Drugs that modify cytochrome P-450 enzyme are referred to as either inhibitors or inducers. Enzyme inhibitors block the metabolic activity of one or several P-450 enzymes. This effect usually occurs immediately. On the other hand, inducers increase P-450 activity by increasing enzyme production, or, in the case of CYP2E1, preventing degradation in the proteasome. There is usually a delay before enzyme activity increases. 3. Competitive inhibition:Some drugs may share the same P-450 specificity and thus competitively block their biotransformation. This may lead to accumulation of drugs metabolized by the enzyme. This type of drug interaction may also reduce the rate of generation of toxic metabolites. Patterns of injury
Chemicals produce a wide variety of clinical and pathological hepatic injury. Biochemical markers (e.g. alanine transferase, alkaline phosphatase and bilirubin) are often used to indicate liver damage. Liver injury is defined as a rise in either (a) ALT level more than three times of upper limit of normal (ULN), (b) ALP level more than twice ULN, or (c) total bilirubin level more than twice ULN when associated with increased ALT or ALP. Liver damage is further characterized into hepatocellular (predominantly initial Alanine transferase elevation) and cholestatic (initial alkaline phosphatase rise) types. However they are not mutually exclusive and mixed types of injuries are often encountered. Specific histo-pathological patterns of liver injury from drug-induced damage are discussed below. Zonal Necrosis
This is the most common type of drug-induced liver cell necrosis where the injury is largely confined to a particular zone of the liver lobule.
Raising the urinary pH to a level higher than 7 (alkalinization) is often difficult to attain, although sodium bicarbonate and/or acetazolamide are sometimes used in an attempt to increase uric acid solubility. Dialysis (preferably hemodialysis) is started if the above measures fail. References
Conger JD (1990). "Acute uric acid nephropathy". Med Clin North Am. 74 (4): 859–71. PMID 2195258. Robinson RR, Yarger WE (1977). "Acute uric acid nephropathy". Arch Intern Med. 137 (7): 839–40. doi:10.1001/archinte.137.7.839. PMID 879920. Yu AS, Brenner BM (2005). "Chapter 266: Tubulointerstitial diseases of the kidney". In Kasper DL, Braunwald E, Fauci A, Hauser S, Longo D, Jameson JL (eds.). Harrisons Principles of Internal Medicine (16th ed.). New York: McGraw-Hill Professional. ISBN 978-0-07-140235-4