From the Guidelines
Propranolol is primarily metabolized by the liver, and liver cirrhosis significantly impacts its metabolism, leading to decreased first-pass metabolism, increased bioavailability, and higher blood concentrations of the drug. According to the study by the European Society of Cardiology Working Group on Cardiovascular Pharmacotherapy 1, age-related changes in the pharmacokinetic parameters of cardiovascular drugs, including propranolol, are significant. The study highlights that the first-pass effect is decreased, and the oral bioavailability of propranolol is increased due to decreased gut wall transporters and first-pass metabolism. Key points to consider when prescribing propranolol to patients with liver cirrhosis include:
- Decreased liver mass and hepatic blood flow lead to increased Cmax and t½ of highly metabolized drugs like propranolol 1
- Decreased CYP450-mediated phase I reactions, which are responsible for propranolol's metabolism, result in decreased dose requirements to minimize the risk of adverse effects in patients with hepatic diseases 1
- Plasma protein binding is also affected, with decreased plasma albumin leading to increased free drug levels of highly albumin-bound drugs like propranolol 1 In clinical practice, starting with a reduced dose of propranolol (typically 25-50% of the standard dose) and titrating slowly while monitoring for adverse effects is recommended for patients with liver cirrhosis. Regular monitoring of liver function and propranolol's clinical effects is essential for safe administration in cirrhotic patients.
From the FDA Drug Label
Propranolol is extensively metabolized by the liver In a study conducted in 6 patients with cirrhosis and 7 healthy subjects receiving 160 mg of a long-acting preparation of propranolol once a day for 7 days, the steady-state propranolol concentration in patients with cirrhosis was increased 2.5-fold in comparison to controls.
Propranolol is metabolized by the liver. Liver cirrhosis impacts propranolol metabolism, with increased steady-state concentrations in patients with cirrhosis compared to healthy subjects 2.
From the Research
Metabolism of Propranolol
- Propranolol is metabolized by the liver 3, 4.
- The liver plays a crucial role in the metabolism of propranolol, and any impairment in liver function can affect its metabolism 3.
Impact of Liver Cirrhosis on Propranolol Metabolism
- Liver cirrhosis can impair the metabolism of propranolol due to reduced liver function and oxygen delivery 3.
- Increasing hepatic arterial blood flow can improve propranolol clearance and oxygen consumption in cirrhotic livers 3.
- Propranolol metabolizing enzyme activity in cirrhosis can be improved by increasing oxygen delivery through increased hepatic arterial blood flow 3.
Comparison with Carvedilol
- Carvedilol has been shown to be more effective than propranolol in patients with cirrhosis and portal hypertension 5, 6, 7.
- Carvedilol may be a better option for patients with cirrhosis and ascites, as it improves renal perfusion and outcome 6.
- The choice between propranolol and carvedilol should be based on individual patient characteristics and liver function 7.