How does dexamethasone affect hypertension?

Dexamethasone and Hypertension

Dexamethasone can significantly elevate blood pressure through multiple mechanisms, and should be used with caution in patients with hypertension or at risk for hypertension. 1, 2

Mechanism of Blood Pressure Elevation

• Dexamethasone, like other corticosteroids, causes increased sodium and water retention while increasing potassium excretion, leading to elevated blood pressure 2
• Dexamethasone decreases plasma atrial natriuretic peptide (ANP) by 40-50%, which correlates negatively with increases in systolic blood pressure 3
• Short-term dexamethasone exposure (5 days) can cause autonomic imbalance to the heart with increased sympathetic activity (+75.93%) and reduced parasympathetic activity (-18.02%), contributing to cardiovascular effects before overt hypertension develops 4
• Dexamethasone enhances vascular reactivity to vasopressin, which contributes to glucocorticoid-induced hypertension 5

Clinical Implications

• The American College of Cardiology and American Heart Association recommend limiting or discontinuing systemic corticosteroids when possible in patients with hypertension 1
• Higher doses of dexamethasone, such as those used in cancer treatment regimens (like those in multiple myeloma protocols), may cause more pronounced blood pressure elevation 6, 1
• Antihypertensive therapy may need to be initiated or intensified in patients requiring dexamethasone who develop hypertension 1
• Dietary salt restriction may ameliorate but not completely abolish the pressor effects of dexamethasone 3

Dose-Related Effects

• Dose-related increases in systolic blood pressure can occur even with low-dose dexamethasone treatment (1-5 μg/day in rat studies) 3
• In clinical studies, dexamethasone at 0.5 mg three times daily has been shown to reduce diastolic blood pressure from 104 ± 5 to 96 ± 8 mm Hg in patients with mild essential hypertension 7
• Higher doses used in cancer treatment regimens (such as 40 mg/day for 4 days in a 28-day cycle) may cause significant fluid retention and edema 6

Special Considerations

• Dexamethasone can cause peripheral edema and pulmonary edema due to fluid retention, which can exacerbate hypertension 6
• Patients with cardiac involvement or heart failure are at particular risk when receiving dexamethasone, as it can worsen fluid overload 6
• Paradoxically, in some cases of hypertension with suppressed renin and aldosterone, dexamethasone treatment can normalize blood pressure by suppressing an unknown ACTH-dependent mineralocorticoid 8

Monitoring and Management

• Blood pressure should be monitored regularly in patients receiving dexamethasone, especially at higher doses or prolonged treatment 2
• Consider lower doses of dexamethasone (e.g., 20 mg instead of 40 mg on days 1-4) in elderly patients or those with pre-existing severe renal or cardiac involvement 6
• When dexamethasone must be used in hypertensive patients, consider:
  • Implementing dietary salt restriction 3
  • Initiating or intensifying antihypertensive therapy 1
  • Using the lowest effective dose for the shortest duration possible 2

Drug Interactions

• Dexamethasone can reduce the efficacy of antihypertensive medications, potentially requiring dose adjustments 2
• When used in combination with other medications that can affect blood pressure (such as immunomodulatory agents in cancer treatment), careful monitoring is essential 6