dicumarol and Jaundice

Even if all problems of liver metabolism have not yet been clarified, it is nevertheless established that medicaments induces enzymes in the hepatic cells which influence the metabolism of drugs. Because their effect is unspecific, these enzymes can catabolize many drugs with different structures. About 200 substances are known which induce such enzymes. Among them, for example, is phenobarbital. It is therefore used in the treatment of some forms of icterus with freee bilirubin and for Cushing's syndrome. But enzyme induction can also lead to acute intermittent porphyrias and distrubances of the phosphorus-calcium metabolism. Extreme catabolism of a drug can be caused by overinduction of enzymes due to the administration of several incompatible medicaments.

Topics: Adult; Animals; Anticonvulsants; Biotransformation; Calcium; Child; Cushing Syndrome; Dicumarol; Drug Synergism; Enzyme Induction; Humans; Infant, Newborn; Jaundice; Kinetics; Liver; Microsomes, Liver; Mitochondria, Liver; Pharmaceutical Preparations; Phenobarbital; Phenylbutazone; Phosphorus; Porphyrias; Protein Binding; Species Specificity; Vitamin D

Jaundiced Gunn rats were found to have a significantly larger apparent volume of distribution and higher rate constant for elimination of dicumarol than their nonjaundiced littermates. Anticoagulant effect-log plasma dicumarol concentration lines were parallel in the two groups of animals, with the line for the jaundiced rats shifted to a lower concentration range. In vitro studies showed that bilirubin can displace dicumarol from serum protein binding sites. There are indications of a genetic influence on the distribution and anticoagulant effect of dicumarol in Gunn rats.

Topics: Animals; Bilirubin; Binding Sites; Blood Proteins; Dicumarol; Female; Jaundice; Male; Protein Binding; Rats

Topics: Adult; Anesthesia, Spinal; Antibodies; Autoimmune Diseases; Blood Coagulation Tests; Blood Protein Electrophoresis; Dicumarol; Eosinophilia; Fibrinogen; Heparin; Humans; Jaundice; Male; Pneumonia; Priapism; Pulmonary Embolism; Steroids; Thrombophlebitis; Vitamin K