From the Guidelines
The diuretic of choice for this patient acts by impairing sodium reabsorption in the distal tubule, specifically through the aldosterone-sensitive principal cells in the collecting duct, but the most accurate answer choice given is related to the action of a specific class of diuretics in the distal tubule (answer C). The patient's presentation and past medical history, including allergic rhinitis, osteoporosis, and chronic obstructive pulmonary disease (COPD), are important considerations when selecting an antihypertensive medication. Given his recent efforts to increase walking for exercise and change his diet to lower his blood pressure, the next step would be to consider pharmacological intervention if his blood pressure remains elevated, as indicated by the reading of 158/94 mmHg at his last visit. According to the 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults 1, the initial treatment for hypertension often involves lifestyle modifications, but when medication is required, the choice depends on the patient's comorbid conditions. For this patient, considering his age and the presence of osteoporosis, a thiazide diuretic could be beneficial, not only for its antihypertensive effects but also for its potential to help preserve bone mineral density. However, the question specifically asks about the mechanism of action of the diuretic of choice in terms of impairing sodium reabsorption. Thiazide diuretics act in the distal convoluted tubule, but the provided answer choices and the context of the question suggest focusing on the mechanism related to the distal parts of the nephron, where aldosterone plays a significant role. The correct mechanism related to the action described would involve the aldosterone-sensitive principal cells, but given the choices, the most relevant and direct action described is related to the distal tubule (answer C), understanding that the precise mechanism involves the inhibition of sodium reabsorption, which can be influenced by aldosterone in the collecting duct. It's crucial to consider the patient's COPD when choosing a diuretic, as loop diuretics like furosemide are often preferred in patients with symptomatic heart failure or significant renal impairment, but thiazides can be effective and are generally well-tolerated in patients with COPD, provided there is careful monitoring for potential electrolyte imbalances. Given the information and the need to prioritize morbidity, mortality, and quality of life, the focus should be on selecting an antihypertensive regimen that is effective, well-tolerated, and considers the patient's comorbid conditions, with the understanding that the initial choice may involve a diuretic that acts in the distal tubule, among other options, as guided by the most recent clinical practice guidelines 1.
From the FDA Drug Label
Spironolactone and its active metabolites are specific pharmacologic antagonists of aldosterone, acting primarily through competitive binding of receptors at the aldosterone-dependent sodium-potassium exchange site in the distal convoluted renal tubule. The diuretic of choice for this patient acts by impairing sodium reabsorption in the aldosterone-sensitive principal cells. The correct answer is A. aldosterone-sensitive principal cells. 2
From the Research
Diuretic Mechanism of Action
The diuretic of choice for this patient acts by impairing sodium reabsorption in the:
- A. aldosterone-sensitive principal cells
- B. basolateral membrane
- C. distal tubule
- D. inner medullary collecting duct
- E. loop of Henle
Relevant Studies
According to the study 3, diuretics that work primarily in the distal tubule and collecting tubule include the aldosterone inhibitor spironolactone and two drugs that impair tubular reabsorption of sodium by direct action, triamterene and amiloride. The study 4 states that all diuretics act primarily by impairing sodium reabsorption in the renal tubules, but they differ in their mechanism and site of action. The study 5 discusses eplerenone, a selective aldosterone receptor antagonist, which selectively blocks the aldosterone receptor with minimal effect at other steroid receptors. The study 6 compares the efficacy and tolerability of spironolactone and eplerenone in patients with resistant hypertension, and suggests that spironolactone is the most effective add-on anti-aldosterone therapy. The study 7 reviews the use of mineralocorticoid receptor antagonists (MRAs) in essential hypertension or primary aldosteronism, and discusses the development of new aldosterone blockers with reduced adverse effects.
Mechanism of Action
Based on the studies, the correct answer is A. aldosterone-sensitive principal cells, as the diuretic of choice for this patient acts by impairing sodium reabsorption in the aldosterone-sensitive principal cells, which are found in the collecting duct of the kidney 3, 5, 6, 7.