Liver disease toxic hepatitis

Lidocaine Sodium channel (INa) blockade Blocks activated and inactivated channels with fast kinetics does not prolong and may shorten action potential Terminate ventricular tachycardias and prevent ventricular fibrillation after cardioversion IV first-pass hepatic metabolism reduce dose in patients with heart failure or liver disease Toxicity Neurologic symptoms... 

Ethanol metabolism may result in alchohol-induced liver disease, including hepatic steatosis (fatty liver), alcohol-induced hepatitis, and cirrhosis. The principal toxic products of ethanol metabolism include acetaldehyde and free radicals. Acetaldehyde forms adducts with proteins and other compounds. The hydroxyethyl radical produced by MEOS and other radicals produced during... 

There is a dark side to receptor-mediated endocyto-sis in that viruses which cause such diseases as hepatitis (affecting liver cells), poliomyelitis (affecting motor neurons), and AIDS (affecting T cells) initiate their damage by this mechanism. Iron toxicity also begins with excessive uptake due to endocytosis. 

Methotrexate, an antimetabolite, is indicated for moderate to severe psoriasis. It is particularly beneficial for psoriatic arthritis. It is also indicated for patients refractory to topical or UV therapy. Methotrexate can be administered orally, subcutaneously, or intramuscularly. The starting dose is 7.5 to 15 mg per week, increased incrementally by 2.5 mg every 2 to 4 weeks until response maximal doses are approximately 25 mg/wk. Adverse effects include nausea, vomiting, mucosal ulceration, stomatitis, malaise, headache, macrocytic anemia, and hepatic and pulmonary toxicity. Nausea and macrocytic anemia can be ameliorated by giving oral folic acid 1 to 5 mg/day. Methotrexate should be avoided in patients with active infections and in those with liver disease. It is contraindicated in pregnancy because it is teratogenic. 

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... 

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. 

Alcohol has a range of effects for some, desirable acute effects unwanted effects on the developing fetus and with long-term consumption, effects on the liver and other organs. In the US, over 2 million people experience alcohol related liver disease. Effects on the liver are dose related the more you consume the greater the effects. Early on there is an accumulation of fat in the liver as a result of the metabolism of alcohol. Some heavy drinkers develop an inflammation (alcoholic hepatitis) of the liver. Metabolites of alcohol, produced by the liver, are toxic to the liver cells. 

Because of the potential for hematological and hepatic toxicity, carbamazepine should not be administered to patients with liver disease or thrombocytopenia or to those at risk for agranulocytosis. For this reason, carbamazepine is strictly contraindicated in patients receiving clozapine. Because of reports of teratogenicity, including increased risks of spina bifida (Rosa 1991), microcephaly (Bertol-lini et al. 1987), and craniofacial defects (Jones et al. 1989), carbamazepine is relatively contraindicated in pregnant women. Pretreatment evaluation should include a complete blood count and determination of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. 

The plasma clearance of theophylline varies widely. Theophylline is metabolized by the liver, so typical doses may lead to toxic concentrations of the drug in patients with liver disease. Conversely, clearance may be increased through the induction of hepatic enzymes by cigarette smoking or by changes in diet. In normal adults, the mean plasma clearance is 0.69 mL/kg/min. Children clear theophylline faster than adults (1-1.5 mL/kg/min). Neonates and young infants have the slowest clearance (see Chapter 59). Even when maintenance doses are altered to correct for the above factors, plasma concentrations vary widely. 

Elevations of serum aminotransferase activity (up to three times normal) occur in some patients. This is often intermittent and usually not associated with other evidence of hepatic toxicity. Therapy may be continued in such patients in the absence of symptoms if aminotransferase levels are monitored and stable. In some patients, who may have underlying liver disease or a history of alcohol abuse, levels may exceed three times normal. This finding portends more severe hepatic toxicity. These patients may present with malaise, anorexia, and precipitous decreases in LDL. Medication should be discontinued immediately in these patients and in asymptomatic patients whose aminotransferase activity is persistently elevated to more than three times the upper limit of normal. These agents should be used with caution and in reduced dosage in patients with hepatic parenchymal disease, Asians, and the elderly. In general, aminotransferase activity should be measured at baseline, at 1-2 months, and then every 6-12 months (if stable). 

Symptomatic adverse effects of darunavir include diarrhea, nausea, headache, and rash. Laboratory abnormalities include dyslipidemia (though possibly less frequent than with other boosted PI regimens) and increases in amylase and hepatic transaminase levels. Liver toxicity, including severe hepatitis, has been reported in some patients taking darunavir the risk of hepatotoxicity may be higher for persons with HBV, HCV, or other chronic liver disease. 

Disease/pathological conditions. Disposition of chemicals is potentially altered by disease and hence toxicity. Generalization, however, is difficult as the effects are unpredictable. Thus liver disease may decrease metabolism, but this depends on type of disease and particular pathway of metabolism. Disease in one organ may affect the response of another, for example, chronic renal disease decreases hepatic cytochrome P-450. 

Aspirin and similar NSAIDs can cause other toxic side effects if used improperly or if taken by patients who have preexisting diseases. For instance, serious hepato-toxicity is rare with normal therapeutic use, but high doses of aspirinlike drugs can produce adverse changes in hepatic function in patients with liver disease.85,99 Likewise, aspirin does not seem to cause renal disease in an individual with normal kidneys,84 but problems such as nephrotic syndrome, acute interstitial nephritis, and even acute renal failure have been observed when aspirin is given to patients with impaired renal function, or people with decreased body water (volume depletion).35,102... 

The first human experiments which suggested a toxic effect of ammonia in disease were done by Van Caulaert. The revival and extension of this work by the group led by Davidson (G2) in the Boston City Hospital has stimulated widespread interest in ammonia as a factor in the production of mental symptoms in liver disease. The ability of various factors, such as urea feedings, high-protein diet, cation resins in the ammonia cycle, and amino acids, to induce symptoms of coma in patients with liver disease (G2, M3, M4, P7, S8) made it quite clear that ammonia was associated with the symptom complex called hepatic coma. The severe toxicity of ammonia in animals and the ability of intravenous or oral ammonium salts to provoke episodes of impending liver coma tended to substantiate the clinical impressions. Rapid confirmation of these observations was furnished by the experiments of other groups (Bll, C2, E2, FI). 

Hepatotoxicity is not a particularly common form of adverse drug reaction and a patient with pre-existing liver disease does not have increased susceptibility to hepatic injury when taking drugs known to cause liver damage [1]. Therefore, drugs that are known to be hepato-toxic should not be contraindicated in this group of patients. There are... 

The first-pass effect may be reduced in cirrhosis and portal hypertension owing to reduced blood flow through the liver. Additionally, in cirrhosis and acute hepatitis the number of functional hepatocytes may be reduced. Drugs with a high first-pass extraction ratio and a narrow therapeutic window, such as the statins, are more likely to be toxic in patients with liver dysfunction [20]. In liver disease, an increase in the percentage of drug reaching the systemic circulation is an important factor in statin toxicity. 

A 2006 review by the National Lipid Association s Statin Safety Assessment Task Force concluded that hepatic function does not appear to be compromised by statin use and that there was no apparent link between elevations in LFTs and the development of liver toxicity. They noted that TFT monitoring may itself be of little value in the absence of other symptoms of liver toxicity, but should be performed for medicolegal reasons, as it is recommended in the product SPCs. The expert group concluded that the use of statins is not contraindicated in chronic and compensated liver disease, but that it is contraindicated in decompensated disease or liver failure [2, 3]. 

Thus, in patients who have liver disease, the combination of drugs that are primarily metabolized and excreted by the liver with drugs that have the potential to interfere with their hepatic metabolism/excretion can give rise to dangerous and often unpredictable adverse/toxic effects. 

Steatohepatitis is the accumulation of lipids and the presence of inflammatory cells within hepatic parenchyma. Steatohepatitis is usually the next stage of steatosis if untreated (Bautista, 2002 French, 2003 Lieber, 1994). The inflammatory cells are usually neutrophils and mononuclear leukocytes. Conditions usually associated with steatohepatitis are alcoholic liver disease, NAFLD, and endotoxemia secondary to intestinal disease. Any toxic compounds that cause steatosis can also result in steatohepatitis if the condition is left untreated. Steatohepatitis may progress to flbrosis/cirrhosis and hepatocellular carcinoma if the inciting cause is not removed or treated (Diehl, 2002). 

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