Methyldopa: An intra-arterial assessment

Abstract

Methyldopa has been in routine use for over 20 years but its profile of blood pressure reduction over 24 hours has not been assessed previously. We have now undertaken such a study using intra-arterial ambulatory blood pressure monitoring which records the blood pressure accurately and continuously for 24 hours.

Twenty-four patients with essential hypertension were recruited and received no therapy for a maximum of 4 weeks before attending for intra-arterial ambulatory blood pressure monitoring. After insertion of the intra-arterial cannula, patients underwent a standardized protocol commencing with supine rest and followed by tilt, isometric hand-grip and dynamic bicycle exercise. Following this baseline study, patients were prescribed 125 mg methyldopa 3-times daily which was titrated to a maximum of 500 mg 3-times daily according to the clinic blood pressure response. The mean daily dosage was 1359 mg. Six weeks after the last dosage increment the study was repeated.

Seventeen out of the 24 patients completed the study. The average pre-treatment supine clinic blood pressure was 179/109 mmHg which decreased to 142/91 mmHg after therapy with methyldopa (p<0.001). Mean daytime intra-arterial blood pressure before treatment was 179/103 mmHg decreasing to 136/92 mmHg after treatment with methyldopa (p<0.001). The circadian curves constructed from pooled hourly mean pressures showed the typical diurnal pattern previously described. Therapy with methyldopa led to reductions in pressures during 17 hours (p<0.01) for systolic blood pressure and 11 hours (p<0.01) for diastolic blood pressures. Blood pressure reductions were not sustained at night. Heart rate was marginally lowered during 9 hours (p<0.01). There was no evidence of postural hypotension. At the peak of isometric hand grip exercise, the pre-treatment blood pressure was 223/126 mmHg decreasing to 199/118 mmHg after therapy, (p<0.01; systolic BP). During bicycle exercise, the pre-treatment blood pressure increased steadily. After methyldopa therapy, the absolute blood pressure was reduced but the percentage increase was unaffected.

Of the 24 patients, 5 withdrew due to adverse drug reactions including lethargy, epigastric pains, diarrhoea and nausea.

These results, which will be reported in detail elsewhere, show that methyldopa is a potent antihypertensive agent during the daytime period, but has less effect during the night. Eve patients were unable to tolerate the drug due to adverse reactions.