Hyperbilirubinaemia

A7. Arias, I. M., and Gartner, L. M., Production of unoonjugated hyperbilirubinaemia in full-term new-born infants ollowing administration of pregnane-3a,20 8-diol. Nature (London) 203, 1292-1293 (1964). 

B14. Billing, B. H., Williams, R., and Richards, T. G., Defects in hepatic transport of bilirubin in congenital hyperbilirubinaemia an analysis of plasma bilirubin disappearance curves. Clin. Sci. 27, 245-257 (1964). 

F4. Fevery, J., Claes, J., Heirwegh, K., and De Groote, J., Hyperbilirubinaemia significance of the ratio between direct-reacting and total bilirubin. Clin. Chim. Ada 17, 73-79 (1967). 

Cl) = 0.30 - 0.92] was offset by an increased risk of death in remission (OR = 2.22, 95% Cl = 1.20 - 4.14), mainly due to infections. Strikingly, 11% of patients in the 6-TG arm compared to less than 2% in the 6-MP arm developed non-fatal hepatic toxicity with features of veno-occlusive disease (VOD) characterized by symptoms including tender hepatomegaly, hyperbilirubinaemia with elevated aminotransferases, thrombocytopenia out of proportion to neutropenia, and portal hypertension. In 85% of affected 6-TG recipients, these symptoms were observed during maintenance or interim maintenance. Of interest, in patients randomized to 6-MP, hepatic toxicity was associated with intensification elements in which both treatment arms received exclusively 6-TG. 

The introduction of cyclosporin, a peptide derived from a fungus, revolutionised immunosuppressive therapy, and was one of the major influences in the improvement of early graft survival in transplant surgery when introduced in the 1980s. The main action is a relatively selective inhibition of IL-2 production and consequently a decreased proliferation of T cells. A major advantage of cyclosporin is that it does not cause myelosuppression in therapeutic doses. The major side effect is nephrotoxicity, which occurs in about 20% of patients, and about 50% of patients develop moderate hypertension. The other major side effect is hepatotoxicity with cholestasis and hyperbilirubinaemia. 

Posner J, Cohen AF, Land G, et al. The pharmacokinetics of lamotrigine (BW430C) in healthy subjects with unconjugated hyperbilirubinaemia (Gilbert s syndrome). Br J Clin Pharmacol 1989 28(1) 117-120. 

Rifampicin can cause renal failure, transient disturbances of liver function tests, hyperbilirubinaemia or severe hepatotoxicity and other side-effects. Streptomycin can cause renal and ototoxicity. The combination of rifampicin and streptomycin increases the risk of streptomycin-induced renal failure. 

Jaundice is the clinical manifestation of hyperbilirubinaemia. Jaundice may be noticeable in the sclera (white) of the eyes at levels of bilirubin of about 30-50 pmol/l, and in the skin at higher levels. Jaundice is classified, depending upon whether the bilirubin is free or conjugated to glucuronic acid, into ... 

Neonatal hyperbilirubinaemia, where the newborn s liver is not able to properly conjugate the bilirubin... 

Gilbert s syndrome results from decreased levels of UDP-glucuronyl transferase. The defect is in the promoter region, the TATAA element, rather than the gene itself. Gilbert s syndrome results in a mild hyperbilirubinaemia, without any clinical sequelae. 

Bilirubin. Jaundice is the clinical manifestation of hyperbilirubinaemia. A raised level of uncongugated bilirubin occurs when there is excessive breakdown of red blood cells, for example in haemolytic anaemia, or where the ability of the liver to conjugate bilirubin is compromised, for example in cirrhosis. A raised blood level of congugated bilirubin occurs in various liver and bile duct conditions. It is particularly high if the flow of bile is blocked, for example by a gallstone in the common bile duct or by a tumour in the pancreas. It can also be raised with hepatitis, liver injury or long-term alcohol abuse. 

May be useful in determining reason for hyperbilirubinaemia - not a routine test. 

The synthetic and metabolic capacity of this patient s liver is unlikely to be affected by cholestasis. However, consideration needs to be given to protein binding (patient has hyperbilirubinaemia) excretion of the drug or metabolites in bile (patient has cholestasis) and lipophilicity of the drug (some lipophilic drugs require bile salts for absorption and these would be reduced in cholestasis). 

They are highly protein bound, and hyperbilirubinaemia may result in increased blood levels of free drug and metabolites through displacement from protein-binding sites. 

ATAZANAVIR INDINAVIR t efficacy and t adverse effects of indinavir t adverse effects of atazanavir, e.g. hyperbilirubinaemia t bioavailability. Inhibition of metabolism via CYP3A4 by atazanavir inhibition of UDGPT by indinavir Avoid co-administration... 

Rubaltelli FF, Griffith PE. Management of neonatal hyperbilirubinaemia and prevention of kernicterus. Drugs 1992 43 64-72. 

Rubaltelli FF. Current drug treatment options in neonatal hyperbilirubinaemia and the prevention of kernicterus. Drugs 1998 56 23-30. 

Fusidic acid interferes with hepatic bilirubin excretion to cause conjugated hyperbilirubinaemia, particularly in patients with sepsis. 

The term jaundice or icterus is used to depict the yellowish discolouring of the skin, mucous membranes and body fluids witnessed as a result of hyperbilirubinaemia in excess of 2.5 mg/dl, with subsequent deposition of bile pigments in tissue which is rich in elastin. In cases of severely impaired liver function or renal insufficiency, bilirubin values can rise dramatically. The term subicterus is used to describe a low-grade icteric condition occurring in the region of the white sclera with a serum bilirubin value of > 1.8 mg/dl for this reason, it is also known as scleral icterus, (s. pp 80, 99)... 

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