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Studies on purified digitalis glucosides. III. The relationship between therapeutic and toxic potency
848
THE
AMERICAN
HEART
Cattell, M., and Gold, II.: Studies on Purified tionship Between Therapeutic and Toxic Therap.
71:
114,
JOURNAL
Digitalis Glucosides. III. The RelaPotency. J. Pharmacol. & Exper.
1941.
The
relative potency with regard to both therapeutic and toxic effects muscles from the cat have been determined for the following ouabain (Merck), digitoxin (Merck), digitaline (Laboratoire Nativelle), A (Sandoz), lanatoside B (Sandoz) and lanatoside C (Cedilanid, Sandoz).
papillary
on isolated glucosides: lanatoside
The minimum concentration of ouabain and digitoxin, i.e., that causing increased force of contraction in 50 per cent of experiments (therapeutic effect) is 1 part in 100 millions of Locke’s solution; for the lanat.oside compounds it is approximately 1 part in 10 millions. When the concentration of any effects are produced, including extra force of contraction.
of the glucosides is sufficiently contractions, loss of excitability,
increased, toxic and diminished
The ratio of the concentrations producing therapeutic and toxic effects is the same for ’ ‘ digitaline nativelle ’ ’ and ouabain. There is also similarity among the several lanatoside glucosides studied, and thus by this technique we have not been able to confirm the wide margin between the therapeutic and toxic dose reported by Moe and Visscher for lanatoside C. Ouabain and l i digitaline nativelle ’ ’ both give a slightly higher value for the ratio of toxic to therapeutic concentration in comparison with the lanatoside compounds. The evaluation of the significance of this finding must await further evidence. The available evidence pertaining ship between toxic and therapeutic and the conclusion is reached that wanting.
to the questions of differences in the relationdoses among different glucosides is discussed, proof of the existence of such differences is still AUTHORS.
Boyd, L. J., and Scherf, D.: The Electrocardiogram in Acute Emetine tion. J. Pharmacol. t Exper. Therap. 71: 362, 1941. The alterations of of emetine hydrochloride
the
electrocardiogram were studied in
after the intravenous dogs and cats.
Intoxica-
administration
Disturbance of intraventricular conduction is the most common change under these circumstances. Bradycardia and prolongation of at,rioventricular duction time develop regularly, but they are not pronounced.
observed con-
If the intravenous dose does not exceed 37 mg. in dogs weighing 5 to 9 kg., the electrocardiographic alterations gradually disappear within forty-five minutes. Cardiac dilatation, especially involving the right ventricle, the development of which is simultaneous with the ventricular conduction disturbances, also vanishes within the same period. The action of emetine is cumulative sult from the second or third injection the normal electrocardiogram had been
since much of an equal restored.
more amount
pronounced effects reof the drug although
The most common arrhythmias to develop are auricular extrasystoles and auricular tachycardias. Alternation of the ventricular complexes is frequently observed during the tachycardia. Advanced stages of intoxication are required for the production of Heart block with dropped beats was encountered only in ventricular extrasystoles. cats. AUTHORS.
THE
AMERICAN
HEART
Cattell, M., and Gold, II.: Studies on Purified tionship Between Therapeutic and Toxic Therap.
71:
114,
JOURNAL
Digitalis Glucosides. III. The RelaPotency. J. Pharmacol. & Exper.
1941.
The
relative potency with regard to both therapeutic and toxic effects muscles from the cat have been determined for the following ouabain (Merck), digitoxin (Merck), digitaline (Laboratoire Nativelle), A (Sandoz), lanatoside B (Sandoz) and lanatoside C (Cedilanid, Sandoz).
papillary
on isolated glucosides: lanatoside
The minimum concentration of ouabain and digitoxin, i.e., that causing increased force of contraction in 50 per cent of experiments (therapeutic effect) is 1 part in 100 millions of Locke’s solution; for the lanat.oside compounds it is approximately 1 part in 10 millions. When the concentration of any effects are produced, including extra force of contraction.
of the glucosides is sufficiently contractions, loss of excitability,
increased, toxic and diminished
The ratio of the concentrations producing therapeutic and toxic effects is the same for ’ ‘ digitaline nativelle ’ ’ and ouabain. There is also similarity among the several lanatoside glucosides studied, and thus by this technique we have not been able to confirm the wide margin between the therapeutic and toxic dose reported by Moe and Visscher for lanatoside C. Ouabain and l i digitaline nativelle ’ ’ both give a slightly higher value for the ratio of toxic to therapeutic concentration in comparison with the lanatoside compounds. The evaluation of the significance of this finding must await further evidence. The available evidence pertaining ship between toxic and therapeutic and the conclusion is reached that wanting.
to the questions of differences in the relationdoses among different glucosides is discussed, proof of the existence of such differences is still AUTHORS.
Boyd, L. J., and Scherf, D.: The Electrocardiogram in Acute Emetine tion. J. Pharmacol. t Exper. Therap. 71: 362, 1941. The alterations of of emetine hydrochloride
the
electrocardiogram were studied in
after the intravenous dogs and cats.
Intoxica-
administration
Disturbance of intraventricular conduction is the most common change under these circumstances. Bradycardia and prolongation of at,rioventricular duction time develop regularly, but they are not pronounced.
observed con-
If the intravenous dose does not exceed 37 mg. in dogs weighing 5 to 9 kg., the electrocardiographic alterations gradually disappear within forty-five minutes. Cardiac dilatation, especially involving the right ventricle, the development of which is simultaneous with the ventricular conduction disturbances, also vanishes within the same period. The action of emetine is cumulative sult from the second or third injection the normal electrocardiogram had been
since much of an equal restored.
more amount
pronounced effects reof the drug although
The most common arrhythmias to develop are auricular extrasystoles and auricular tachycardias. Alternation of the ventricular complexes is frequently observed during the tachycardia. Advanced stages of intoxication are required for the production of Heart block with dropped beats was encountered only in ventricular extrasystoles. cats. AUTHORS.