Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0003873 (rheumatoid arthritis)
 53,068 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Seventy-three patients with early, active rheumatoid arthritis (RA) were randomly allocated either to a group that received penicillamine or to a control group from which penicillamine was barred, any other second-line drug being permitted. Most (87%) of the controls received chrysotherapy at some stage. Clinical, serological and radiographic progress was observed for at least 5 years. Outcome after 5 years for the 27 remaining in the penicillamine group was compared with that for the 23 surviving controls. Both groups had improved clinically but deteriorated radiographically, with much individual variation. A subset of patients, mostly seronegative, who were radiographically normal at the outset remained so, regardless of treatment. Penicillamine was as effective as the control group treatments in relieving synovitis and as ineffective in arresting radiographic deterioration.
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PMID:A prospective five-year comparison of treatment which included penicillamine with that excluding penicillamine in early rheumatoid arthritis. The Multicentre Trial Group. 287 87

A long-term comparative study of the classic basic drug-d-Penicillamin and 2 new sulfa drugs: sulfasalazin and salazopyridazin used for the first time in rheumatology, was conducted. Both drugs were shown to produce a "basic" effect in rheumatoid arthritis and to exceed d-Penicillamin in their therapeutic action. Better results were obtained with salazopyridazin. The tolerance to the new antirheumatic sulfa drugs was quite satisfactory; no severe side-effects were noted. Both drugs extend the potentialities of antirheumatoid therapy of prolonged action and warrant further use and study.
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PMID:[New basic preparations with prolonged action in the treatment of rheumatoid arthritis]. 288 35

In a 6-month open pilot study 25 patients with Rheumatoid Arthritis (RA) whose disease was refractory to Gold or D-Penicillamine (DPA) were given Sulphasalazine (SAS) in addition. Three patients withdrew because of nausea. Twenty-two patients who completed therapy showed significant improvement in clinical and laboratory measures of disease activity.
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PMID:Improving the response to gold or D-penicillamine by addition of sulphasalazine. A pilot study in 25 patients with rheumatoid arthritis. 288 41

In the present study, the side effects of d-Penicillamine therapy in 54 patients with rheumatoid arthritis are analyzed. The therapeutic efficacy of the drug is emphasized; but in the meantime, the necessity is also stressed that the choice of this antirheumatic agent must imply the knowledge of the possible complications caused by its use and of the clinical features and laboratory data which would be useful for their early detection.
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PMID:[Side effects of d-penicillamine in the treatment of rheumatoid arthritis]. 294 98

The mechanism by which D-Penicillamine is effective in the treatment of rheumatoid arthritis has been investigated. The results indicate that D-Penicillamine in synergism with copper or ceruloplasmin in vitro inhibits the proliferation of T-lymphocytes and the activity of helper T-cells in supporting the generation of antibody-forming cells. This effect is mediated by the production of H2O2. The significance of these findings for in vivo processes is discussed.
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PMID:Suggested mode of action of D-penicillamine as an immunosuppressive agent in rheumatoid arthritis. 297 7

Glutathione peroxidase (Se-GPx) is a selenoenzyme which catalyzes the reduction of hydroperoxides by glutathione (GSH), in most mammalian cells. Several Slow-acting drugs that are used in the treatment of rheumatoid arthritis, including D-Penicillamine, alpha-mercaptopropionylglycine and gold salts, are specific inhibitors of Se-GPx. In situation of oxidant stress, Se-GPx activity is a major source of glutathione disulfide (GSSG), an essential activator of leucocyte collagenase. Hence the possibility that the enzymatic reduction of hydroperoxides produced during chronic inflammation would play an important role in the destruction of joint tissue of arthritic patients. Inhibition of a protective system such as Se-GPx may therefore be involved in the mechanism of action of D-Penicillamine and gold salts, but it could also explain some of their undesirable or toxic effects. Confirmation of this hypothesis would open the way to new pharmacological strategies.
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PMID:[Possible role of glutathione peroxidase in the regulation of collagenase activity]. 301 86

Twenty-five patients with rheumatoid arthritis (RA) who developed toxicity while taking remission inducing drugs and 30 without toxicity were studied for possible associations with class I and II HLA antigens. A strong association has been found between nephritis and dermatitis due to Tiopronin (a D-Penicillamine like compound) and class I antigens B35-Cw4, and between dermatitis due to gold thiosulphate and B35. Compared to healthy controls a lower DR5 frequency was observed in patients with RA except for the Tiopronin related nephritis group.
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PMID:Toxicity due to remission inducing drugs in rheumatoid arthritis. Association with HLA-B35 and Cw4 antigens. 308 82

A 41-year-old woman with rheumatoid arthritis developed massive breast enlargement while taking penicillamine. Her endocrine evaluation was unremarkable, and the breast enlargement resolved with danazol therapy. Penicillamine may increase breast tissue sensitivity to steroid hormones in some patients, resulting in breast growth. This rare complication resolves spontaneously in men, but in women reversal of breast enlargement requires androgen therapy.
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PMID:Penicillamine induced mammary hyperplasia: report of a case and review of the literature. 318 79

A total of 232 patients with rheumatoid arthritis were treated with DPA. Withdrawal from treatment was mainly due to adverse events in the first year of treatment, while in the subsequent years it was mainly due to loss of efficacy. Of the patients treated, 68 were included in the present study, as they fulfilled the criteria of continuous long-term observation regularly performed. The effects of therapy were graded after 1 year of treatment, at the last examination in the outpatient department or before withdrawal, respectively. It could be seen that a long duration of the disease did not exclude positive effects of therapy; however, early use of DPA led to more favourable results with respect to the number of successfully treated patients and to the extent of the grading of efficacy. In patients who did not respond to DPA therapy, not only was the duration of the disease longer, but also previous therapy with other slow acting antirheumatic agents had been stopped because of inefficacy. This group of patients seems to cover therapy-resistant cases. After 1 year of treatment, improvement was measured in 54 patients. During further treatment, a tendency to return to initial values of clinical and laboratory parameters was noted. In about half the patients with only moderate improvement after 1 year, subsequent treatment was terminated (because of inefficacy) quite soon in most cases, i.e. within 5 years. Optimal improvement after 1 year, however, seems to indicate a long-term positive response to DPA therapy. In cases with no obvious effect of DPA after 1 year a response is not to be expected with ongoing treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Effectiveness and limits of D-penicillamine therapy]. 321 69

Penicillamine exists as 2 stereoisomers, but only the D-isomer is used therapeutically. Its chemical reactivity derives from its functional groups, of which the thiol group seems the most important. It is difficult to determine penicillamine in biological fluids because of its instability, the presence of endogenous compounds with a thiol function, and the various chemical forms in which it occurs, namely reduced free penicillamine, penicillamine bound to proteins, and internal (P-S-S-P) and mixed (P-S-S-C) disulphides. The earliest assay methods (colourimetry, isotopic methods, gas-phase chromatography) were neither sensitive nor specific. High performance liquid chromatography with electrochemical detection has led to a more specific assay for D-penicillamine, with detection based on either derivatisation reactions or on electro-oxidisation of the thiol function. With dual-electrode detectors (Au/Hg) disulphides can be assayed directly. D-penicillamine is absorbed rapidly but incompletely (40 to 70%) in the intestine, with wide interindividual variations. Food, antacids and, in particular, iron reduce absorption of the drug. Its bioavailability is also dramatically decreased in patients with malabsorption states. The peak plasma concentration occurs at 1 to 3 hours after ingestion, regardless of dose, and is of the order of 1 to 2 mg/L after an oral dose of 250 mg; some investigators have reported a double peak in plasma, which is probably not due to an enterohepatic cycle. The concentration in plasma then decreases rapidly, generally following a biphasic curve. When long term treatment is discontinued, there is a slow elimination phase lasting 4 to 6 days, which suggests that there is a 'deep compartment' or 'slow pool of the drug reversibly bound to tissues', particularly the skin. This may explain the persistence of its therapeutic effect and the occurrence of undesirable side effects after treatment has been stopped. During long term treatment plasma concentrations are highly variable between individuals. They do not seem to be correlated with the activity or the toxicity of D-penicillamine in patients with rheumatoid arthritis. More than 80% of plasma D-penicillamine is bound to proteins, particularly albumin. The rest is mainly in the free reduced form or as disulphides. Only a small portion of the dose is metabolised in the liver to S-methyl-D-penicillamine. The route of elimination is mainly renal; disulphides represent the main compounds found in the urine. Faecal excretion corresponds mainly to the non-absorbed fraction of the drug.
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PMID:Clinical pharmacokinetics of D-penicillamine. 331 47


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