This section is from the book "A Text-Book Of Pharmacology, Therapeutics And Materia Medica", by T. Lauder Brunton. Also available from Amazon: A text-book of pharmacology, therapeutics and materia medica.
A useful method of testing the action of the drug itself on the respiratory centre is to perform artificial respiration vigorously so as to produce apnoea, to allow the respiration to become normal again, then to inject the drug and again try to produce apnoea. If the drug has excited the respiratory centre, apnoea will be much more difficult to produce after its injection than before, and will last a shorter time; if it has depressed it, apnoea will be more easily produced, and will last longer.
Apnoea lasting for a short time may be readily produced by taking five or six very deep breaths, and the effect of drugs on the respiratory centre may be readily tried by anyone in the following way. Laying a watch before him, shutting his mouth and holding his nose, let him first ascertain how many seconds he can hold his breath after previous ordinary respiration. Next let him produce a certain amount of apnoea by six or more deep respirations, and again ascertain how long he can hold his breath. After repeating these observations several times, let him take the drug to be tested and repeat them again, taking care that all the circumstances should be the same as before.
The activity of the respiratory centre is augmented by heat, so that the respirations become both quicker and deeper, and more respiratory work is done. Strychnine, ammonia, atropine, duboisine, brucine, thebaine, apomorphine, emetine, members of the digitalis group, salts of zinc and copper, have a similar action.
It appears to be first excited and then depressed by caffeine, colchicin, nicotine, quinine, and saponine.
It is diminished by cold, so that the respirations become slow and shallow. Chloral, chloroform, ether, alcohol, opium, physostigmine, muscarine, gelsemine, aconite, and veratrine in large doses, all have a similar action.
The action of drugs on the respiratory centre is one of great importance, not only as giving us a definite basis on which to found a plan of treatment in respiratory diseases, but as helping us to preserve life in cases of poisoning - drugs which stimulate being antagonised by those which depress the respiratory centre, and vice versa.
The chief afferent nerves, by which the distribution of the respiratory movements is altered, may be divided into two classes - those having an inspiratory and those having an expiratory action.
The expiratory are the nasal branches of the fifth, the superior laryngeal, the inferior laryngeal, and the cutaneous nerves, especially of the breast and belly.
The chief inspiratory are the branches of the vagus going to the lung, but all sensory nerves when slightly stimulated appear also to have an inspiratory action.
The vagus appears, however, to contain both expiratory and inspiratory fibres, which are alternately stimulated by the condition of the lung. Expansion of the lung appears to stimulate mechanically the inhibitory or expiratory fibres; while its collapse stimulates the accelerating or inspiratory fibres.
When the expiratory nerves are stimulated, the respiratory movements become slower and deeper; and if the stimulation be strong they may stop altogether in expiration, with the diaphragm in complete relaxation.
Stimulation of the inspiratory nerves causes the respiration to become quicker and shallower, and at length to stop in inspiration, the diaphragm being in a state of tetanic contraction.
These are the general results, but they are not quite constant. The reason for this inconstancy may be either that all the nerves contain both inspiratory and expiratory fibres, or that the same fibres may stimulate either the inspiratory or expiratory centres, according to the strength of the stimulus and the condition of the animal. Thus, when the vagus is divided, the stimulus which is conveyed to the respiratory centre being removed, the respirations usually become very slow; when the central end of the divided nerve is irritated they become quick, and a very strong current may stop them in inspiration. But this is not always so : when the nerve is very much exhausted, irritation by a strong current may have an entirely opposite effect, and cause the respiration to stop in expiration instead of inspiration.
The probability that the same nervous fibres may, under different conditions, excite either inspiration, expiration, or the two alternately, is rendered still greater when we consider some other experiments; and the contradictory results which have been obtained by various observers in regard to the action of drugs may depend to a great extent on the strength of the stimulus they have used and the state of exhaustion of the animal. Thus Langendorf has found that all sensory nerves in the body when slightly stimulated have an inspiratory, but when stimulated more strongly have an expiratory action. Rosenthal found that irritation of the crural nerves caused alternately deep inspiration and expiration in animals which were not narcotised. In narcotised animals, Langendorf, on slight irritation, observed an inspiratory effect, indicated by quickening of the respiration or slight inspiratory tetanus; but when the experiment was continued long, or the irritation was increased, the contrary or expiratory effect was observed, indicated by a slowing of the respiration.
On the hypothesis that the various actions of respiration depend upon individual centres, inspiratory, expiratory, and inhibitory, it is exceedingly difficult, or impossible, to understand the contradictory results of various experimenters; but the question seems much less intricate when we regard it as due to the
Fig. 81. - Diagram showing the position of the respiratory centre, and the afferent nerves which influence it. Inspiratory nerves are indicated by plain, and expiratory by dotted, lines.
interference of stimuli passing at different rates in different directions, or to different distances, according to the strength of the stimulus and the irritability or exhaustion of the nervous system.
In regard then to inhibitory or slowing, and to stimulating or accelerating nerves or fibres, it must be carefully borne in mind that the same fibres may possibly have either the one or the other action, according to the conditions under which they are acting.
If we keep this carefully in view we may continue to use the terms accelerating and slowing or inspiratory and expiratory nerves as convenient means of expression. These are shown in the accompanying diagram (Fig. 81).
The movements of respiration are most easily counted, and their depth and the relation of inspiration to expiration are best noted by causing them to register themselves on a revolving cylinder. Various means of doing this have been suggested by different authors. One of the simplest consists of a needle pushed into the diaphragm, and connected by a thread with one of Marey's levers. Marey's pneumograph consists of a cylinder of soft indiarubber, enclosing a spiral spring, whose extremities are connected with two pieces of metal which form the ends of the cylinder. A band is passed round the thorax of the animal, and attached to the ends of the cylinder. The interior of the cylinder is brought into communication with one of Marey's levers, and as each respiratory movement draws the ends of the cylinders wider apart, or allows them to approach, the air is rarefied or compressed, and a corresponding movement is transmitted to the lever. Bert has modified this, and made it more sensitive by making the cylinder itself of metal, and its ends of indiarubber. Another method - one more ordinarily employed - is to introduce one limb of a T-tube into the nostril or trachea of an animal, or connect it with a tracheal cannula. The respired air passes through the other end, and the third limb is connected with one of Marey's levers.
In the attempt to find out whether the alteration in respiration produced by any drug is due to its action on the respiratory centre, or on some of the nerves which influence it, we may find the following table useful by showing at a glance the chief ways in which the respirations may be rendered quicker or slower: -
The respiratory movements may-be quickened by
Excitement of nerves
Stimulation of the vagus.
Stimulation of optic nerve.
Stimulation of acoustic nerve.
Greater excitement of respiratory centre.
Action of brain (voluntary).
Increased temperature of blood.
Increased venosity of blood.
Action of drugs.
The respiratory movements may be rendered slow by
Diminished excite- ment of respiratory centre.
Diminished venosity of blood.
Action of drugs.
Action of brain (voluntary).
Paralysis of vagi.
Stimulation of superior laryngeal nerves.
Stimulation of inferior laryngeal nerves.
Stimulation of nasal nerves.
Stimulation of cutaneous nerves.
Stimulation of splanchnic nerves.
If the drug to be experimented on be injected subcutaneously or into the veins, the actions on the respiratory centre and on the vagi are the chief points which require attention; but if we are experimenting with a vapour, its local action on the nasal, laryngeal, and possibly, also, on the pharyngeal nerves1 must be carefully attended to, as it may greatly modify its general action on the respiratory centres. Thus Kratschmer has found that tobacco-smoke inhaled by a rabbit through its nostrils, or blown upward into the nasal cavity from an aperture in the trachea, will cause arrest of breathing in a state of expiration from the irritating effect of the vapour of the nasal branches of the fifth, while it has no such effect when blown into the lungs. Ammonia, when inhaled, also arrests the respiratory movements in the same way; but Knoll2 has observed that if it be blown into the lungs while the nostrils are carefully protected from its influence, it causes accelerated and shallow breathing, alternating with slow and deep respirations, and occasional stoppages in the position of expiration, obviously from its action on the different fibres of the vagi.