Fibrosis drug-induced

Parenteral Anticoagulant-induced prothrombin deficiency hypoprothrombinemia secondary to conditions limiting absorption or synthesis of vitamin K (eg, obstructive jaundice, biliary fistula, sprue, ulcerative colitis, celiac disease, intestinal resection, cystic fibrosis of the pancreas, regional enteritis) drug-induced hypoprothrombinemias due to interference with vitamin K metabolism (eg, antibiotics, salicylates) prophylaxis and therapy of hemorrhagic disease of the newborn. 

Drug-induced hepatotoxicity can present in variable manifestations, such as cell death (necrosis, apoptosis), infiammation, degeneration (steatosis), fibrosis/cirrho-sis and the development of tumors. The manifestations of drug toxicity may not be mutually exclusive and may occur sequentially, or in combination. ALT and ALP can be used to generally classify the pattern of liver injury as either hepatocellular (ALT >3x ULN), cholestatic (ALP >2x ULN, ALT/ALP <2) or mixed (elevated ALP and ALT). The successful monitoring of hepatotoxicity would identify cases before irreversible injury occurs. The activity levels of ALT, AST and ALP only increase after hepatic or cholestatic injury has occurred. Waiting for activity levels to exceed the established thresholds may be too late [3]. New biomarkers are needed to monitor/predict the specific sequence of events for different classes of hepatotoxic compounds. 

A biopsy is often required to make a diagnosis of most types of liver disease. A specimen of liver can be used to identify fibrosis, cirrhosis, cholestasis and hepatitis, both acute and chronic, and tumours. Biochemical measurements can also be taken from a biopsy specimen to determine iron and copper content, virology, microbiology and haematology (e.g. increased numbers of eosinophils in a drug-induced cause). The biopsy can give an indication of the extent of the liver damage. See Chapter 3 for slides of liver biopsies. 

Begin R, Masse S, Rola-Pleszczynski M, et al. 1987b. Asbestos exposure dose-bronchoalveolar milieu response in asbestos workers and the sheep model Evidences of a threshold for chrysotile-induced fibrosis. Drug Chem Toxicol 10 87-107. 

A retrospective analysis of allergic reactions (drug-induced fever and rash) in 90 adults with cystic fibrosis, of whom 26 developed probable allergic reactions to parenteral beta-lactams. There was drug-induced fever in 54 and skin reactions in 28 of 897 treatment courses (6 and 3.1% respectively). There was one case of non-fatal anaphylaxis. The numbers of allergic reactions per number of patients receiving specific antibiotics were carbenicillin 4/56, mezlocillin 7/42, piperacillin 11/31, ticarcUlin 1/20, cefazolin 0/24, ceftazidime 1/35, imipenem + cilastatin 4/16, and nafcillin 3/36 (17). 

Miscellaneous Causes of Diabetes Mellitus These include diseases of the exocrine pancreas (e.g., cystic fibrosis, hemochromatosis, pancreatitis) and drug-induced causes (e.g., thiazides, glucocorticoids). 

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