BELLADONNA (from the Ital. bella donna, “beautiful lady,” the berries having
been used as a cosmetic), the roots and leaves of Atropa belladonna, or deadly
nightshade (q.v.), widely used in medicine on account of the alkaloids which
they contain. Of these the more important are atropine (or atropia), hyoscyamine,
hyoscine and belladonine; atropine is the most important, occurring as the
malate to the extent of about o~47 % in the leaves, and from o’ó to o~25 % in
the roots.
Atropine, Cf7HnNOi, was discovered in 1833 by P. L. Geiger and Hesse and by
Mein in the tissues of Atropa belladonna, from which it may be extracted by
means of chloroform. By crystallization from alcohol it is obtained as
colourless needles, melting at l15°. Hydrolysis with hydrochloric acid or
baryta water gives tropic acid and tropine; on the other hand, by boiling
equimolecular quantities of these substances with dilute hydrochloric acid,
atropine is reiormed. Since both these substances have been synthesized (see
TR0PINE), the artificial formation of atropine is accomplished. Atropine is
optically inactive; hyoscyamine, possibly a physical isomer, which yields
atropine when heated to io8’6°, is laevorotatory.
Medicine.—The official doses of atropine are from -r’~--rto 1+0 grain,
and the sulphate, which is in. general use in medicine, has a similar dose. It
is highly important to observe that the official doses of the various
pharmacopoeias may with safety be greatly exceeded in practice. They are based
on the experimental toxic, as distinguished from lethal dose. A toxic dose
causes unpleasant symptoms, but in certain cases, such as this, it may require
very many times a toxic dose to produce the lethal effect. In. other words,
whilst one-fiftieth of a grain may cause unpleasant symptoms, it may need more
than a grain to kill. So valuable are certain of the properties of atropine that
it is often desirable to give doses of one-twentieth or onetenth of a grain; but
these will never be ventured upon by the practitioner who is ignorant of the
great interval between the minimum toxic and the minimum lethal dose. It
actually needs twenty to thirty grains of atropine to kill a rabbit: the animal
is, however, somewhat exceptional in this regard. The most valuable preparations
of this potent drug are the liquor atropinae sulphatis, which is a I % solution,
and the lamella—for insertion within the conjunctival sac—which contains one
five-thousandth part of a grain of the alkaloid.
Pharmacology—When. rubbed into the skin with such substances as alcohol or
glycerine, which are absorbed, atropine is carried through the epidermis with
them, and in this manner— or when simply applied to a raw surface—it
paralyses the terminals of the pain-conducting sensory nerves. It acts
similarly, though less markedly, upon the nerves which determine the secretion
of the perspiration, and is therefore a local anaesthetic or anodyne and an
anhidrotic. Being rapidly absorbed into the blood, it exercises a long and
highly important series of actions on nearly every part and function of the
nervous system. Perhaps its most remarkable action is that upon the terminals of
nearly all the secretory nerves in the body. This causes the entire skin to
become dry—as in the case of the local action above mentioned; and it arrests
the secretion of saliva and mucus in the mouth and throat, causing these parts
to become very dry and to feel very uncomfortable. This latter result is due to
paralysis of the chorda tympani nerve, which is mainly responsible for the
salivary secretion. Certain nerve fibres from the sympathetic nervous system,
which can also cause the secretion of a
(specially viscous) saliva, are entirely unaffected by atropine. A ctrrious
parallel to this occurs in its action on the eye. There is much uncertainty as
to the influence of atropine on the secretions of the stomach, intestines,
liver, pancreas and kidneys, and it is not possible to make any definite
statement, save that in all probability the activities of the nerves innervating
the glandcells in these organs are reduced, though they are certainly not
arrested, as in the other cases. The secretion of mucus by the bronchi and
trachea is greatly reduced and their muscular tissue is paralysed—a fact of
which much use is made in practical medicine. The secretion of milk, if
occurring in the mammary gland, is much diminished or entirely arrested. Given
internally, atropine does not exert any appreciable sedative action upon the
nerves of pain.
The action of atropine on the motor nerves is equally important. Those that
go to the voluntary muscles are depressed only by very large and dangerous
doses. ,The drug appears to have no influence upon the contractile cells that
constitute muscle-fibre, any more than it has directly upon the secretory cells
that constitute any gland. But moderate doses of atropine markedly paralyse the
terminals of the nerves that go to involuntary muscles, whether the action of
those nerves be motor or inhibitory. In the intestine, for instance, are layers
of muscle-fibre which are constantly being inhibited or kept under check by the
splanchnic nerves. These are paralysed by atropine, and intestinal penstalsis is
consequently made more active, the muscles being released from nervous control.
The motor nerves of the arteries, of the bladder and rectal sph’incters, and
also of the bronchi, are paralysed by atropine, but the nervous arrangements of
those organs are highly complex and until they are further unravelled by
physiologists, pharmacology will be unable to give much information which might
be of great value in the employment of atropine. The action upon the vaso-motor
system is, however, fairly clear. Whether effected entirely by action on the
nerve terminals, or by an additional influence upon the vaso-motor centre in the
medulla oblongata, atropine certainly causes extreme dilatation of the
blood-vessels, so much so that the skin becomes flushed and there may appear,
after large doses, an erythematous rash, which must be carefully distinguished,
in cases of supposed belladonna poisoning, from that of scarlet fever:
more especially as the temperature may be elevated and the pulse is very
rapid in both conditions. But whilst the characteristic action of atropine is to
dilate the blood-vessels, its first action is to stimulate the vaso-motor centre—thereby
causing temporary contraction of the vessels—and to increase the rapidity of
the heart’s action, so that the blood-pressure rapidly rises. Though
transient, this action is so certain, marked and rapid, as to make the
subcutaneous injection of atropine invaluable in certain conditions. The
respiratory centre is similarly stimulated, so that atropine must be regarded as
a temporary but efficient respiratory and cardiac stimulant.
Toxic doses of atropine—and therefore of belladonna—raise the temperature
several degrees. The action is probably nervous, but in the present state of our
knowledge regarding the control of the temperature by the nervous system, it
cannot be further defined. In small therapeutic and in small toxic doses
atropine stimulates the motor apparatus of the spinal cord, just as it
stimulates the centres in the medulla oblongata. This is indeed, as Sir Thomas
Fraser has pointed out, “a strychnine action.” In large toxic and in lethal
doses the activity of the spinal cord is lowered.
No less important than any of the above is the action of atropine on the
cerebrum. This has long been a debated matter, but it may now be stated, with
considerable certainty, that the higher centres are incoordinately stimulated, a
state closely resembling that of delirium tremens being induced. In cases of
poisoning the delirium may last for many hours or even days. Thereafter a more
or less sleepy state supervenes, but it is not the case that atropine ever
causes genuine coma. The stuporose condition is the result of exhaustion after
the long period of cerebral excitement. It is to be noted that children, who are
particularly susceptible to the influence of certain of the other
potent alkaloids, such as morphine and strychnine, will take relatively large
doses of atropine without ill-effect.
The action of atropine on the eye is of high theoretical and practical
importance. The drug affects only the involuntary muscles of the eye, just as it
affects only the involuntary or non-striated portion of the oesophagus. The
result of its instillation into the eye—and the same occurs when the atropine
has been absorbed elsewhere—is rapidly to cause wide dilatation of the pupil.
This can be experimentally shown—by the method of exclusion—to be caused by
a paralysis of the terminals of the third cranial nerve in the sphincter
pupillae of the iris. The action of atropine in dilating the pupil is also aided
by a stimulation of the fibres from the sympathetic nervous system, which
innervate the remaining muscle of the iris—the dilator pupillae. As a result
of the extreme pupillary dilatation, the tension of the eyeball is greatly
raised. The sight of many an eye has been destroyed by the use of atropine—in
ignorance of this action on the intra-ocular tension—in cases of incipient
glaucoma. The use of atropine is absolutely contra-indicated in any case where
the intra-ocular tension already is, or threatens to become, unduly high. This
warning applies notably to those—usually women—who are accustomed
indiscriminately to use belladonna or atropine in order to give greater
brilliancy to their eyes. The fourth ocular result of administering atropine is
the production of a slight but definite degree of local anaesthesia of the
eyeball. It follows from the above that a patient who is definitely under the
influence of atropine will display rapid pulse, dilated pupils, a dry shin and a
sense of discomfort, due to dryness of the mouth and throat.
Therapeutics.—The external uses of the drug are mainly analgesic. The
liniment or plaster of belladonna will relieve many forms of local pain.
Generally speaking, it may he laid down that atropine is more likely than iodine
to relieve a pain of quite superficial origin; and conversely. Totally to be
reprobated is the use, in order to relieve pain, of belladonna or any other
application which affects the skin, in cases where the surgeon may later be
required to operate. In such cases, it is necessary to use such anodyne measures
as will not interfere with the subsequent demands that may be made of the skin,
i.e. that it be aseptic and in a condition so sound that it is able to undertake
the process of healing itself after the operation has been performed. Atropine
is universally and constantly used in ophthalmic practice in order to dilate the
pupil for examination of the retina by the ophthalmoscope, or in cases where the
inflamed iris threatens to form adhesions to neighbouring parts. The drug is
often replaced in ophthalmology by homatropine—an. a]kaloid prepared from
tropine—which acts similarly to atropine but has the advantage of allowing the
ocular changes to pass away in a much shorter time. The anhidrotic action of
atropine is largely employed in controlling the night-sweats so characteristic
of pulmonary tuberculosis, small doses of the solution of the sulphate being
given at night.
The uses of atropine in cardiac affections are still obscure and dubious. It
can only be laid down that the drtig is a valuable though temporary stimulant in
emergencies, and that its use as a plaster or internally often relieves cardiac
pain. Recollection of the extraordinary complexity of the problems which are
involved in the whole question of pain of cardiac origin will emphasize the
extreme vagueness of the above assertion. Professor Schafer recommended the use
of atropine prior to the administration of a general anaesthetic, in cases where
the action of the vagus nerve upon the heart is to be dreaded; and there is
little doubt of the value of this precaution, which has no attendant
disadvantages, in all such cases. Atropine is often of value as an antidote, as
in poisoning by pilocarpine, muscarine (mushroom poisoning), prussic acid,
&c.
Omitting numerous minor applications of this drug, we may pass to two
therapeutic uses which are of unquestionable utility. In cases of whooping-cough
or any other condition in which there is spasmodic action of the muscular fibre
in the bronchi— a definition which includes nearly every form of asthma and
many cases of bronchitis—atropine is an almost invaluable
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