A 42-year-old man comes to the office due to increased abdominal girth associated with a 9-kg (19.8-lb) weight gain over the past month. He drinks a liter of vodka daily and denies smoking or using intravenous drugs. Blood pressure is 110/70 mm Hg. The abdomen is moderately distended, and a fluid wave is elicited. Multiple spider angiomas are present. Laboratory studies reveal thrombocytopenia, hypoalbuminemia, a normal sodium level, and an elevated PT. An upper endoscopy is performed, which shows no esophageal or gastric varices. Pharmacotherapy aimed at inhibiting which of the following should be considered for this patient?

Question

A 42-year-old man comes to the office due to increased abdominal girth associated with a 9-kg (19.8-lb) weight gain over the past month.  He drinks a liter of vodka daily and denies smoking or using intravenous drugs.  Blood pressure is 110/70 mm Hg.  The abdomen is moderately distended, and a fluid wave is elicited.  Multiple spider angiomas are present.  Laboratory studies reveal thrombocytopenia, hypoalbuminemia, a normal sodium level, and an elevated PT.  An upper endoscopy is performed, which shows no esophageal or gastric varices.  Pharmacotherapy aimed at inhibiting which of the following should be considered for this patient?

Quizplus · Accepted Answer

This patient with abdominal distension and a fluid wave has ascites. His heavy alcohol use and evidence of chronic liver disease (eg, spider angiomas, thrombocytopenia, hypoalbuminemia, elevated PT) suggest the ascites developed due to alcohol-associated cirrhosis. In cirrhosis, portal hypertension leads to splanchnic vasodilation, which decreases the effective arterial volume and lowers the systemic blood pressure. Renal perfusion is reduced, leading to activation of the renin-angiotensin-aldosterone system (RAAS), which promotes vasoconstriction (due to angiotensin) and fluid and sodium retention by the kidneys (due to aldosterone). Although this improves systemic blood pressure and renal perfusion, due to the altered hemodynamics in patients with cirrhosis (eg, elevated hydrostatic pressure due to portal hypertension, low oncotic pressure due to hypoalbuminemia) it ultimately results in third spacing of fluid with edema and ascites. Spironolactone, an aldosterone antagonist, is used to interrupt this cycle. It induces natriuresis without blocking the critical vasoconstrictive effects of angiotensin. Spironolactone is typically used with furosemide (a loop diuretic) to increase the efficacy of natriuresis and prevent electrolyte disturbances. (Choices B and C) Patients with cirrhosis have low mean arterial pressure due to splanchnic vasodilation and are dependent on the RAAS to help normalize blood pressure and renal perfusion. ACE inhibitors (eg, lisinopril) and angiotensin receptor blockers blunt this critical response and promote organ hypoperfusion. Likewise, blockade of alpha-adrenergic receptors would cause widespread vasodilation with decreased systemic blood pressure, worsening renal perfusion and causing additional fluid accumulation. (Choice D) Antidiuretic hormone (ADH) levels are increased in cirrhosis, which contributes to the development of hypervolemic hyponatremia. Although ADH inhibitors (eg, tolvapatan) have been used to treat severe hyponatremia in cirrhosis, they are not indicated in patients with normal sodium levels. (Choice E) Nonsteroidal anti-inflammatory drugs inhibit prostaglandin production, which can cause renal vasoconstriction and may precipitate gastrointestinal bleeding. These medications should be avoided in patients with cirrhosis due to impaired renal perfusion at baseline and high risk of variceal bleeding. Educational objective: Ascites in cirrhosis develops from hemodynamic changes related to portal hypertension. Splanchnic vasodilation decreases the systemic vascular resistance, which causes activation of the renin-angiotensin-aldosterone system and promotes vasoconstriction and sodium and water retention. Spironolactone, an aldosterone antagonist, is used to induce natriuresis and resolve ascites without blocking the critical vasoconstrictive effects of angiotensin. __________ References: Introduction to the revised American Association for the Study of Liver Diseases practice guideline management of adult patients with ascites due to cirrhosis 2012. (http://www.ncbi.nlm.nih.gov/pubmed/23463403)

A 42-Year-Old Man Comes to the Office Due to Increased