Hyperbilirubinemias

Capecitabine is used for the treatment of colorectal and breast cancers. It is contraindicated in patients with known hypersensitivity to capecitabine or any of its components or to 5-fluorouracil and in patients with known dihydropyrimidine dehydrogenase (DPD) deficiency. The use of capecitabine is restricted in patients with severe renal impairment. The drag can induce diarrhea, sometimes severe. Other side effects include anemia, hand-foot syndrome, hyperbilirubinemia, nausea, stomatitis, pyrexia, edema, constipation, dyspnea, neutropenia, back pain, and headache. Cardiotoxicity has been observed with capecitabine. A clinically important drag interaction between capecitabine and warfarin has been demonstrated. Care should be exercised when the drag is co-administered with CYP2X9 substrates. 

When bifimbin in the blood exceeds 1 mg/dL (17.1 lmol/L), hyperbifimbinemia exists. Hyperbilirubinemia may be due to the production of more bilirubin than the normal fiver can excrete, or it may result from the failure of a damaged fiver to excrete bilirubin produced in normal amounts. In the absence of hepatic damage, obstmction of the excretory ducts of the fiver—by preventing the excretion of bilirubin—will also cause hyperbilirubinemia. In all these situations, bifimbin accumulates in the blood, and when it reaches a certain concentration (approximately 2-2.5 mg/dL),... 

Depending on the type of bilirubin present in plasma—ie, unconjugated or conjugated—hyperbihru-binemia may be classified as retention hyperbilirubinemia, due to overproduction, or regurgitation hyperbilirubinemia, due to reflux into the bloodstream because of bihary obstmction. 

Unconjugated hyperbilirubinemia can result from toxin-induced liver dysfunction such as that caused by chloroform, arsphenamines, carbon tetrachloride, acetaminophen, hepatitis virus, cirrhosis, and Amanita... 

Obstruction in the BiiiaryTree Is the Commonest Cause of Conjugated Hyperbilirubinemia... 

Conjugated hyperbilirubinemia commonly results from blockage of the hepatic or common bile ducts, most often due to a gallstone or to cancer of the head of the pancreas. Because of the obstruction, bilirubin diglu-curonide cannot be excreted. It thus regurgitates into the hepatic veins and lymphatics, and conjugated bilirubin appears in the blood and urine (choluric jaundice). 

The term cholestatic jaundice is used to include all cases of extrahepatic obstructive jaundice. It also covers those cases of jaundice that exhibit conjugated hyperbilirubinemia due to micro-obstruction of intrahepatic biliary ductules by swollen, damaged hepatocytes (eg, as may occur in infectious hepatitis). 

This benign autosomal recessive disorder consists of conjugated hyperbilirubinemia in childhood or during adult life. The hyperbilirubinemia is caused by mutations in the gene encoding MRP-2 (see above), the protein involved in the secretion of conjugated bilirubin into bile. The centrilobular hepatocytes contain an abnormal black pigment that may be derived from epinephrine. 

This is a rare benign condition characterized by chronic conjugated hyperbilirubinemia and normal liver histology. Its precise cause has not been identified, but it is thought to be due to an abnormality in hepatic storage. 

Berk PD, Wolkoff AW Bilirubin metabolism and the hyperbilirubinemias. In Harrison s Principles of Internal Medicine, 15th ed. Braunwald E et al (editors). McGraw-Hill, 2001. 

Other possible laboratory abnormalities include elevated white blood cell count, hyperglycemia, hypocalcemia, hyperbilirubinemia, elevated serum lactate dehydrogenase (LDH), and hypertriglyceridemia. 

Host factors can help to ensure selection of the most appropriate antimicrobial agent. Age is an important factor in antimicrobial selection. With regard to dose and interval, renal and hepatic function varies with age. Populations with diminished renal function include neonates and the elderly. Hepatic function in the neonate is not fully developed, and drugs that are metabolized or eliminated by this route may produce adverse effects. For example, sulfonamides and ceftriaxone may compete with bilirubin for binding sites and may result in hyperbilirubinemia and kernicterus. Gastric acidity also depends on... 

Drugs that should not be combined due to overlapping toxi-cities include amprenavir oral solution plus ritonavir oral solution, atazanavir plus indinavir (due to enhanced hyperbilirubinemia), and any combination of didanosine, stavudine, and zalcitabine. Emtricitabine and lamivudine should not be combined because of their similar chemical structures, and antagonism can result when lamivudine is combined with zalcitabine, or stavudine is combined with zidovudine. 

Crixivan 400-mg caps IDV 800 mg + RTV 100 bid IDV 800 mg + RTV 200 mg bid insufficiency due to cirrhosis 600 mg q8hours Take 1 hour before or 2 hours after heavy meals, or concomitantly with low-fat meal No restrictions when used with RTV nausea indirect hyperbilirubinemia hyperlipidemia headache, asthenia, blurred vision, dizziness, rash, metallic taste, thrombocytopenia, alopecia, hemolytic anemia hyperglycemia fat maldistribution increased bleeding episodes in patients with hemophilia (less than RTV)... 

Myelosuppression mild, anorexia, low emetoginic potential dry skin rash, photosensivity hepatotoxicity jaundice and hyperbilirubinemia occur after 1-2 months of therapy and may be dose-limiting... 

Hyperbilirubinemia Abnormally high concentrations of the bile pigment bilirubin in the bloodstream. Hyperbilirubinemia is defined as a total serum bilirubin level greater than 5 mg/dL. 

Phototherapy The use of ultraviolet light applied to the skin, for example in treating psoriasis or neonatal hyperbilirubinemia. 

As far as sinusoidal uptake is concerned, drug-drug interactions have also been reported between antituberculosis agents (rifamycin SV and rifampicin) and bromosulfophthalein in humans both drugs reduce the clearance of bromosul-fophthalein and also induce hyperbilirubinemia [108]. These results may be ac-... 

Jansen PL, Peters WH, Lamers WH. Hereditary chronic conjugated hyperbilirubinemia in mutant rats caused by defective hepatic anion transport. Hepatology 1985 5(4) 573—579. 

Kurisu H, Kamisaka K, Koyo T, Yama-suge S, Igarashi H, Maezawa H et al. Organic anion transport study in mutant rats with autosomal recessive conjugated hyperbilirubinemia. Life Sci 1991 ... 

Wada M, Toh S, Taniguchi K, Nakamura T, Uchiumi T, Kohno K et al. Mutations in the canalicular multispecific organic anion transporter (cMOAT) gene, a novel ABC transporter, in patients with hyperbilirubinemia I I/Dubin-Johnson syndrome. Hum Mol Genet 1998 7(2) 203-207. 

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