Cirrhosis phase 2 enzymes

Most drugs used in anaesthesia are metabolised in the liver by phase I reactions, mediated by cytochrome P-450 enzymes. These are susceptible to destruction by cirrhosis, so that the biotransformation of drugs, such as opioids (except morphine), benzodiazepines, barbiturates, and inhalational agents, may be markedly altered in severe liver disease. These enzymes are found in the centrilobular areas, which are more prone to hypoxia. In contrast, the enzymes responsible for phase II reactions, found predominantly in the peripheral areas, often function normally even in advanced disease. The disposition of benzodiazepines that are eliminated primarily by glucuronidation, e.g. lorazepam and oxazepam, are unaffected by chronic liver disease. For drugs with low hepatic extraction, advanced hepatocytic dysfunction decreases phase I and II biotransformation with a reduced clearance and prolongation of the elimination half-life. This is often partially offset by an increased free fraction due to decreased protein binding. 

Drug metabolism is impaired in patients with liver disease, with CYP-mediated reactions affected more than phase 2 enzymes [35]. Impairment of CYP expression and activity correlates with the severity of liver disease and also, for some of the enzymes, the aetiology of cirrhosis. 

The effects of liver cirrhosis on the phase 2 enzymes has recently been reviewed by Elbekai et al. [36]. 

An a,globulin with a molecular weight of approximately 45 000. It inhibits proteolytic enzymes in the blood and it is one of the acute phase proteins. There are several genetic variants of the protein. A congenital deficiency of ai-antitrypsin can occur producing the symptoms of infantile liver cirrhosis and early onset emphysema. The latter may be due to release of proteolytic enzymes when lung tissue is infected. 

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