Pituitary extract (hypophysis sicca, desiccated hypophysis) consists of the posterior lobe of the pituitary gland of cattle, cleaned, dried, and powdered. Dose, grain 1/2 (0.03 gm.). A solution, liquor hypophysis, containing the water-soluble principles from the posterior lobe is also official. Subcutaneous dose, 15 minims (1 c.c.). This amount, diluted 20,000 times, is required by the Pharmacopoeia to have the same activity on the isolated uterus of the virgin guinea-pig as a 1: 20,000,000 solution of beta-iminazolylethylamine hydrochloride (see Ergot). Roth found commercial preparations exceedingly variable. So far the posterior lobe has yielded no active principle. Its activity is not destroyed by boiling (Cushing). The anterior lobe and pars intermedia are not official. (See below.)

Pharmacologic Action

The main action of the drug is to stimulate smooth muscle. It is in some degree antagonistic to the anterior lobe, as it tends to diminish sexual development and activity (Goetsch).

Locally

Applied to mucous membranes or injected beneath the skin it causes moderate constricton of the arterioles.

Circulation

The intravenous administration induces slowing and weakening of the heart and a rise in arterial pressure, the rise beginnning in a minute or less and lasting usually from 5 to 10 minutes, though occasionally for as much as half an hour. The administration of atropine or cutting the vagi results in strengthening both auricle and ventricle, with an added rise in pressure (Lieb). The rise in pressure takes place in a decapitated cat and is therefore not due to an effect on the vasoconstrictor center. The maximum rise in pressure may be as great as that from epinephrine, but is more slowly attained. There is practically no circulatory effect from a subcutaneous dose, and as a rule only a slight one from an intramuscular injection. From intramuscular doses Schmidt obtained regularly a rise in diastolic pressure, though no constant effect on the systolic pressure.

Its effects therefore resemble those from epinephrine, but there is a marked difference in the site of action. For after apocodeine or ergotoxine, while the effect of epinephrine changes to vasodilatation, pituitary constricts the arteries as much as it did before. Furthermore, pituitary constricts the coronary, pulmonary, and cerebral arteries. Hence it must act by stimulating the arterial muscles and not the vasoconstrictor myoneural junctions.

Fig. 28.

Fig. 28. - Action of pituitary on the rabbit's duodenum, longitudinal coat. At signal 1 c.c. of pituitary liquid was added to the cylinder which contained the intestinal muscle in 200 c.c. of Ringer's fluid. Upstroke = contraction. Time marked in five seconds. (Tracing made by C. C. Lieb.)

With isolated arteries the doses may be repeated indefinitely, with vasoconstriction as the invariable result. In the intact animal McCord reported a fall in arterial pressure after several repetitions of the dose, attributing it to the conversion of the constrictor action into a peripheral dilator effect on the arterial muscles; but Lieb and Bastedo failed to obtain any dilator effect from nine successive large doses. Hewlett claims that it is the only drug that will convert the abnormal pulse form seen in fever to the normal pulse form.

Fig. 26.

Fig. 26. - Pituitary extract. At a, that of one manufacturer; at b, that of another, in each case 0.1 c.c. per kilo intravenously. The dose at b stopped the auricle (upper tracing), lowered the tone and contractility of the ventricle (middle tracing), and caused a moderate but fairly prolonged rise of arterial pressure (lower tracing), with slowing of the pulse from 162 to about 84. (Tracing made by Dr. C. C. Lieb.)

Fig. 27.

Fig. 27. - Pituitary extract. a, Subcutaneously, 2 c.c., no effect; b, intramuscularly in thigh, 2 c.c.; c, intravenously, 2 c.c. From last dose contractility is lessened, and there are auricular extrasystoles. The pulse is slowed from 138 to about 90, and the arterial pressure (lower tracing) is raised from 96 to 134. (Tracing made by Dr. C. C. Lieb.)

Blood

Kahn and Gordon report a reduction in coagulation time in fifteen minutes after a hypodermic injection.

Intestines

Both subcutaneous and intravenous doses have usually a marked effect on the muscles of the intestines, causing increased tone and peristalsis even in so-called paralytic distention of the bowel. But Shamoff (1916) reported depression in some cases in isolated segments of the small intestine, and Hoskins reports depression of tonus and peristalsis in the intact animal in five dogs out of six after the intravenous injection of commercial pituitrin.

Kidneys

In perfusing the isolated kidney in an oncometer the addition of pituitary regularly results in a diminution in size with a lessened venous output owing to local arterial constriction. But in an intact animal, the intravenous or subcutaneous dose results in increased volume (after a primary shrinkage), increased venous output, and increased urination which may last as much as thirty minutes. Pilcher and Sollmann have shown that there is no effect on the vasomotor centers, and Lieb finds that the diuresis depends directly on the rise in arterial pressure. On the other hand, destruction of the posterior lobe results in polyuria, and in this and other forms of polyuria the administration of pituitary has resulted in diminished urination (see below). Motzfeldt says that it does this whether given by mouth, sub-cutaneously, or intravenously. It stimulates both the ureteral and bladder muscles.

Other External Secretions

Following Schaefer's report that it increased the amount of milk, Hill and Simpson found that, administered to a nursing animal subcutaneously, intramuscularly, or intravenously, it caused an immediate marked increase both in the amount of milk and in its fat content, but that this was compensated for by a diminished secretion of poor milk so that the total change in twenty-four hours was practically none. In three experiments on a woman in the fifth month of lactation 15 minims (1 c.c.) of pituitrin, equivalent to 1/3 grain (20 mg.) of dried posterior lobe, resulted in a few minutes in a marked increase of secretion and an increase in the fat average from 3.4 to 5.5 per cent. It has been suggested that the action is one of stimulation of the smooth muscle in the gland whereby the already formed milk is expressed more rapidly.