What are the oral medications for hypotension (low blood pressure)?

From the Guidelines

Midodrine is the recommended first-line oral medication for hypotension, specifically for neurogenic orthostatic hypotension, due to its efficacy in increasing standing blood pressure and relatively favorable side effect profile. According to the study by 1, midodrine exerts a pressor effect through both arteriolar constriction and venoconstriction of the capacitance vessels, making it an effective treatment option. The dosing should be individually tailored, with a typical starting dose of 10 mg/day, taken before arising, and avoided several hours before planned recumbency to minimize the risk of supine hypertension.

Key Considerations

• Midodrine is the only medication approved by the Food and Drug Administration for the treatment of symptomatic orthostatic hypotension, as noted in the study by 1.
• Other treatment options, such as fludrocortisone, erythropoietin, desmopressin acetate, somatostatin analogues, caffeine, and acarbose, may be considered in specific cases or when midodrine is not effective or tolerated.
• Non-pharmacological measures, including compression stockings, adequate hydration, salt intake, and avoiding rapid position changes, should be tried first and continued in conjunction with medication therapy.
• Treatment should be monitored regularly for effectiveness and side effects, such as supine hypertension, headache, or urinary retention, as reported in the study by 1.

Treatment Approach

• Start with midodrine 10 mg/day, taken before arising, and titrate up as needed to a maximum of 40 mg/day, divided into two to four doses.
• Avoid taking midodrine several hours before planned recumbency to minimize the risk of supine hypertension.
• Consider alternative treatment options if midodrine is not effective or tolerated, taking into account the underlying cause of hypotension, comorbidities, and individual response to therapy, as discussed in the study by 1.

From the FDA Drug Label

Midodrine hydrochloride tablets are indicated for the treatment of symptomatic orthostatic hypotension (OH) Midodrine forms an active metabolite, desglymidodrine, that is an alpha1-agonist, and exerts its actions via activation of the alpha-adrenergic receptors of the arteriolar and venous vasculature, producing an increase in vascular tone and elevation of blood pressure. The answer is midodrine (PO), as it is indicated for the treatment of symptomatic orthostatic hypotension (OH) and has been shown to increase standing systolic blood pressure in patients with orthostatic hypotension of various etiologies 2, 2.

• Key points:
  • Midodrine is an oral medication that can cause marked elevation of supine blood pressure.
  • It should be used in patients whose lives are considerably impaired despite standard clinical care.
  • The indication is based on midodrine's effect on increases in 1-minute standing systolic blood pressure.
  • Midodrine has no clinically significant effect on standing or supine pulse rates in patients with autonomic failure 2.

From the Research

Oral Medication for Hypotension

• Midodrine is a prodrug that undergoes enzymatic hydrolysis to the selective alpha 1-adrenoceptor agonist desglymidodrine after oral administration, and it significantly increases 1-minute standing systolic blood pressure compared with placebo 3.
• Comparative studies have shown midodrine to have similar efficacy to dihydroergotamine mesylate, norfenefrine, fludrocortisone, and etilefrine, and to be more effective than dimetofrine and ephedrine in patients with orthostatic hypotension 3, 4.
• Fludrocortisone is a mineralocorticoid that increases blood volume and blood pressure, and it is considered the first- or second-line pharmacological therapy for orthostatic hypotension alongside mechanical and positional measures 5.
• The haemodynamic effects of fludrocortisone and midodrine, alone or combined, in patients with symptoms due to hypotension have been assessed, and both drugs effectively increased 24-h SBP and reduced SBP drops on ABPM, but fludrocortisone seemed to be more effective than midodrine 6.
• Midodrine and fludrocortisone have been used in the treatment of neurogenic shock, and they have been shown to be effective in reducing the need for vasopressors 7.

Mechanism of Action

• Midodrine works by increasing the levels of desglymidodrine, a selective alpha 1-adrenoceptor agonist, which increases blood pressure by causing vasoconstriction 3, 4.
• Fludrocortisone works by increasing blood volume and blood pressure through its mineralocorticoid activity, which helps to increase the levels of sodium and water in the body 5.

Efficacy and Safety

• Midodrine has been shown to be effective in increasing standing blood pressure and improving symptoms of orthostatic hypotension, such as dizziness, light-headedness, and syncope 3, 4.
• Fludrocortisone has been shown to be effective in increasing blood pressure and reducing symptoms of orthostatic hypotension, but the evidence is very uncertain due to the limited number of studies and the small sample sizes 5.
• Both midodrine and fludrocortisone have been shown to be generally well-tolerated, but they can cause side effects such as piloerection, pruritus, and urinary retention 3, 4, 6.