Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.3.44 (P-glycoprotein)
 13,344 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

P-glycoprotein (Pgp) is encoded by the multidrug resistance gene (MDR1) in humans and is the product of MDR1. It is expressed in various tissues and is related to drug distribution in intestinal erythrocytes, capillary endotel of brain, proximal tubules cells of kidneys and liver canalicular cells. Expression of Pgp is affected by Pgp polymorphism, and exon 26 C3435T polymorphism is the most common one. It has been thought that expression of Pgp is high in C-allele subjects and this situation is responsible for the resistance against some drugs and substances. Pgp may have a role in the distribution of thyroid hormones, drugs used for hypo- and hyperthyroidism and the resistance occurred. For this purpose possible relationship between T and C alleles and frequency of Pgp polymorphism as well as thyroid hormone distribution in patients with hypo- and hyperthyroidism was investigated. Thirty five hyperthyroidism patients diagnosed as Graves' disease, 78 hypothyroidism patients diagnosed as Hashimoto's thyroiditis and 100 healthy volunteers were included in the study. According to the results obtained no statistically significant difference was found in Pgp C3435T polymorphism between hypo- and hyperthyroidism patients. In addition, the serum free T3 levels of hyperthyroidism patients with C alleles was higher than those of subjects with T alleles. No statistically significant difference was seen in the CC, CT and TT genotype frequencies between the patients and control groups. In conclusion, it seems that Pgp polymorphism is not a predictor factor for the occurrence of hypo- and hyperthyroidism. There is a significant relationship between Pgp and the elevated serum free T3 levels of hyperthyroidism patients, and further research will help understand this situation.
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PMID:P-glycoprotein polymorphism in hypo- and hyper-thyroidism patients. 1789 78

The impact of thyroid dysfunction on the regulation, expression, and function of ABCB1 remains unclear. We therefore investigated ABCB1 mRNA expression and function in patients with thyroid dysfunction and studied the disposition of the ABCB1 substrate digoxin before and after treatment for thyroid disease. In patients with hypothyroidism, normalization of thyroid function was associated with a 1.8-fold increase in mRNA expression and a 26% increase in rhodamine efflux from CD56(+) cells. In hypothyroidism, digoxin clearance was significantly decreased, whereas bioavailability, volume of distribution, half-life time, and protein binding were unaltered. In hyperthyroidism, ABCB1 mRNA expression, rhodamine efflux, and disposition of digoxin were not significantly affected other than in relation to renal clearance. Experiments using the LS174T cell line indicated that the gene is a direct target of thyroid hormone receptors. In conclusion, thyroid abnormalities can exert significant effects on the expression of P-glycoprotein, thereby altering the disposition and action of drugs that are substrates of P-glycoprotein.
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PMID:The impact of thyroid disease on the regulation, expression, and function of ABCB1 (MDR1/P glycoprotein) and consequences for the disposition of digoxin. 2084 84

Objective: To describe the various pharmacotherapeutic strategies in managing thyroid disease-induced pericarditis (TDIP). Considerations for both hypothyroid-induced and hyperthyroid-induced pericarditis will be discussed. Data Sources: A literature search of MEDLINE, including PubMed, was performed inclusive of all years, using the following search terms: thyroid disease, pericardial diseases, pericarditis, acute pericarditis, cholesterol pericarditis, hypothyroidism, hyperthyroidism, colchicine, corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs), aspirin, methimazole, propylthiouracil, and P-glycoprotein. Product monographs were reviewed as well. Study Selection and Data Extraction: Relevant English-language studies and data as well as the most current guidelines for diagnosis and management of thyroid and pericardial diseases were considered. Because of limited data regarding the subject matter, no date range limits were established during literature search. Data Synthesis: It is well documented that thyroid dysfunction can adversely affect cardiovascular function. Additionally, there are published guidelines on the diagnosis and management of pericarditis and, separately, thyroid disease. There are limited data, however, on managing TDIP. The sequela of untreated TDIP can be detrimental. Relevance to Patient Care and Clinical Practice: Strategies on managing TDIP are scarcely reported in the literature. This review provides clinicians with a single reference source for treatment strategies toward managing hypothyroidism-induced and hyperthyroidism-induced pericarditis as well as significant drug interactions that can potentially confound the management of hypothyroidism- and hyperthyroidism-induced pericarditis. Conclusions: Treatment of TDIP involves addressing both the thyroid disease as well as the pericarditis. Along with treatment strategies, clinicians should also consider potential drug-drug and drug-disease interactions that can potentially worsen clinical outcomes.
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PMID:Pharmacotherapeutic Management Strategies for Thyroid Disease-Induced Pericarditis. 3174 11