Alanine aminotransferase

Serious hepatotoxicity of tacrine has been documented. More recent data suggest, however, that this toxicity can be reduced by carehiUy monitoring semm alanine aminotransferase levels (125). The side effects of tacrine also include gastrointestinal disturbances and emesis, and alternative AChE therapies are being advanced. Velnacrine (20), a metaboUte of tacrine, was expected to have reduced hepatotoxicity. However, its limited efficacy and side-effect profile, which includes dmg-related hematological changes, caused it to be dropped from further development. 

ALT, alanine aminotransferase ASC, apoptosis-associated speck-like protei containing a CARD AST, aspartate aminotransferase CARD, caspase activation and recruitment domains CD, Crohn s disease COP, CARD-only protein DD, death domain DED, death effector domains DIABLO, direct LAP-binding protein with low pi... 

Pyridoxamine phosphate serves as a coenzyme of transaminases, e.g., lysyl oxidase (collagen biosynthesis), serine hydroxymethyl transferase (Cl-metabolism), S-aminolevulinate synthase (porphyrin biosynthesis), glycogen phosphoiylase (mobilization of glycogen), aspartate aminotransferase (transamination), alanine aminotransferase (transamination), kynureninase (biosynthesis of niacin), glutamate decarboxylase (biosynthesis of GABA), tyrosine decarboxylase (biosynthesis of tyramine), serine dehydratase ((3-elimination), cystathionine 3-synthase (metabolism of methionine), and cystathionine y-lyase (y-elimination). 

When administering tacrine, the nurse must monitor the patient for liver damage. This is best accomplished by monitoring alanine aminotransferase (AIT) levels. ALT is an enzyme found predominately in the liver. Disease or injury to the liver causes a release of tiiis enzyme into the bloodstream, resulting in elevated ALT levels, hi patients taking tacrine, ALT levels should be obtained weekly from at least week 4 to week 16 after die initiation of tiierapy. After week 16, transaminase levels are monitored every 3 months. 

The nurse immediately reportsany elevated alanine aminotransferase (ALT) level to the primary health care provider. The primary health care provider may want to continue monitoring the ALT level or discontinue use of the drug because of the danger of hepatotoxidty. However, abrupt discontinuation may cause a decline in cognitive functioning. 

The choice of IFN-a as a potential treatment for chronic hepatitis C in 1986 was empirical (Hoofnagle et al. 1986). At this time, the causative agent of chronic non-A, non-B hepatitis had not yet been identified, and there was no way of evaluating HCV replication or, thus, the antiviral activity of a drug. In the first cohort of 10 patients with chronic non-A, non-B hepatitis treated with IFN-a, a significant decline in alanine aminotransferase (ALT) levels was observed in 8 patients, and liver histology had improved at the end of therapy in the three patients who were biopsied (Hoofnagle et al. 1986). Ten years later, 5 of the 10 patients were free of infection (Lau et al. 1998). 

HCV infection is rarefy diagnosed in the acute phase, as most acutely infected individuals are asymptomatic. Between 50% and 90% of patients develop chronic infection, however, and this warrants early therapy. After occupational exposure with a known date, treatment should not be started before the acute episode characterized by alanine aminotransferase elevation, but it should always be started within 24 weeks after the onset of symptoms. The optimal treatment schedule for acute hepatitis C is controversial. Pegylated IFN-a monotherapy at the standard dose for 24 weeks yielded SVR rates close to 100% in symptomatic patients referred to tertiary care centers (De Rosa et al. 2006 Jaeckel et al. 2001 Santantonio et al. 2005 Wiegand et al. 2006). Shorter therapy may be envisaged (Calleri et al. 2007). Combination with ribavirin is recommended if a first course of pegylated IFN-a monotherapy fails to eradicate the infection. Viral elimination appears to be independent of the HCV genotype and the HCV RNA level (Calleri et al. 2007 De Rosa et al. 2006 Jaeckel et al. 2001). 

Ribavirin is a guanosine analog synthesized more than 35 years ago, which possesses broad-spectrum antiviral activity against several RNA and DNA viruses in vitro (Sidwell et al. 1972). When administered as monotherapy in patients with chronic hepatitis C, ribavirin induces a decline of serum alanine aminotransferase (ALT) levels while no effect on sustained virologic response is detectable (Di Bisceglie et al. 1992). 

Use of the plasma enzyme alanine aminotransferase (ALT) in monitoring the progress of infectious hepatitis. 

Aminotransferases Aspartate aminotransferase (AST, or SCOT) Alanine aminotransferase (ALTorSGPT) Myocardial infarction Viral hepatitis... 

Alanine-pyruvate aminotransferase (alanine aminotransferase) and glutamate-a-ketoglutarate aminotransferase (glutamate aminotransferase) catalyze the transfer... 

Figure 29-4. Alanine aminotransferase (fop) and glutamate aminotransferase (bottom).

In the bile-duct-ligated rat, hepatic mitochondrial lipid peroxides are increased and correlate with serum levels of alkaline phosphatase, bilirubin and alanine aminotransferase (Sokol et al., 1991). Dietary vitamin E deficiency resulted in relatively higher lipid peroxide and bilirubin... 

Use of zileuton is uncommon due to the need for dosing four times a day, potential drug interactions, and the potential for hepatotoxicity with the resulting need for frequent monitoring of liver enzymes. In patients started on zileuton, serum alanine aminotransferase concentrations should be monitored before treatment begins, monthly for the first 3 months, every 2 to 3 months for the remainder of the first year, and then periodically thereafter for as long as the patient continues to receive the medication. Zileuton also inhibits the cytochrome P-450 (CYP) mixed function enzyme system and has been shown to decrease the clearance of theophylline, R-warfarin and propranolol.34... 

Serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, y-glutamyl transferase, and bilirubin may be elevated in patients with hepatobiliary disease. 

Hepatocellular damage manifests as elevated serum aminotransferases [alanine aminotransferase (ALT) and aspartate aminotransferase (AST)]. The degree of transaminase elevation does not correlate with the remaining functional metabolic capacity of the liver. An AST level two-fold higher than ALT is indicative of alcoholic liver damage. 

ALT, alanine aminotransferase AST, aspartate aminotransferase GGT, gamma-glutamyl transferase INR, international normalized ratio LDH, lactate dehydrogenase PT, prothrombin time. 

Tolcapone has been associated with several cases of severe liver failure, including fatalities, and has been removed from the market in some countries. Thus, it should only be used in patients who cannot take or do not respond to entacapone. Serum alanine aminotransferase and aspartate aminotransferase concentrations should be monitored at baseline, then every 2 to 4 weeks for 6 months, and then periodically for the remainder of therapy. Patients who fail to show symptomatic benefit after 3 weeks should discontinue tolcapone. Entacapone has not been associated with liver damage, so monitoring of liver enzymes is not currently recommended.24,25,29... 

A few cases of hepatotoxicity have been reported with rosiglitazone and pioglitazone, but no serious complications have been reported, and symptoms typically reverse within several weeks of discontinuing therapy. Therefore, periodic liver function tests should be performed at baseline and during thiazolidinedione therapy. Patients with a baseline alanine aminotransferase (ALT) level greater than 2.5 times the upper limit of normal should not receive a TZD. If ALT levels rise to greater than 3 times the upper limit of normal in patients receiving a TZD, the medication should be discontinued. 

May present with high fever with significant leukocytosis with left shift, anemia, elevated alanine aminotransferase, and dull abdominal pain on palpation... 

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