Chlorpromazine jaundice

R7. Read, A. E., Harrison, C. V., and Sherlock, S., Chronic chlorpromazine jaundice with particular reference to its relationship with primary biliary cirrhosis. Am. ]. Med. 31, 249-258 (1961). 

Shay, H., and Siplet, H., Study of chlorpromazine jaundice, its mechanism and prevention. Special reference to serum alkaline phosphatase and glutamic oxalacetic transaminase. Gastroenterology 32, 571-591 (1957). 

Zelman S (1959) Liver cell necrosis in chlorpromazine jaundice (allergic cholangiolitis) A serialstudy of twenty six beedle biopsy specimens in nine patients. Am J Med 27 708... 

Cholestatic jaundice can occur during treatment with antipsychotics, and is most often reported in chlorpromazine-treated patients (Hansen et ah, 1997). Elevations in liver transaminases have also been observed in a few cases of children treated with risperi-... 

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. 

Reduced bile output can result in an accumulation of bilirubin, a dark-colored pigment produced by the breakdown of blood heme. When this product is not discharged at a sufficient rate with bile, it accumulates in skin and eyes, giving the characteristic sickly color of jaundice. Impaired production and excretion of bile is known as canalicular choleostasis. It can be caused by a number of xenobiotic substances, such as chlorpromazine. Reduced bile output can also result from damage to bile ducts. Methylene dianiline used in epoxy resins is known to harm bile ducts. 

In addition, biliary obstructive jaundice can also be caused by drug-induced toxicity, e.g. with Ciy-substi-tuted steroids, erythromycin estolate, chlorpromazine, chlorpropamide, ajmaline, halothane, methylthiouracil. 

Chlorpromazine Cholestatic Elevations occur in approximately 20% of patients (S32). These may be marked and prolonged in some instances (R7), although, even in the presence of jaundice, fewer than half of the patients have activities greater than 4 times the upper reference limit (Z3). 

Tricyclic antidepressants resemble the phenothiazine antipsychotics such as chlorpromazine in structure and function. Like the phenothiazine derivatives (e.g., chlorpromazine), tricyclic antidepressants (e.g., amitriptyline) may reduce the seizure threshold and precipitate seizures in epileptic patients, cause cholestatic jaundice, movement disorders, and hematologic side effects. Unlike the phenothiazine derivatives, the tricyclic antidepressants may increase motor activity, have a very slow onset and long duration of action, a relatively narrow margin of safety, and a strong anticholinergic effect. In fact, dry mouth is the most common side effect, and other anticholinergic effects such as tachycardia, loss of accommodation, constipation, urinary retention, and paralytic ileus have been reported following amitriptyline. 

They resemble the phenothiazide derivatives such as chlorpromazine in structure and function. Like the phe-nothiazine derivatives (e.g., chlorpromazine), tricyclic antidepressants (e.g., imipramine) may reduce the seizure threshold and precipitate seizures in epileptic patients, and may cause cholestatic jaundice, movement disorders, and hematologic side effects. 

Occasional Confusion amnesia disinhibition paradoxical excitement depression dizziness witiidrawal symptoms, including convulsions, on abrupt discontinuance (witiidrawal may be especially difficult with alprazolam) rebound insomnia or excitement Rare Hypotension blood dyscrasias jaundice allergic reactions paradoxical rage reactions stuttering with alprazolam BUPROPION, Anxiety agitation insomnia tremor anorexia BUSPIRONE, Dizziness headache nausea paresthesias diarrhea CHLORDIAZEPOXIDE, see Benzodiazepines CHLORPROMAZINE, see Phenothiazines, aliphatic CHLORPROTHIXENE, similar to Phenothiazines CLOMIPRAMINE, see Tricyclic antidepressants CLORAZEPATE, see Benzodiazepines CLOZAPINE... 

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. 

Cooperberg AA, Eidlow S. Haemol3dic anemia, jaundice and diabetes mellitus following chlorpromazine therapy. CanMedAssocJ ( 95 75, 746-9. 

Undesirable hypotension occurred in two patients taking chlorpromazine or trifluoperazine with trazodone. Thioridazine causes a moderate rise in trazodone plasma levels. A fatal case of jaundice and hepatic encephalopathy has been reported with the use of trifluoperazine, thioridazine and trazodone. 

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). 

The phenothiazines, of which chlorpromazine is the prototype, have been reported to produce a variety of clinical reactions apparently on an allergic basis including rash, eosinophilia, cholestatic jaundice, agranulocytosis, vasculitis, systemic lupus erythematosus (SLE), and hemolytic anemia (Parker 1980 a van Arsdel 1978). 

Because there is no evidence of damage to the bile ducts, it was at first assumed that intrahepatic jaundice was caused by kinking of the connection between hepatic cells and the bile ducts, the cholangioles. Inflammation and fibrosis were believed to cause the kinking. This pathogenic interpretation became untenable when jaundice and cholestasis were observed with drugs such as steroids or chlorpromazine without inflammation. 

Chlorpromazine is a tranquilizer that causes clinical jaundice in 1 % of human users. It decreases sodium-potassium-ATPase and calcium-magnesium-ATPase activity, reducing actin polymerization and membrane fluidity. 

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