Untoward Effects

Excitement instead of quiet, an effect seen mostly in women, and common among eastern women; it is the regular effect in cats. Occasionally there is diarrhea. The author has observed the following striking untoward effects, viz.: (1) Suspension of breathing and asphyxial convulsions from 1/2 grain (0.03 gm.) in locomotor ataxia. (2) Partial heart-block from a hypodermatic of 1/4 grain (0.008 gm.). (3) Death from a change of partial heart-block to complete. On several occasions even small doses had caused an increase in the block, with Cheyne-Stokes respiration. The fatal dose, 1/6- grain (0.01 gm.), was given by a newcomer for terrific pain. (4) A mottled rash with fever of 102.6° F., and pains in the joints. (5) Edema of the lungs in a case of myocarditis and in several cases of pneumonia. Hering reports cases of heart-block and auricular fibrillation. Arkin states that morphine tends to inhibit phagocytosis in streptococcus infections.

Susceptibility

Very young and very old people are especially susceptible to morphine, and in such the drug must be used with special caution. The dose should be below that called for by the ordinary rules for dosage. The too ready use of paregoric for infants cannot be too strongly condemned, for many deaths have occurred from its employment, and in numerous instances an opium habit has been formed.

Tolerance is fairly easily set up, and not only is there an increased power of the body cells to oxidize the morphine, but also an increased resistance of the cells, so that they are affected less strongly by the same amounts of morphine. Mclver and Price believe that an antitoxic substance is developed. Faust found in dogs that the ability of the tissues to destroy morphine was increased, so that as tolerance was established none of the morphine was excreted. Rubsamen, experimenting with rats, and Cloetta with dogs, in which tolerance had been established, isolated large quantities of unchanged morphine from the tissues. Van Dongen (1915) found that he could increase the tolerance of the respiratory center even to 1800 times the normal dose. Wholey reports cases taking 25 grains (1.7 gm.) and 60 grains (4 gm.) as the daily dosage. We have encountered a case that was reported to be receiving 96 grains (6.4 gm.) a day. Dr. Alex. Lambert has told me of a case taking 45 grains (3 gm.) at one dose. Leu reports the consumption by a man of 34,800 grains (2255 gm.) of morphine in about two years. In dogs having an acquired tolerance for morphine, there is an altered susceptibility to related narcotics, diarrhea, for example, resulting from codeine or heroine (Myers).

Toxicology

Acute poisoning is not uncommon, among both children and adults. Death has been reported from about 3 grains of morphine sulphate. A single large dose has occasionally resulted in prompt vomiting and the expulsion of the drug, but this is unusual. Practically, the poisoning shows three stages or degrees.

Poisoning in the first degree is not infrequently seen from the physician's administration of the drug to relieve pain. There are: Rather slow respiration, slow heart but good blood-pressure, and contracted, though not pin-point, pupils. The patient is sluggish and inattentive, may or may not be sleeping, and, on being spoken to or asked to do something, may rouse up for a time and look better and brighter; but he soon relapses into the previous state of lethargy and inattention, or sleep There may be nausea, perhaps retching or vomiting. The treatment is strong coffee by mouth or rectum, or hypodermatics of caffeine, and plenty of air. Atropine and strychnine may also be of value. Lavage of the stomach is sometimes useful to lessen nausea and remove some of the drug.

The second degree of poisoning results in stupor, a stage which supervenes in from fifteen to thirty minutes. The face is cyanotic, flushed, the skin warm, the respirations regular, and only 4 to 10 per minute, or Cheyne-Stokes in character, the heart slow, though blood-pressure remains good, the pupils pin-point, and the patient in a state of unconsciousness from which he can be aroused only with great difficulty. When aroused, he brightens up, has intelligence, can talk distinctly, and can be made to walk about (difference from alcoholism); but if allowed, he relapses at once into sleep, which soon again becomes a deep stupor. There may be retention of urine.

Treatment

(1) Potassium permanganate, 1 to 2 grains (0.06-0.12 gm.) in solution at intervals by mouth to oxidize any morphine that may be in the stomach, that excreted as well as that which has not been absorbed. (2) Lavage of the stomach at intervals with water or 1: 2000 potassium permanganate solution. (3) Colon irrigation to remove the morphine as it is excreted, and so prevent its reabsorption. (4) The hourly administration of maximal doses of caffeine, atropine, or black coffee until the depression of respiration is overcome. (5) Ceaseless activity - above all things keep patient awake and active, for in this stage if he relapses into sleep the patient rapidly and seriously loses ground. As the heart usually continues strong and there is no muscular weakness, vigorous measures may be employed to keep him active, e. g., he may be walked about, and if necessary lashed with a wet towel or whip. (6) Catheterization, if required.

The third degree of poisoning is manifested by coma and collapse. The patient cannot be aroused, the skin is cyanotic, cold, and clammy, the pulse is weak, the respirations are very infrequent and shallow - either regular, at the rate of three or four a minute, or Cheyne-Stokes in type. Rarely, there are strychninelike convulsions or the convulsions of asphyxia. Death takes place from paralysis of the respiratory center. Shortly before death the pupil may widely dilate. The treatment is that for severe collapse, with absolute repose, artificial respiration, oxygen, carbon dioxide, and the administration of caffeine. The prognosis after the patient passes into this coma stage is exceedingly unfavorable.