Liver enzyme abnormalities

As we soon learned, tetrahydro-aminoaeridine (THA) is less effeetive in some respeets than physostigmine in reversing seopolamine induced decrements in NF% scores (Fig. 67) but surprisingly, does seem to shorten the duration of belladonnoid intoxication. This may reflect a greater affinity for the cholinesterase enzyme. THA s tendency to cause temporaiy liver enzyme abnormalities, however, persuad us to avoid its further use. 

Hepatomegaly, jaundice, and altered liver function tests have been reported in accidental poisonings with DME An outbreak of toxic liver disease was associated with DME exposure at a fabric coating factory. Thirty-six of 58 workers had elevations of either aspartate aminotransferase or alanine aminotransferase. Serological tests excluded known infectious causes of hepatitis in all but two cases. After modification of work practices and removal of the most severely affected from exposure, improvement in liver enzyme abnormalities and symptoms occurred in most patients. Medical surveillance of the working population for 14 months revealed no further cases of toxic liver... 

Diarrhea nausea vomiting jaundice liver enzyme abnormalities. Azotemia elevated BUN/creatinine increased serum uric acid levels (in patients predisposed to gouty arthritis) thrombocytopenia megaloblastic anemia weakness dizziness Hypokalemia headache dry mouth anaphylaxis. ... 

Adverse reactions occurring in at least 3% of patients include the following Diarrhea, dyspepsia, rash, liver enzyme abnormalities, headache. 

Hepatic function impairment Ritonavir is principally metabolized by the liver. Exercise caution when administering this drug to patients with pre-existing liver diseases, liver enzyme abnormalities, or hepatitis. 

Sitaxsentan is a potent and selective agent which inhibits ET-1 binding to ETA receptors (IC50 = 1.4 nM), while being essentially inactive at ETB receptors (IC50 = 9.8 pM).23 In the clinic, it was found to have excellent oral bioavailability (70-100%) and a terminal elimination half-life of 10 h, and is administered as a once daily 100 mg dose. It is highly protein bound in plasma (> 99%) and extensively metabolized in the liver to inactive metabolites, predominantly by CYPs 2C9 and 3A4. Excretion is 50 60% renal, with the balance in the feces.25 Sitaxsentan inhibits CYP 2C9, and was observed to increase exposure to warfarin by over twofold. The use of cyclosporine A is also contraindicated, but no interactions were observed with sildenafil.15 Sitaxsentan was well tolerated in trials, with only minor side effects reported. Reversible liver enzyme abnormalities were also observed, but less frequently than with bosentan.15 25... 

The common adverse effects of itraconazole are similar to those of terbinaflne, such as gastrointestinal disturbance, dermatologic disorders, and headache less common adverse effects include dizziness, fatigue, fever, decreased libido, and asymptomatic liver enzyme abnormalities (1% to 5% with continuous dosing and about 2% with... 

Soler, N. G., and Khardori, R., Liver enzyme abnormalities after insulin-induced hypogly-caemic coma. Br. Med. J. 291, 1541 (19850. 

A retrospective study of itraconazole use found that 11 of 12 leukaemic patients given amphotericin B and itraconazole had raised liver enzymes. These abnormalities resolved in 7 patients when the amphotericin B was discontinued. Itraconazole alone, given to another 8 patients did not cause liver enzyme abnormalities, even though it was used in high doses. Amphotericin B has only rarely been associated with adverse effects on the liver and increases in liver enzymes may occur in patients treated with itraconazole. 

The use of bosentan in patients with mildly symptomatic pulmonary arterial hypertension has been studied in a multicenter, double-blind, randomized, placebo-con-trolled trial (the EARLY study) [85 ]. Patients over 12 years of age ( = 185) with less functional compromise (WHO functional class 2) were randomized to bosentan or placebo and followed for 6 months double-blind, followed by an open extension period. Adverse events were common in both groups and included nasopharyngitis and abnormal liver enzymes in the bosentan arm. Laboratory tests identified increases in aminotransferases of more than three times the upper limit of normal in 12 (13%) patients taking bosentan compared with two (2%) patients taking placebo. Liver enzyme abnormalities invariably resolved on dose reduction or drug withdrawal. 

Somavert ) daily daily fatigue, abnormal liver enzymes monthly for 6 months, then every 6 months MRI every 6 months. IGF-I (not GH) after first year, then yearly. levels not responsive to somatostatin analog-therapy... 

Initial inhibition of sodium uptake and whole body sodium content that were normal by day 28. Abnormal liver enzyme activity. Liver copper increased from 23 mg/kg FW at start to 113 mg/kg FW at day 28... 

Mirex has considerable potential for chronic toxicity because it is only partly metabolized, is eliminated very slowly, and is accumulated in the fat, liver, and brain. The most common effects observed in small laboratory mammals fed mirex included weight loss, enlarged livers, altered liver enzyme metabolism, and reproductive failure. Mirex reportedly crossed placental membranes and accumulated in fetal tissues. Among the progeny of mirex-treated mammals, developmental abnormalities included cataracts, heart defects, scoliosis, and cleft palates (NAS 1978 Blus 1995). 

On rare occasions, pemoline can cause a chemical hepatitis (liver dysfunction). For this reason, patients with known liver disease should not be prescribed pemoline. A baseline laboratory assessment of liver enzymes before starting therapy with pemoline is advised, and liver function monitoring must be repeated periodically. If liver abnormalities are detected, then pemoline must be discontinued. The recognition of this side effect resulting from therapy with pemoline has markedly restricted its use. 

Ora/-Adverse reactions requiring discontinuation include Pulmonary infiltrates or fibrosis paroxysmal ventricular tachycardia CHF elevation of liver enzymes visual disturbances solar dermatitis blue discoloration of skin hyperthyroidism hypothyroidism. Adverse reactions occurring in at least 3% of patients include CFIF Gl complaints (nausea, vomiting, constipation, anorexia) dermatologic reactions (photosensitivity, solar dermatitis) neurologic problems (malaise, fatigue, tremor/abnormal involuntary movements, lack of coordination, abnormal gait/ataxia, dizziness, paresthesias) abnormal liver function tests. 

Lab test abnormalities Increased platelet count increased transaminases and increased liver enzymes (eg, ALT, AST) were usually asymptomatic and reversible. Special senses - Visual adverse events most often included blurred vision, diplopia, or difficulty focusing. 

Hepatotoxicity Itraconazole has been associated with rare cases of serious hepatotoxicity, including liver failure and death. Some of these cases had neither pre-existing liver disease, nor a serious underlying medical condition. If liver function tests are abnormal, discontinue treatment. In patients with raised liver enzymes or an active liver disease or who have experienced liver toxicity with other drugs, do not start treatment unless the expected benefit exceeds the risk of hepatic injury. In such cases, liver enzyme monitoring is necessary. 

Lab test abnormalities Elevations of liver enzymes and CPK, lymphopenia, and neutropenia occurred. These were reported in similar proportions of zanamivir and lactose-vehicle placebo recipients with acute influenza-like illness. 

Liver Methotrexate causes hepatotoxicity, fibrosis, and cirrhosis, but generally only after prolonged use. Acutely, liver enzyme elevations are frequent, usually transient and asymptomatic, and also do not appear predictive of subsequent hepatic disease. Liver biopsy after sustained use often shows histologic changes, and fibrosis and cirrhosis have occurred these latter lesions often are not preceded by symptoms or abnormal liver function tests (see Precautions). For this reason, periodic liver biopsies are usually recommended for psoriatic patients who are under long-term treatment. Persistent abnormalities in liver function tests may precede appearance of fibrosis or cirrhosis in the RA population. 

Mild to moderate side effects, including nausea, vomiting, abdominal pain, diarrhea, anorexia, and headache, occur in up to 33% of patients taking this drug. Skin rash and discoloration, fever, reversible male infertility, and liver enzyme elevation occur less frequently. Rare hematological abnormalities, such as agranulocytosis, aplastic anemia, hemolytic anemia, neutropenia, or other blood dyscrasias, can be fatal. Hypersensitivity reactions occur rarely. 

As a group, the azoles are relatively nontoxic. The most common adverse reaction is relatively minor gastrointestinal upset. All azoles have been reported to cause abnormalities in liver enzymes and, very rarely, clinical hepatitis. Adverse effects specific to individual agents are discussed below. 

Relationship between Fructose 1,6-Bisphosphatase and Blood Lactate Levels A congenital defect in the liver enzyme fructose 1,6-bisphosphatase results in abnormally high levels of lactate in the blood plasma. Explain. 

Two patients developed significantly abnormal liver function tests after receiving pegvisomant for 12 weeks (2,3). Transaminase activities rose to more than 10-fold the upper limits of the reference ranges and returned to normal after withdrawal. One of the two was treated for autoimmune hepatitis (5). Monitoring of liver enzymes every 4-6 weeks is recommended for 6 months or if symptoms of hepatitis develop. 

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