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February 3, 1951


Author Affiliations

Ann Arbor, Mich.

From the Department of Pharmacology, University of Michigan Medical School.; Dr. Wyngaarden is presently located at Massachusetts General Hospital, Boston.

JAMA. 1951;145(5):277-282. doi:10.1001/jama.1951.02920230001001

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During recent years we have witnessed the development of an increasing number of effective antihistaminic agents, whose role in the therapy of allergic disease has now become well established. Recently a great mass experiment has begun in the treatment of the common cold with these compounds, and striking claims have been made for the efficacy of their early administration. An avid public has been eagerly supplied by various manufacturers until at present the consumption of these agents is enormous. Reliable estimates are that the total sale of these drugs will reach $100,000,000 in 1950.1

Fortunately, the antihistaminic compounds have proved to be relatively nontoxic in the usual doses, though they do frequently give rise to bothersome side effects. There are, however, certain serious potentialities embodied in these agents, and a small number of deaths have occurred. It is our purpose in this report to call attention to the toxicity

 Antihistaminics for Colds , editorial, J. A. M. A. 142:570 ( (Feb. 25) ) 1950.Article
The cases reported herein have been collected by communication with manufacturers and distributors of various antihistaminic drugs and, in many instances, by communication with physicians acquainted with the patients involved. It is believed that this represents all of the known cases of fatal poisoning.
Loew, E. R.:  Pharmacology of Antihistamine Compounds , Physiol. Rev. 27:542-573 ( (Oct.) ) 1947.
Loveless, M. H.:  Therapeutic and Side Effects of Pyribenzamine and Benadryl , Am. J. Med. 3:296-308 ( (Sept.) ) 1947.Article
Waldbott, G. L.:  The Antihistaminic Drugs , J. A. M. A. 135:207-209 ( (Sept. 27) ) 1947.Article
Waldbott, G. L., and Young, M. I.:  Antistine, Neoantergan, Neohetramine, Trimeton, Antihistaminique RP-3277—An Appraisal of Their Clinical Value , J. Allergy 19:313-316 ( (Sept.) ) 1948.Article
Spain, W. C., and Pflum, F. A.:  An Evaluation of the Present Status of Antihistaminic Substances , New York State J. Med. 48:2272-2275 ( (Oct. 15) ) 1948.
Feinberg, S. M.:  The Antihistamine Drugs, Pharmacology and Therapeutic Effects , Am. J. Med. 3: 560-570 ( (Nov.) ) 1947.Article
Sacks, B. A.:  The Toxicity of Benadryl: Report of a Case and Review of the Literature , Ann. Int. Med. 29: 135-144 ( (July) ) 1948.Article
Because of lack of space these bibliographic references are omitted from The Journal; they will appear in the authors' reprints.
Winter, I. C.: Personal communication to the authors.
Wittich, F. W.: Personal communication to W. A. Wright.
Whiting, E. G.: California & West. M., to be published; personal communication to the authors.
Waldbott.3c Friedlander and Friedlander.4e Sulzberger, Baer and Levin.4n′ Rattner and Graffin.4s′ Strauss.4t′
Gruhzit, O. M., and Fiskin, R. A.:  A Toxicologic Study of Two Histamine Antagonists of the Benzhydril Alkamine Ether Group , J. Pharmacol. & Exper. Therap. 89: 227-233 ( (March) ) 1947.
Vander Brook, M. J.; Olson, K. J.; Richmond, M. T., and Kuizenga, M. H.:  Pharmacology of a New Antihistamine, β-Pyrrolidine-Ethyl-Phenothiazine (Pyrrolazote) , J. Pharmacol. & Exper. Therap. 94: 197-208 ( (Oct.) ) 1948.
Gay.4s Winter.5
Clement and Godlewski.4v′ Blanton and Owens.4w′ Cahan, Meilman and Jacobson.4x′ Drake.4y′ Glassmire.4z′ Van Loon and Kanters.4b″ Hilker.4c″ Martland and Guck.4d″
Kracke, R. R., and Parker, F. P.:  The Relationship of Drug Therapy to Agranulocytosis , J. A. M. A. 105: 960-966 ( (Sept. 21) ) 1935.
Blanton and Owens.4w′ Cahan, Meilman, and Jacobson.4x′ Hilker.4c″ Martland and Guck.4d″