Induced Jaundice

Jaundice induced by certain medications is usually associated with alterations in serum bile salt concentrations. Increased serum bile salt concentrations have been observed with chlorpromazine, 5-fluorouracil, nilevar, Carbarsone, tolbutamide, and Dilantin (1,53). With all of these drugs, cholate predominated in the serum, and thus the cholate/chenodeoxycholate ratio was greater than 1. This is consistent with the elevation in alkaline phosphatase and cholestasis that occurred in all of these patients. The estrogenic component of Enovid, mestranol, has also been shown to produce similar changes in cholate/chenodeoxycholate concentration ratio and cholestasis (1,54). In jaundice associated with isoniazid ingestion, chenodeoxycholate predominates and the concentration is Jess than 1, which is compatible with the more severe type of hepatocellular injury induced by this group of compounds (1). 

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Hepatotoxicity Prolonged use of high doses of androgens has been associated with the development of potentially life-threatening peliosis hepatis, hepatic neoplasms, and hepatocellular carcinoma. Cholestatic hepatitis and jaundice occur with fluoxymesterone and methyltestosterone at relatively low doses. Drug-induced jaundice is reversible when the medication is discontinued. 

In a study of our own, we were able to demonstrate thiamazole-induced jaundice (maximum serum bilirubin 8.2 mgidl with constantly normal values of AP, LAP and transaminases) over a period of more than five months, (s.fig. 29.4)... 

Prolonged duration of treatment and increasing age were risk factors for flucloxacillin-induced jaundice (181), and cholestatic liver injury has been described most often with flucloxacUhn (182,183) and other isoxazolylpenicillins (184). Whether cholestatic hepatitis after the combination of amoxicUhn with clavulanic acid (co-amoxiclav) is related to one of these categories is not yet clear. 

Wong FS, Ryan J, Dabkowski P, Dudley FJ, Sewell RB, Smallwood RA. Augmentin-induced jaundice. Med J Aust 1991 154(10) 698-701. 

Hebbard GS, Smith KG, Gibson PR, Bhathal PS. Augmentin-induced jaundice with a fatal outcome. Med J Aust 1992 156(4) 285-6. 

Mager A, Birnbaum Y, Zlotikamien B, Strasberg B, Rechavia E, Sagie A, Sclarovsky S. Streptokinase-induced jaundice in patients with acute myocardial infarction. Am Heart J 1991 121(5) 1543-4. 

Phillips E, Woohrey S, Cameron E. Streptokinase-induced jaundice. Postgrad Med J 1994 70(819) 55. 

A mild jaundice, typically occurring early in therapy, may be seen in some patients receiving chlorpromazine. Pruritus is rare. The reaction probably is a manifestation of hypersensitivity, because eosinophilia and eosinophilic infiltration of the liver occur. For uninterrupted drug therapy in a patient with neuroleptic-induced jaundice, it probably is safest to use low doses of a potent, dissimilar agent. Hepatic dysfunction with other antipsychotic agents is uncommon. Clozapine can cause potentially severe ileus and sialorrhea. 

Nayar M, Cunliffe W, Cross P, Oppong K. Mesalazine-induced jaundice, eosino-philia, and thrombocytopenia. Inflamm Bowel Dis 2008 14 1320-1. 

In a recent clinical study [200] of intravenous fusidic acid, 34 % of the patients (38 patients) developed jaundice. The mechanism of the induction of jaundice in these patients is unknown, but the structural resemblance of fusidic acid to the steroids, which can also induce jaundice, and its surface activity and resemblance to the bile salts may well be important factors. 

Den Boer, W. and Loeliger, E. A. (1976) Phen-procoumon-induced jaundice. Lancet, /, 912. 

Human incidents have been reported in workers involved in the production or uses of PCNs. In the United States as well as in Germany and Austraha, the severity of the PCN-induced toxicosis was higher after exposure to the higher chlorinated PCN mixtures. In humans the inhalation of hot vapors was the most important route of exposure and resulted in symptoms including rashes or chloracne, jaundice, weight loss, yellow atrophy of the hver, and in extreme cases, death (75,77—79). 

Chronic hepatitis (disease lasting longer than 6 months) is usually associated with hepatitis B, C, and D. Chronic viral hepatitis may lead to the development of cirrhosis, which may induce end-stage liver disease (ESLD). Complications of ESLD include ascites, edema, jaundice, hepatic encephalopathy, infections, and bleeding esophageal varices. Therefore, prevention and treatment of viral hepatitis may prevent ESLD. 

Physiologic jaundice in the newborn, especially premature infimts (enzymes may not be fuUy induced)... 

Ora/. Anticoagulant-induced prothrombin deficiency (see Warnings) hypoprothrombinemia secondary to salicylates or antibacterial therapy hypoprothrombinemia secondary to obstructive jaundice and biliary fistulas, but only if bile salts are administered concomitantly with phytonadione. 

Parenteral Anticoagulant-induced prothrombin deficiency hypoprothrombinemia secondary to conditions limiting absorption or synthesis of vitamin K (eg, obstructive jaundice, biliary fistula, sprue, ulcerative colitis, celiac disease, intestinal resection, cystic fibrosis of the pancreas, regional enteritis) drug-induced hypoprothrombinemias due to interference with vitamin K metabolism (eg, antibiotics, salicylates) prophylaxis and therapy of hemorrhagic disease of the newborn. 

Monitor carefully in first 3 mo of therapy for signs of intolerance/drug-induced hepatitis (rash, fever, jaundice, hepatomegaly)... 

Experimentally induced obstructive jaundice in animals (by ligation of bile ducts) decreases rate of metabolism of certain drugs like hexobarbitone, chlorpromazine, codeine etc. 

Skin reactions occur early in therapy but can subside with continued treatment. Jaundice, which can also occur early, is of the cholestatic type, similar to that attributed to chlorpromazine. Agranulocytosis is a rare complication, as are cases of leukocytosis, leukopenia, and eosinophilia. There are no data on the incidence of antidepressant-induced agranulocytosis, except to note that it is rare with all of the agents discussed in this chapter. 

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