Hepatic disease alcoholic

Liver diseases Alcoholic hepatitis (A), hepatitis B and C (A), non-alcoholic steatohepatitis (A), liver transplantation (A), Wilson s disease (A)... 

Apart from these two Vertex compounds, only one other caspase inhibitor, BDN-6556, has been used in clinical trials. This compound belongs to the class of oxamyl dipeptides and was originally developed by Idun Pharmaceuticals (taken over by Pfizer). It is the only pan-caspase inhibitor that has been evaluated in humans. BDN-6556 displays inhibitory activity against all tested human caspases. It is also an irreversible, caspase-specific inhibitor that does not inhibit other major classes of proteases, or other enzymes or receptors. The therapeutic potential of BDN-6556 was first evaluated in several animal models of liver disease because numerous publications suggested that apoptosis contributes substantially to the development of some hepatic diseases, such as alcoholic hepatitis, hepatitis B and C (HBV, HCV), non-alcoholic steato-hepatitis (NASH), and ischemia/reperfusion injury associated with liver transplant. Accordingly, BDN-6556 was tested in a phase I study. The drug was safe and... 

Amantadine is used cautiously in patients with seizure disorders, hepatic disease, psychosis, cardiac disease, and renal disease The antihistamines, pheno-thiazines, disopyramide, and alcohol increase the risk of adverse reactions when administered with amantadine... 

Suicide risk even in patients without psychiatric disease Avoid in uncontrolled narrow-angle glaucoma (causes mydriasis) Hepatotoxic avoid in alcoholics even if signs/symptoms of hepatic disease are absent. 

Shiraishi K, Matsuzaki S, Ishida H, Nakazawa H (1993) Impaired erythrocyte deformability and membrane fluidity in alcoholic liver disease participation in disturbed hepatic microcirculation. Alcohol Alcohol Suppl lA 59-64... 

The main indications for liver transplantation include chronic hepatitis C, alcoholic liver disease, nonalcoholic fatty liver disease, and cryptogenic cirrhosis. 

The main causes are hepatitis B and C, drug induced damage, metabolic disease (alcohol, haemochro-matosis and Wilsons disease) and autoimmune disease. Management depends upon the diagnosis. 

Pharmacokinetics Poorly absorbed from the G1 tract. Protein binding greater than 98%. Metabolized in the liver. Minimally eliminated in urine. Plasma levels are markedly increased in chronic alcoholic hepatic disease, but are unaffected by renal disease. Half-life 14 hr. 

Unlabeled Uses Glaucoma, severe renal or hepatic disease, bronchial asthma, respiratory depression, convulsive disorders, acute alcoholism, hypersensitivity to belladonna or opium or its components... 

Assess the patient for burning, numbness, and tingling of the extremities. Be aware that patients at risk for neuropathy, such as alcoholics, those with chronic hepatic disease, diabetics, the elderly, and malnourished individuals, may receive pyridox-ine prophylactically... 

Contraindications Hepatic disease or renal impairment, preexisting myelosuppres-sion, psoriasis or rheumatoid arthritis with alcoholism... 

Pharmacokinetics Well absorbed from theGl tract minimally absorbed after topical application. Protein binding less than 20%. Widely distributed crosses blood-brain barrier. Metabolized in the liver to active metabolite. Primarily excreted in urine partially eliminated in feces. Removed by hemodialysis. Half-life 8 hr (increased in alcoholic hepatic disease). 

Usefulfortreatment of anxiety in patients with hepatic disease consider for alcohol withdrawal... 

Similarly, covert substance abuse is also common in depression (Akiskal 1982 MacEwan and Remick 1988) and a leading cause of TRD. In a survey of 6,355 patients with substance abuse, M. S. Gold et al. (1994) found that 43.7% had a lifetime prevalence of major depression. Not only does comorbid substance abuse lead to TRD, but the presence of resulting hepatic disease alters antidepressant pharmacokinetics, making these patients more difficult to treat (Ciraulo and Jaffe 1981 Ciraulo et al. 1988 Mason and Kocsis 1991). In this regard, SSRls may offer some advantages over other antidepressants. One recent study of alcoholic patients with depression found a modest advantage for an SSRI over a TCA (G. Invernizzi et al. 1994). 

Most sedative drugs, including narcotics and alcohol, potentiate the sedative effects of benzodiazepines. In addition, medications that inhibit hepatic cytochrome P450 (CYP) 3A3/4 increase blood levels and hence side effects of clonazepam, alprazolam, midazolam, and triazolam. Lorazepam, oxazepam, and temazepam are not dependent on hepatic enzymes for metabolism. Therefore, they are not affected by hepatic disease or the inhibition of hepatic enzymes. 

Liver disease is the most common medical complication of alcohol abuse an estimated 15-30% of chronic heavy drinkers eventually develop severe liver disease. Alcoholic fatty liver, a reversible condition, may progress to alcoholic hepatitis and finally to cirrhosis and liver failure. In the United States, chronic alcohol abuse is the leading cause of liver cirrhosis and of the need for liver transplantation. The risk of developing liver disease is related both to the average amount of daily consumption and to the duration of alcohol abuse. Women appear to be more susceptible to alcohol hepatotoxicity than men. Concurrent infection with hepatitis or C virus increases the risk of severe liver disease. 

Biguanide drugs are contraindicated in patients with renal disease, alcoholism, hepatic disease, or conditions predisposing to tissue anoxia (eg, chronic cardiopulmonary dysfunction) because of an increased risk of lactic acidosis induced by biguanide drugs. 

Liver cirrhosis is among the top 10 causes of death in the Western world. The disease occurs after chronic damage to hepatic cells, mainly hepatocytes, which can be caused by viral hepatitis, chronic alcohol abuse or toxic injury, biliary disease, and metabolic liver disorders [64], Liver cirrhosis is characterized by an abnormal deposition of connective tissue in the liver, which hampers the normal functions of the liver. Other features of the disease are general tissue damage, chronic inflammation, and the conversion of normal liver architecture into structurally abnormal nodules. Secondary to these anatomical changes are disturbances in the liver function and in the hemodynamics leading to portal hypertension and intrahepatic shunting [39, 64, 103],... 

Adverse effects Adverse effects are a minor problem with rifampin, but can include nausea and vomiting, rash, and fever. The drug should be used judiciously in patients with hepatic failure because of the jaundice that occurs in patients with chronic liver disease, alcoholics, or in the elderly. 

Medications that are metabolised by the liver must be used with caution in patients with hepatic disease such patients may need lower doses of the drug. Alcohol is primarily metabolised by the liver, and accumulation of its products can lead to cell injury and death. 

Decompensated hepatic disease (e.g., active alcoholism, ascites, coagulopathy, hypoalbuminemia, or jaundice) should not be treated with PEG-interferon a-2b... 

Liver diseases severe acute (necrotic) hepatitis, chronic hepatitis, chronic alcoholic liver damage, liver cirrhosis, cardiac liver, liver abscess, liver tumours and liver metastases, toxic liver damage, etc. A severe and, above all, constant reduction in ChE activity (e. g. < 500 U/1) is usually suggestive of an unfavourable prognosis and the foreseeable moment of liver death . 

Niemela, O., Risteli, X, Blake, J.E., Rlsteli, L., Compton, K.V., Orr o, H. Markers of fibrogenesis and basement membrane formation in alcoholic liver disease. Relation to severity, presence of hepatitis, and alcohol intake. Gastroenterology 1990 98 1612-1619... 

ITie second stage of alcoholic liver disease, alcoholic hepatitis, is characterized by the death of a number of liver cell and inflammation of the affected areas. The damage in this stage sometimes proves fatal. 

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