Hepatotoxic agent

Educate patients to avoid hepatotoxic agents (e.g., some dietary supplements). 

D/C antiretrovirals D/C all hepatotoxic agents rule out other causes do not rechallenge with NVP... 

Hepatitis C virus (HCV), 3 135, 137-138 anitiviral therapy, 3 161-164 infection process, 3 159-161 Hepatitis infection, immunoglobulin-transmitted, 12 139 Hepatitis viruses, 12 153 Hepatotoxic agents, exposure to, 23 118-119... 

Landon EJ, Naukam RJ, Sastry BVR. 1986. Effects of calcium channel blocking agents on calcium and centrilobular necrosis in the liver of rats treated with hepatotoxic agents. Biochem Pharmacol 35 697-705. 

Masuda Y, Nakayama N. 1982. Protective effect of diethyldithiocarbamate and carbon disulfide against liver injury induced by various hepatotoxic agents. Biochem Pharmacol 31 2713-2725. 

Hepatotoxicity There have been fatalities associated with jaundice in patients with liver disease or patients receiving rifampin concomitantly with other hepatotoxic agents. Carefully monitor liver function, especially AST and ALT, prior to therapy and then every 2 to 4 weeks during therapy. 

Hepatic Effects. Carbon tetrachloride has been known for many years to be a powerful hepatotoxic agent in humans and in animals. The principal clinical signs of liver injury in humans who inhale carbon tetrachloride are a swollen and tender liver, elevated levels of hepatic enzyme (aspartate aminotransferase) in the serum, elevated serum bilirubin levels and the appearance of jaundice, and decreased serum levels of proteins such as albumin and fibrinogen (Ashe and Sailer 1942 McGuire 1932 New et al. 1962 Norwood et al. 1950 Straus 1954). In cases of acute lethal exposures, autopsy generally reveals marked liver necrosis with pronounced steatosis (Jennings 1955 Markham 1967 Smetana 1939), and repeated or chronic exposures leads in some cases to fibrosis or cirrhosis (McDermott and Hardy 1963). 

Bhattacharyya K. 1965. Foetal and neonatal responses to hepatotoxic agents. J Path Bact 90 151-161. 

Lopez del Pino V, Bolt HM. 1977. [Effects of hepatotoxic agents on hepatic microsomal metabolism of estrogens in the rat.] Drug Res 27 2117-20. (German). 

Bioactivation is a classic toxicity mechanism where the functional group or the chemical structure of the drug molecule is altered by enzymatic reactions. For example, the enzymatic breakdown of the analgesic acetaminophen (paracetamol), where the aromatic nature and the hydroxyl functionality in paracetamol are lost, yields A -acetyl-p-benzoquinone imine, a hepatotoxic agent. Paracetamol can cause liver damage and even liver failure, especially when combined with alcohol. 

Table 14.1 Examples of Hepatotoxic Agents and Associated Liver Injury...

Acute hepatitis induced by intranasal cocaine, with transient increases in liver enzymes, has been reported in three HIV-positive patients (202). All had non-active chronic viral hepatitis with normal immunological status one was seropositive for hepatitis B virus and two were positive for hepatitis C virus. A few days after intranasal cocaine use, serum transaminases rose to high values, and two of the patients had fever, stiffness, sweats, and hepatomegaly. Alcohol and hepatotoxic agents were ruled out. Within a few days, the clinical and laboratory signs of hepatitis improved in all three cases. 

Concomitant treatment with other hepatotoxic agents can predispose to phenylbutazone-induced liver toxicity. 

A 50-year-old man with history of chronic hepatitis B had transient rises in serum transaminases after two successive episodes of autologous stem cell transplantation, with spontaneous resolution at that time PCR for hepatitis B virus was negative (76). Later he was given thalidomide and after 5 months suddenly experienced dizziness and jaundice. The concentration of hepatitis B virus DNA was 1641 pg/ml and serological tests for other viruses were negative. Despite conventional supportive care, he died of septicemic shock caused by Klebsiella pneumonia. Other hepatotoxic agents were excluded. 

Although the horse appears to be refractory to the hepatic effects of most NSAIDs, their hepato-toxic potential should be considered, especially when they are concomitantly administered with other potentially hepatotoxic agents, such as fluoroquinolones, potentiated sulfonamides or anabolic steroids. In addition, many herbal preparations are potential hepatotoxic agents and clients may administer these compounds concurrently with prescribed NSAIDs without consulting their veterinarian. Echinacea and kava kava products, for example, are reported to be potential hepatotoxins and both are used in herbal remedy products that claim to produce calming or sedating effects in horses (Abebe 2002). 

Flowever, ampelopsin C and the mixture of (-i-)-vitisin A (698) and (+)-cw-vitisin A (702) were found to be powerful hepatotoxins. The coexistence of hepatoprotective and hepatotoxic agents in the same plant is very interesting, and the plant has been used to cure hepatic diseases such as hepatitis and liver cirrhosis [519]. 

Nitrosamines are strong hepatotoxic agents. Large, acute doses produce liver necrosis and hemorrhages in the liver and other tissues. 

Skaare JU, Nafstad I. 1978. Interaction of vitamin E and selenium with the hepatotoxic agent dimethylnitrosamine. Acta Pharmacol Toxicol 43 119-128. 

Liver injury that results in fulminant hepatic necrosis and acute hver failure is relatively rare. Wheu it occurs, death results iu days or weeks in nearly 80% of cases. Any potential hepatotoxic agent (e.g., acetaminophen) can be responsible, although viral hepatitis is the most common cause worldwide, especially HB V (1 % of patieuts with acute hepatitis B develop fuhniuaut hepatitis). " Fulmiuaut hepatitis caused by HAV occasiouaUy occurs acute liver failme caused by HCV is rare. ... 

The effects of smoking on serum alkaline phosphatase do not appear to have been investigated in humans. The effects of ethanol and various other hepatotoxic agents are discussed in Section 7.5.1. An extensive list... 

Hepatotoxic Agents Other than Ethyl Alcohol... 

Effect on Sebum Alkaune Phosphatase of Various Hepatotoxic Agents... 

Sidransky, H., Murty, C. N., and Vemey, E., Effect of tryptophan on the inhibitory action of selected hepatotoxic agents on hepatic protein synthesis, Exp. Mol. Pathol, 37[3], 305, 1982. 

Sidransky et al.197 reported that mice or rats fasted overnight and treated intraperitoneally for 2 to 3 h with ethionine, a hepatotoxic agent that inhib-... 

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