlorides are more satisfactory. The sulphate is a hygroscopic, straw-colored residue, which tends to crystallize on standing over sulphuric acid. Agglomerated groups of small crystals form on the edge of the receptacle, and the entire residue takes on a semicrystalline appearance. Adrenalin is a more stable compound.

Physiological Action. - With aqueous solutions of fresh specimens of the dried gland or with solutions of the salts this drug has a marked action on mucous membranes. A few drops of the solution act as a rapid and strong astringent, whitening the mucous membrane by stimulating the contractile muscles of the bloodvessels. This action is local, and is manifest in the mucous membranes of the conjunctivae, nares, pharynx, membrana tympani, vagina, urethra, and rectum. The parts to which it is applied are rendered practically bloodless. This action persists for from fifteen minutes to half an hour following a single application. Partial anesthesia may occur. Repeated applications do not seem to cause paralysis of the blood-vessel, but often following the application an extreme secondary dilatation may occur.

When administered by the mouth, some of the systemic effects of the drug may be developed, but it is by subcutaneous injection or intravenous infusion that the systemic effects are best brought out. In general, these resemble those produced by the glucosides of the digitalis group. The heart action is rendered more forcible by direct muscular stimulation ; the rate is decreased by stimulation of the vagus centers; and there is a very rapid and extreme rise in the blood-pressure, due to at least three elements - the strengthening of the heart's contractions, marked general direct contraction of the muscular fibers, and a stimulation of the vasomotor centers.

It has been observed that the pulmonary and cerebral vessels, and to a slight extent the vessels of the muscles, are less influenced than are the other vessels of the body. The retinal vessels have been observed to be dilated. The vessels of the abdominal organs are most influenced.

The most potent factor in this constriction of blood-vessels is probably the direct irritant action of the drug on smooth muscle fibers, for throughout the body this tissue is decidedly stimulated. The pupil dilates, the intestines are stimulated to greater peristaltic activity, and the uterus contracts.

In fact it has been demonstrated that as weak a solution as 1 : 20,000,000 of adrenalin in water will cause the uterus of a gravid rabbit to contract with great vigor.1 Adrenalin may cause abortion in rabbits if injected into the body of the uterus.

The secretions, particularly of the saliva, tears, and bile, are stimulated, and adrenalin, by injection or by painting on the pancreas, exerts a distinct action on the pancreatic function, causing glycosuria (Herter). The cause of adrenalin glycosuria is not yet positively known.

Therapy. - This is still in its infancy.

The suprarenal extract should be freshly prepared, its active principle being weakened by heat and preservation. It is the most powerful astringent known, a single drop of a 1 per cent. solution instilled into the eye resulting in a whitening of the conjunctiva and lids in from two seconds to forty minutes. It is useful in all forms of inflammation of the eye, whether traumatic, infectious, or proceeding from constitutional diseases, such as rheumatism, syphilis, or tuberculosis. The pupil is not contracted by it, and tolerance is not established by its use. It possesses neither antiseptic nor anesthetic properties, the rapid cures attending its employment being entirely due to its blood-constricting influence.

In suppurative otitis and dry catarrh the extract is often valuable in relieving congestion. By it tinnitus is permanently relieved. It lessens the congestion of turbinated bodies immediately, often benefiting catarrhal affections when cocaine and other astringents fail. It reduces the congestion of an inflamed eye sufficiently to 1 Kurdinowsky," On Isolated Uterus of Pregnant Rabbits," Arch.f. Gyn., lxxii., No. 2.

permit cocaine anesthesia. It has been found efficacious in relieving various strictures, as of the nasal duct, the urethra, and the esophagus. Velich found that the extract occasions local anemia when applied to the skin, not only where there is a lesion, but also where the cuticle is unbroken. It has been used to whiten an eczema-tous patch and to prevent vesiculation. Dr. Douglas Stanley found that in one case of pernicious anemia the freshly prepared aqueous extract produced a marked increase in the number of red corpuscles. It is valuable in Addison's disease (Osier), and is a tonic to the heart-muscles (Oliver and Schafer), "the tension being enormously increased by intravenous injections," though its action is less marked in subcutaneous use, and is uncertain when administered per os. It is much more rapid and distinct in its vessel-constructing action than either digitalis or ergot, but also very evanescent.

Its field of usefulness as a local astringent has not yet been fully explored. In nasal operations it renders the field of operation bloodless, and there is no reason why it cannot be used, when rendered aseptic, in abdominal or brain surgery, especially where continous oozing is a bar to good technic.

The field for its systemic use will probably widen. It is a powerful heart tonic, and is particularly to be recommended in poisoning by those drugs that cause vasomotor paralysis, notably chloroform and chloral, and in threatened heart failure its use is to be commended. Addison's disease, confessedly related to the suprarenal gland in some obscure manner, may in time be benefited by its use, but as yet no markedly encouraging progress has been made in this direction.

It has been of service in some cases of gastric hemorrhage, and may be tried in typhoid, but it is doubtful whether its secondary action may not prove harmful in this connection.

The general toxicity of adrenalin seems more marked in men than in some animals, suggesting a special sensitiveness to it on the part of the human organism.

Owing to the vascular lesions which are produced by the intravenous and intratracheal injections, and for other reasons, these methods should be rejected from practice. As regards hypodermic injections, however, authorities seem to be in accord that they are not followed by vascular alterations. Nevertheless, taking into consideration the very great sensibility to adrenalin exhibited by the human subject, it is advisable not to continue the administration of the drug over a long period, no matter by what route it is introduced. In fact, it is not considered prudent to give adrenalin for more than ten days at a time at the outside limit. In the author's opinion the dose as given is too large. A dose of one-half to one milligramme in the twenty-four hours is sufficient.

There are certain distinct contraindications: (1) when the arterial tension is already elevated; (2) when the cerebral arteries are brittle or degenerate, and (3) when there is an arterial aneurism.