Doses of from 35-15 grains have caused death in from eight to nine hours.

Therapeutics. - Externally and Locally. - The indications for the local anesthetic action of cocaine are very numerous. The general surgeon will find many opportunities to employ the drug advantageously; indeed, in many instances it has replaced all other anesthetics. In many operations on the genito-urinary tract, rectum, nose, throat, ear, and eye it serves a most valuable purpose. The urethra can be rendered perfectly insensible to pain by the application of a 2 to 4 per cent. solution, repeated two or three times at intervals of five or ten minutes. Even the sensibility of the bladder itself can be benumbed to a great extent by the local application of a cocaine solution, so that sounding for stone and its removal may be painlessly accomplished.

Urethral caruncles may be removed successfully and without inconvenience to the patient by the injection of a 4 per cent. solution at the lines of attachment. An injection of a small amount of the same solution into the cellular tissue of the prepuce prevents pain in circumcision and in the operation for phimosis. In the treatment of fistula in ano, hemorrhoids, both internal and external, and other diseases of the rectum, cocaine is of signal value.

Cocaine is an important anesthetic in many minor operations, such as opening of felons, abscesses, etc; it is also highly serviceable in dentistry and for the removal of small neoplasms. Probably its most extensive use in this respect is in operations upon the eye, nose, and throat, its widest field of usefulness being in operative ophthalmic surgery.

Small doses of cocaine in combination with antipyrine and adrenalin are very useful in acute coryza. Great care must be taken lest its use in this regard lead to the habit.

The peculiar qualities of cocaine render it one of the safest, as well as most convenient and serviceable, mydriatics. It quickly dilates the pupil, which regains its normal condition in from ten to twenty hours. The dilatation, too, is easily overcome by the application of eserine, a solution of 1/2 grain (0.03 Gm.) to 1 ounce (30.0 Cc.) of the latter drug being strong enough to neutralize the effects of a 4 per cent. solution of cocaine.

It should be remembered that local applications to the conjunctivae, nares, and fauces may produce in susceptible persons systemic effects.

Cocaine combined with atropine forms a mydriatic which for many purposes is superior to either drug separately, the mydriasis being of longer duration than that produced by cocaine, while the paralysis of the accommodative apparatus is briefer than that occasioned by atropine. It should be remembered that iso-tropyl cocaine may cause great cardiac depression.

The phenate of cocaine is less toxic than the hydrochlorate, owing to its power of coagulating albumin, and thereby being less readily absorbed. It is also more agreeable to the taste. While it does not produce anesthesia so readily as the hydrochlorate, its effect is more permanent, and, in addition, it possesses powerful antiseptic properties. By many physicians it is preferred in laryn-gological work.

Internally. - Coca has been successfully used in gastralgia and to improve the digestion. Cocaine is frequently an efficient remedy in sea-sickness and to allay excessive vomiting.

Bartholow has highly recommended the drug in chorea, asthma, paralysis agitans, and alcoholic, and senile tremor. It has also been suggested as a cure for the opium, alcohol and tobacco habits.

Spinal Analgesia. - Within recent years the use of cocaine, thrown into the spinal cord, has been very widespread. It was first pointed out by Corning, of New York, a number of years ago, that the injection of cocaine into the spinal nerve-roots would induce analgesia of the lower limbs, but little practical use was made of this suggestion. Bier, of Kiel, rehabilitated the procedure, adopting the newer points of technic brought out by Quincke in his observations on lumbar puncture, and performed major operations below the umbilicus during the analgesia conferred by the drug. Tuffier, Murphy, Fowler, Bainbridge, Reclus, and many others have supplemented the early observations, and at the present time there is a large literature concerning the intrarachidian injections of cocaine in surgery. Many operations, heretofore impossible to perform by reason of accompanying cardiac or renal disease, thus making the employment of ether or chloroform unwise, have been done successfully under cocaine analgesia. In many respects an ideal has been reached, but there are a number of drawbacks to its use here. Headache, nausea, vomiting, great prostration, and weakness, accompanied by dizziness, have been noted with varying constancy as following the use of the drug in this manner. Its use, therefore, presents some questions of expediency that subsequent experience must answer.

A logical outcome of the use of cocaine in this manner in surgery is its use in persistent neuralgias - sciatic and others. These have been relieved in many instances, most often to return, yet at times not. The pains of tabes have also been markedly relieved by the same procedure.

Time and experience alone will determine what the subsequent developments may be along these lines.

Similar Products. - In coca leaves there are other cocaines, and still others are made synthetically from the ecgonine base, but these have not been used to any great extent. Cocainine, benzoyl-ecgonine, tropacocaine have been used sparingly. The last has been employed in spinal analgesia in the place of cocaine.

Eucaine. - Alpha and beta-eucaine are newer artificial alkaloids used as substitutes for cocaine. They differ from cocaine in that they may be subjected to boiling and are not thereby decomposed. Moreover, they are less toxic and have about equal analgesic properties. Beta-eucaine is to be preferred, as it is less irritating. On the eye, they do not dilate the pupils so widely and are capable of extensive employment in ophthalmic practice.

Holocaine is a synthetic derivative from phenacetine, used widely in ophthalmic practice for much the same purposes. It is not so satisfactory in many respects.

Orthoform - C6H3OH(NH1)(COOCH3) - meta-amidopara-oxy-benzoic-acid methyl ester, is another product of radically different chemical composition, being derived from benzoic acid. It possesses many of the analgesic properties of cocaine. It is a white, slightly soluble powder, and is useful as a dusting-powder, proving antiseptic and analgesic at the same time. It is extensively used in the treatment of ulcers - rectal, urethral, laryngeal, gastric, etc. - of tuberculous, syphilitic, or carcinomatous origin, and offers excellent opportunities as a local analgesic, as it remains in contact for a considerable space of time because of its comparative insolubility.