In Crigler-Najjar syndrome type 2, patients with symptomatic jaundice are occasionally treated to improve their quality of life.
In patients with Crigler-Najjar syndrome type 1, phenobarbital, ursodeoxycholic acid, calcium (infusions), metalloporphyrins, cholestyramine, chlorpromazine, and clofibrate (no longer on the US market), as well as alkalinization of urine, have all been considered as potential therapies. Problems associated with the use of cholestyramine include taste and concern about bile salt depletion and fat malabsorption. The exact roles and adverse effects of many of these drugs are not yet defined.
Metalloporphyrins have been used as a synthetic analogue of heme to inhibit the heme oxygenase enzyme, the rate-limiting step in heme catabolism to bilirubin. Tin mesoporphyrin (SnMp) is the drug of choice (DOC) for clinical use because of its increased potency, stability, and photophysical properties.
For Gilbert syndrome, no medical therapy is needed. As with Crigler-Najjar syndrome type 2, phenobarbital has been shown to decrease bilirubin production.
These drugs induce hepatic-enzyme metabolism, decreasing serum bilirubin levels. They are used to avoid potentially devastating neurologic sequelae in Crigler-Najjar syndrome type 1 and for the management of neurologic symptoms in Crigler-Najjar syndrome type 2.
Phenobarbital increases the conjugation and excretion of bilirubin. It reduces serum bilirubin levels by at least 25%.
The drug functions by means of phenobarbital-responsive enhancer module that stimulates the gene for UGT 1A1 to induce production of bilirubin-conjugating enzyme. It does not, however, directly act on the UGT enzyme, as previously thought.
Phenobarbital is used to treat Crigler-Najjar syndrome type 2 and as an adjunct to phototherapy in some cases of Crigler-Najjar syndrome type 1. In addition, it has been shown to be effective in the treatment and prevention of neonatal hyperbilirubinemia.
Agents in this class reduce serum bilirubin levels. They have been used for their effects in lowering bilirubin levels in newborns.
Fenofibrate lowers serum triglycerides and very low-density lipoprotein (VLDL) levels. However, in addition to its hypolipidemic action, it also has the ability to induce bilirubin conjugation.
These agents bind bilirubin in the gut, enhancing bilirubin’s fecal excretion.
Calcium phosphate (Posture)
Calcium phosphate may reduce plasma bilirubin concentration in Crigler-Najjar syndrome type 1 and may be a useful adjunct to phototherapy in reducing serum bilirubin levels.
Ursodeoxycholic acid (or ursodiol) partially replaces the circulating pool of endogenous bile acids. Because it is highly hydrophilic, it replaces toxic detergent bile acids (eg, chenodeoxycholic acid, lithocholic acid). This effect may enhance the biliary excretion of the toxic bile acids and may protect cells against liver-cell toxicity induced by detergent bile acids.
This agent decreases liver enzymes (by decreasing liver-cell toxicity) and is therefore recommended in chronic liver disease. Routine administration in Crigler-Najjar syndrome has not been universally adopted.
These drugs are used in therapy for acute intermittent porphyria, psychotic disorders, nausea, and vomiting.
This agent is usually employed to treat acute intermittent porphyria, psychotic disorders, nausea, and vomiting. It is recommended as an adjunct to phototherapy in the treatment of Crigler-Najjar syndrome type 1.
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