Hepatic injuries

Acute intoxication with DHBs occurs mainly by the oral route symptoms are close to those induced by phenol poisoning including nausea, vomiting, diarrhea, tachypnea, pulmonary edema, and CNS excitation with possibiUty of seizures followed by CNS depression. Convulsions are more frequent with catechol as well as hypotension due to peripheral vasoconstriction. Hypotension and hepatitis seem more frequent with hydroquinone and resorcinol. Methemoglobinemia and hepatic injury may be noted within a few days after intoxication by DHBs. 

The plasma half-life of 6-MP after intravenous bolus injection is 21 min in children and is twofold greater in adults. After oral intake peak levels are attained within 2 h. 6-MP is used for the treatment of ALL and has shown certain activity in chronic myelogenous leukemia. The major side effects involve myelosuppression, nausea, vomiting, and hepatic injury. 

Hepatic Effects. Hepatic failure was reported in the case of an accidental ingestion of trichloroethylene that led to an acute overdose (Kleinfeld and Tabershaw 1954). In other case studies, blood analyses revealed no hepatic injury in a man who drank several tablespoons of trichloroethylene (Todd 1954) or in women who drank about 20 mL (Morreale 1976) or an unknown quantity (Perbellini et al. 1991). Self-reported liver problems were not increased among persons in the trichloroethylene subregistry who were exposed to trichloroethylene in their drinking water (ATSDR 1994 Burg et al. 1995). 

Popper H, Schaffner F. 1959. Drug induced hepatic injury. Ann Intern Med 51 1230-1252. 

Steup DR, Hall P, McMillan DA, et al. 1993. Time course of hepatic injury and recovery following coadministration of carbon tetrachloride and trichloroethylene in Fischer-344 rats. Toxicol Pathol 21 327-334. 

Arthur, M.J.P., Bentley, I., Kowalski-Saunders, P., Tanner, A.K, MiUward-Sadler, G.H. and Wright, R. (1985). Oxygen-derived free radicals promote hepatic injury in the rat. Gastroenterology 89, 1114-1122. 

Bacon, B.R. and Britton, R.S. (1989). Hepatic injury in chronic iron overload role of lipid peroxidation. Chem. Biol. Interact. 70, 183-226. 

Koo, A., Komatsu, H., Tao, G., Inoue, M., Guth, P.H. and Kaplowitz, (1991). Contribution of no-reflow phenomenon to hepatic injury after ischaemia-reperfusion evidence for a role for superoxide anion. Hepatolt, 15, 507-514. 

Sokol, R.J., Devereaux, M. and Khandwala, R,A. (1991). Effect of dietary lipid and vitamin E on mitochondrial lipid peroxidation and hepatic injury in the bile duct-ligated rat. J. Lipid Res. 32, 1349-1357. 

Tanner, A.R., Bantock, K.I., Hinks, L., Lloyd, B., Turner, N.R. and Wri t, R. (1986). Depressed selenium and vitamin E levels in an alcoholic population. Possible relationship to hepatic injury through increased lipid peroxidation. D. Dis. Sci. 31, 1307-1312. 

Lieber, C.S. (1990). Mechanisms of ethanol induced hepatic injury. Pharmac. Ther. 46, 1-41. 

Thiazolidinediones15 Pioglitazone 15-45 mg by mouth daily rosiglitazone 4-8 mg by mouth daily Weight gain increase in total, LDL, and HDL cholesterol edema headache fatigue hepatic injury (rare)... 

Hogaboam, C.M. et al., Exaggerated hepatic injury due to acetaminophen challenge in mice lacking C-C chemokine receptor 2, Am. J. Pathol., 156, 1245, 2000. 

Increased bilirubin levels are caused due to the intake of large doses of such drugs as chloroquine, vitamin K, sulpha-drugs, tetracyclines, paracetamol, nicotinic acid and monoamine oxidase inhibitors (e.g., iproniazid RP 1.0 nialamide RP 1.8 isocarboxazid RP 3.1 phenelzine RP 18 pheniprazine RP31 and tranylcypromine RP 45), where RP designates the Relative Potency based on the tiyptamine potentiation test. The elevated levels are due to hepatic injury, and... 

The flavonoid content of the tinctures of Calendula officinalis L., Passiflora incarnata L and Silybum marianum (L.) Gaertn. was investigated by HPLC-DAD and HPLC-MS. The anti-inflammatory effect, and the beneficial influence to treat hepatic injuries, tension... 

The hepatic injury caused by iproniazid could also be due to the formation of the toxic metabolite hydrazine by A-dealkylation followed by hydrolysis. Indeed, A-dealkylation is a main route in the metabolism of iproniazid, with plasma levels of hydrazine in rabbits three- to sixfold higher than after isoniazid [188],... 

Death. Chloroform levels of 40,000 ppm cause death in patients under chloroform anesthesia (Featherstone 1947 Whitaker and Jones 1965). Death is usually due to severe respiratory depression/ failure or disturbances in cardiac rhythm. Accidental or intentional ingestion of large doses of chloroform may lead to death (Piersol et al. 1933). Death in humans after oral exposure to chloroform is usually caused by respiratory obstruction by the tongue due to jaw relaxation, central respiratory paralysis, acute cardiac failure, or severe hepatic injury (Piersol et al. 1933 Schroeder 1965). 

Another antioxidative enzyme that has been targeted to the liver is catalase (CAT). Suc-cinylation and mannosylation resulted in an increased accumulation of the protein in the non-parenchymal cells of the liver. Furthermore, the CAT derivatives reduced hepatic injury in an ischaemia/reperfusion injury model [56]. 

Vulnerability of the liver to injury necessitates routine evaluation of hepatic function in patients and asymptomatic individuals to avert or control adverse clinical conditions. Thus, a plethora of methods has been developed for the diagnosis of liver diseases and dysfunctions. One such method uses physical palpation to determine alterations or changes in the orientation of the liver, which provides valuable information about the organ status but the quality of information is subjective and imprecise [3]. Another common method for the diagnosis of more serious hepatic injuries involves liver biopsies coupled with biochemical tests to determine the extent of liver injury and prognosis [4-7]. However, in acute and some chronic hepatic disorders, dynamic and continuous hepatic function monitoring would be advantageous. 

Subchronic exposure to bromodichloromethane in the range of 100-3 00 mg/kg/day has caused hepatic injury in mice and rats characterized by increased liver weight, pale discoloration, increased levels of hepatic enzymes, and focal areas of inflammation or degen-eration. Mild effects, including slightly increased liver weights and microscopic changes, have been noted at doses as low as 40-50 mg/kg/day for 2 weeks. 

Hepatic injury Serious liver injury (eg, cirrhosis) may enhance the anticoagulant effect of lepirudin caused by coagulation defects secondary to reduced generation of vitamin K-dependent coagulation factors. 

The margin of separation between the apparently safe dose of naltrexone and the dose causing hepatic injury appears to be only 5-fold or less. Naltrexone does not appear to be a hepatotoxin at the recommended doses. 

Warn patients of the risk of hepatic injury and advise them to stop the use of naltrexone and seek medical attention if they experience symptoms of acute hepatitis. 

Monitoring A high index of suspicion for drug-related hepatic injury is critical if the occurrence of liver damage induced by naltrexone is to be detected at the earliest possible time. 

In patients with life-threatening arrhythmias, weigh the potential risk of hepatic injury against the potential benefit of therapy. Monitor carefully for evidence of progressive hepatic injury. Give consideration to reducing the rate of administration or withdrawing amiodarone IV in such cases. 

Acute hepatic injury In rare instances, symptoms consistent with acute hepatic injury, as well as significant elevations in enzymes such as alkaline phosphatase, CPK, LDH, AST, and ALT have occurred with diltiazem and nifedipine. 

Antidote To prevent or lessen hepatic injury that may occur following ingestion of a... 

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