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Drugs that activate alpha adrenergic receptors in vascular smooth muscle increase peripheral resistance and maintain or elevate blood pressure. These agents may be useful for the treatment of orthostatic hypotension.

Midodrine is a prodrug that is converted to a direct–acting α₁-agonist after oral administration. The activation of α₁ receptors causes arterial and venous smooth muscle contraction resulting in a rise in blood pressure. Supine hypertension is a frequent complication associated with midodrine. This side effect can be minimized by avoiding dosing prior to bedtime. Cautious use of a short-acting antihypertensive agent at bedtime may also be helpful.