Heart

In perfusing the isolated heart the addition of cocaine does not change the rate or force of the beat, therefore neither the muscle nor the accelerator endings nor the vagus endings are affected. But in the intact mammal, after a moment of slowing from slight vagus center stimulation, the heart beats faster, and as it does not do so when both accelerators are cut, the effect must be stimulation of the accelerator center. The vagus endings retain their sensitiveness, for even late in the poisoning stimulation of a vagus nerve results in slowing.

After lethal doses the heart eventually becomes weak and slow from direct muscular depression (or perhaps vagus stimulation), and death may take place from cardiac failure. Occasionally, an unexplained, almost instant, collapse follows the absorption of the drug, even when it is used locally. In the hearts of coldblooded animals, C. C. Lieb has repeatedly obtained auriculo-ventricular dissociation (heart-block).

Arteries

The vasoconstrictor center is stimulated and blood-pressure rises; in severe poisoning this center is depressed. From ordinary amounts there is no direct effect upon the arteries, such as occurs from the local application, as the drug is not sufficiently selective in its great dilution by the blood. Kuroda (1915) showed that perfusion of an organ resulted in dilatation of the arteries.

Crile calls attention to the important fact that after an intravenous injection of cocaine the splanchnic arteries are more resistant to influences which usually cause their dilatation, e. g., 27 shock, handling the viscera, etc. Hatcher and Wilbert state that an intravenous dose of cocaine too small to affect the circulation will increase the sensitiveness of the vasomotor system to epinephrine.

Respiration

The respiratory center is strongly stimulated, and the respiration is increased both in rate and in depth. Death is usually due to respiratory failure, though it is not so always.

Cerebrum

This is stimulated in much the, same way as with atropine, even the local use of the drug being followed by talkativeness and cheerfulness, and even delirium and cerebral convulsions. But as an intellectual stimulant it seems to rank higher than atropine, for the cocaine jag is characterized by increased intellectual power and self-possession, in addition to loquacity. The reaction time is shortened, and it is more difficult to put and keep an animal under chloroform or ether, i. e., cocaine antagonizes narcosis.

The motor areas of the brain are stimulated, and also the reflex centers of brain and cord, and there is a tendency to motor activity and restlessness, so that the patient wants to walk about. A dog will run amuck, usually in a circle, and quite indifferent to his surroundings. The ergograph shows an actual increase in muscular power. All these things are evidences of true central stimulation, exactly the opposite of the effect of alcohol or morphine.

After highly poisonous doses the stimulation is followed by depression, stupor, cerebral (not spinal) convulsions, and coma.

Medulla

The respiratory, vasoconstrictor, and accelerator centers are stimulated. Whether the vagus center is stimulated to any great extent or not is a moot question. In poisoning, the thermogenetic center in the caudate nucleus is affected, so that the temperature may rise several degrees.

Muscle

There is no direct effect, but the motor areas are stimulated so that muscular power is increased and fatigue is lessened.

Temperature

See under Medulla. The rise in temperature has probably the same explanation as that after atropine. The temperature does not rise in chloralized animals.

Excretion

Some of it is destroyed in the body, though experiments at the University of Berlin (1913) would indicate that cocaine is in some degree excreted unchanged by the kidneys. The urine is sometimes increased, sometimes diminished, probably through changes in the kidney circulation. The effect upon it is unimportant.

Untoward Effects

Untoward effects following its use for anesthesia are:

(a) From protoplasmic irritation - cloudiness or ulceration of the cornea; necrotic area or sterile abscess at the site of injection.

(b) After absorption - (1) Talkativeness, excitement, and wakefulness. (2) A profound narcosis instead of excitement. (3) Nausea, vomiting, and diarrhea, sometimes distressing. (4) Sudden collapse without warning.

Acute Poisoning

A number of cases are reported. An overwhelming dose may cause prompt stoppage of heart and respiration, or complete relaxation of the arteries with collapse (Smith and Porter). In some cases there is great susceptibility and there are many reports of sudden collapse and death in the physician's office after the local use in nose, throat, eye, and urethra. Great excitement, collapse, and respiratory failure have resulted from 2 drops of a 4 per cent. solution in the eye; also conjunctivitis. One of my cases has twice, following cocaine in the eye, had a dilatation of the arterioles on that side of the face, so that it was flushed and hot, an effect which regularly follows sympathetic paralysis. Harris reports death from very small amounts in a case with status lymphaticus.

In ordinary poisoning the central symptoms resemble those from atropine. They are often observed after a cocaine debauch in a habitue. These symptoms are garrulousness, restlessness, motor activity, with incoordination like in a drunken man, excitement, hallucinations, and delusions; nausea and vomiting; rapid heart with raised blood-pressure; respiration quick and deep, or even panting; pupil dilated; throat dry. There are frequently great anxiety and fear that death will take place, and anginal pains about the heart. Magnan's sign is a subjective sensation as of pimples or worms beneath the skin or of vermin on the skin. Following the excitement there are drowsiness, stupor, coma, collapse, cerebral convulsions, and death from failure of the heart or respiratory center. It may be distinguished from atropine poisoning by Magnan's sign and the reaction of the pupil to light, and by the fact that atropine checks sweating, and may be found in the concentrated urine in sufficient amount to dilate the pupil of a cat's eye. Failure of the heart to react to pressure on the vagus in the neck would suggest atropine.