92 CIRCULATORY DEPRESSANTS 



Summary of Action. 1. Stimulation followed by paralysis of 

 many different nerve endings, sensory, motor, and secretory. 



2. Stimulation followed by depression of certain parts of the 

 central nervous system. 



External Action. If applied to the skin in aqueous solution 

 there is little if any action, because it is not absorbed, but if mixed 

 with alcohol, or some other absorbable material, it stimulates, then 

 depresses the sensory nerve endings, producing a tingling, tickling 

 or a burning sensation, followed by numbness or anesthesia. This 

 same effect is seen if the drug is taken internally in large doses. 

 The above action, however, is not accompanied by any signs of in- 

 flammation, so that aconite is not a protoplasmic poison and must 

 be considered as having a selective action. 



Digestive System. Here we have the same action as described 

 under the head of external action together with salivation when the 

 drug is taken in the mouth. Large doses cause considerable irrita- 

 tion to the. mouth and stomach, but as in case of its external action 

 there are no signs of inflammation. There is also a sense of con- 

 striction of the fauces and anesthesia to taste. Medicinal doses may 

 serve as sedatives to the stomach, increasing the secretions, while 

 large doses may cause pain, nausea and vomiting. 



Circulatory System. The action upon the heart is due to vagus 

 and accelerator stimulation and to direct action upon the heart itself. 

 After a very brief period of activity from accelerator stimulation, 

 which is unimportant, aconite slows the heart by vagus stimulation 

 and lowers blood pressure. Since there is no increased strength of 

 contraction with the slowing, less blood is forced through the heart 

 per unit of time, and pressure falls. In toxic doses, however, 

 aconite has a direct stimulating action upon the heart muscle, increas- 

 ing its irritability and causing it to become more rapid, weak and 

 irregular. As the action becomes more intense, the irregularity in- 

 creases until delirium cordis suddenly takes place. The arterioles 

 may be constricted for a short time on account of stimulation of the 

 vasomotor center, but the lessened force of the heart brings about a 

 marked though variable reduction in blood pressure. 



In therapeutics it has been assumed that aconite would produce 

 pure vagus stimulation with slowing of the rate of the heart and fall 

 in blood pressure, but Mackenzie, in 1911, gave large doses of the 

 tincture frequently to men and in many cases obtained no action. 

 Price pushed the drug in fibrillation of the auricles where digitalis 

 was effective, and in rapid heart due to fevers and other causes, but 

 without any evidence of a reaction upon the heart or blood vessels. 

 Eudolf and Cole (1913) in a test of 55 human patients with and 

 without fever failed to get any change in the pulse rate. 



From therapeutic doses there is no depression of the vasocon- 

 strictor mechanism, and the drug lowers pressure, if at all, by pure 

 cardiac depression and not by dilatation of the arteries. 



