Other prominent symptoms present are spasm of accommodation and decreased intra-ocular tension and myopia. Irritation of the third nerve is the principal cause of these phenomena. The intra-ocular pressure is lowered (1) by lessening the blood-supply to the eye through contraction of the blood-vessels; (2) by diminishing the secretion of the aqueous humor from the glands on the surface of the ciliary body; (3) by contracting the iris, so that the aqueous humor can more readily pass through the canal of Schlemm.

Unstriped Muscle. - The full influence of the drug tends to produce uterine contractions, and it also influences the unstriped muscles of the bladder, ureter, bronchi, as well as the intestines, to increased contractions.

Absorption and Elimination. - The active principles of physos-tigma and its alkaloids are rapidly diffused in the blood. They are largely excreted by the kidneys, the bile and saliva contributing to the process of elimination, and have been detected in the gastric juices after intravenous injection.

Untoward Action. - When eserine is applied to the eye it occasionally produces a nervous contractile pain in the entire eyeball, which extends in a manner similar to ciliary neurosis along the course of the supra-orbital nerve, resembling migraine.

Small doses have in some individuals produced nausea and general uneasiness, and occasionally intense pain in the epigastrium.

Poisoning. - Taken in poisonous doses, physostigma causes in from 1/4-1/2 hour, occasionally 2 hours, nausea, giddiness, and muscular tremors and weakness, followed by complete muscular relaxation. There are muscular tremors and intense salivation, increased tear-flow, and profuse perspiration. Involuntary urination and defecation have been observed. Cardiac action is diminished; the reflexes are in abeyance; the respiration is retarded: and myosis and motor paralysis are manifest. The pupils visibly contract, and purging and vomiting may ensue. Fatal results are possible through paralysis of the respiratory center and consequent asphyxia. The more rapid collapse succeeding the administration of lethal doses is due to cardiac syncope.

Doses of 4-9 grains (0.3-0.6 Gm.) of the seed have caused serious symptoms. Physostigmine salicylate 3/4 grain (0.05 Gm.) has resulted in severe poisoning with recovery.

Treatment of Poisoning. - The stomach should be evacuated, the process being followed by the hypodermic injection of a solution of atropine, which may prove an efficient physiological antidote. Tannic acid may be used as a chemical antagonist. Diffusible stimulants, such as ether or ammonia, may serve to arrest cardiac and respiratory failure. Digitalis and alcohol have also been successfully employed. Temperature should be maintained by the application of external heat.

Therapeutics. - Externally and Locally. - Physostigmine and eserine sulphate are the preparations usually employed, their only action of importance being in diseases of the eye. They are of value in breaking up adhesions of the iris to the cornea or lens, strengthening the muscle of accommodation, reducing intra-ocular pressure, and removing the effects of atropine, although Jessup claims that complete ciliary paralysis by atropine and the mydriasis induced by hyoscine are unaffected by eserine.

In certain cases of ulcer of the cornea uncomplicated with iritis and sloughing keratitis, where there is little inflammation or ciliary irritation, eserine sometimes produces prompt improvement when atropine has failed.

Paralytic mydriasis and paralysis of accommodation are temporarily relieved by this drug, and weak solutions have been employed with varying success in accommodative asthenopia without refractive errors.

The remedy is of unquestioned value in the early stages of glaucoma, but only at the commencement of an acute attack and contra-indicated in the hemorrhagic form. If the drug fails to contract the pupil when used for glaucoma, it may induce irritating spasm of the ciliary muscles by increasing the blood-supply to the iris.

Physostigmine is sometimes employed to prevent prolapsus of the iris, following peripheral perforation of the cornea or cataract extraction, particularly without iridectomy.

The remedy serves a useful purpose also in coal-miners' nystagmus, 1 drop of a collyrium containing 1/2 grain (0.096 Gm.) of physostigmine sulphate in I ounce (30.0 Cc.) of distilled water being dropped into the eye three times a day. Eserine is also employed in neuralgia of the eyeball and photophobia.

Internally. - Physostigma has proved efficacious in constipation due to an atonic condition of the intestines with deficient secretion. The state of the muscular intestinal layer frequently allows gas to accumulate in the bowels, with consequent troublesome flatulence. The drug, by imparting tone to the muscles and increasing peristalsis, greatly relieves this unpleasant condition. It is of inestimable value in the treatment of intestinal paresis following abdominal operations.

Gastric and intestinal dilatation have been successfully treated by Hare with this remedy. It is valuable in chronic bronchitis with dilatation of the bronchial tubes, and is said to relieve bronchial asthma and emphysema.

It has been recommended in tetanus and in general spasmodic disorders, but its efficacy is of questionable value.

Contraindications. - The same as for conium.

Administration. - The extract or the tincture is usually preferred for internal administration, although the alkaloid fully represents the drug and may be given either by the mouth or hypo-dermically. For application to the eye the salts of the alkaloid are used. A convenient form of physostigmine in ophthalmic practice is the medicated gelatin disks.