Phenothiazines jaundice

Cholestatic hepatocanalicular jaundice can occur in up to 2% of patients receiving phenothiazines. 

Phenothiazines Use phenothiazines with caution in patients with cardiovascular disease, liver dysfunction, or ulcer disease. Promethazine has been associated with cholestatic jaundice. 

Gl dysmotility Esophageal dysmotility and aspiration have been associated with antipsychotic drug use. Use quetiapine, ziprasidone, risperidone, olanzapine, aripiprazole, and others cautiously in patients at risk for aspiration pneumonia. Hypersensitivity reactions Patients who have demonstrated a hypersensitivity reaction (eg, blood dyscrasias, jaundice) with a phenothiazine should not be re-exposed to any phenothiazine unless the potential benefits of treatment outweigh the possible hazards. 

Reports of extrapyramidai symptoms, jaundice, hyperrefiexia, hyporefiexia in infants whose mothers took a phenothiazine during pregnancy... 

Cholestatic hepatocanalicular jaundice has been reported in up to 2% of patients receiving phenothiazines. Additionally, liver function test (LFT) abnormalities (elevated aminotransferases and alkaline phosphatase), often asymptomatic, were reported in up to 50% of patients. If aminotransferases are greater than three times the upper limit of normal, antipsychotic therapy should be changed to a chemically unrelated antipsychotic. 

Regal RE, Bilh JE, Glazer HM. Phenothiazine-induced cholestatic jaundice. Chn Pharm 1987 6 787-794. 

Toxic Effects. All the phenothiazines are capable in varying degrees of toxic effects. Obstructive jaundice is more common in the older members of the series but most have produced this complication. Blood dyscrasias are not uncommon (17). Skin rashes, photosensitivity, pruritus, and other varieties of dermatitis have been observed. A host of other effects have been observed which probably are more inherent in the drug s action than a true toxicity. These include dry mouth, tachycardia, sedation, lethargy, hypothermia, lactation, hypotension, convulsions, and extrapyramidal reactions. 

Imipramine, a substance with a structure similar to the phenothiazines (Figure 5) but varying in that the ring is a dibenzazepine rather than a phenothiazine, was the first active antidepressant of the nonmomoamine oxidase inhibitor series of agents. It, like the monoamine oxidase inhibitors, is effective in less than half the patients treated. Its mode of action is not clearly understood, but there is increasing evidence that it too exerts an effect on catechol amine metabolism (19). Although serious toxic effects have been uncommon, excitement, jaundice, and blood dyscrasias have occurred (17). 

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. 

Phenothiazine derivatives have been observed to cause jaundice in 5% of the patients. The jaundice is accompanied by intense pruritus, fever, chills, nausea, epigastric or right upper quadrant abdominal pain, and malaise. The jaundice is not dose dependent, and develops after a typical delay of 2 to 3 weeks. With discontinuation of medication, the prognosis has been excellent. 

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 study, undertaken to confirm the involvement of the cytochrome P450 isoenzyme CYT2D6 in the metabolism of trazodone, found that when 11 depressed patients were given trazodone 150 to 300 mg at bedtime for 18 weeks, and then with thioridazine 20 mg twice daily for one week, the plasma levels of the trazodone and its active metabolite, /w-chlorophenyl-piperazine, rose by 36% and 54%, respectively. No adverse reactions were described. In contrast, a case of fatal hepatic necrosis with cholestasis has been attributed to the concurrent use of trazodone and phenothiazines. A 72-year-old woman taking trifluoperazine, trazodone and lithium carbonate developed an elevated alanine aminotransferase level. Trifluoperazine was replaced with thioridazine, but 9 weeks later she became jaundiced and developed hepatic encephalopathy, and died 6 weeks after the onset of jaundice. The authors consider that the combination of the phenothiazines and trazodone were the cause of her hepatic necrosis both phenothiazines and trazodone have been reported to individually cause hepatic adverse effects. ... 

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). 

Although hepatic complications of thioridazine treatment are rare, cases occasionally occur. The case is reported of a 58-year-old patient who became jaundiced and showed abnormal liver function tests after taking thioridazine for 15 months. The jaundice cleared and the liver function tests returned to normal when treatment was stopped. Seventeen years previously the patient had become jaundiced when taking chlorproma-zine. The authors warn of the dangers of giving phenothiazines to patients who have previously shown adverse reactions to them (50 ). 

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