Drug induced liver injury risk factors: Difference between revisions
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Latest revision as of 20:38, 24 October 2016
Drug induced liver injury Microchapters |
Differentiating Drug Induced Liver Injury from other Diseases |
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Diagnosis |
Treatment |
Case Studies |
Drug Induced Liver Injury On the Web |
American Roentgen Ray Society Images of Drug induced liver injury |
Risk calculators and risk factors for Drug induced liver injury |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Rachita Navara, M.D. [2]
Overview
Common risk factors in the development of drug induced liver injury include age, alcohol intake, drug usage, and female gender. However, most reactions are idiosyncratic and do not follow predictable responses, making it difficult to predict the risk of liver injury from a given drug in an individual patient.
Risk Factors
Common risk factors in the development of drug induced liver injury include:
- Age: Apart from accidental exposure, hepatic drug reactions are rare in children. Elderly persons are at increased risk of hepatic injury because of decreased clearance, drug-to-drug interactions, reduced hepatic blood flow, variation in drug binding, and lower hepatic volume. In addition, poor diet, infections, and multiple hospitalizations are important reasons for drug-induced hepatotoxicity.
- Alcohol ingestion: Alcoholic persons are susceptible to drug toxicity because alcohol induces liver injury and cirrhotic changes that alter drug metabolism. Alcohol causes depletion of glutathione (hepatoprotective) stores that make the person more susceptible to toxicity by drugs.
- Drug formulation: Long-acting drugs may cause more injury than shorter-acting drugs.
- Gender: Although the reasons are unknown, hepatic drug reactions are more common in females.
- Genetic factors: A unique gene encodes each P-450 protein. Genetic differences in the P-450 enzymes can result in abnormal reactions to drugs, including idiosyncratic reactions. Debrisoquine is an antiarrhythmic drug that undergoes poor metabolism because of abnormal expression of P-450-II-D6. This can be identified by polymerase chain reaction amplification of mutant genes. This has led to the possibility of future detection of persons who can have abnormal reactions to a drug.
- Host factors that may enhance susceptibility to drugs, possibly inducing liver disease:
- AIDS - Dapsone, trimethoprim-sulfamethoxazole
- Diabetes mellitus - Methotrexate, niacin
- Fasting or malnutrition - Acetaminophen
- Female - Halothane, nitrofurantoin, sulindac
- Hepatitis C - Ibuprofen, ritonavir, flutamide
- Large body mass index / obesity - Halothane
- Male - Amoxicillin-clavulanic acid (Augmentin)
- Old age - Acetaminophen, halothane, INH, amoxicillin-clavulanic acid
- Preexisting liver disease - Niacin, tetracycline, methotrexate
- Renal failure - Tetracycline, allopurinol
- Young age - Salicylates, valproic acid
- Liver disease: In general, patients with chronic liver disease are not uniformly at increased risk of hepatic injury. Although the total cytochrome P450 is reduced, some may be affected more than others. The modification of doses in persons with liver disease should be based on the knowledge of the specific enzyme involved in the metabolism. Patients with HIV infection who are co-infected with hepatitis B or C virus are at increased risk for hepatotoxic effects when treated with antiretroviral therapy. Similarly, patients with cirrhosis are at increased risk of decompensation by toxic drugs.
- Other comorbidities: Persons with AIDS, persons who are malnourished, and persons who are fasting may be susceptible to drug reactions because of low glutathione stores.
- Race: Some drugs appear to have different toxicities based on race. For example, African Americans and Hispanics may be more susceptible to isoniazid (INH) toxicity. The rate of metabolism is under the control of P450 enzymes and can vary from individual to individual.
Drugs that Effect Cytochrome P450
Inducers
- Carbamazepine
- Ethanol
- Glucocorticoids
- Griseofulvin
- Omeprazole (Induces P450 1A2)
- Phenobarbital
- Phenytoin
- Primidone
- Quinine
- Rifampin
Inhibitors
- Amiodarone
- Cimetidine
- Erythromycin
- Grape fruit
- Isoniazid
- Ketoconazole
- Metronidazole
- Omeprazole (Inhibits P450 2C8)
- Quinidine
- Sulfonamides
Drugs which cause Hepatotoxicity[1][2]
References
- ↑ Andrade RJ, Robles M, Fernández-Castañer A, López-Ortega S, López-Vega MC, Lucena MI (2007). "Assessment of drug-induced hepatotoxicity in clinical practice: a challenge for gastroenterologists". World J Gastroenterol. 13 (3): 329–40. PMC 4065885. PMID 17230599.
- ↑ Shah RR (1999). "Drug-induced hepatotoxicity: pharmacokinetic perspectives and strategies for risk reduction". Adverse drug reactions and toxicological reviews. 18 (4): 181–233. PMID 10687025.