Spinal Cord

In some of the lower mammals, e. g., the cat, there is increased activity of the reflexes, and there may be convulsions of the typical strychnine type. In man, however, there is probably moderate depression of the reflexes, but the cord reflexes are not so much depressed as by chloral or bromides, and the tone of muscle is not lost, i. e., there is no essential muscular relaxation. Hence morphine is not good in strychnine poisoning. Occasionally in fatal poisoning in man the patient has manifested convulsions of the strychnine type. McGuigan and Rose attribute this to an oxidation product formed in the body, but undoubtedly asphyxia plays a part in its production. The author has seen typical asphyxial convulsions in a case of locomotor ataxia a few minutes after a hypodermic of \ grain (0.03 gm.).

Medulla

By good-sized therapeutic doses the vagus, vasoconstrictor, and pupil-contracting centers are stimulated, while the respiratory, the cough, the temperature-regulating, and the secretory centers lose their sensitiveness.

Peripheral Nerves

There is a slight local analgesia (Macht), but skin sensitiveness is diminished because of diminished perception of stimuli.

The Eye

After good-sized therapeutic doses, or sometimes after the habitual dose of a morphine devotee, the pupils become contracted. In marked poisoning the contraction is extreme and makes the so-called "pin-point" pupils which are characteristic of opium poisoning. After a lethal dose the pupil, owing to asphyxia, very widely dilates a short time before death, so that after death from morphine poisoning the pupils are found to be dilated. In animals like the cat, in which there is stimulation of the cerebrum, morphine dilates the pupil from the beginning.

Morphine solution dropped in the eye, or injected into an enucleated eyeball (as of an ox), has no effect upon the pupil, so its action is not local or peripheral. It also does not affect the eye through the third nerve ganglia or the cervical ganglia, therefore its action must be purely central. That it stimulates the pupil-contracting center rather than depresses the pupil-dilating center is evident, because paralysis of the latter will not result in pinpoint pupils, or produce the wide dilatation of the late stage of poisoning. This late dilatation is probably entirely the result of asphyxia.

The Secretions

From depression of the secretory center almost all the secretions are diminished, but this is a minor effect in therapeutics. The sweat is increased, but not markedly so, unless the drug is given with a copious hot drink. In health the urine is not essentially changed; but in nephritis it is believed by Tyson and others to be decreased. A satisfactory explanation of this is not forthcoming.

Metabolism

The quiet and the depressed respiration result in lessened tissue-waste and decreased oxidation. The glycogen of the liver may disappear, and increased lactic acid and sugar appear in the blood, the hyperglycemia sometimes resulting in glycosuria.

Temperature

In poisoning the fall of temperature may be as much as 2 degrees; and since 80 per cent. of the fall is due to diminished production of heat, and only a slight amount to increased heat dissipation, the drop in temperature must result from the bodily quiet, rather than from the dilatation of the cutaneous vessels and sweating. Morphine is not employed in therapeutics as an antipyretic. The author has seen fever of 102.6° F. with a skin rash and sickness of three or four days follow a single dose of morphine, the patient reporting that this was his second experience of the kind. An irregular temperature has been reported in chronic opium takers.

Excretion

After a hypodermatic injection, the drug has been found in the mouth in two and a half minutes, and in the stomach in three minutes, and it continues to be found in the stomach all through the period of morphine action (Marme). In dogs, about 30 per cent. of morphine given hypodermatically can be recovered from the stomach, a fact which suggests the value of lavage in poisoning. About 30 or 40 per cent. more may be recovered in the feces (Faube, Faust). It is evident, therefore, that a certain amount of reabsorption and reexcretion must go on in the alimentary tract, with the final result of either destruction of the morphine or its discharge with the feces. Traces of morphine also appear in the milk, sweat, and urine, and the remainder is oxidized to the comparatively inactive oxydimorphine, some of which is excreted in the urine. Heffter claims that one-third is eliminated by the kidneys, but most authors report only traces. Cloetta was unable to obtain tests of morphine in the blood after twenty minutes, and determined that it had totally disappeared from the body in two days.

Rarely some morphine-glycuronic acid appears in the urine and may react with Fehling's solution. Rarely also there is a true glycosuria. The odorous substances of opium are excreted mostly in the urine.

Though it is found in the fetal blood, it does not seem to affect the fetus, probably because the latter does not maintain its vitality by its respiratory apparatus. The newborn babe of a habitue may, however, fail to breathe, or if it lives may require its habitual dose if the amount excreted in the mother's milk is insufficient, or if the child is taken from the breast. If a large dose of morphine is given to a non-habituated mother just before delivery, it may disastrously affect the infant's breathing.

The Bladder

In poisoning there may be failure of the reflexes, and spasm of the sphincter with retention of urine.

Kidneys

Ordinarily there is no effect, but in uremia the drug seems to increase the inefficiency of the kidneys (Tyson).

After-Effects

Not uncommon after a medicinal dose are: nausea, vomiting and constipation, with perhaps headache, dizziness, and general lassitude. For a short time after a hypodermic dose there may be a very slow "vagus" pulse.