Spironolactone and triamterene in volume-dependent essential hypertension

Abstract

The effects of 2 potassium-retaining diuretics on arterial pressure, intravascular volume, responses of the renin-angiotensin-aldosterone system, serum electrolytes, and renal function were compared by means of an 8-wk double-blind, crossover trial in 13 patients with "volume-dependent" essential hypertension. The fall in systolic, diastolic, and mean arterial pressures in the supine and erect positions (all p less than 0.005) induced by spironolactone was greater than that by triamterene. The pressure fall induced by spironolactone was also associated with a persistent contraction in plasma volume (p less than 0.05) and a secondary hyperaldosteronism that was not accompanied by hypokalemic alkalosis. The pressure fall induced by triamterene was not associated with reduced plasma volume, effect on plasma renin activity, or aldosterone excretion. Both drugs produced significant rises in blood urea nitrogen and creatinine levels that never exceeded normal limits.

Antihypertensive Therapy: Newer Concepts and Agents

“…Its action, at the distal tubule of the kidney, inhibits the active sodium-for-potassium exchange mechanism [62]. It may be more potent than the simi larly acting triamterene [10]; because amilo ride preceded the development of triam terene, the latter's mechanism has been termed 'amiloride-like' [46]. In addition to sparing urinary potassium excretion, the compound is also a natriuretic; and 5 mg is slightly less potent than 50 mg of hydrochlo rothiazide [50], Like other potassium-sparing agents, it is available in a single tablet com pounded with hydrochlorothiazide (5 mg amiloride and 50 mg hydrochlorothiazide); and when administered once or twice daily, it maintains serum potassium at pretreatment levels [50].…”

Triamterene and the Kidney

“…The observed declines in renal function have occurred in normal volunteers [56,68], hypertensive subjects [18,21,30], edematous individuals [3,29,[57][58][59]62] and diabetics [56], and would suggest that TA manifests intrinsic nephrotoxicity independent of an underlying disease state.…”

“…TA has been utilized either alone [18,19] or in combi nation with potassium-wasting diuretics, such as thia zides [4,[20][21][22] or furosemide [23,24], to both increase natriuresis as well as to minimize the ensuing kaliuresis. TA inhibits passive sodium transport from the luminal side of transporting epithelia [25][26][27], resulting in im paired movement of potassium from cell to lumen, since the latter is functionally coupled to sodium movement.…”

“…A variety of indices of renal function have been em ployed as markers for TA's nephrotoxicity including increases in serum creatinine [18,21,58] or blood urea nitrogen [3,57,59,62] or decreases in creatinine clearance [56,68] and/or renal blood flow [30,58], with the latter most commonly attributed to the decline in cardiac out put [67] accompanying the administration of high doses of TA. Typically, the observed declines in glomerular filtration rate and renal blood flow with TA have oc curred in the dose range of 100-200 mg/day with or without concurrent administration of HCT.…”

“…TA has only mild antihypertensive properties either when administered alone [18][19][20]30] or when it is utilized in a complementary fashion with thiazide-type diuretics [20], Consequently, the major pharmacodynamic consid eration for TA relates not to its antihypertensive proper ties but, rather, to its dose proportionality relative to potassium supplements [21,31] or other potassium-spar ing diuretics [31] in normalizing extra-and intracellular potassium deficiencies consequent to diuretic use.…”