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Drugs-Inducing Hepatotoxicity


Affiliations
1 Department of Pharmacology and Toxicology, University of Tabuk, Saudi Arabia
2 Department of Pharmaceutics, Northern Border University,, Saudi Arabia
3 Department of Pharmacology and Toxicology, Northern Border University, Saudi Arabia
 

The liver is the largest solid organ, the largest gland, and one of the most vital organs that functions as a center for the metabolism of nutrients and excretion of waste metabolites. Hepatotoxicity is becoming a leading cause of death worldwide and its prevalence is increasing exponentially, there are several causes behind hepatotoxicity such as administration of acetaminophen that induced hepatotoxicity through the excessive formation of the toxic metabolite N-acetyl-para-benzoquinone imine (NAPQI). Drug-induced liver injury may account for approximately 10% of all cases of acute hepatitis, 5% of all hospital admissions, and 50% of all acute liver failures. Remarkably, more than 75% of cases of idiosyncratic drug reactions result in liver transplantation or death. This review will help researchers to understand the hepatotoxicity mechanism of common drugs that have a hepatotoxic effect.

Keywords

Acetaminophen, Anti-Tuberculosis Drugs, Hepatotoxic Drugs, Hepatotoxicity, Phenytoin.
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  • Gulati K, Reshi MR, Rai N, Ray A. Hepatotoxicity: Its mechanisms, experimental evaluation, and protective strategies. American Journal of Pharmacology. 2018; 1(1):1004.
  • Singh A, Bhat TK, Sharma OP. (2011). Clinical biochemistry of hepatotoxicity. J Clin Toxicol. 2011; 4(0001):1-9.
  • Thompson M, Jaiswal Y, Wang I, Williams L. Hepatotoxicity: Treatment, causes and applications of medicinal plants as therapeutic agents. The Journal of Phytopharmacology.2017; 6(3):186-193.
  • Stickel F, Patsenker E, Schuppan D. Herbal hepatotoxicity. Journal of hepatology. 2005; 43(5):901. https://doi.org/10.1016/j.jhep.2005.08.002 PMid:16171893
  • Jahnavi K, Reddy PP, Vasudha B, Narender B. Non-steroidal anti-inflammatory drugs: an overview. Journal of Drug Delivery and Therapeutics. 2019; 9(1-s):442-448. https://doi.org/10.22270/jddt.v9i1-s.2287
  • Sriuttha P, Sirichanchuen B, Permsuwan U. Hepatotoxicity of nonsteroidal anti-inflammatory drugs: a systematic review of randomized controlled trials. International Journal of Hepatology. 2018. https://doi.org/10.1155/2018/5253623 PMid:29568654 PMCid:PMC5820561
  • Liver Tox: Clinical and Research Information on DrugInduced Liver Injury. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012.
  • Mahmoud NM. Ppar-γ dependent protective effect of pioglitazone against methotrexate-induced hepatotoxicity in rats. Al-AzharAssiut Medical Journal. 2015; 13(2).
  • Kumari S, Kumari S, Sharma AK, Kaur I. Methotrexate induced hepatotoxicity and its management. Inter J Sci Res. 2016; 5:1477-81.
  • García DS, Saturansky EI, Poncino D, Martínez-Artola Y, Rosenberg S, Abritta G, Cravero A. Hepatic toxicity by methotrexate with weekly single doses associated with folic acid in rheumatoid and psoriatic arthritis. What is its real frequency? Annals of Hepatology. 2019; 18(5):765-769.https://doi.org/10.1016/j.aohep.2019.01.011 PMid:31105018
  • Ayano G. Bipolar disorders and valproate: Pharmacokinetics, pharmacodynamics and therapeutic effects and indications of valproate: review of articles. Bipolar Disord. 2016; 2(109):2472-77. https://doi.org/10.4172/2472-1077.1000109
  • Najafi N, Jamshidzadeh A, Fallahzadeh H, Omidi M, Abdoli N, Najibi A, Niknahad H. Valproic Acid-Induced Hepatotoxicity and the Protective Role of ThiolReductants. Trends in Pharmaceutical Sciences. 2017; 3(2):63-70.
  • Stephens JR, Levy RH. Valproate hepatotoxicity syndrome: hypotheses of pathogenesis. Pharmaceutisch Weekblad. 1992; 14(3):118-21. https://doi.org/10.1007/BF01962700 PMid:1502010
  • Yaari Y, Selzer ME, Pincus JH. Phenytoin: mechanisms of its anticonvulsant action. Annals of Neurology: Official Journal of the American Neurological Association and the Child Neurology Society. 1986; 20(2):171-184. https://doi.org/10.1002/ana.410200202 PMid:2428283
  • Ekaidem IS, Usoh IF, Akpanabiatu MI, Uboh FE, Akpan HD. Urate synthesis and oxidative stress in phenytoin hepatotoxicity: the role of antioxidant vitamins. Pak J Biol Sci. 2014; 17(11):1179-1184. https://doi.org/10.3923/pjbs.2014.1179.1184 PMid:26027163
  • National Institutes of Health. Livertox: Clinical and research information on drug-induced liver injury; 2017. Available from: Nih. gov https://livertox.nih.gov
  • Satishchandra P, Nagappa M. Role of phenobarbitone as an antiepileptic drug in 21st century. Medicine. 2012; 22.
  • Bryant AE, Dreifuss FE. Hepatotoxicity associated with antiepileptic drug therapy. Cns Drugs. 1995; 4(2):99-113. https://doi.org/10.2165/00023210-199504020-00003
  • Raksha MA, Lal V, HimaBindu P, Inayathulla K, ManasaG. Hepatotoxicity Induced by Prolonged Use of Phenobarbital: A Case Report. ‏International Journal of Science and Healthcare Research. 2020; 5(2):2455-7587.
  • Tostmann A, Boeree MJ, Aarnoutse RE, De Lange WC, Van Der Ven AJ, Dekhuijzen R. Antituberculosis drug‐ induced hepatotoxicity: concise up‐to‐date review. Journal of Gastroenterology and Hepatology. 2008; 23(2):192202. https://doi.org/10.1111/j.1440-1746.2007.05207.x PMid:17995946
  • Ramappa V, Aithal GP. Hepatotoxicity related to antituberculosis drugs: mechanisms and management. Journal of Clinical and Experimental Hepatology. 2013; 3(1):37-49. https://doi.org/10.1016/j.jceh.2012.12.001 PMid:25755470 PMCid:PMC3940184
  • Ambreen K, Sharma R, Singh KP, Kumar S. Antituberculosis drug-induced hepatotoxicity: a review. International Journal of Advanced Biotechnology and Research. 2014; 5(3):423-37.
  • Stancu C, Sima A. Statins: Mechanism of action and effects. Journal of Cellular and Molecular Medicine. 2001; 5(4):378-87. https://doi.org/10.1111/j.1582-4934.2001. tb00172.x PMid:12067471 PMCid:PMC6740083
  • Golomb BA, Evans MA. Statin adverse effects. American Journal of Cardiovascular Drugs. 2008; 8(6):373-418. https://doi.org/10.2165/0129784-200808060-00004 PMid:19159124 PMCid:PMC2849981
  • Karahalil B, Hare E, Koç G, Uslu İ, Şentürk K, Özkan Y. Hepatotoxicity associated with statins. Archives of Industrial Hygiene and Toxicology. 2017; 68(4):25460. https://doi.org/10.1515/aiht-2017-68-2994 PMid:29337684
  • Bond P, Llewellyn W, Van Mol P. Anabolic androgenic steroidinduced hepatotoxicity. Medical Hypotheses. 2016; 93:150-3. https://doi.org/10.1016/j.mehy.2016.06.004 PMid:27372877
  • Solimini R, Rotolo MC, Mastrobattista L, Mortali C, Minutillo A, Pichini S, Palmi I. .Hepatotoxicity associated with illicit use of anabolic androgenic steroids in doping. Eur Rev Med Pharmacol Sci. 2017; 21(1):7-16.
  • Takyar V, Stolz A. Spectrum of Drug Induced Liver Injury Caused by Anabolic Androgenic Steroids Abuse. Current Hepatology Reports. 2019; 18(4):417-24. https://doi. org/10.1007/s11901-019-00490-0
  • Ramalingappa P, Aradhya HV, Hanumantharaya N, Bolarigowda P. Alpha methyldopa induced hepatotoxicity in pregnancy. International Journal of Reproduction, Contraception, Obstetrics and Gynecology. 2014; 3(3):806. https://doi.org/10.5455/2320-1770.ijrcog20140938
  • Maddrey WC, Boitnott JK. (1975). Severe hepatitis from methyldopa. Gastroenterology. 1975; 68(2):351-360. https://doi.org/10.1016/S0016-5085(75)80018-7
  • KashkooliS, Baraty B, Kalantar J. α-Methyldopa-induced hepatitis during the postpartum period. Case Reports; 2014: bcr2014203712. https://doi.org/10.1136/bcr-2014203712 PMid:24577181 PMCid:PMC3939412
  • Knowles HJ, Tian YM, Mole DR, Harris AL. Novel mechanism of action for hydralazine: induction of hypoxiainducible factor-1 α, vascular endothelial growth factor, and angiogenesis by inhibition of prolyl hydroxylases. Circulation Research. 2004; 95(2):162-9. https://doi.org/10.1161/01.RES.0000134924.89412.70 PMid:15192023
  • Amjad W, John G, Gulru S. Hydralazine-Induced Autoimmune Hepatitis Precipitated by the Blood Transfusion. American Journal of Therapeutics. 2018; 25(4):e514-e516. https://doi.org/10.1097/MJT.0000000000000605 PMid:29045246
  • Sharma M, Foge M, Mascarenhas D. A Suspected Case of Hydralazine-Induced Hepatotoxicity: A Case Report and Review of Literature. The American journal of case reports. 2018; 19:800. https://doi.org/10.12659/AJCR.909279 PMid:29980661 PMCid:PMC6066965
  • Van Tyle JH. Ketoconazole; mechanism of action, spectrum of activity, pharmacokinetics, drug interactions, adverse reactions and therapeutic use. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy. 1984; 4(6):34373. https://doi.org/10.1002/j.1875-9114.1984.tb03398.x PMid:6151171
  • Greenblatt HK, Greenblatt DJ. Liver injury associated with ketoconazole: review of the published evidence. The Journal of Clinical Pharmacology. 2014; 54(12):1321-9. https://doi.org/10.1002/jcph.400 PMid:25216238
  • Khoza S, Moyo I, Ncube D. Comparative hepatotoxicity of fluconazole, ketoconazole, itraconazole, terbinafine, and griseofulvin in rats. Journal of Toxicology. 2017. https://doi.org/10.1155/2017/6746989 PMid:28261269 PMCid:PMC5316457
  • January CT, Wann LS, Alpert JS, et al. AHA/ACC/ HRS Guideline for the management of patients with atrial fibrillation: A report of the American College of Cardiology/ American Heart Association Task Force on Practice Guideline and the Heart Rhythm Society. Circulation. 2014; 130:e199-e267.
  • Tsuda T, Tada H, Tanaka Y, Nishida N, Yoshida T, Sawada T, Sasaki M. Amiodarone-induced reversible and irreversible hepatotoxicity: two case reports. Journal of Medical Case Reports. 2018; 12(1):95. https://doi.org/10.1186/s13256018-1629-8 PMid:29653592 PMCid:PMC5899395
  • Pendyala VS. A Case of Amiodarone-induced Hepatitis and Review of the Literature. J Hepatol Gastroint Dis. 2016; 2(120):2.
  • Patrono C. Antiplatelet strategies. European Heart Journal Supplements. 2002; 4(suppl_A):A42-A47. https://doi.org/10.1016/S1520-765X(02)90072-6
  • Tsai MH, Tsai SL, Chen TC, Liaw YF. Ticlopidine-induced cholestatic hepatitis with anti-nuclear antibody in serum. Journal of the Formosan Medical Association. 2000; 99(11):866-869.
  • KraslovaI, Muchova L, Vitek L, Novotny A, Svestka T, Bruha R. Ticlopidine-induced cholestatic inflammatory hepatitis: new insights into pathogenetic mechanisms of drug-related hepatotoxicity. European Journal of Inflammation. 2006; 4(1):55-67. https://doi.org/10.1177/1721727X0600400107
  • Carrion AF, Czul F, Arosemena LR, Selvaggi G, Garcia MT, Tekin A, Ghanta RK. Propylthiouracil-induced acute liver failure: role of liver transplantation. International Journal of Endocrinology. 2010. https://doi.org/10.1155/2010/910636 PMid:21234410 PMCid:PMC3014703
  • Akmal A, Kung J. Propylthiouracil, and methimazole, and carbimazole-related hepatotoxicity. Expert opinion on drug safety. 2014; 13(10):1397-406. https://doi.org/10.151 7/14740338.2014.953796 PMid:25156887
  • Gomez-Peralta F, Velasco-Martínez P, Abreu C, Cepeda M, Fernández-Puente M. Hepatotoxicity in hyperthyroid patient after consecutive methimazole and propylthiouracil therapies. Endocrinology, Diabetes and Metabolism Case Reports. 2018; (1). https://doi.org/10.1530/EDM-17-0173 PMid:29340156 PMCid:PMC5763277
  • Jena SK, Suresh S, Sangamwar AT. Modulation of tamoxifen‐ induced hepatotoxicity by tamoxifen-phospholipid complex. Journal of Pharmacy and Pharmacology. 2015; 67(9):1198-206. https://doi.org/10.1111/jphp.12422 PMid:25904227
  • Zhou WB, Zhang XX, Cai Y, Sun W, Li H. Osthole prevents tamoxifen-induced liver injury in mice. Acta Pharmacologica Sinica. 2019; 40(5):608-19. https://doi.org/10.1038/s41401018-0171-y PMid:30315252 PMCid:PMC6786423
  • Wyffels K, Horsmans Y. Tamoxifen-induced hepatotoxicity caused by drug interaction with direct-acting antiviral agents for hepatitis C. Journal of Oncology Pharmacy Practice. 2019; 25(8):2038-2040. https://doi.org/10.1177/1078155218819742 PMid:30563414
  • Black GW. A review of the pharmacology of halothane. British Journal of Anaesthesia. 1965; 37(9):688-705. https://doi.org/10.1093/bja/37.9.688 PMid:5320091
  • Rosenak D, Halevy A, Orda R. Halothane and liver damage. Postgraduate medical journal. 1989; 65(761):129. https://doi.org/10.1136/pgmj.65.761.129 PMid:2682584 PMCid:PMC2429259
  • Elliott RH, Strunin L. Hepatotoxicity of volatile anaesthetics. British Journal of Anaesthesia. 1993; 70(3):339-48. https://doi.org/10.1093/bja/70.3.339 PMid:8471380
  • Jóźwiak-Bebenista M, Nowak JZ. Paracetamol: mechanism of action, applications and safety concern. Actapoloniae pharmaceutica. 2014; 71(1):11-23.
  • Yoon E, Babar A, Choudhary M, Kutner M, Pyrsopoulos N. Acetaminophen-induced hepatotoxicity: A comprehensive update. Journal of Clinical and Translational Hepatology. 2016; 4(2):131. https://doi.org/10.14218/JCTH.2015.00052
  • Lee WM. Acetaminophen (APAP) hepatotoxicity-isn’t it time for APAP to go away? Journal of Hepatology. 2017; 67(6):1324-31. https://doi.org/10.1016/j.jhep.2017.07.005 PMid:28734939 PMCid:PMC5696016
  • Yoon E, Babar A, Choudhary M, Kutner M, Pyrsopoulos N. Acetaminophen-induced hepatotoxicity: a comprehensive update. Journal of Clinical and Translational Hepatology. 2016; 4(2):131. https://doi.org/10.14218/JCTH.2015.00052
  • Mutschler J, Grosshans M, Soyka M, Rösner S. Current findings and mechanisms of action of disulfiram in the treatment of alcohol dependence. Pharmacopsychiatry. 2016; 49(04):137-41. https://doi.org/10.1055/s-0042-103592 PMid:26987743
  • Forns X, Caballeria J, Bruguera M, Salmerón JM, Vilella A, Mas A, Rodés J. Disulfiram-induced hepatitis. Report of four cases and review of the literature. Journal of Hepatology. 1994; 21(5):853-7. https://doi.org/10.1016/S0168-8278(94)80249-1
  • National Institutes of Health. Livertox: Clinical and research information on drug-induced liver injury; 2017. Available from; Nih. gov https://livertox. nih. gov
  • Hirsh J, Warkentin TE, Dalen JE, Deykin D, Poller L. Heparin: mechanism of action, pharmacokinetics, dosing considerations, monitoring, efficacy, and safety. Chest. 1995; 108(4):258S-5S. https://doi.org/10.1378/chest.108.4_ Supplement.258S PMid:7555181
  • Bosco M, Kish T. (2019). Hepatotoxicity With Elevated Bilirubin Secondary to Prophylactic Doses of Unfractionated Heparin: A Case Report and Review of Heparin-Induced Hepatotoxicity. Journal of Pharmacy Technology. 2019; 35(1):36-40. https://doi.org/10.1177/8755122518803363 PMCid:PMC6313267
  • Arora N, Goldhaber SZ. Anticoagulants and transaminase elevation. Circulation. 2006; 113(15):e698-e702. https://doi.org/10.1161/CIRCULATIONAHA.105.603100 PMid:16618822

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  • Drugs-Inducing Hepatotoxicity

Abstract Views: 387  |  PDF Views: 141

Authors

Mohammed M. Alshehri
Department of Pharmacology and Toxicology, University of Tabuk, Saudi Arabia
Muhammad Wahab Amjad
Department of Pharmaceutics, Northern Border University,, Saudi Arabia
Mahmoud M. E. Mudawi
Department of Pharmacology and Toxicology, Northern Border University, Saudi Arabia

Abstract


The liver is the largest solid organ, the largest gland, and one of the most vital organs that functions as a center for the metabolism of nutrients and excretion of waste metabolites. Hepatotoxicity is becoming a leading cause of death worldwide and its prevalence is increasing exponentially, there are several causes behind hepatotoxicity such as administration of acetaminophen that induced hepatotoxicity through the excessive formation of the toxic metabolite N-acetyl-para-benzoquinone imine (NAPQI). Drug-induced liver injury may account for approximately 10% of all cases of acute hepatitis, 5% of all hospital admissions, and 50% of all acute liver failures. Remarkably, more than 75% of cases of idiosyncratic drug reactions result in liver transplantation or death. This review will help researchers to understand the hepatotoxicity mechanism of common drugs that have a hepatotoxic effect.

Keywords


Acetaminophen, Anti-Tuberculosis Drugs, Hepatotoxic Drugs, Hepatotoxicity, Phenytoin.

References





DOI: https://doi.org/10.18311/ajprhc%2F2020%2F25518