Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0013395 (dyspepsia)
 4,879 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Effects and side-effects of treating patients with rheumatoid arthritis with methotrexate given as weekly pulse-treatment are examined in an open observation study. One hundred and ten consecutive patients with active rheumatoid arthritis entered the study. Six criteria of remission were registered as effect variables. Median length of treatment at the time of investigation was 17.8 months. At this point, 34 patients were in complete remission, with a median effect score of five point five out of six possible points. Twenty-nine were in partial remission and 47 (42.7%) had not improved. The median effect score for all patients was three point 6 (95% confidence limits (2-4). Methotrexate treatment was stopped in 24 patients, in 15 of these because of a combination of side-effects and lack of therapeutic response. Prednisone treatment could be discontinued in 20 out of 57 patients during the course of methotrexate treatment. Side-effects were registered in 67 cases (62.7%), and led to treatment being discontinued in 21 cases. Nearly half the side-effects consisted of dyspepsia and rises in amino-transferase levels (48 of 67 patients). Consistently raised amino-transferase levels were found in five cases, all returned to normal after methotrexate was stopped. Serious side-effect were registered in four cases, consisting of two cases of short-term pancytopenia following overdosage and two cases of severe hypoxia following methotrexate-induced alveolitis.
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PMID:[Methotrexate therapy of rheumatoid arthritis. An open observation study of 110 patients with median length of treatment of 17.8 month]. 834 72

Treatments for inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), functional dyspepsia, or motility disorders are not adequate, and purinergic drugs offer exciting new possibilities. Gastrointestinal symptoms that could be targeted for therapy include visceral pain, inflammatory pain, dysmotility, constipation, and diarrhea. The focus of this review is on the potential for developing purinergic drugs for clinical trials to treat gastrointestinal symptoms. Purinergic receptors are divided into adenosine P1 (A(1), A(2A), A(2B), A(3)), ionotropic ATP-gated P2X ion channel (P2X(1-7)), or metabotropic P2Y(1,2,4,6,11-14) receptors. There is good experimental evidence for targeting A(2A), A(2B), A(3), P2X(7), and P2X(3) receptors or increasing endogenous adenosine levels to treat IBD, inflammatory pain, IBS/visceral pain, inflammatory diarrhea, and motility disorders. Purine genes are also potential biomarkers of disease. Advances in medicinal chemistry have an accelerated pace toward clinical trials: Methotrexate and sulfasalazine, used to treat IBD, act by stimulating CD73-dependent adenosine production. ATP protects against NSAID-induced enteropathy and has pain-relieving properties in humans. A P2X(7)R antagonist AZD9056 is in clinical trials for Crohn's disease. A(3) adenosine receptor drugs target inflammatory diseases (e.g., CF101, CF102). Dipyridamole, a nucleoside uptake inhibitor, is in trials for endotoxemia. Drugs for pain in clinical trials include P2X(3)/P2X(2/3) (AF-219) and P2X(7) (GSK1482160) antagonists and A(1) (GW493838) or A(2A) (BVT.115959) agonists. Iberogast is a phytopharmacon targeting purine mechanisms with efficacy in IBS and functional dyspepsia. Purinergic drugs have excellent safety/efficacy profile for prospective clinical trials in IBD, IBS, functional dyspepsia, and inflammatory diarrhea. Genetic polymorphisms and caffeine consumption may affect susceptibility to treatment. Further studies in animals can clarify mechanisms and test new generation drugs. Finally, there is still a huge gap in our knowledge of human pathophysiology of purinergic signaling.
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PMID:Potential for developing purinergic drugs for gastrointestinal diseases. 2485 98