A 57-year-old man with a history of alcohol-induced cirrhosis is brought to the emergency department due to altered mental status. Over the weekend, he ate a lot of smoked meats at a local barbecue competition. Since then, he has been sleeping most of the day and is confused and disoriented when awake. On examination, he has abdominal distension with shifting dullness. The patient answers correctly when asked for his name but does not know that he is in the hospital and says the year is "1997." When asked to extend his hands as if stopping traffic, the patient makes rhythmic flapping movements. He is started on rifaximin. Which of the following is the most likely mechanism of action of this drug when used to treat this patient's current condition?

Question

A 57-year-old man with a history of alcohol-induced cirrhosis is brought to the emergency department due to altered mental status.  Over the weekend, he ate a lot of smoked meats at a local barbecue competition.  Since then, he has been sleeping most of the day and is confused and disoriented when awake.  On examination, he has abdominal distension with shifting dullness.  The patient answers correctly when asked for his name but does not know that he is in the hospital and says the year is "1997."  When asked to extend his hands as if stopping traffic, the patient makes rhythmic flapping movements.  He is started on rifaximin.  Which of the following is the most likely mechanism of action of this drug when used to treat this patient's current condition?

Quizplus · Accepted Answer

This patient likely has hepatic encephalopathy (HE), a neurologic complication of cirrhosis due in part to the liver's inability to convert ammonia (a neurotoxin) to urea. Excess ammonia is shunted past the liver and crosses the blood-brain barrier, leading to altered mental status (thought due to impaired neurotransmitter release, astrocyte dysfunction, neuroinflammation, and/or edema). Asterixis, the rhythmic flapping of dorsiflexed hands, is another common manifestation of HE. A primary source of ammonia is degradation of nitrogen products by intestinal bacteria. Therefore, gastrointestinal (GI) bleeding can precipitate HE as hemoglobin breakdown leads to increased nitrogen products in the gut. Excess dietary protein intake (eg, large steak meal) is another common trigger. Others include infection, sedatives, and metabolic derangements (eg, hypokalemia). Rifaximin is a nonabsorbable antibiotic that alters GI flora to decrease intestinal production and absorption of ammonia. In patients with HE, rifaximin is generally used in addition to lactulose, which is catabolized by intestinal bacterial flora to short chain fatty acids, lowering the colonic pH and increasing conversion of ammonia to ammonium (Choice E). Rifaximin is also sometimes used for traveler's diarrhea, as it inhibits bacterial RNA synthesis through binding with DNA-dependent RNA polymerase. (Choices A and C) Phosphate binders (eg, calcium acetate) lower serum phosphate in patients with end-stage renal disease. Sodium polystyrene resin (eg, sodium polystyrene sulfonate) exchanges intraluminal sodium for potassium ions and can lower serum potassium in patients with hyperkalemia. However, neither effectively treats HE. (Choice D) Bile acid sequestrants (cholestyramine, colestipol) bind intestinal bile acids to lower serum cholesterol, but they are not used for treating HE. Educational objective: Treatments for hepatic encephalopathy include lactulose (increases conversion of ammonia to ammonium) and rifaximin (decreases intraluminal ammonia production). __________ References: Treatment options for hepatic encephalopathy. (http://www.ncbi.nlm.nih.gov/pubmed/20412036)

A 57-Year-Old Man with a History of Alcohol-Induced Cirrhosis Is Brought