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Verapamil Hcl Er


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Verapamil Hcl Er

Related post: 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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