This section is from the book "A Treatise On Therapeutics, And Pharmacology Or Materia Medica Vol1", by George B. Wood. Also available from Amazon: Part 1 and Part 2.
The first effect of a cerebral stimulant, given in doses calculated to bring its characteristic influence into operation, is more or less to excite the stomach. In a short time, its influence extends to the general system, showing itself usually, in the beginning, by a moderate increase in the activity of the sensorial functions, and in the movements of the heart. Bat very quickly more obvious cerebral phenomena are exhibited; while the circulation may or may not be propor-tionably excited. The sensorial functions are now perverted Abnormal sensations are felt in the head, such as fulness, pressure, confusion, swimming, giddiness, singing in the ears, perhaps pain; the mind wanders more or less; the voluntary movements are apt to become irregular; and intoxication or delirium may supervene. Next succeeds a gradual diminution of the sensorial functions. Heaviness and languor, or a feeling of general and pleasing calmness, soon deepens into drowsiness, and this at length into stupor, which more or less closely resembles natural Bleep, according to the character of the narcotic used. All these are the direct effects of the medicine. The stupor continues for a length of time varying from one or two to twelve hours or more, according to the particular article used, gradually diminishing from its greatest intensity, till the patient at length becomes fully awake, when the direct operation of the medicine is passed. But now a condition of depression takes place,more or less corresponding with the previous excitement, and the strength of the direct impression. This is characterized by feelings of languor and dejection, often with more or less general or local uneasiness, especially headache, by a pale, cool, and relaxed state of the surface, and feebleness of the pulse, and by a depressed state of the gastric functions, as indicated by want of appetite, nausea, and perhaps vomiting. These symptoms may be so slight as to be scarcely noticed, or they may be severe and extremely uncomfortable to the patient, but from appropriate doses ate seldom serious. After a few hours they gradually pass away, under healthy vital influences, and the previous state of system returns with little or no appreciable change.
From larger doses of the medicine, the primary excitant impression is stronger, but shorter, the succeeding period of stupefaction deeper and more lasting, and the secondary depression greater, more protracted, and more serious.
In very large quantities these medicines become poisonous. The symptoms of excitement and exhilaration, though sometimes intense, are very brief, and the subsequent stupor profound and alarming. Instead of being confined mainly to the cerebral centres, the influence of the poison extends to the centre of respiration in the medulla oblongata, which may be overwhelmed by the force of the poison, and death may result from this cause. Or the direct effects of the narcotic may pass over without fatal consequences, and the patient may lapse into the secondary condition, and perish from the universal prostration of his functions. If the dose of the poison has not been quite sufficient to destroy life, he rises slowly and with difficulty from the profound depression, and may not for several days recover his previous state of health, perhaps even for a much longer time, if any organic lesion shall have taken place.
The course of the symptoms has been given above; but they require explanation. First, it may be proper to observe that the description is applicable only as a general rule. Special phenomena are sometimes exhibited by the individual narcotics, which it will be most convenient to treat of along with their other properties and effects.
The first impression on the stomach is due to the direct contact of the medicine, which operates both on the nervous and vascular tissue of the organ, exciting it to an increase of function, which is followed by the same stupor, locally, if we may so express ourselves, as that experienced by the general system. It is not impossible that the original gastric excitation may be sympathetically propagated to the cerebral centres, giving rise to the first phenomena of general stimulation, and afterwards increasing the direct influence of the medicine when it reaches the brain through absorption; but we have no positive evidence to this effect; nor indeed have we, in relation to some of the narcotics, any demonstrative proof that they are absorbed at all. But, as some of them are known to be so, the inference is quite allowable that they are all taken into the circulation, or at least their active principles; and it is most probable that their constitutional effects are chiefly, if not exclusively, produced in this way.
The impression of the medicine on the cerebral centres is probably throughout, so long as its direct influence remains, of a stimulating character. That it is so at first, is rendered obvious by the symptoms. Some have ascribed the stupefaction which ensues to a sedative operation. I cannot agree with them. I cannot conceive that a medicine, in its direct influence on an organ, shall pass so speedily from a stimulant to a sedative action. A true sedative condition will result, but that is after the medicine has ceased to act directly. It is not difficult to explain the occurrence of intoxication and stupor upon the principle of continued stimulation. I have demonstrated elsewhere that, in the continuous operation of an excitant directly upon any organ, the first effect is an increase, the next a derangement, and the last a depression or suspension of its function. These results probably follow the gradually increasing amount of blood drawn into the organ by the irritation, at first in quantities merely sufficient for the support of the increased function, afterwards sufficient to derange it, though still increased, and lastly congesting the organ to a point at which its function is embarrassed and impaired, or quite overwhelmed. Applying this general rule to the operation of the cerebral stimulants, we have first the simple excitation, as shown by the obvious phenomena; next, the perverted excitation, exhibited in the mental confusion, or intoxication; and thirdly, the overwhelming congestion, as evinced by the drowsiness and stupor. But when the immediate operation of the medicine has ceased, either in consequence of its decomposition or elimination, the stimulated organ is left to its own powers, Its excitability having been exhausted by the previous over-action, it is insusceptible to the ordinary healthful influences of the blood and other vital agents, and consequently acts feebly, or for a time ceases to act. Hence the prostration which follows the cessation of the direct opera-tion of the medicine. The exhausted organ, however, if not fatally depressed, recovers its excitability by rest, and, being again able to feel and respond to its healthy stimuli, returns to its normal state of action. When poisonous quantities have been taken, death occurs in one of two ways. Either a nervous centre essential to life, as the respiratory centre in the medulla oblongata, is so far overwhelmed by the active congestion as to be unable longer to perform its office, in which case the function of respiration ceases as a necessary consequence; or the general depression following the enormous preceding excitement of the cerebral centres generally, and of the whole system, is too great for reaction, and the patient dies completely prostrated. In the former case, which is by far the most common, the respiration ceasing, the blood is no longer oxygenated in the lungs; the capillaries consequently refuse to carry it forward; the heart, failing to receive a supply necessary to the support of its function, now in its turn ceases to act; and death takes place finally because the blood no longer circulates. In proof that the above is the true explanation of the operation of the cerebral stimulants, dissection after death always shows congestion of the brain, when the patient has not died of pure prostration after the poison has ceased to act.