TITLE

Antidepressant induced cholestasis: hepatocellular redistribution of multidrug resistant protein (MRP2)

AUTHOR(S)
Milkiewicz, P.; Chilton, A.P.; Hubscher, S.G.; Elias, E.
PUB. DATE
February 2003
SOURCE
Gut;Feb2003, Vol. 52 Issue 2, p300
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Background: We report two cases of antidepressant induced cholestasis. Case reports: We describe the first reported case of acute cholestasis due to citalopram (selective serotonin reuptake inhibitor) occurring in a patient who also experienced obstetric cholestasis in association with each of three pregnancies; in a second patient cholestasis developed due to dothiepin (tricyclic antidepressant), and six years later due to paroxetine. In both cases liver biopsies showed features of a "pure" cholestasis with total resolution within 1-6 months after withdrawal of the causative drug. Immunostaining for the canalicular transporter, multidrug resistant protein 2 (MRP2), responsible for biliary secretion of several organic anions including bilirubin glucuronides, showed sustained expression in both biopsies as well as relocalisation with appearance of strong staining of the basolateral membrane of the hepatocyte. This finding has also not been reported previously. Conclusions: We postulate that intracellular redistribution of MRP2 may reflect an adaptive compensatory mechanism which helps in the elimination of the drug or its cholestatic metabolites from the hepatocyte back to the sinusoidal space and subsequent excretion in urine. Changes seen in these two patients differ from findings previously reported in rats where downregulation of mrp2 occurs in response to experimentally induced cholestasis. We speculate that the rat is more advanced than humans in its ability to downregulate canalicular transporter expression as protection against progressive intrahepatic cholestasis.
ACCESSION #
9704725

 

Related Articles

  • HEPATOCELLULAR REDISTRIBUTION OF MULTIDRUG RESISTANT PROTEIN (MRP2): A COMPENSATORY MECHANISM IN ANTIDEPRESSANT INDUCED CHOLESTASIS. Milkiewicz, P.; Chilton, A.; Hubscher, S.G.; Elias, E. // Gut;Apr2003 Supplement 1, Vol. 52, pA105 

    Background: Antidepressive drugs such as tricyclic antidepressants and monoamine-oxidase inhibitors may occasionally induce prolonged or even fatal jaundice. The mechanisms by which the liver responds to antidepressive drug induced cholestasis are unknown. Patients: We report two cases of...

  • Cholestasis in patients with acquired immunodeficiency... Liu, Katherine J.M.; Atten, Mary Jo // American Surgeon;Jun1997, Vol. 63 Issue 6, p519 

    Reviews cholestasis in patients with acquired immunodeficiency syndrome (AIDS). Underlying causes of cholestasis; Predominant findings in patients with AIDS and hepatocellular diseases; Acalculous cholecystitis described; Two disease entities of abnormalities of intraheptic/extraheptic duct.

  • Everolimus.  // Reactions Weekly;6/19/2010, Issue 1306, p23 

    The article describes the cases of two patients who developed cholestasis after receiving everolimus.

  • Corrigendum.  // Journal of Clinical Investigation;Jul2004, Vol. 114 Issue 1, p142 

    Presents a correction to the article "Cathepsin B Inactivation Attenuates Hepatic Injury and Fibrosis During Cholestasis" that was previously published in the vol. 112, 2003 issue of the "Journal of Clinical Investigation."

  • Determining when to change to a different antidepressant. Huffman, Grace Brooke // American Family Physician;2/15/1997, Vol. 55 Issue 3, p947 

    Focuses on a study by F.M. Quitkin, et al, published in the `Archives of General Psychiatry,' which tries to determine when patients should be considered unresponsive to antidepressant therapy and should have their treatment changed. `Chronological milestones to guide drug change. When should...

  • New antidepressant drugs called major treatment advances.  // Executive Health's Good Health Report;Oct93, Vol. 30 Issue 1, p3 

    Reports on the acknowledgement of antidepressant drugs Zoloft and Paxil as improvements over previously available antidepressants. Selective serotonin reuptake inhibitors; Effectiveness in treating obsessive compulsive disorders, hypochondriasis and anorexia nervosa; Testing on impulsive behavior.

  • Focus on mirtazapine: A new antidepressant with noradrenergic and specific serotonergic activity. Kehoe, William A.; Schorr, Robert B. // Formulary;Jun96, Vol. 31 Issue 6, p455 

    Focuses on the antidepressant mirtazapine. Chemistry and pharmacology; Serotonic receptors and possible therapeutic applications; Pharmacokinetics; Clinical trials; Adverse effects; Drug interactions; Formulary considerations; Dose and administration. INSET: Formulary considerations..

  • The power of Prozac. Rust, Michael // Insight on the News;09/14/98, Vol. 14 Issue 34, p16 

    Presents information on the antidepressant Prozac. Annual cost of antidepressants in the United States as a result of early death, lost workdays and lowered productivity; Details on Prozac; Investigations being conducted by the Food and Drug Administration on the effort of antidepressants and...

  • Half of antidepressants' benefit attributed to placebo effect.  // Executive Health's Good Health Report;Nov96, Vol. 33 Issue 2, p8 

    Reports that 50 percent of an antidepressant medication's effect can be attributed to the placebo response according to a study made by Doctor Guy Sapirstein from the University of Connecticut. Result of 25 ears' analysis of 3,250 patients with depression.

Share

Read the Article

Courtesy of VIRGINIA BEACH PUBLIC LIBRARY AND SYSTEM

Sign out of this library

Other Topics