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This combination therapy consists of midodrine, an oral small molecule $\alpha_1$-adrenergic agonist, and propranolol, a non-selective beta-adrenergic receptor blocker. It was investigated by the Institute of Liver and Biliary Sciences (ILBS) in India for the primary prevention of variceal bleeding in patients with decompensated cirrhosis and severe ascites. Midodrine acts as a prodrug that is metabolized in the liver to its active form, desglymidodrine, which increases systemic and splanchnic blood pressure, thereby improving effective circulating blood volume and renal perfusion. Propranolol reduces portal pressure by decreasing cardiac output and inducing splanchnic vasoconstriction. The combination is intended to optimize portal hypertensive therapy by maintaining mean arterial pressure while achieving target heart rate reduction in high-risk cirrhotic patients who may otherwise be intolerant to high-dose beta-blockers due to hypotension.
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