Glucuronyl Transferase Deficiency Medication
- Author: Dena Nazer, MD; Chief Editor: Carmen Cuffari, MD more...
Medication Summary
Phenobarbital, ursodeoxycholic acid, calcium (infusions), metalloporphyrins, cholestyramine, chlorpromazine, clofibrate (no longer on US market), and alkalinization of urine have all been considered as potential therapies for patients with Crigler-Najjar (CN) syndrome type 1. 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.
Barbiturates
Class Summary
These drugs are used to induce hepatic-enzyme metabolism to decrease serum bilirubin levels.
Phenobarbital (Solfoton)
Functions by means of phenobarbital-responsive enhancer module that stimulates gene for UGT 1A1 to induce production of bilirubin-conjugating enzyme; does not directly act on UGT enzyme as previously thought. Used to treat CN syndrome type 2 and as adjunct to phototherapy in some cases of CN syndrome type 1. Considered effective when bilirubinemia decreases by two thirds after 2-3 wk of therapy.
Metalloporphyrins
Class Summary
These agents are used as a synthetic analog of heme to inhibit the heme oxygenase enzyme, the rate-limiting step in heme catabolism to bilirubin.
Tin mesoporphyrin (SnMp)
DOC for clinical use because of its increased potency, stability, and photophysical properties. In animal studies, more stable and potent than tin protoporphyrin, another heme oxygenase inhibitor (enzyme involved in converting heme to bile pigments).
Calcium supplements
Class Summary
These agents bind bilirubin in the gut and, thus, enhance its fecal excretion.
Calcium phosphate (Posture)
May reduce plasma bilirubin concentration in CN syndrome type 1 and may be a useful adjunct to phototherapy in reducing serum bilirubin level.
Naturally occurring bile acids
Class Summary
Ursodiol partially replaces the circulating pool of endogenous bile acids with ursodeoxycholic acid, which is highly hydrophilic, and, thus, 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.
Ursodeoxycholic acid (Actigall, Urso)
Also called ursodiol. Decreases liver enzymes (by decreasing liver-cell toxicity) and, therefore, recommended in chronic liver disease. Routine administration in CN syndrome not universally adopted.
Phenothiazines
Class Summary
These drugs are used in the therapy of acute intermittent porphyria, psychotic disorders, nausea, and vomiting.
Chlorpromazine (Thorazine)
Usually used to treat acute intermittent porphyria, psychotic disorders, nausea, and vomiting. Recommended as adjunct to phototherapy to treat CN syndrome type 1.
Antihyperlipidemic agents
Class Summary
Clofibrate has been used for its effect in reducing bilirubin in newborns.
Clofibrate (Atromid-S)
No longer on US market. Used as adjunct to phototherapy. Antihyperlipidemic agent that decreases serum lipids by reducing levels of very low–density lipoprotein, LDL, and triglycerides.
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