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H. Mitchell Perry Jr., M.D.; Henry A. Schroeder, M.D.
JAMA. 1954;154(8):670-673. doi:10.1001/jama.1954.02940420032009.
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The continued, combined oral administration of hexamethonium chloride and hydralazine hydrochloride (called hyphex therapy) in adequate doses effectively controls severe and malignant forms of hypertension.1 Hydralazine (Apresoline) hydrochloride is a highly reactive compound that combines with carbonyl and sulfhydryl radicals and has a strong affinity for certain heavy metal ions.2 Late reactions to this active chemical agent were, therefore, predicted3; these have taken the form of collagen disease in all stages of severity.4 Others have also described the same phenomena,5 and one case of pancytopenia has been reported.6

Of 211 patients receiving both drugs for 9 to 30 months, definite symptoms due to delayed toxic effects of hydralazine developed in 17 (8.1%). The preceding period of combined medication (hyphex) varied from 2 to 22 months, and the total ingestion of the offending drug ranged from 25 to 350 gm. (table 1). At its mildest


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