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Cedilanid, with special reference to its intravenous use
CEDILANID,
WITH
SPECIAL
INTRAVENOUS NAURICESOKOLOW,
REFERENCE
TO ITS
USE
M.D., ANDFRANCISL. CHAMBER.LAIN, SAN FRANCISCO, CALIF.
M.D.
T
HE use of the ordinary whole leaf of digitalis, the digitalis purpurea of the United States Pharmacopeia, has never been considered ideal for several reasons. First, it required bio-assay ; second, it was impure and hence could not be given intravenously with assurance; third, its potency has varied from time to time, as shown by the fact that the 1J.S.P. XI digitalis is one-third stronger than that of the U.S.P. X. In recent years the glycosides of digitalis have been isolated in pure crystalline form, and work is being done with these pure substances. In addition to the ordinary digitalis, digitalis purpurea, there is another plant, digitalis lanata, which is indigenous to the Balkan countries. Stolll has isolated the glycosides of this new digitalis. There are three glycosides in each, but digitalis lanata differs in that it alone contains lanatoside C, or cedilanid. Clinical interest in lanatoside C began with the pharmacologic work of Moe and Vissche? on heart-lung preparat,ions. This suggested that lanatoside C was the least toxic and the most potent of the lanata glycosides and could be obtained in pure orystalline form. Early preliminary work in Europe3 (the drug was first available in Switzerland) indicated that lanatosicle C was a potent drug. It has been used in the United States for the past two years. Gold and his coworkers4 in New York, ancl Fahr and LaDue,5 in Minneapolis, have made preliminary reports. During the past two years we have been studying t.he oral and intravenous use of lanatoside C at the University of California Hospital, and our reports are based on that, work.‘j To date we have followed eighty-five patients. The drug* comes in tablets of 0.5 mg., as well as in 2 C.C.and 4 C.C.ampoules which contain 0.2 mg. per cubic centimeter. It has been established that the cat unit is equal to 0.28 mg. ; however, Gold showed that 1 mg. of cedilanid is equal to 293 mg. of digitalis leaf when they are compared by the cat method, to 438 mg. when they are compared by the frog method, and to 170 mg. when they are compared in man by oral administration. Therefore, the clinieal pot.ency of these pure glycosides should be ascertained by clinical assay and not by animal assay. The intravenous administration of cedilanid has proved to be of great value. We have used it in thirty-eight casesin dosesup to 14 C.C.per -From the Department of Medicine, University of California Medical School. San Francisco. Presented before the meeting of the California Heart Association, Del Monte, Calif.. May 4, 1941. Received for publication Sept. 2, 1941. *Mark&cd by the Sandoz Chemical Works, Jncorporated, to whom we are grateful for supplies. 213
244
AMERICAN
HEART
.JOURNAL
day, some of which were divided. In general, 8 C.C. per day is the digitaliz,ing dose, and 6 C.C. to 14 e.c. in twenty-four hours in divided doses will digitalize almost all patients. In only three instances was mild nausea produced by 8 C.C. of cedilanid given in one dose, and in many instances beneficial effects were noted in ten to twenty minutes. In auricular fibrillation the ventricular rate may fall 40 to 50 beats within thirty minutes to two hours; in aurieular flutter a fixed 4 to 1 block, and, subsequently, normal rhythm may be produced by a single dose of 8 C.C. administered intravenously. In cases of normal rhythm with congestive failure, cligit.alization may be accomplished within twenty-four hours. The advantages of rapid, safe digitalization are self evident in cases of desperate cardiac failure. Frequently, partial digitalization may be accomplished by the intravenous administration of 4 C.C. to 6 c.c., and then maintained by the oral preparation. The intravenous preparation is not, recommended for maintenance because frequent injections are necessitated by the rapid excretion of the drug. It is, therefore, better to use the oral preparation of cedilanid for maintenance. In general, WC find that a daily maintenance dose of 1 C.C. to 3 es. is needed when the drug is given intravenously. COXCIAJSIONS
1. Cedilanid is a pure, crystalline glycoside which is obtained from digitalis lanata and is not present in digitalis purpurea. 2. Cedilanid is marketed in tablets of 0.5 mg. for oral use, and in ampoules in which each cubic centimeter is equal to 0.2 mg. 3. The intravenous digitalizing dose varies from 8 C.C. to 14 CL in twenty-four hours. 4. Rapidity of action is t,he most striking clinical feature of cedilanid. REFERENCES
1. Stall, 2. Moe, 3.
4.
5. 6.
Arthur: The Cardiac Glycosides, London, 1937, Pharmaceutical Press. Studies on the Native Glueosides of Digitalis G. K., and Visseher, M. B.: Lanata, J. Pharmacol. & Exper. Therap. 64: 65, 1938. Etude clinique d’un nouveau cligitalique : le (a) Junet, R., and Bianchi, M.: cligilanide, Rev. med. de la Suisse Rom. 59: 139, 1939. (b) Michaud, L. : L’emptoi du digilanide C en clinique, Schweiz. med. Wchnschr. 19: 133s. 1938. Clinical Observations on Two Pure Glucosides of Digitalis, (c) Wayne, E. J.: Digoxin and Digitalinum Verum, Clin. SC. 1: 63, 1933. (a) Gold, Harry: Digitalis in Heart Failure, N. Y. State J. Med. 41: 496, 1941. (b) Gold, Harry, Kwit, N. T., and Cattell, McKeen: Studies on Purified Digitalis IGlucosides. I., J. Pharmacol. & Exper. Therap. 69: 177, 1940. (c) Kwit, N. T., Gold, H., and Cattell, MeKeen: Studies on Purified Digitalis Glucosides. II., J. Pharmacol. & Exper. Therap. 70: 254, 1940. (d) Cattell, McKeen, and Gold, Harry: Studies on Purified Digitalis Glucosides. III., J. Pharmaeol. & Exper. Therap. 71: 114, 1941. Fahr, George, and LaDue, John: A Preliminary Investigation of the Therapeutic Value of Lanatoside C (Cedilanid), AM. HEART J. 21: 133, 1941. Chamberlain, Francis L., and Sokolow, Maurice: Clinical Experience With the Oral Administration of Cedilanid, and a Comparison of the Oral and Intravenous Preparations of Cedilanid With Digitalis Purpurea, AN. HEART J.23: 245,1942.
WITH
SPECIAL
INTRAVENOUS NAURICESOKOLOW,
REFERENCE
TO ITS
USE
M.D., ANDFRANCISL. CHAMBER.LAIN, SAN FRANCISCO, CALIF.
M.D.
T
HE use of the ordinary whole leaf of digitalis, the digitalis purpurea of the United States Pharmacopeia, has never been considered ideal for several reasons. First, it required bio-assay ; second, it was impure and hence could not be given intravenously with assurance; third, its potency has varied from time to time, as shown by the fact that the 1J.S.P. XI digitalis is one-third stronger than that of the U.S.P. X. In recent years the glycosides of digitalis have been isolated in pure crystalline form, and work is being done with these pure substances. In addition to the ordinary digitalis, digitalis purpurea, there is another plant, digitalis lanata, which is indigenous to the Balkan countries. Stolll has isolated the glycosides of this new digitalis. There are three glycosides in each, but digitalis lanata differs in that it alone contains lanatoside C, or cedilanid. Clinical interest in lanatoside C began with the pharmacologic work of Moe and Vissche? on heart-lung preparat,ions. This suggested that lanatoside C was the least toxic and the most potent of the lanata glycosides and could be obtained in pure orystalline form. Early preliminary work in Europe3 (the drug was first available in Switzerland) indicated that lanatosicle C was a potent drug. It has been used in the United States for the past two years. Gold and his coworkers4 in New York, ancl Fahr and LaDue,5 in Minneapolis, have made preliminary reports. During the past two years we have been studying t.he oral and intravenous use of lanatoside C at the University of California Hospital, and our reports are based on that, work.‘j To date we have followed eighty-five patients. The drug* comes in tablets of 0.5 mg., as well as in 2 C.C.and 4 C.C.ampoules which contain 0.2 mg. per cubic centimeter. It has been established that the cat unit is equal to 0.28 mg. ; however, Gold showed that 1 mg. of cedilanid is equal to 293 mg. of digitalis leaf when they are compared by the cat method, to 438 mg. when they are compared by the frog method, and to 170 mg. when they are compared in man by oral administration. Therefore, the clinieal pot.ency of these pure glycosides should be ascertained by clinical assay and not by animal assay. The intravenous administration of cedilanid has proved to be of great value. We have used it in thirty-eight casesin dosesup to 14 C.C.per -From the Department of Medicine, University of California Medical School. San Francisco. Presented before the meeting of the California Heart Association, Del Monte, Calif.. May 4, 1941. Received for publication Sept. 2, 1941. *Mark&cd by the Sandoz Chemical Works, Jncorporated, to whom we are grateful for supplies. 213
244
AMERICAN
HEART
.JOURNAL
day, some of which were divided. In general, 8 C.C. per day is the digitaliz,ing dose, and 6 C.C. to 14 e.c. in twenty-four hours in divided doses will digitalize almost all patients. In only three instances was mild nausea produced by 8 C.C. of cedilanid given in one dose, and in many instances beneficial effects were noted in ten to twenty minutes. In auricular fibrillation the ventricular rate may fall 40 to 50 beats within thirty minutes to two hours; in aurieular flutter a fixed 4 to 1 block, and, subsequently, normal rhythm may be produced by a single dose of 8 C.C. administered intravenously. In cases of normal rhythm with congestive failure, cligit.alization may be accomplished within twenty-four hours. The advantages of rapid, safe digitalization are self evident in cases of desperate cardiac failure. Frequently, partial digitalization may be accomplished by the intravenous administration of 4 C.C. to 6 c.c., and then maintained by the oral preparation. The intravenous preparation is not, recommended for maintenance because frequent injections are necessitated by the rapid excretion of the drug. It is, therefore, better to use the oral preparation of cedilanid for maintenance. In general, WC find that a daily maintenance dose of 1 C.C. to 3 es. is needed when the drug is given intravenously. COXCIAJSIONS
1. Cedilanid is a pure, crystalline glycoside which is obtained from digitalis lanata and is not present in digitalis purpurea. 2. Cedilanid is marketed in tablets of 0.5 mg. for oral use, and in ampoules in which each cubic centimeter is equal to 0.2 mg. 3. The intravenous digitalizing dose varies from 8 C.C. to 14 CL in twenty-four hours. 4. Rapidity of action is t,he most striking clinical feature of cedilanid. REFERENCES
1. Stall, 2. Moe, 3.
4.
5. 6.
Arthur: The Cardiac Glycosides, London, 1937, Pharmaceutical Press. Studies on the Native Glueosides of Digitalis G. K., and Visseher, M. B.: Lanata, J. Pharmacol. & Exper. Therap. 64: 65, 1938. Etude clinique d’un nouveau cligitalique : le (a) Junet, R., and Bianchi, M.: cligilanide, Rev. med. de la Suisse Rom. 59: 139, 1939. (b) Michaud, L. : L’emptoi du digilanide C en clinique, Schweiz. med. Wchnschr. 19: 133s. 1938. Clinical Observations on Two Pure Glucosides of Digitalis, (c) Wayne, E. J.: Digoxin and Digitalinum Verum, Clin. SC. 1: 63, 1933. (a) Gold, Harry: Digitalis in Heart Failure, N. Y. State J. Med. 41: 496, 1941. (b) Gold, Harry, Kwit, N. T., and Cattell, McKeen: Studies on Purified Digitalis IGlucosides. I., J. Pharmacol. & Exper. Therap. 69: 177, 1940. (c) Kwit, N. T., Gold, H., and Cattell, MeKeen: Studies on Purified Digitalis Glucosides. II., J. Pharmacol. & Exper. Therap. 70: 254, 1940. (d) Cattell, McKeen, and Gold, Harry: Studies on Purified Digitalis Glucosides. III., J. Pharmaeol. & Exper. Therap. 71: 114, 1941. Fahr, George, and LaDue, John: A Preliminary Investigation of the Therapeutic Value of Lanatoside C (Cedilanid), AM. HEART J. 21: 133, 1941. Chamberlain, Francis L., and Sokolow, Maurice: Clinical Experience With the Oral Administration of Cedilanid, and a Comparison of the Oral and Intravenous Preparations of Cedilanid With Digitalis Purpurea, AN. HEART J.23: 245,1942.