Cirrhosis toxic

Percutaneous Hver biopsy after each 1.5 g of total accumulated methotrexate dosage to detect hepatic fibrosis or cirrhosis not rehably predicted by semm aminotransferase tests are recommended (1,50). Concurrent use of NSAIDs may increase toxicity of methotrexate, although toxicity may be avoided if the dmgs are separated by 12 h. 

Some authorities question whether dmnkeimess can result from the inhalation of ethyl alcohol vapors. Experience has demonstrated that in any event such intoxication is indeed rare (281). There is no concrete evidence that the inhalation of ethyl alcohol vapor will cause cirrhosis. Liver function is definitely impaired during alcohol intoxication (282), making the subject more susceptible to the toxic effects of chlorinated hydrocarbons. 

Yellow phosphorus was the first identified liver toxin. It causes accumulation of lipids in the liver. Several liver toxins such as chloroform, carbon tetrachloride, and bromobenzene have since been identified. I he forms of acute liver toxicity are accumulation of lipids in the liver, hepartxiellular necrosis, iii-trahepatic cholestasis, and a disease state that resembles viral hepatitis. The types of chrome hepatotoxicity are cirrhosis and liver cancer. 

While ammonia, derived mainly from the a-amino nitrogen of amino acids, is highly toxic, tissues convert ammonia to the amide nitrogen of nontoxic glutamine. Subsequent deamination of glutamine in the liver releases ammonia, which is then converted to nontoxic urea. If liver function is compromised, as in cirrhosis or hepatitis, elevated blood ammonia levels generate clinical signs and symptoms. Rare metabolic disorders involve each of the five urea cycle enzymes. 

The ammonia produced by enteric bacteria and absorbed into portal venous blood and the ammonia produced by tissues are rapidly removed from circulation by the liver and converted to urea. Only traces (10—20 Ig/dL) thus normally are present in peripheral blood. This is essential, since ammonia is toxic to the central nervous system. Should portal blood bypass the liver, systemic blood ammonia levels may rise to toxic levels. This occurs in severely impaired hepatic function or the development of collateral links between the portal and systemic veins in cirrhosis. Symptoms of ammonia intoxication include tremor, slurred speech, blurred vision, coma, and ultimately death. Ammonia may be toxic to the brain in part because it reacts with a-ketoglutarate to form glutamate. The resulting depleted levels of a-ketoglutarate then impair function of the tricarboxylic acid (TCA) cycle in neurons. 

Iron overload is known to be toxic and potentially fatal. The major pathological effects of hepatic iron overload are fibrosis and cirrhosis, and hepatocellular carcinoma (Bonkovsky, 1991). The role of free radicals in the pathology of hepatic iron overload has been the subject of a detailed review recently (Bacon and Britton, 1990). 

Alcohol abuse is a major clinical problem in many countries and has been the subject of investigation for many years by those interested in determining the molecular basis of ethanol-induced liver dam e (see Lieber, 1990). These intensive and extended efforts have revealed much about the metabolism of ethanol in the liver and about the toxicity of its primary oxidative product, acetaldehyde. They have not, however, folly elucidated the molecular mechanisms that lead to the typical features of alcoholic liver injury steatosis, necrosis and eventually cirrhosis. 

Wilson s disease is another autosomal recessive disease leading to cirrhosis. Protein abnormalities result in excessive copper deposition in body tissues. The faulty protein is responsible for facilitating copper excretion in the bile, so copper accumulates in hepatic tissue. High copper levels within hepatocytes are toxic, and fibrosis and cirrhosis may develop in untreated patients. Those with Wilson s disease usually present with symptoms of liver or neurologic disease while still in their teens. 

A 4>-year-old male with alcoholic cirrhosis is seen in the ED because of a laceration of the scalp. Of the following local anesthetics, which would potentially be toxic ... 

Toxicities are GI (stomatitis, diarrhea, nausea, vomiting), hematologic (thrombocytopenia, leukopenia), pulmonary (fibrosis, pneumonitis), and hepatic (elevated enzymes, rare cirrhosis). Concomitant folic acid may reduce some adverse effects without loss of efficacy. Liver injury tests (aspartate aminotransferase or alanine aminotransferase) should be monitored periodically, but a liver biopsy is recommended during therapy only in patients with persistently elevated hepatic enzymes. MTX is teratogenic, and patients should use contraception and discontinue the drug if conception is planned. 

If no toxicity is manifested during the first year of therapy, then redraw liver enzymes every 6-12 months assess liver for cirrhosis every 1-2 years by ultrasound and every 4-6 years by CT or MRI scan biopsy as... 

Some toxic effects are reversible. Everyone has been exposed to some agent, household ammonia for example, that produces irritation to the skin or eyes. Exposure ends and, sometimes perhaps with a delay, the irritation ends. Some readers have no doubt been poisoned on occasion by the ingestion of too much alcohol. The effects here also reverse. The time necessary for reversal can vary greatly depending upon the severity of the intoxication and certain physiological features of the person intoxicated. But most people also realize that chronic alcohol abuse can lead to a serious liver disorder, cirrhosis, which may not reverse even if alcohol intake ceases. This type of effect is irreversible or only very slowly reversible. It is important in making a toxicological evaluation to understand whether effects are reversible or irreversible, because one is obviously much more serious than the other. 

The common side effects of naltrexone are nansea, headache, and dizziness. In addition, naltrexone has the potential for toxic effects on the liver and should not be used in an alcoholic with cirrhosis or other known liver disease. Because it blocks opiate receptors, patients treated with naltrexone are unable to benefit from the analgesic effects of opiates such as codeine or morphine. Naltrexone may increase serum levels of acamprosate in patients taking both medications. 

Although chelation is not helpful for Alzheimer s disease patients, it is the key to treating patients with dementia due to Wilson s disease. Wilson s disease is a genetically inherited disorder that usually strikes before age 30. The disease causes toxic levels of copper to accumulate in the liver, brain, eyes, and kidney. Untreated, Wilson s disease leads to tremors, cirrhosis, depression, psychosis, dementia, and ultimately death. Chelation with penicillamine (Cuprimine) can stop and even reverse the accumulation of copper. 

Acetyls alley lie acid was shown to prevent cirrhosis under certain experimental conditions [125]. Naproxen and indomethacin partially protected against LPS and D-galactosamine-in-duced hepatotoxicity [126] Acetylsalicylic acid and ibuprofen were also protective in endo-toxic shock [127]. Endotoxaemia is one of the complications in cirrhotic patients [128] and is probably caused by an impaired ability of the liver to take up and detoxify gut-derived LPS [116]. The presence of portosystemic shunts in cirrhotic patients may also contribute to this spill-over of LPS into the systemic circulation [129]. NSAIDs, however, are also reported to provoke deleterious effects on renal function in cirrhosis [130], and can therefore not be used in cirrhotic patients. Cell-specific delivery of NSAIDs to SECs and/or KCs may make application of these drugs in cirrhosis feasible by circumventing the renal side-effects. 

Other intermediate-duration oral studies with 1,4-dichlorobenzene have reported liver toxicity. In female rats dosed with 1,4-dichlorobenzene by gavage for about 6 months, doses of 188 mg/kg/day and above resulted in increased liver weights. At 376 mg/kg/day, slight cirrhosis and focal necrosis of the liver were also observed (Hollingsworth et al. 1956). No effects on the liver were seen at a dose of 18.8 mg/kg/day. Based on a minimal LOAEL (increased liver weight) of 188 mg/kg/day, an intermediate-duration MRL of 0.4 mg/kg/day was calculated as described in the footnote to Table 2-2 and Appendix A (Hollingsworth et al. 1956). 

Hepatic Effects. Liver effects reported in case studies in humans exposed to 1,4-dichlorobenzene via inhalation have included jaundice, cirrhosis, and atrophy (Cotter 1953). Estimates of exposure duration ranged from 1 to 18 months however, quantitative data on 1,4-dichlorobenzene levels were not available. One report was located that described a 3-year-old boy who may have ingested 1,4-dichlorobenzene crystals. Jaundice was reported, indicating that liver function was in some way compromised, although no further details were reported. No dermal exposures to 1,4-dichlorobenzene in humans were reported. The lack of reliable information regarding human exposures to 1,4-dichlorobenzene by all three routes of exposure makes it difficult to draw any helpful conclusions about the toxicity of 1,4-dichlorobenzene in humans. 

Hepatic - Methotrexate has the potential for acute (elevated transaminases) and chronic (fibrosis and cirrhosis) hepatotoxicity. Chronic toxicity is potentially fatal it generally occurs after prolonged use (generally 2 years or more) and after a total dose of at least 1.5 g. 

Following intravenous injection of Thorotrast, cirrhosis of the liver was the primary systemic effect in humans and animals. Hematological disorders (aplastic anemia, leukemia, myelofibrosis, and splenic cirrhosis), cardiovascular effects (myocardial infarction, severe coronary luminal narrowing and internal alteration of the carotid artery), and Thorotrastoma (localized fibrosis surrounding deposits of Thorotrast) were also found in patients injected with Thorotrast. The effects of Thorotrast were a result of the radiological toxicity of thorium. 

A variety of conditions may predispose certain segments of the population to carbon tetrachloride toxicity. Persons with alcoholic cirrhosis, or other liver diseases which have significantly diminished the functional reserve of the liver, have a reduced capacity to tolerate carbon tetrachloride-induced hepatotoxicity. The same is true for carbon tetrachloride-induced nephrotoxicity in people with significant renal dysfunction from other causes. Diabetics may be particularly susceptible to carbon... 

Murray M, Farrell GC. 1984. Different effects of carbon tetrachloride toxicity and cirrhosis on substrate binding to rat hepatic microsomal cytochrome P-450. Biochem Pharmacol 33 687-9. 

Alcohol abuse and dependence, widely known as alcoholism, is a major cause of morbidity and mortality. Its acute and chronic toxicity spreads across multiple systems and organs, from child abuse to domestic or public violence to traffic accidents and from cirrhosis to hypertension. Mean life expectancy of alcohol abusers is around 55 years. Alcohol seems involved in several hundred thousand deaths each year in Europe, with considerable added social and health care costs. This is in clear contrast with the little attention paid to the treatment of alcohol dependence and abuse. On the other hand, much is made of the French Paradox , the J curve and the demonstrated cardiovascular benefits of regular moderate wine intake. 

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