Abstract
Administration of atropine preparations over a period of time leads in certain animals to a decrease in the effectiveness of the drug. Cloetta 1 found that normal rabbits excrete a dose of atropine during a period of 2 or 3 days but excretion is complete in one day according to Fickewirth and Heffter 2 if atropine is administered to rabbits habituated to the drug. Normal cats excrete very little atropine (Doeblin and Fleisehmann 3 ) but after habituation, the excretion is markedly augmented.
Another type of increased resistance to atropine preparations was noted in a series of experiments in this laboratory performed on fasting dogs and man in which objective records of gastro-intestinal motility were made by the balloon method. (The triple, tandem balloon was used in the human experiments.) It was thus determined that injection of an atropine preparation shortly after recovery (i. e., return to preinjection tone and motility) from a preceding administration of atropine was less effective than the initial injection.
When administered as the initial medication, 0.065 mg./Kg. atropine intravenously administered to the unanesthetized dog uniformly completely inhibited the stomach and recovery was complete in 80 ± 30 minutes. (Results of initial medications are presented in detail elsewhere.) Following complete return of preinjection tone and motility, a second injection of the same quantity of atropine (8 experiments) produced inhibition with recovery in approximately 30 minutes (3 experiments) or failed to produce complete inhibition (5 experiments). Reduced effectiveness from a second administration was likewise demonstrated when both the first and second dose were smaller (0.032 mg./Kg.) or larger (0.13 mg./Kg.). For example, the initial administration of 0.13 mg./Kg. produced complete gastric inhibition with recovery in 150 ± 30 minutes. Repetition of this dosage after recovery (4 experiments) produced transient complete inhibition (3 experiments) or incomplete inhibition (1 experiment).
Gastric hypermotility is produced by administration of insulin (Quigley, Johnson, Solomon 4 ) This hypermotility in the normal human was uniformly completely inhibited by 0.65 mg. atropine administered subcutaneously when given as the initial medication and recovery was complete in 45 ± 15 minutes. However, when given as the second injection (8 experiments), this dose either produced only a transient complete inhibition (5 experiments) or inhibition was incomplete (3 experiments).
Reduced effectiveness from repetition of administration was also observed with Novatropin (methylhomatropine bromide), a drug with an atropinelike action. Initially, 0.1 mg./Kg. in the dog always produced complete gastric inhibition with complete recovery in 55 ± 10 minutes. After recovery, a second injection of this drug in 6 experiments produced no effect in one experiment, incomplete inhibition with complete recovery in 25 minutes in 3 experiments and in 2 experiments complete inhibition developed but was followed by full recovery in 45 minutes. As the initial medication, 0.2 mg./Kg. Novatropin in the dog produced complete gastric inhibition with full recovery in 90 ± 25 minutes (3 experiments). A repetition of this dose failed to produce complete inhibition in 2 experiments and in one experiment inhibition was complete but full recovery occurred in 25 minutes. Similar results with Novatropin were obtained in man.
A decrease in effectiveness was obtained in the dog or human when atropine followed Novatropin or vice versa. This is illustrated by 3 experiments on man, in each of which 1.3 mg. atropine was given after recovery from 1.5 mg. Novatropin. In one experiment, complete inhibition developed but recovery was complete in 39 minutes. In another case, the region of the upper 2 balloons was
Get full access to this article
View all access options for this article.