10 PRELIMINARY CONSIDERATIONS 



blood the drug may form unknown combinations with the tissues for 

 which it has an affinity — thereby exerting its remedial effect — and is 

 oxidized or decomposed, or rarely accumulates in the body, but usually 

 is eliminated either unchanged or as decomposition-products in the breath, 

 or by the excretions or secretions of the kidneys, bowels, liver, sudorip- 

 arous, salivary and mammary glands, and mucous membranes. The urine 

 is the most frequent channel of elimination for soluble drugs. The bowels 

 constitute the next more common pathway of elimination. Volatile drugs 

 (chloroform, ether) are eliminated very rapidly, usually, in the breath. 

 If a drug is eliminated slowly the duration of its action is correspond- 

 ingly long, and vice versa. This fact will guide us in the frequency of 

 administration of medicines, since if a drug which is tardily eliminated 

 be given at frequent intervals it may be absorbed faster than it is ex- 

 creted and so accumulate in the body and cause poisoning. The so-called 

 Cumulative Action of a drug refers to the occurrence of a sudden and 

 violent effect during its medicinal administration. This may be due (1) 

 to delayed elimination followed by rapid absorption; or (2) to slow — or 

 sudden arrest of — elimination. The salts of the heavy metals, as lead, 

 mercury, etc., and arsenical preparations are eliminated slowly. Digi- 

 talis and strychnine are said to be especially prone to produce a cumu- 

 lative action. Strychnine may, however, be given subcutaneously in 

 gradually increasing doses without the likelihood of poisoning. Digitalis 

 may cause a cumulative effect in being slowly oxidized in the body or in 

 leading to contraction of the renal vessels and suppression of urine-elimi- 

 nation. The drugs likely to cause a cumulative action must be adminis- 

 tered infrequently, once, twice, or thrice daily; whereas medicines which 

 are rapidly decomposed and eliminated (alcohol, nitrites, etc.) may be 

 given at very frequent intervals if desirable. The term excretion is often 

 used synonymously with elimination, but, strictly speaking, a drug is not 

 eliminated unless it has been first absorbed. On the other hand, an in- 

 soluble drug passing unabsorbed through the alimentary canal is said 

 properly, to be excreted in the feces. 



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