The structural basis of altered hepatic function in viral hepatitis

Schaffner, Fenton

doi:10.1016/s0002-9343(70)80132-2

Cited by 30 publications

(9 citation statements)

References 30 publications

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“…As already described, this may be another manifestation of the hyperglycemic effect of VSE. The disturbed function of the disrupted endoplasmic reticulum seen by us in surviving cells suggests an anatomic basis for the impairment of several functions, such as protein synthesis and detoxification (Schaffner 1970). In our experiment a decrease of total protein in serum has been observed in cats (Neuman et al 1983a).…”

Section: Morphologic Changessupporting

confidence: 60%

Hepatotoxicity Induced by the Oriental Hornet (Vespa orientalis) Venom Sac Extract

Neuman

Ishay

Waron

et al. 1991

Pharmacology & Toxicology

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Experiments were performed to investigate the nature of the in vitro and human liver damage exposed to hornets' acute or repeated stings. The hornet investigated is the one ubiquitous in Israel - Vespa orientalis. Experiments were performed in living cats and rats, after single or multiple exposures to venom-sac extracts (VSE) and in various doses. The injury was demonstrated by the increased levels of enzymes, bile acids and cholesterol in serum. Also measured was Beta-N-acetyl hexosaminidase (BNAH) which probably is the only biochemical indicator available of Kupffer-cell function. This, too, was found increased. Other experiments consisted of perfusion of the isolated, intact, rat liver in situ with measurements of enzyme leakage into perfusate and of bile flow. Another set of experiments involved the effects of VSE on in vitro monolayer tissue culture of rat embryos' livers. We examined damage to organelles and compared the damage produced by intact VSE with that produced by the venom sac extract after treatment by heat or dialysis. Light morphology, special stains, electron microscopy and morphometry were all performed. In the first set of experiments no shock was observed in cats and rats exposed to VSE. The increases in enzymes' activity in serum and liver perfusion fluid were significant. Histochemistry indicated decrease of hepatic glycogen and of cellular succinic dehydrogenase as well as hepatic fat infiltration and an increase of alkaline phosphatase activity in liver cells close to the bile capillaries.(ABSTRACT TRUNCATED AT 250 WORDS)

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Section: Morphologic Changessupporting

confidence: 60%

Hepatotoxicity Induced by the Oriental Hornet (Vespa orientalis) Venom Sac Extract

Neuman

Ishay

Waron

et al. 1991

Pharmacology & Toxicology

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“…During hepatitis, the rough endoplasmic reticulum (the site of protein synthesis of the hepatocyte) dilates with swelling of veicles and ribosomal detachment, while the smooth endoplasmic reticulum, a site of drug transformation in the hepatocyte, often appears normal. 25,26 These contrasting effects of hepatitis on the morphology of parenchymal cells provide histologic evidence for the disassociation between drug disposition from the pharmacologic effect that we observed.…”

Section: Discussionmentioning

confidence: 56%

Influence of acute viral hepatitis on disposition and pharmacologic effect of warfarin

Williams

Schary

Blaschke

et al. 1976

Clin Pharma and Therapeutics

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Five patients received a small oral dose of warfarin during and after recovery from acute viral hepatitis. Mean (+/- SD) clearance, volume of distribution, and half-life of the drug were 6.1 +/- 0.9 ml/hr/kg, 0.09 +/- 0.04 L/kg, and 23 +/- 5 hr, respectively, during the acute period. After apparent recovery, observed values were 6.1 +/- 0.7 ml/hr/kg, 0.21 +/- 0.02 L/kg, and 25 +/- 3 hr. These differences were not significant. Pattern of renal elimination of warfarin metabolites and drug protein binding did not change between the two phases. During the acute period of illness, prothrombin time increased in 2 of the 5 subjects, but remained within normal limits in all participants during the recovery period. This study shows that warfarin disposition may not change as a consequence of mild or moderate hepatic impairment.

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“…Warfarin clearance and protein binding are unaltered in patients with acute viral hepatitis during or after the acute episode (Williams et al 1976), but increased sensitivity to anticoagulant therapy, probably secondary to impaired protein synthesis, occurs in viral hepatitis as indicated by histological abnormalities of rough endoplasmic reticulum in the hepatocytes (Schaffner 1970).…”

Section: Plasma Warfarinmentioning

confidence: 99%

Clinical Pharmacokinetic Considerations in the Control of Oral Anticoagulant Therapy

Shetty

Fennerty

Routledge

1989

Clinical Pharmacokinetics

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Aspects of the pharmacokinetics of warfarin that are clinically relevant are reviewed here. Since warfarin is normally completely absorbed, resistance to treatment due to impaired absorption is unusual, even in severe short bowel syndrome. Warfarin is highly albumin-bound; thus, hypoalbuminaemic states result in an increased free fraction of the drug and a decreased half-life but, as might be expected, there is no evidence of altered response at steady-state. Warfarin is completely metabolised by the liver to hydroxy-warfarins and warfarin alcohols, and although the latter have some biological activity they do not contribute significantly to the drug effect. No information is available concerning the metabolism of warfarin in chronic liver disease, but there is evidence of increased sensitivity due to impaired vitamin K-dependent clotting factor synthesis. Impaired renal function does not appear to alter the effect of warfarin. Lowered response to the drug may be secondary to poor compliance, kinetic resistance or pharmacodynamic resistance. These factors can be identified using algorithms based on population values for plasma warfarin concentrations and clearances at steady-state. The pharmacokinetics and pharmacodynamics of warfarin indicate that several days' overlap with heparin on initiation of warfarin, and gradual (rather than sudden) discontinuation of warfarin, might theoretically be necessary. However, those studies which have been performed have indicated that a long overlap and gradual discontinuation are not associated with greater safety or efficacy of the drug. Because of the long elimination half-life of warfarin and the short elimination half-life of vitamin K, many days' treatment with phytomenadione may be required after warfarin overdose. The elimination half-life and therefore the duration of therapy may be reduced by regular oral cholestyramine, although the means by which the latter enhances warfarin elimination is still unknown.

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The structural basis of altered hepatic function in viral hepatitis

Cited by 30 publications

References 30 publications

Hepatotoxicity Induced by the Oriental Hornet (Vespa orientalis) Venom Sac Extract

Hepatotoxicity Induced by the Oriental Hornet (Vespa orientalis) Venom Sac Extract

Influence of acute viral hepatitis on disposition and pharmacologic effect of warfarin

Clinical Pharmacokinetic Considerations in the Control of Oral Anticoagulant Therapy

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