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Factors affecting drug-induced liver injury: antithyroid drugs as instances.

Heidari R, Niknahad H, Jamshidzadeh A, Abdoli N - Clin Mol Hepatol (2014)

Bottom Line: The purpose of this article is to give an overview on possible susceptibility factors in liver injury induced by antithyroid agents.Age, gender, metabolism characteristics, alcohol consumption, underlying diseases, immunologic mechanisms, and drug interactions are involved in enhancing antithyroid drugs-induced hepatic damage.An outline on the clinically used treatments for antithyroid drugs-induced hepatotoxicity and the potential therapeutic strategies found to be effective against this complication are also discussed.

View Article: PubMed Central - PubMed

Affiliation: Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.

ABSTRACT
Methimazole and propylthiouracil have been used in the management of hyperthyroidism for more than half a century. However, hepatotoxicity is one of the most deleterious side effects associated with these medications. The mechanism(s) of hepatic injury induced by antithyroid agents is not fully recognized yet. Furthermore, there are no specific tools for predicting the occurrence of hepatotoxicity induced by these drugs. The purpose of this article is to give an overview on possible susceptibility factors in liver injury induced by antithyroid agents. Age, gender, metabolism characteristics, alcohol consumption, underlying diseases, immunologic mechanisms, and drug interactions are involved in enhancing antithyroid drugs-induced hepatic damage. An outline on the clinically used treatments for antithyroid drugs-induced hepatotoxicity and the potential therapeutic strategies found to be effective against this complication are also discussed.

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Antithyroid drugs glucuronidation. UGTs catalyze glucuronic acid transfer to drugs: a way to prepare these medications for excretion. (A) Proposed glucuronic acid conjugates of the methimazole. (B) PTU glucuronidation. The differences in UGT enzymes activities between different persons might alter antithyroid drugs pharmacokinetic which consequently lead to hepatotoxicity. UGT, uridinediphospho glucuronosyltransferase.
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Figure 2: Antithyroid drugs glucuronidation. UGTs catalyze glucuronic acid transfer to drugs: a way to prepare these medications for excretion. (A) Proposed glucuronic acid conjugates of the methimazole. (B) PTU glucuronidation. The differences in UGT enzymes activities between different persons might alter antithyroid drugs pharmacokinetic which consequently lead to hepatotoxicity. UGT, uridinediphospho glucuronosyltransferase.

Mentions: PTU is metabolized by glucuronidation in liver and prepared to exert from body (Fig. 2).42 In another study, the methylated and sulfate conjugate PTU was detected in rat urine.43 No PTU-related reactive metabolite(s) has been suggested yet to induce hepatotoxic reactions. But, it has been founded that myeloperoxidase (MPO)-mediated metabolism of PTU led to a reactive metabolite formation which covalently bounded to leukocytes proteins.44 This reactions might be responsible for agranulocytosis as a deleterious adverse effect of PTU.44,45


Factors affecting drug-induced liver injury: antithyroid drugs as instances.

Heidari R, Niknahad H, Jamshidzadeh A, Abdoli N - Clin Mol Hepatol (2014)

Antithyroid drugs glucuronidation. UGTs catalyze glucuronic acid transfer to drugs: a way to prepare these medications for excretion. (A) Proposed glucuronic acid conjugates of the methimazole. (B) PTU glucuronidation. The differences in UGT enzymes activities between different persons might alter antithyroid drugs pharmacokinetic which consequently lead to hepatotoxicity. UGT, uridinediphospho glucuronosyltransferase.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4197171&req=5

Figure 2: Antithyroid drugs glucuronidation. UGTs catalyze glucuronic acid transfer to drugs: a way to prepare these medications for excretion. (A) Proposed glucuronic acid conjugates of the methimazole. (B) PTU glucuronidation. The differences in UGT enzymes activities between different persons might alter antithyroid drugs pharmacokinetic which consequently lead to hepatotoxicity. UGT, uridinediphospho glucuronosyltransferase.
Mentions: PTU is metabolized by glucuronidation in liver and prepared to exert from body (Fig. 2).42 In another study, the methylated and sulfate conjugate PTU was detected in rat urine.43 No PTU-related reactive metabolite(s) has been suggested yet to induce hepatotoxic reactions. But, it has been founded that myeloperoxidase (MPO)-mediated metabolism of PTU led to a reactive metabolite formation which covalently bounded to leukocytes proteins.44 This reactions might be responsible for agranulocytosis as a deleterious adverse effect of PTU.44,45

Bottom Line: The purpose of this article is to give an overview on possible susceptibility factors in liver injury induced by antithyroid agents.Age, gender, metabolism characteristics, alcohol consumption, underlying diseases, immunologic mechanisms, and drug interactions are involved in enhancing antithyroid drugs-induced hepatic damage.An outline on the clinically used treatments for antithyroid drugs-induced hepatotoxicity and the potential therapeutic strategies found to be effective against this complication are also discussed.

View Article: PubMed Central - PubMed

Affiliation: Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.

ABSTRACT
Methimazole and propylthiouracil have been used in the management of hyperthyroidism for more than half a century. However, hepatotoxicity is one of the most deleterious side effects associated with these medications. The mechanism(s) of hepatic injury induced by antithyroid agents is not fully recognized yet. Furthermore, there are no specific tools for predicting the occurrence of hepatotoxicity induced by these drugs. The purpose of this article is to give an overview on possible susceptibility factors in liver injury induced by antithyroid agents. Age, gender, metabolism characteristics, alcohol consumption, underlying diseases, immunologic mechanisms, and drug interactions are involved in enhancing antithyroid drugs-induced hepatic damage. An outline on the clinically used treatments for antithyroid drugs-induced hepatotoxicity and the potential therapeutic strategies found to be effective against this complication are also discussed.

Show MeSH
Related in: MedlinePlus