How much does fludrocortisone affect blood pressure?

Effect of Fludrocortisone on Blood Pressure

Fludrocortisone significantly increases blood pressure through sodium retention, water expansion, and increased peripheral vascular resistance, with effects that are considerably heightened and prolonged compared to hydrocortisone. 1

Mechanism of Action

• Fludrocortisone acts on the distal tubules of the kidney to enhance sodium reabsorption from tubular fluid into plasma while increasing urinary excretion of potassium and hydrogen ions 1
• It causes direct sodium retention and water expansion, leading to increased intravascular volume 2
• The medication has a direct constricting effect on partially denervated blood vessels and increases the water content of vessel walls, reducing their distensibility 2
• While initial blood pressure elevations are associated with plasma volume expansion, long-term treatment shows that hypertension is primarily related to increased peripheral vascular resistance rather than sustained volume changes 3

Magnitude of Blood Pressure Effect

• In therapeutic doses (0.05-0.2 mg daily), fludrocortisone produces marked sodium retention and increased urinary potassium excretion, causing a measurable rise in blood pressure 1
• Studies show that blood pressure can increase from baseline levels (e.g., 117/67 mmHg) to hypertensive levels (121/76 mmHg) within one week of treatment 4
• In patients with orthostatic hypotension, fludrocortisone increases blood pressure in both recumbent and standing positions, with hypertensive levels often achieved in the recumbent position 3
• In children with congenital adrenal hyperplasia, fludrocortisone treatment has been associated with systolic hypertension in up to 57.6% of patients at 18 months of age 5

Clinical Applications and Dosing

• For orthostatic hypotension, fludrocortisone is typically dosed at 0.05-0.2 mg daily 2
• In vasovagal syncope (VVS), fludrocortisone might be reasonable for patients with recurrent episodes and inadequate response to salt and fluid intake 6
• For orthostatic hypotension syndromes, fludrocortisone (0.1-0.3 mg once daily) is recommended as adjunctive therapy when needed 6
• In primary adrenal insufficiency, the standard dose is 0.05-0.2 mg once daily, taken upon awakening 2

Monitoring and Adverse Effects

• Regular monitoring of blood pressure and serum electrolytes is essential to prevent overdosage 1
• Signs of overdosage include hypertension, edema, hypokalemia, excessive weight increase, and increased heart size 1
• Hypokalemia is a common side effect that may require potassium supplementation 2
• Supine hypertension is a significant risk of fludrocortisone treatment in patients with orthostatic hypotension 3
• If transient hypertension develops, the dose should be reduced to 0.05 mg daily 1

Special Considerations

• Blood pressure effects may be more pronounced in older adults and those prone to polypharmacy effects 6
• Patients on fludrocortisone should be advised to consume sodium salt and salty foods without restriction but avoid potassium-containing salts 2
• Several medications can interact with fludrocortisone, including diuretics, acetazolamide, carbenoxolone, and NSAIDs 2
• Liquorice and grapefruit juice can potentiate the mineralocorticoid effect and should be avoided 2

Evidence Quality

• The evidence for fludrocortisone's effect on blood pressure is well-established, but evidence for its efficacy in specific conditions like orthostatic hypotension is of very low certainty 7
• A Cochrane review found very low-certainty evidence about the effects of fludrocortisone versus placebo on drop in BP in people with diabetes and Parkinson's disease 7
• Despite widespread clinical use, there is a lack of high-quality, long-term studies on fludrocortisone for orthostatic hypotension in various disease states 7

In summary, fludrocortisone has a significant effect on blood pressure through multiple mechanisms, with the potential to cause hypertension, particularly in the recumbent position. Careful monitoring and dose adjustment are essential to balance therapeutic benefits with the risk of adverse effects.