Mechanism of Action: How Fludrocortisone Increases Blood Pressure
Fludrocortisone increases blood pressure primarily by enhancing sodium reabsorption in the distal tubules of the kidney, leading to increased blood volume and vascular tone.
Primary Mechanisms of Action
- Fludrocortisone acts on the distal tubules of the kidney to enhance the reabsorption of sodium ions from the tubular fluid into the plasma 1
- It simultaneously increases urinary potassium excretion and hydrogen ion elimination 1
- These effects on electrolyte balance lead to increased blood volume and subsequently elevated blood pressure 1
- Fludrocortisone has a biological half-life of 18-36 hours, allowing for once-daily dosing 1
Physiological Effects
- Fludrocortisone causes sodium retention and water expansion, directly increasing intravascular volume 2
- It has a direct constricting effect on partially denervated blood vessels 2
- The medication increases the water content of vessel walls, reducing their distensibility 2
- In small oral doses, it produces marked sodium retention and increased urinary potassium excretion 1
- These combined effects on electrolyte levels contribute to blood pressure elevation 1
Clinical Applications
- Fludrocortisone is considered a first-line therapy for orthostatic hypotension alongside mechanical and positional measures 3
- It is typically dosed at 0.05-0.2 mg daily for orthostatic hypotension 2
- For primary adrenal insufficiency, the standard dose is 0.05-0.2 mg once daily, taken upon awakening 2, 4
- Higher doses (up to 0.5 mg daily) may be needed in children, younger adults, or during pregnancy 2, 4
Monitoring and Adverse Effects
- Signs of overdosage include hypertension, edema, hypokalemia, excessive weight gain, and increased heart size 1
- Regular monitoring of blood pressure and serum electrolytes can help prevent overdosage 1
- Hypokalemia is a common side effect that may require potassium supplementation 2, 1
- Potassium supplementation can actually ameliorate fludrocortisone-induced sodium retention 5
Comparative Effectiveness
- Recent evidence suggests fludrocortisone may be more effective than midodrine in increasing 24-hour systolic blood pressure and reducing blood pressure drops 6
- In patients with orthostatic hypotension, fludrocortisone treatment increased 24-hour systolic blood pressure from 107.1 ± 9.9 mmHg to 116.3 ± 14.9 mmHg (p = 0.0001) and decreased the number of daily systolic blood pressure drops <90 mmHg by 73% 6
Clinical Pearls
- Patients on fludrocortisone should be advised to consume sodium salt and salty foods without restriction 2, 7
- Patients should avoid potassium-containing salts, which are often marketed as "healthy" 2, 7
- Several medications can interact with fludrocortisone, including diuretics, acetazolamide, carbenoxolone, and NSAIDs 2, 4
- Liquorice and grapefruit juice potentiate the mineralocorticoid effect and should be avoided 2, 7