This section is from the book "A Text-Book Of Pharmacology, Therapeutics And Materia Medica", by T. Lauder Brunton. Also available from Amazon: A text-book of pharmacology, therapeutics and materia medica.
One of the most important circumstances affecting the action of any drug is the mode in which it is brought into contact with the various parts of the organism.
The local action of a drug is that which it exerts on the part to which it is applied. Thus sulphuric acid has a direct irritant or destructive action, and when applied to the skin or mucous membrane will produce local redness, inflammation, or sloughing. When swallowed, it produces weakness of the circulation, stoppage of the heart, and death.
This effect on the circulation is not due to the direct action of the acid upon the heart, the vessels, or the nervous system, after its absorption : it is due to the reflex action exerted upon them by the irritation of the nerves of the stomach which the sulphuric acid produces. This action on different parts through the nervous system is termed its remote action, in contradistinction to the local action of the acid upon the gastric mucous membrane.
The Interaction of various functions in the body is one of the greatest difficulties in the way of our readily understanding the action of drugs.
One function alters another, and the second reacts upon the first, so that in some cases it is almost impossible to say precisely how far the alteration in any function is due to the direct effect of the drug upon it, and how far to some indirect action. Thus curare when applied to a wound usually kills without producing any convulsion whatever. It paralyses the ends of the motor nerves, so that all the muscles in the body become powerless. But when it is given by the stomach, and excretion through the kidneys prevented, death is preceded by convulsions. These convulsions are not caused by any direct irritating action of the curare itself upon the nerve-centres; they are due to irritation of these centres by a venous condition of the blood. This venosity of the blood is due to imperfect respiration, produced by paralysis of the respiratory muscles through the action of curare on the motor nerves.1
The effect of curare is a purely paralysing one, both when the animal dies quietly and when it dies with convulsions. In both cases it paralyses the motor nerves of the respiratory muscles and of the extremities. In both cases it causes death by arresting the respiration and producing asphyxia. But in the latter case the motor nerves of the extremities being only partially paralysed when asphyxia occurs, they respond by convulsive movements to the irritation of the nerve-centres, which the venous blood produces. In the former, the paralysis of the limbs being complete, the muscles remain perfectly quiet, notwithstanding the irritation of the nerve-centres.
Convulsions also sometimes occur previous to death from narcotic poisons: and in a description of the action of these poisons we frequently meet with the phrase, ' coma, convulsions, and death.' In such cases the convulsions are also caused by the irritation of the nerve-centres by asphyxial blood.
The drug causes the coma; the coma causes imperfect respiration; imperfect respiration renders the blood venous; and the venous blood causes convulsions.