Early hemodynamic and humoral effects of lofexidine

Hemodynamic and humoral effects of lofexidine were assessed in 11 patients with essential hypertension after a total of 1.5 mg were given orally over 24 hr. Heart rate (bpm) slowed (-12 +/- 6 [SEM], p less than 0.05) and cardiac output (liters per minute) was reduced (-0.78 +/-0.18, p less than 0.01) irrespective of blood pressure response; the latter was related to changes in systemic resistance (TPR) (r = 0.72, p less than 0.01). Cardiac performance judged from ejection fraction (0.61 +/- 0.03 to 0.59 +/- 0.03, NS) and mean transit time (8.73 +/- 0.53 sec to 9.20 +/- 0.35, NS) were not altered. Plasma volume was expanded more than 10% in two patients but not changed in the others. Supine plasma catecholamines determined in five patients were reduced in all but one with no correlation to changes in either TPR or diastolic blood pressure. On the other hand, there was an increase in plasma catecholamines during head-up tilt in four of five patients, indicating normal catecholamines release. Orthostatic hypotension occurred de novo in three patients; two of them had simultaneous slowing of heart rate (vasovagal attack). Results suggested that reduction of blood pressure by lofexidine depended on lack of increase in TPR in response to reduction of cardiac output; the hemodynamic pattern of this centrally acting adrenergic blocker closely resembled that reported for beta blockers.