Pindolol versus methyldopa for hypertension: Comparison of adverse reactions

• Published in: The American heart journal Vol. 104; no. 2; pp. 479 - 486
• Main Authors: Carr, Albert A, Mulligan, Olivia F, Sherrill, L.N
• Format: Journal Article
• Language: English
• Published: United States Mosby, Inc 01.01.1982
• Subjects: Adult; Clinical Trials as Topic; Double-Blind Method; Humans; Hypertension - drug therapy; Methyldopa - adverse effects; Pindolol - adverse effects; Prospective Studies; Random Allocation
• ISSN: 0002-8703; 1097-6744
• DOI: 10.1016/0002-8703(82)90143-0

In a prospective, randomized study, hypertensive patients after a placebo period were treated with either pindolol or methyldopa. There were 31 patients in each group; 17 received pindolol alone and 14 methyldopa alone; 14 received pindolol in combination with either hydralazine or hydrochlorothiazide or guanethidine; 17 received methyldopa plus hydrochlorothiazide or an addition of either hydralazine or guanethidine. The most serious adverse reaction was the occurrence of liver toxicity seen in the methyldopa group. This toxicity is defined as three consecutive elevations of serum glutamic oxaloacetic transaminase (SGOT) or serum glutamic pyruvic transaminase (SGPT) or two consecutive elevations of both. Liver toxicity occurred in 9 of 31 patients taking methyldopa as compared to 1 of 31 taking pindolol. The one patient taking pindolol who developed toxicity had elevated SGOT during the placebo period and while the patient was on pindolol the SGOT remained elevated but was declining. The enzyme elevations of the patients taking methyldopa were much more than trivial. The levels returned to normal after methyldopa was discontinued. The antinuclear antibody test (ANA) was positive in all the patients with evidence of liver toxicity. In addition, antibodies on red blood cells (positive Coombs test) were demonstrated in four of nine patients with liver enzyme elevations on methyldopa. For all the patients taking methyldopa, red blood cell antibodies were found in 6 of 31. This compares to 1 of 31 of those taking pindolol. The ANA test was positive in 15 of 31 patients taking methyldopa and 10 of 31 of those taking pindolol. There was no evidence of hemolytic anemia or a systemic lupus erythematosus skin or arthritis syndrome in any of the patients. Dyspnea or edema was a more common complaint of those patients taking pindolol as compared to methyldopa. There was no evidence of heart failure or weight gain. The heart rate was actually slower in those taking methyldopa alone as compared to those taking pindolol alone. Detailed pulmonary function studies in 10 patients taking pindolol alone and six taking methyldopa alone failed to demonstrate any reduction in large or small pulmonary airway flow. Dizziness and postural hypotension were much more frequent in those taking methyldopa. Standing diastolic blood pressure was significantly lower in the methyldopa patients and this may explain the greater frequency of dizziness. Complaints of muscle cramps, headache, and insomnia were more frequent for those taking pindolol, but they were not dose related. Pindolol is safe for the treatment of hypertension. The mean blood pressure-lowering effect is comparable to methyldopa in the supine position, and it does not cause postural hypotension or bradycardia. Liver toxicity and antibodies to red cells or nuclei are seen much more frequently with methyldopa. The frequency of liver toxicity in the methyldopa group is disturbing and caused us to review our data on 197 patients taking or who have taken methyldopa for hypertension. There was evidence of liver toxicity in 18.7%. Two have evidence of chronic active hepatitis.