The specific therapeutic action of most drugs is generally well established and their action may be predicted with a fair degree of certainty. The use of drugs in combination has also led to recognition of the fact that certain drugs enhance the action of others—a synergistic effect. That certain drugs counteract the action of others, i. e., physiologic antagonïsm, is also common knowledge. However, the administration of one drug may produce a sensitization of the tissues, which so modifies the functional response of the tissues that a second drug exerts an effect diametrically opposed to its customary and expected action. This alteration of the functional activity of the cells may be produced by physical-chemical forces, by disease or by drugs.1 There are many examples of drugs exhibiting this reversal of action under varying conditions.
Calcium may produce a varying cardiac response, depending on existing circumstances. Its action is affected not only by the state of the cardiac musculature but by the earlier administration of other drugs. Furthermore, when calcium is employed beforehand, the action of other drugs may be modified.
BOWER JO, MENGLE HAK. THE ADDITIVE EFFECT OF CALCIUM AND DIGITALIS: A WARNING, WITH A REPORT OF TWO DEATHS. JAMA. 1936;106(14):1151–1153. doi:10.1001/jama.1936.02770140013004
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