To test strychnine clinically, Cook and Briggs injected 1/60 to 1/10 grain (0.001-0.006 gm.). In persons ill enough to be in bed, they obtained a slow rise of pressure lasting from one to four hours. There was no effect on the pressure in the normal persons or in patients that were moribund. Richard C. Cabot made about 5000 observations of the arterial pressure before and after strychnine in 50 fever cases, Including 31 of typhoid and 4 of pneumonia. In 32 of the 50 cases the drug was given by mouth, in 18 hypodermatically. The usual daily dosage totaled 1/8 grain (0.08 gm.). In 16 cases there was a rise in blood-pressure of 5 mm. or more; in 24 cases no change in blood-pressure, and in 17 cases a fall of pressure; the average change in blood-pressure was no greater than in that of the controls (18 cases). Newburgh gave 1 4/10 grain (0.09 gm.) in three days to each of 5 patients without any effect on circulation or respiration, though toxic symptoms appeared. These experiments must not be too convincing, however, for we have evidence in man that the circulation may be greatly improved without the arterial pressure being raised. (See Digitalis.) Yet they are in line with the findings of the experimental laboratory.

On the other hand, Marvin, 1913, tested 10 healthy students by intramuscular injection. From 1/30 grain (0.002 gm.) he obtained a slowing of 7 beats and a rise in pressure of 13 mm. (average). The pressure returned to its previous level in forty to sixty minutes.

During a convulsion the blood-pressure is very high, because of the great general muscular contraction, but this is of no interest to us in therapeutics. The skin vessels, especially those of the face, may be dilated from a special vasodilator action.

Blood

In the Journal of Infectious Diseases, 1913, Arkin gives evidence that strychnine has a marked stimulating action on the phagocytosis of streptococci by human leukocytes in the presence of human serum.

Respiratory

Large therapeutic doses scarcely affect respiration. Parkinson and Rowlands and Edsall and Means obtained no effect from 1/15 grain (0.004 gm.), and Newburgh no effect from 1 4/10 grains (0.09 gm.) in three days in each of 5 patients. It is possible that strychnine increases the sensitiveness of the center to other drugs. Large poisonous doses overwhelm and quickly exhaust the center. Death takes place from asphyxia, due either to the setting of the respiratory muscles during a convulsion, or to exhaustion of the respiratory center (between the convulsions).

Under therapeutic doses, the bronchial muscles are improved in tone, so the drug may be useful in relaxed conditions of the bronchi; while in spasmodic conditions, as in bronchial asthma, it will be harmful.

In cough the reflex excitability is increased, so that when there is abundant secretion to be coughed up, strychnine may change a weak, ineffective cough into an effective one. But when the cough is from a dry or tickling throat and cannot be made effective in getting rid of the offending stimulus, strychnine only uselessly increases the cough and distresses the patient.

Metabolism

Because of the heightened muscular tone there is some increased metabolism, as shown by increased absorption of oxygen and increased output of carbon dioxide. In convulsions the metabolism is greatly increased.

Temperature

There is greater production of heat, owing to the increased metabolism, and greater dissipation of heat from the dilatation of the cutaneous vessels; the net change is not enough to be important. During a convulsion there is a great production of heat.

Excretion

Some of the drug is oxidized and destroyed quite rapidly in the tissues; the remainder is eliminated in the urine. It can be detected in the urine very soon after the dose is administered, and most of it is excreted within twelve hours, but traces may be present for four or five days. From maximum doses cumulative poisoning may occur, though this is infrequent. In strychnine poisoning the urine, concentrated by boiling and injected into a frog, may give the characteristic convulsions.

Tolerance

Hare has given some evidence that there is no tolerance for strychnine (Amer. Jour. Physiol., v). Worth Hale produced it with difficulty in dogs, but more readily in guinea-pigs. In human beings, if the dose is increased very slowly, a certain amount of tolerance may be set up. For example, if a patient is started on 1/30 grain (0.002 gm.) three times a day, the dose may be slowly and steadily increased until in five or six weeks the patient is getting 1/6 or 1/5 grain (0.01 or 0.012 gm.) three times a day with no untoward symptoms, though such dosage would have been poisonous in the beginning. In locomotor ataxia, progressive muscular atrophy, optic nerve atrophy, etc., Troisfontaines has reached doses of 3/10 to 6/10 grain (0.018-0.035 gm.) daily, and Graeme Hammond has been able to increase the daily dosage to 2/3 or 4/5 grain (0.04-0.05 gm.), without untoward effects. Other neurologists have had similar experience in producing tolerance to these large doses.

Toxicology

After the repeated administration of large doses of strychnine the patient may become restless and nervous and twitchy, may make abrupt movements, as shrugging one shoulder or twitching the fingers or an arm or a leg, and may feel a stiffness of the face muscles, especially when he laughs, or a stiffness in the gait. These are the first signs of strychnine poisoning, and the drug should at once be stopped. If considered necessary, spinal sedatives, such as bromides, may be administered.

In a more marked stage of poisoning the twitches become spasms, and soon there are general convulsions of the spinal type. During a convulsion all the voluntary muscles are affected, so of two opposing sets of muscles the action of the stronger set predominates. The extensors are mostly the stronger, hence the arms, legs, and back are extended and the head is thrown back; in addition, the hands may be clinched and the eyes wide open, and there is a ghastly grin, the risus sardonicus, produced by the spasmodic drawing out of the corners of the mouth. During the poisoning the mind remains clear, consequently there is great anxiety on the part of the patient; and while the convulsions last there is great muscular pain (cramps).