This section is from the book "Materia Medica Pharmacy, Pharmacology And Therapeutics", by W. Hale White. Also available from Amazon: Materia Medica Pharmacy, Pharmacology And Therapeutics..
The action of belladonna and atropine is the same.
Atropine placed by itself upon the unbroken skin cannot be absorbed, but rubbed in with substances which are absorbed, such as alcohol, glycerin, camphor, etc., or applied to a broken surface, it paralyzes the terminations of the sensory nerves, especially if pain is present. It is thus a local anaesthetic and an anodyne. These are its chief actions, but to a much less extent it locally paralyzes the terminations of the motor nerves, first contracts and then dilates the vessels, and renders the secretions of the skin less active.
Gastro-intestinal tract. - It will be convenient to describe the effects of belladonna on all secretions when speaking of its action on nerves, and we need not mention here its influence on the muscular coat of the intestine, for that is secondary to its action on the nervous system.
Blood. - Atropine is quickly absorbed, but does not affect the blood. Its main action is on the nervous system, and that must be considered in detail.
Secretory nerves. - The activity of the peripheral termina-tions of all the secretory nerves in the body is, as far as we know, depressed. These nerves fall under the following headings:
(a) Mouth. - Even small doses of atropine make the mouth dry from lack of saliva and mucus. In health, secretion of submaxillary saliva always follows stimulation of the chorda tympani nerve, and, as is well known, this is due to the fact that this nerve is the secretory nerve for this gland, and not to any vascular dilatation. If atropine be given to an animal, stimulation of the chorda no longer causes an increased flow of saliva, however close to the gland the nerve is excited, the reason being that atropine has paralyzed the terminations of the chorda tympani. In the same way the terminations of the secretory nerves of the other salivary glands and the mucous glands are paralyzed, and hence the mouth is dry, because normal impulses cannot reach the cells of the glands.
Stomach, liver, and intestines. - We do not know what influence atropine has on the secretions of these organs.
Sweat glands. - Atropine paralyzes the terminations of the nerves in the sudoriparous glands. Thus it causes the skin to become dry.
Kidneys. - The effect of atropine on the amount of urine secreted is necessarily uncertain, as the urinary flow depends so much on the secretion of sweat.
Bronchial mucous membrane. - The secretion of bronchial and tracheal mucus, like that of the mouth, is diminished.
Mammary gland. - The activity of the peripheral terminations of the secretory nerves in the cells of the mammary gland is inhibited, hence the flow of milk, if any is present, is arrested, and belladonna is called an antigalactagogue.
Sensory nerves. - It has already been mentioned that belladonna rubbed into the skin depresses the function of the terminations of the sensory nerves. It does the same when given by the mouth, but its action on sensory nerves - that is to say, its anaesthetic and anodyne action - is very inferior to that on the secretory nerves, and is not powerful enough for atropine to relieve pain when given internally. It is only used as a local anodyne.
Voluntary muscles and their nerves. - Voluntary muscles are quite unaffected even by toxic doses of atropine; towards the end of a case of belladonna poisoning the motor nerves are slightly paralyzed.
Involuntary muscles and their nerves. - The splanchnics are the inhibitory nerves of the intestinal movements, and if they are stimulated, the peristaltic movements stop; impulses are constantly descending these nerves to restrain these movements. If atropine in small doses is given to animals, it is observed that the bowels are relaxed, because intestinal peristalsis is much increased, and that stimulation of the splanchnics is powerless to arrest it; clearly the drug has paralyzed the terminations of the splanchnics in the involuntary muscles of the intestine. Larger doses stop peristalsis.
All involuntary nerve terminations, as those of the muscles of the bladder, ureters, urethra, vesiculae seminales, uterus and vagina are paralyzed like those in the intestinal muscles.
The eye and its nerves. - Atropine acts only on the terminations of the nerves in the involuntary muscles of the eye. If it be dropped into the eye or given by the mouth the pupil dilates widely, and cannot be made to contract by stimulation of the third nerve. That this dilatation is not due to any marked action on the muscular fibres of the iris themselves is shown by the fact that the atropinized pupil will contract if the muscle itself be stimulated. Therefore it must be that the terminations of the third nerve in the iris are paralyzed. The ending of this nerve in the ciliary muscle is affected in the same way, and consequently accommodation is paralyzed. It is certain that this mydriasis and defective accommodation is in no part central, as is the contraction of the pupil produced by opium. So strong is the local action of belladonna that if atropine be dropped into the recently excised eye the pupil will dilate. When the third nerve is cut the pupil dilates, and if, after this, atropine be dropped into the eye it dilates still further. Some have concluded, from this and other reasons, that atropine also stimulates the terminations of the sympathetic in the iris; but this action is slight. The pupil dilates because the elastic fibres in the iris have an opportunity to act. The intra-ocular tension is increased by large doses. There is, as a result of the paralysis of the ciliary muscle, disturbance of vision. Atropine does not act on the pupils of birds.
The heart and its nerves. - The main action of atropine is to paralyze the terminations of the vagus in the heart, and consequently the pulse is rendered more rapid, and cannot be slowed by strongly stimulating the vagus. If the rate of the heart has been lowered by muscarine, which can be shown to have a local stimulating influence on the termination of the vagus in the heart, the application of atropine renders the heart quick again, the two drugs being, in their effect on the heart, exactly antagonistic. This quickening of the pulse from inhibition of the vagal cardiac terminal filaments is the chief action of atropine on the heart, but the following minor actions must be noticed. The vagus centre and the trunk of the nerve are also depressed, but to a much less extent. Before the pulse is quickened it is occasionally slowed for a short time by atropine; this is probably owing to a brief excitation of the vagus centre. Some authorities believe that part of the quickening of the pulse is due to a slight stimulation of the cardiac accelerator nerves, just as we have seen that some consider that the sympathetic fibres in the iris are excited; but if the accelerator nerves are stimulated, the stimulation is quite subsidiary to the important paralysis of the vagal terminations. Although the pulse is quickened by belladonna, its force is not diminished. Toxic doses abolish the function of the cardiac muscle, and the heart stops in diastole.
Vaso-motor system and its nerves. - After a considerable dose of belladonna the skin is flushed, and a scarlatiniform erythematous rash may be present in belladonna poisoning. It is thus obvious that such a dose of belladonna relaxes the peripheral vessels. The exact cause of this has not definitely been made out, but it is extremely probable that it is largely a peripheral action, quite harmonizing with the peripheral action we have seen atropine to have on the involuntary muscles of the intestines, eye and heart; that is to say, the vaso-constrictor nerve-filaments supplying the arterioles are paralyzed, and consequently the vessels dilate. The action of atropine on the medullary vaso-motor centre is more marked than that on the cardiac medullary centre; but it is the same, - the centre first-being stimulated, and then depressed. The primary stimulation is sufficient to overcome the tendency of the peripheral vessels to dilate, so that belladonna at first contracts them; and as this stage of contraction lasts well into the period during which, owing to paralysis of the vagal terminations, the heart is accelerated, the blood-pressure rises considerably; subsequently it falls, the fall being due to the depression of the vaso-motor centre and the peripheral action of belladonna on the vessels, causing their wide dilatation. Ultimately, when the heart itself is paralyzed, the blood-pressure is very low. The spinal vaso-motor centres are acted on as powerfully and in the same way as the medullary centre.
Respiration and its nerves. - Here also belladonna paralyzes peripheral nerve-filaments, in this case those of the vagus in the bronchial tubes. Both the afferent and efferent pulmonary vagal fibres are effected. The result is that the muscular coat of the bronchial tube is relaxed, and that the secretions (the activity of the afferent fibres being depressed) do not irritate the nerves so much as before, and therefore cough is lessened. It will be remembered that the quantity of bronchial secretion is diminished. The medullary and spinal respiratory centres are influenced precisely as the vaso-motor, - that is to say, they are first stimulated, and so the respirations are quicker and deeper, then large doses paralyze them, and the breathing is slow and shallow. The patient becomes asphyxiated, and this contributes to the result in a fatal case.
Temperature. - This is decidedly raised by toxic doses of belladonna (it may be 4o F., about 2o C or more). This rise is independent of the blood-pressure and of the diminution of perspiration. It is said that heat-production is greatly exaggerated. The heat-loss is also increased, probably because the flushing of the skin leads to a greater loss by radiation.
Spinal cord. - Except for the action on the vaso-motor and respiratory spinal centres, belladonna has little influence on the spinal cord in man, but has a well-marked tetanizing effect in frogs. It is said slightly to increase and afterwards diminish general reflex excitability.
Cerebrum. - A considerable dose of belladonna causes delirium, showing that the higher centres are stimulated. Generally the stimulation takes place inco-ordinately. That it is powerful is indicated by the fact that in poisoning by belladonna the delirium will last for a long while. The subsequent quietude is not more than the exhaustion of the cerebrum from the continued delirium will explain. Belladonna rarely, if ever, produces genuine coma. Other symptoms that may be observed with large doses, and which are probably due to disorder of the brain, are staggering gait, giddiness and occasionally convulsions.
Elimination. - Atropine is probably eliminated entirely by the kidneys.
It will be seen that the dominant action of belladonna is to depress the activity of the terminations of nearly all varieties of nerves. In addition, it first stimulates and then depresses the three great medullary centres, and it is a deliriant. A summary of its effects on man will be given under the heading of Toxicology.
Children can take considerable doses of belladonna without any symptoms of poisoning. Pigeons and rodents are peculiarly insusceptible to it.