Effects of combined therapy with amiloride and hydrochlorothiazide on plasma and total body potassium, blood pressure, and the renin-angiotensin-aldosterone system in hypertensive patients

• Published in: European journal of clinical pharmacology 1986-01, Vol.30 (2), p.151-156
• Main Authors: SVENDSEN, U. G, IBSEN, H, RASMUSSEN, S, LETH, A, NIELSEN, M. D, DIGE-PETERSON, H, GIESE, J
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aldosterone - blood; Amiloride - administration & dosage; Amiloride - therapeutic use; Angiotensin II - blood; Antihypertensive agents; Biological and medical sciences; Blood Pressure - drug effects; Cardiovascular system; Clinical Trials as Topic; Drug Therapy, Combination; Female; Humans; Hydrochlorothiazide - administration & dosage; Hydrochlorothiazide - therapeutic use; Hypertension - drug therapy; Hypertension - physiopathology; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Potassium - blood; Potassium - metabolism; Random Allocation; Renin - blood; Renin-Angiotensin System - drug effects
• ISSN: 0031-6970; 1432-1041
• DOI: 10.1007/BF00614293

After a run-in period of 8 weeks on a regimen of hydrochlorothiazide (HCT, median dosage 75 mg/day), patients with essential hypertension were randomly allocated to continued hydrochlorothiazide therapy (Group I) or additional treatment with amiloride (Group II, median dosage 15 mg/day, or 5 mg per 25 mg hydrochlorothiazide) for the following 12 weeks. Thereafter all the patients were changed to treatment with a fixed combination tablet containing 5 mg amiloride and 50 mg hydrochlorothiazide (Moduretic), keeping the thiazide dosage unchanged for an additional 12 weeks. In Group I patients there was no change in plasma potassium, total body potassium content or the renin-angiotensin-aldosterone system during the 12 weeks on HCT. When the treatment was changed to Moduretic, significant increases were found of 10% in plasma potassium and 3% in total body potassium content. No important stimulation of the renin-angiotensin-aldosterone system was found. In Group II patients addition of an average of 15 mg amiloride to the hydrochlorothiazide treatment led to significant increases in plasma potassium and total body potassium content of approximately 15% and 4%, respectively. There was also a significant increase in the plasma concentrations of renin, angiotensin II and aldosterone. Reducing the average dose of amiloride to 7.5 mg/day by use of Moduretic did not lead to decrease in plasma potassium or total body potassium content. Plasma concentrations of renin, angiotensin II, and aldosterone were decreased, but the individual changes varied markedly and no significant overall change was found.