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ITERATRUM ALKALOIDS are powerful V hypotensive agents with many desirable ( haracteristies,1-3 but the usefulness of the available preparationis has been limited by a narrow dosage range between hypotensive aud emnetic effects. After the physicochemical separation of some of the alkaloids had been accomplished,4 a search for an alkaloid with a wider spread between hypotensive and emetic doses was undertaken. Parenteral studies in dogs demoiistrated that the hypotensive activity of protoveratrine A was slightly greater than that of protoveratrine B, but did not show differing degrees of dissociation of hypotensive from emetic activity.5 A comparison between protoveratrine A and protoveratrine B in man, however, revealed marked differences when the alkaloids were administered orally: protoveratrine A had strong hypotensive activity but a narrow therapeutic dosage range, whereas protoveratrine B required much larger doses to elicit hypotensive effects but had a wider range between hypotemisive and emetic effects.6-8 These differences prompted a comparative study of the responses of hypertensive patients to intravenous administration of the 2 alkaloids. Material and MethodsComparative bioassays of protoveratrine A and protoveratrine B were obtained in 13 patients who were known to have essential or renal hypertension, sustained despite the oral or intravenous adininistration of placebos. At least 4 different hypotensive doses of eaeh alkaloid were given intravenously to each subject. The largest dose given to each patient was determined by the production of a fall in blood pressure to or on 81 occasions, protoveratrine B on 109. No more than 1 study was conducted in a given patient on the same day. Each alkaloid was admninistered in a measured period of 2 nminutes. With the patient in the recumbent position, a technician deternmined blood pressure and pulse rate at intervals of a few minutes during periods of at least 20 nminutes before and several hours after adaministration. Blood pressure was measured by the auscultatory technic according to the criteria of the American Heart Association. Mean blood pressure was calculated as the diastolic pressure plus one third of the difference between systolic and diastolic pressures. The mean value of the lowest 2 mean blood pressures obtained within 25 minutes after administration of an alkaloid was taken as the maximal response to the given dose of the alkaloid. These responses were used to construct logarithmie dose-response curves. The occurrence and severity of paresthesias, nausea, and vonmiting were noted. Electrocardiograms were taken during studies of the larger doses and whenever bradyeardia was marked.Observations of the effects of protoveratrine B intravenously were muade an additional 48 times in 21 other adult hypertensive patients. This information was used with the above to estimate the dose of protoveratrine B required to produce a fall in blood pressure to 150/100 anm. Hg or less.Results Qualitative Similarities Each alkaloid had strong hypotensive and br...

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Spinal epidural hematoma complicated the course of anticoagulant therapy of cerebrovascular disease in a patient in whom observations of multiple aspects of coagulation had been obtained. Examination of this case and a review of the literature allow delineation of a syndrome that should aid in early diagnosis of spinal epidural hematoma. It is clear that coumarin derivatives induce multiple coagulation defects, which vary quantitatively and qualitatively with time. Contemporary evaluation of the benefits and risks of long-term anticoagulants is beset by many problems that have not been fully resolved.