External

None.

Internal

Mouth. - After physostigmine is absorbed it increases the salivary secretion; and this has been shown to be due to stimulation of the terminations of the secretory nerves in the glands. Other secretions are increased, probably in the same way. After a time the flow of saliva ceases, because the drug has so acted on the circulation as to constrict the vessels, and consequently the flow of blood through the salivary glands is diminished.

Stomach and intestines. - The muscular coat of the stomach and intestines is stimulated by the direct action of the drug circulating through it. The result is that after a large dose vomiting and purging occur. Physostigmine is quickly absorbed.

Circulation. - No influence on the blood is known. The effect on the heart is obscure, but it appears that the irritability of the peripheral terminations of the vagus is at first increased, and that consequently the heart is slowed. Very large doses are said to decrease the irritability of the vagus. In addition to its effects on the vagus, physostigmine powerfully stimulates the contractile force of the heart. The beat is therefore both more forcible and slower. Ultimately the organ is paralyzed and stops in diastole.

The blood-pressure rises very much; this is largely due to the increased force of the cardiac beat, and partly to contraction of all unstriped muscle of the abdominal viscera, driving much blood out of the abdomen. It is not known for certain if the unstriped muscle of the arteries is stimulated. Analogy would leave us to suppose that it is.

Respiration. - This is first quickened, but soon retarded, and death takes place from asphyxia. Three factors at least are probably concerned in bringing about these results. The ends of the vagi in the lungs are stimulated, for if these nerves are cut and physostigmine is administered there is no primary quickening of respiration. Physostigmine, from its action on involuntary muscular fibre, causes contraction of that in the bronchial tubes, with consequent constriction of them. Lastly and the most important, the activity of the respiratory centres in the medulla and cord is depressed.

Neriwus system. - Brain. - Even in fatal doses consciousness is unimpaired. The only part of the brain known to be affected is the respiratory centre.

Spinal cord. - It is here that physostigmine produces its most characteristic effects. Reflex activity is inhibited; by exclusion it can be shown that this is not owing to any influence on the nerves or voluntary muscles, therefore it is due to depression of the anterior cornua of the spinal cord. The most conclusive proof of this is the direct application of the drug to the cord. There is then, at first, from the irritation, which is caused by almost any substance, a slight increase of reflex excitability, but this soon gives way to complete abolition of it. Later on the posterior part of the cord is also paralyzed, so that there is a diminution of cutaneous sensibility.

Voluntary muscles and their nerves. - Muscular twitchings follow large doses in many animals. These appear to be due to the action on the motor nerve terminations; sensory nerves are unaffected.

Involuntary muscles. - We have already seen that the involuntary muscles of the intestines, stomach, and bronchial tubes are stimulated by physostigmine; so also are those of the spleen, uterus, bladder, and iris. Probably in all these instances it is the terminations of the motor nerves that are affected.

Eye. - Physostigmine applied locally to the conjunctiva or introduced into the circulation causes contraction of the pupil, spasm of accommodation from direct stimulation of the ends of the motor nerves of the iris and the ciliary muscle. There is a diminution of intra-ocular tension. Thus, as regards both secretions and the eye, physostigmine is antagonistic to atropine.

The action of physostigmine is much more constant than that of Calabar bean, perhaps because the other active principles in the bean interfere with the action of physostigmine.