![]() 15-17 As such, pharmacists can play a role in optimizing medications to prevent drug-drug interactions, adverse side effects, and toxicities. On average, patients with cirrhosis are prescribed between three and 10 medications. 14 Therefore, a dose reduction may be needed for highly protein-bound medications such warfarin, phenytoin, diazepam, fluoxetine, digoxin, and valproic acid. 12,13 As such, in the setting of hypoalbuminemia, medications with a high protein-binding affinity to albumin (e.g., medications circulating in bound form >90% of the time) will become unbound in the serum, increasing the risk of toxicity. 11 Albumin may also decrease due to the dilution effect from water and salt retention. In patients with cirrhosis, albumin production is decreased by 60% to 80%, in some cases leading to hypoalbuminemia. 10Īlbumin is produced and secreted by the liver. ![]() 8,9 Because medications with a low extraction ratio (e.g., warfarin, phenytoin, carbamazepine, and lorazepam) rely heavily on the metabolic capacity of the liver for intrinsic clearance through CYP 450 enzymes, these medications will be impacted more significantly than medications with a high extraction ratio (e.g., verapamil, morphine, propranolol, and ketamine). In general, cytochrome enzymes 1A2 and 3A4 have at least a 50% reduction in activity in cirrhosis while 2C, 2A, and 2B are mostly unaltered. 7 Typically, CYP 450 enzyme activity is reduced, resulting in decreased drug clearance and, thereby, increased serum drug concentrations. Pharmacokinetic ChangesĬhanges in cytochrome P450 (CYP 450) activity may occur depending on the degree of liver impairment and other comorbidities. This article will provide pharmacists a practical overview of the impact of cirrhosis on medication therapy and considerations to help prevent adverse drug reactions. Pharmacists have a responsibility to ensure safe medication use in patients with cirrhosis. 6 Patients with compensated cirrhosis have a lesser extent of impaired drug metabolism compared with patients with decompensated cirrhosis. 6 This is because 20% of the drugs in patients with liver cirrhosis are dosed incorrectly. Nearly 30% of patients with cirrhosis suffer adverse drug reactions or hepatoxicity if these risk factors are not considered or monitored closely. ![]() Risk factors for impaired drug effects include altered hepatic blood flow, altered drug pharmacokinetics, reduced drug-binding proteins, and severity of liver dysfunction. Since the liver is the primary site of drug metabolism, the disposition and clinical effects of drugs can be altered in patients with cirrhosis. Prognosis and survival are markedly better in patients with compensated cirrhosis than in those with decompensated disease. Patients with decompensated cirrhosis often exhibit serious symptoms and complications such as ascites, bacterial infections, variceal bleeding, portal hypertension, or encephalopathy. Decompensated cirrhosis typically follows compensated cirrhosis. Compensated cirrhosis patients are asymptomatic and the liver is still able to perform basic functions. 2-4Ĭirrhosis is characterized by fibrosis and nodule formation from liver insults and is classified as compensated or decompensated depending on the degree of liver distortion. 1,2 Risk factors for the development of cirrhosis include hypertension, hyperlipidemia, diabetes, obesity, moderate alcohol consumption, chronic hepatitis B or C, male sex, and age above 50 years. 1 Cirrhosis is the leading cause of liver-related deaths. In the United States, cirrhosis affects about 1.8% of the adult population. Chronic liver disease usually progresses to cirrhosis. 1 Chronic liver diseases include alcoholic liver disease, chronic viral hepatitis, nonalcoholic fatty liver disease, and hemochromatosis. Pharmacists can play a key role in modifying medications based on liver function to ensure safe medication use in patients with cirrhosis.Īpproximately 4.5 million Americans have been diagnosed with chronic liver disease. Furthermore, no evidence-based guidelines exist for the use of medications in patients with liver cirrhosis. While scoring systems may assist in classifying the severity of liver disease, no test can determine drug dosing in patients with cirrhosis. Approximately 30% of patients with cirrhosis experience adverse drug reactions. Because the liver is the primary site of drug metabolism, the pharmacokinetic profiles of drugs can be altered in patients with cirrhosis. ABSTRACT: Cirrhosis results when chronic insults to the liver finally cause irreversible fibrosis.
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