Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018099 (gout)
 5,192 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A case of colchicine-induced rhabdomyolysis is reported. A 48 year old African-American male with history of hypertension and chronic gout on colchicine 0.6 mg daily presented with symptoms of a community acquired pneumonia. The patient was started on 500 mg of clarithromycin orally twice daily and represented to the emergency room after 3 days complaining of severe muscle pain. His liver panel showed elevations in the serum aminotransferases; AST 513 mU/ml (nl 15-41) and ALT 182 mU/ml (nl 17-63). His complete blood count showed an elevated white blood cell count of 18,800/ml (nl 4,000-10,000/ml). Urine analysis was positive for myoglobin with no red cells present. Serum creatine kinase (CK) was 22,996 mU/ml (nl 31-221) with a normal troponin I 0.18 (nl <0.4).Investigations confirmed the presence of rhabdomyolysis and discontinuation of colchicine and clarithromycin resulted in resolution of clinical and biochemical features of rhabdomyolysis. By hospital day four, his muscle soreness had improved markedly. His serum CK improved to 3,389 mU/ml (nl 31-221 mU/ml) and serum creatinine improved to 1.5 mg/dl (nl 0.8-1.2). On hospital day five, the patient was discharged on oral anti-hypertensive medication and a ten-day course of doxycycline. Metabolism of colchicine by the cytochrome P450 3A4 system has been previously described, but this is the first published report of colchicine associated rhabdomyolysis secondary to drug metabolism interactions with an antibiotic. A review of medications that are metabolized via the cytochrome 3A4 and A-SLAVED-LIVER (Amiodarone, Simvastatin, Lovastatin, Atorvastatin, Verapamil, Erythromycin, Diltiazem, cLarithromycin, Itraconazole, Voriconazole, colchicinE, Ritonavir) pneumonic was established.
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PMID:Short term treatment with clarithromycin resulting in colchicine-induced rhabdomyolysis. 2541 92

Repurposing existing drugs for new therapeutic indications can improve success rates and streamline development. Use of large-scale biomedical data repositories, including eQTL regulatory relationships and genome-wide disease risk associations, offers opportunities to propose novel indications for drugs targeting common or convergent molecular candidates associated to two or more diseases. This proposed novel computational approach scales across 262 complex diseases, building a multi-partite hierarchical network integrating (i) GWAS-derived SNP-to-disease associations, (ii) eQTL-derived SNP-to-eGene associations incorporating both cis- and trans-relationships from 19 tissues, (iii) protein target-to-drug, and (iv) drug-to-disease indications with (iv) Gene Ontology-based information theoretic semantic (ITS) similarity calculated between protein target functions. Our hypothesis is that if two diseases are associated to a common or functionally similar eGene - and a drug targeting that eGene/protein in one disease exists - the second disease becomes a potential repurposing indication. To explore this, all possible pairs of independently segregating GWAS-derived SNPs were generated, and a statistical network of similarity within each SNP-SNP pair was calculated according to scale-free overrepresentation of convergent biological processes activity in regulated eGenes (ITSeGENE-eGENE) and scale-free overrepresentation of common eGene targets between the two SNPs (ITSSNP-SNP). Significance of ITSSNP-SNP was conservatively estimated using empirical scale-free permutation resampling keeping the node-degree constant for each molecule in each permutation. We identified 26 new drug repurposing indication candidates spanning 89 GWAS diseases, including a potential repurposing of the calcium-channel blocker Verapamil from coronary disease to gout. Predictions from our approach are compared to known drug indications using DrugBank as a gold standard (odds ratio=13.1, p-value=2.49x10-8). Because of specific disease-SNPs associations to candidate drug targets, the proposed method provides evidence for future precision drug repositioning to a patient's specific polymorphisms.
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PMID:Precision drug repurposing via convergent eQTL-based molecules and pathway targeting independent disease-associated polymorphisms. 3086 32