Next Antihypertensive Agent in Hypertension with Hyponatremia
Add a thiazide-type diuretic (hydrochlorothiazide 12.5-25 mg or chlorthalidone 12.5-25 mg daily) as the next step, despite the hyponatremia, because this represents standard triple therapy for uncontrolled hypertension and the sodium level of 128 mEq/L requires separate evaluation and management before it influences antihypertensive selection. 1, 2
Rationale for Adding a Diuretic
The International Society of Hypertension 2020 guidelines explicitly recommend adding a thiazide or thiazide-like diuretic as the third agent when blood pressure remains uncontrolled on an ARB plus calcium channel blocker. 1
This creates the preferred three-drug combination of ARB + CCB + diuretic, which represents the standard stepwise approach before considering fourth-line agents. 1, 2
The patient is already on maximum doses of losartan (100 mg) and amlodipine (10 mg), making dose escalation impossible. 1
Addressing the Hyponatremia Concern
The hyponatremia (sodium 128 mEq/L) must be investigated separately as it is likely unrelated to current medications—neither ARBs nor CCBs typically cause hyponatremia. 3, 4
Common causes to evaluate include SIADH, hypothyroidism, adrenal insufficiency, or volume depletion. The hyponatremia should not automatically exclude diuretic use until the etiology is determined.
If the hyponatremia is determined to be problematic or worsens with diuretic addition, then proceed directly to fourth-line therapy with spironolactone 25 mg daily (or alternatives if contraindicated). 1, 2
Fourth-Line Options if Diuretic is Contraindicated
Spironolactone is the preferred fourth-line agent for resistant hypertension, as it addresses aldosterone escape that can occur with long-term ARB therapy. 2
The International Society of Hypertension recommends spironolactone when hypertension remains uncontrolled despite maximum doses of ARB + CCB + diuretic. 1, 2
Alternative fourth-line agents include amiloride, doxazosin, eplerenone, clonidine, or beta-blockers if spironolactone is not tolerated or contraindicated. 1
Critical Monitoring Parameters
Recheck sodium levels within 1-2 weeks after adding any new antihypertensive agent, particularly a diuretic. 1
Monitor potassium levels closely, especially if transitioning to spironolactone, as the combination of ARB plus aldosterone antagonist increases hyperkalemia risk. 1
Target blood pressure should be achieved within 3 months of medication adjustment. 1
Common Pitfall to Avoid
Do not skip the diuretic step and jump directly to fourth-line agents without first determining the cause of hyponatremia. The hyponatremia may be coincidental and correctable, and omitting standard triple therapy (ARB + CCB + diuretic) deviates from evidence-based guidelines. 1, 2
Thiazide diuretics at appropriate doses (hydrochlorothiazide 12.5-25 mg or chlorthalidone 12.5-25 mg) are generally well-tolerated and effective. 1