This section is from the book "Materia Medica: Pharmacology: Therapeutics Prescription Writing For Students and Practitioners", by Walter A. Bastedo. Also available from Amazon: Materia Medica: Pharmacology: Therapeutics: Prescription Writing for Students and Practitioners.
In normal sleep, or in the sleep following the ordinary hypnotic dose of chloral or sulfonal, the breathing is slowed because of the lessened need of the inactive body for oxygen, but there is no change in the percentage of carbon dioxide in the blood. But in morphine narcosis the breathing is reduced below the requirements of the body, and the blood slowly accumulates a percentage of Co2 above the normal.
Experiments show that when the respiratory center loses its sensitiveness, a greater than normal percentage of Co2 in the blood is required to bring about respiration; and that slow breathing, or even Cheyne-Stokes breathing, may be the result of a diminished sensitiveness of the respiratory center. Cheyne-Stokes respiration consists of alternating periods of apnea and hyperpnea, and indicates depression of the respiration. In it there must be a larger than normal percentage of Co2 in the blood or the center is not stimulated to activity. During the pauses of apnea the Co2 accumulates, and during the active breathing Co2 is given off until a state of acapnia and overoxy-genation results. However, the amount of oxygen available makes no difference, for it is not a question of the amount of oxygen in the blood, but of the amount of Co2. Indeed, the depression of respiration may be in large measure overcome by the inhalation of Co2 (Leonard Hill).
In this we find an explanation of the depression of respiration and the Cheyne-Stokes breathing of morphine; viz., a lessened sensitiveness of the respiratory center to stimulation by Co2. The center is still subject to reflex stimulation, for a sudden arousing of the patient is accompanied by improved breathing for a time, and a dash of cold water, even in coma, may induce several deep respirations. Macht has shown that the combination of morphine with narcotine or papaverine is much less depressing to the respiration than morphine alone.
Cough is also overcome, the central depression lessening the reflex from mucus or from an area of irritation in the respiratory tract. This effect on cough is a highly valuable one in therapeutics, but it is undesirable or even dangerous when there is an excessive production of mucus or exudate, which should be coughed out.
The bronchial secretions are somewhat decreased, but this is not an important property in therapeutics.
A therapeutic dose of morphine lengthens the reaction time to stimuli, lessens the sensitiveness to pain and other disturbing factors, and promotes a dreamy, abstracted state of the mind; or it induces sleep. These effects occur without any essential muscular relaxation or circulatory depression. That the senses are less keen has been shown in the case of touch by the esthesiometer, in the case of sight by special apparatus, in the case of pain by vast clinical experience. That mental activity is lessened is demonstrated by the increased time required to add a column of figures or to answer questions; but there is never such depression of the intellect as from alcohol. Morphine acts chiefly by dulling the perceptions. It is noteworthy that slight stimuli, such as ordinary pinching or noises, or steady continuous stimuli, like continuous pain (unless very severe), are unappreciated after a moderate dose of morphine and do not prevent sleep; yet a sudden strong stimulus, such as a flash of lightning or the deep prick of a pin, may arouse one almost as promptly as usual, unless a large dose has been taken.
Morphine has the power, above all other drugs, to overcome pain and to compel sleep, in spite of everything which ordinarily tends to keep the patient awake. But in the presence of very severe pain sleep from large doses may not be any deeper or more prolonged than, without pain, it would be from a much smaller dose. Unfortunately, morphine has undesirable side-effects, and in some chronic cases with severe pain these prevent the administration of sufficient quantities to give ease to the patient.
Morphine stands by itself in its power to allay pain, to lessen anxiety and nervous fear, and to change discomfort into comfort. In chronic incurable diseases it may, even in doses as small as 1/20 - 1/12 grain (0.003-0.005 gm.), dull the perceptions, promote ease of mind, and prevent worry and physical distress.
Ordinarily after a dose of morphine there is no appreciable period of exhilaration; but in the habitue, as the dreamy condition comes on, the emotional, imaginative, and animal tendencies are set free to some extent before sleep supervenes. This suggests the alcohol effect, but the narcosis of morphine differs from that of alcohol in that there is not the great depression of the intellectual and motor powers. For when a morphine patient is aroused he can reply to questions rationally, i. e., with the intelligence that any one might show on being aroused from a deep sleep, and he can speak clearly and can use his limbs, though he relapses promptly into sleep on being left alone. There is no effect from morphine that corresponds with the stupidity and muscular relaxation of a drunken man. A morphine patient always brightens up on being aroused, and his breathing improves, so that from a person who looks dangerously depressed and "doped," he changes to one that can smile and reply to questions. If allowed, he promptly relapses into sleep, but the sleep is at first light, and it is some time before he again reaches the stage of deep depression. In cats and some human beings, mostly women, cerebral stimulation and excitement regularly result instead of depression.
The motor area of the cortex is not found to have lost its excitability to any great extent, as after chloral or bromide, so that a dog will die from respiratory depression before there is lessened response to electric stimulation (Hitzig and others). But voluntary muscular activity is sluggish because of the diminished perception of stimuli and the sluggishness of cerebral activity. There may be some incoordination, and this is attributed to depression of the cerebellum.