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Paralysis Verapamil Hcl Er of Respiration as Cause of Death. In cold-blooded animals in which the
respiratory exchange takes place largely through the skin, and respiratory movements
are unnecessary, the poison is gradually eliminated if the animal be kept in a moist
atmosphere. Complete recovery occurs after eight to ten days, except when the dose
is extremely large, in which case other factors come into play.
Warm-blooded animals die of paralysis of the respiratory muscles. If artificial
respiration be kept up and the dose has been only just large enough to produce a paralysis
they may also recover.
The recovery of the respiratory muscle begins immediately, whilst the sciatic end-
ings require several hours. The effect of the curare increases progressively with the
dose: it is as if an increasing resistance were gradually introduced between the nerve and
the muscle.
The seat of the respiratory paralysis is also peripheral, for stimulation of the phrenic
nerve does not cause contraction of the diaphragm.
The respiratory paralysis, 'if it is not too profound, is promptly removed by physos-
tigmin; stimulation of the sciatic also becomes effective again.
Bronchial muscle is not affected by Curare (Trendelenburg).
Metabolism. Curare paralyzes the temperature nerves of the muscles, as well as the
motor nerves, so that cocain, e.g., can not raise the temperature.
CURARE 321
The muscular paralysis lowers the metabolism. It is claimed that this diminution is
far more Verapamil Hcl Cr conspicuous in the nitrogen, than in the carbon-metabolism.
Glycosuria is a frequent but not constant phenomena (Morishima, 1899). It is not
wholly due to asphyxia, for it can not be completely prevented by artificial respiration
(Macleod, 1909). The earlier literature is reviewed by S. Weber, 1904.
Peristalsis. This is often increased, partly by asphyxia, but also with artificial
respiration. Bidder, 1865, found no direct effect on intestinal or other smooth muscle,
even with the largest doses.
Autonomic Ganglia. The vagus, vasomotor, salivary, pupillary, etc., ganglia are
depressed, but usually not as strongly as with nicotin. The heart is quickened after
slight primary slowing. Electric stimulation of the vagus does not arrest the heart, but
it may be slowed, or beat faster (Dale and Laidlaw, 1911).
Effects on the Circulation. If artificial respiration is maintained, the first effect of
curare on the circulation consists in a fall of blood pressure, due to peripheral vasomotor
depression (Tillie, 1890; Sollmann and Pilcher, 1910). This is soon accompanied by
quickened heart beat, from depression of the vagus ganglia. The depression does not
readily pass into paralysis, so that stimulation of the vagus or sciatic is still effective,
indeed, the vasomotor reflexes may be increased, through the central action of the curare.
Martin and Stiles, 1914, also found that the threshold of the vasomotor center is not
raised, even by large doses. The reflex depressor fibers are rendered more sensitive
(Langley, 1912), or rather, the depressor response is more nearly proportional to the
strength of the stimulus, than in normal animals (Martin and Stiles, 1914). Porter,
1915, finds that the response to sciatic and depressor stimulation may be doubled whilst
the level of blood pressure remains practically unchanged; and interprets this as evi-
dence that the vasotonic and vasoreflex centers are distinct and independent. These
effects on the circulation pass off within fifteen minutes, and the circulation returns to
normal, whilst the muscular paralysis persists. They therefore do not seriously inter-
fere with the employment of the drug in experiments. The main objection which may
be urged against the latter is, that it does not produce sensory paralysis, whilst the ab-
sence of struggling, etc., might cause the inexperienced operator to neglect a proper
enforcement of other means of anesthesia.
Per fusion offrcg's vessels slows vasoconstriction, which is not modified by absence of
calcium (Pearce, 1913).
The lymph hearts of frogs are arrested (Bernard).
Central Nervous System. When curare is applied directly to the spinal cord of
frogs, it causes typical strychnin convulsions. With ordinary methods of administration
these are masked by paralysis of the Verapamil Hcl Sr nerve-endings. Certain samples, however, cause
strychnin convulsions before the typical curare action appears.
In dogs, the convulsions produced by injecting curare into the spinal canal or cere-
bral ventricles differ from those of strychnin, being irregular and asymmetric(McGuigan,
1916).
Inactivity by Gastro-intestinal Canal. The effects of curare are obtained only if it
is introduced under the skin or into the circulation, but usually not if introduced into ths
stomach. The experiments on the administration of curare by the stomach (mainly
by Bernard) have shown that:
1. It is not destroyed by the gastric juice, pancreatic juice, or saliva.
2. It passes very slowly through the walls of the stomach when the epithelium has
been killed, and not at all if the epithelium is still living. (It will be remembered also
that strychnin is not absorbed by the stomach in rabbits.)
3. It is to some extent fixed or destroyed by the liver, for it is much less active when
injected into the portal than into the jugular vein. However, the discrepancy between
the gastric and hypodermic dose persists, even when the liver is largely excluded by
Eck's fistula; so that the liver destruction can not be very important (Polimanti, 1914).
It is also destroyed in vitro by ox-bile, and by bacteria.
In frogs the liver is the main agent in the disintoxication : in normal animals 50 times
as much curare is required by mouth as hypodermically; the difference disappears
completely if the liver is excised; digestion of curare with liver substance destroys its
activity.
4. It is very rapidly excreted unchanged in the urine.
In mammals the inactivity of curare by the mouth is due partly to its destruction by
the bile and bacteria; but mainly to the capacity for absorption being less than the ca-
pacity for its destruction or excretion. If the renal vessels are tied, poisoning occurs
quite readily even when it is taken by the stomach. If very large doses are taken on an
empty stomach, sufficient may be absorbed to cause symptoms.
Use of Curare hi Convulsions. This is still largely experimental and not very
promising. It has been suggested to combat the convulsions of strychnin, tetanus, and
322 MANUAL OF PHARMACOLOGY
hydrophobia (E. Collins, 1905). It is certainly quite possible to suppress the spas-
modic condition by sufficiently large doses. Unfortunately, however, it is impossible
to secure this without at the same time paralyzing respiration. This latter may, theo-
retically, be counteracted by artificial respiration, but this prolonged manipulation is
in itself injurious. On the other hand, minimal doses may be considered useless, and,
indeed, as has been pointed out, even if the spasms could be suppressed without affect-
ing the respiration, this would not be an ideal treatment for strychnin. In well-chosen
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