Post by
RReis09 on Dec 03, 2020 8:45pm
KEN.W can get those boobs he Always he wanted
Gigantism of the breasts, probably induced by bucillamine, has been reported [16]. After attempts with chrysotherapy and lobenzarit, a 24-year-old woman was given bucillamine 300 mg/day and a glucocorticoid, predonine, for rheumatoid arthritis. After 10 months she noticed bilateral breast enlargement, which over 6 months progressed to extreme proportions, the left breast ultimately reaching as far as her pubis. The skin of the breasts was thin and erythematous, with marked dilatation of the superficial veins. The nipple areola complexes were elongated and poorly defined from the surrounding skin. There were no abnormalities of prolactin, sex hormones, growth hormone, or TSH (but the values were not stated). Bilateral total mastectomy was performed and the nipple-areola complexes were removed from the resected tissue and grafted on to the breasts after insertion of a tissue expander. The breast tissue removed from the right side weighed 5 kg and that from the left side 7 kg. Histologically there was increased fibrosis and duct dilatation and no malignancy. This reaction, attributed here to bucillamine, is a rare but well-established adverse reaction to penicillamine. Although the patient had also taken isoniazid for pulmonary tuberculosis, that was unlikely to have played a part, since the breast enlargement started earlier and progressed after the isoniazid had been withdrawn. Drugs in the Pipeline Talia F. Igel MBBS, ... Michael H. Pillinger MD, in Gout, 2019 Bucillamine Bucillamine is a cysteine derivative originally developed as a disease-modifying antirheumatic drug for rheumatoid arthritis. Bucillamine replenishes the thiol group in glutathione to reactivate endogenous defense systems exerting antioxidant effects.13 Bucillamine additionally has antiinflammatory effects beyond its antioxidant action, particularly through its capacity to promote the transcriptional activity of Nrf2.13,14 In murine models, bucillamine inhibits IL-1 and IL-6 release from MSU crystalstimulated macrophages and inhibits IL-1, IL-8, and TNF- release from lipopolysaccharide-stimulated macrophage-derived THP-1 cells.15 These preclinical observations suggest that bucillamine may inhibit MSU crystalinduced stimulation of the NLRP3 inflammasome. Evidence supporting the use of bucillamine to treat gout is limited to a single phase IIa randomized, multicenter, open-label, active-comparator trial, which is still in progress. This study is assessing the efficacy and safety of bucillamine compared with colchicine for treating acute flares in patients with moderate to severe gout. Subjects received either bucillamine (900 or 1800 mg over 7 days) or colchicine according to current American College of Rheumatology (ACR) treatment guidelines (1.2 mg initially, followed by 0.6 mg 1 h later). The treatment phase of the study has been completed, and analysis of the results is underway.16 Nonimmunosuppressive disease-modifying antirheumatic drugs Vivian P. Bykerk, in Rheumatology (Sixth Edition), 2015 Bucillamine Introduction BUC is a DMARD known to be an analogue of d-penicillamine that was introduced in the 1980s for the treatment of RA. d-Penicillamine was historically used as a DMARD in many Western countries during the 1970s and 1980s. Because of only moderate efficacy and a disproportionately high incidence of side effects, it was effectively abandoned in place of more effective DMARDs such as MTX. BUC reportedly has fewer side effects than d-penicillamine does and has been used widely as one of the first-line DMARDs for RA in Japan and Korea. It is approved in Asia only for the treatment of RA. Pharmacology BUC, a thiol compound [N-(2-mercapto-2-methylpropionyl)-l-cysteine], differs from d-penicillamine by the presence of two free sulfhydryl groups and has two S-H bonds in its chemical structure.23 Mode of action BUC is considered to be a DMARD with immunologic effects. It has been shown to suppress IL-6 and IL-8 production by synovial cells in vitro and is thought to have pharmacologic actions that are different from those of d-penicillamine.24 In an in vitro study of its effect on T-cell proliferation, cytokine production, and migration of T cells, BUC significantly inhibited T-cell proliferation, reduced the expression of CD44 on T cells, and inhibited the production of IL-2, interferon- (IFN-), TNF-, and IL-6, thus indicating that it is an inhibitor of type 1 T helpertype cytokine production, proinflammatory cytokine production, and transendothelial migration of T cells.25 The latter appears to be mediated partly through the reduced expression of CD44, an adhesion molecule on the T-cell surface. Efficacy The beneficial effects of BUC for the treatment of RA have been published in several observational studies and clinical trials, with varying effects reported. In a retrospective cohort study of 86 patients with active RA who received BUC between 1998 and 2004, 20% reported improvement from 44% to 56% in ACR core set measures 6 months after initiation of therapy, 50% reported improvement of between 22% and 34% in ACR core set measures, and 70% reported improvement between 11% and 19% in ACR core set measures 6 months after initiation of therapy.26 A 16-week open-label trial of BUC (300mg/day) suggested that this agent is effective as a slow-acting drug for RA in patients who had previously failed gold salt or d-penicillamine therapy.27 In a small randomized controlled trial (N = 46) of d-penicillamine and BUC, BUC was found to be at least as effective as d-penicillamine in improving the swollen joint count, tenderness score, morning stiffness, modified health assessment questionnaire, and erythrocyte sedimentation rate (ESR). It was more effective in terms of improvement in the tender joint count, grip strength, C-reactive protein, and rheumatoid factor titer. However, responses were low, with only 27% of the BUC group and 33% of the d-penicillamine group responding to treatment.28 In a cross-sectional analysis from the IORRA study, a long-term observational database, responses to BUC treatment were noted to be better in males, in patients with a shorter duration of illness, and in those who were rheumatoid factor negative. In a longitudinal analysis from the same study, European League Against Rheumatism improvement criteria were higher in patients receiving BUC (41.0%) than in those receiving MTX (33%) or SSZ (26%).29 A multicenter trial of BUC known as the SNOW study was conducted in patients with early RA. In this 24-month study of 81 DMARD-naive patients with early RA, 87.5% showed moderate improvement in their 28-joint disease activity score (DAS28). After 24 months of BUC therapy, 7 patients (43.8%) met the remission criterion of a DAS28 lower than 2.6, and 60.5% of patients continued BUC either as monotherapy or in combination with other DMARDs after 24 months.30 A multicenter, double-blind controlled trial studying a combination of MTX and BUC was performed in 71 patients with active early RA within 2 years of onset. Patients received 8mg MTX with 5mg folic acid per week, 200mg BUC per day, or both. After 96 weeks they noted an ACR20 response rate of 79.2% in the combination group but only 44% in the MTX group (P = .01) and 46% in the BUC group (P = .02). Also, the combination group exhibited significantly less radiographic progression (total Sharp score over a 96-week period of 12.6 9.0 versus 28.0 28.3 for the single-therapy arms; P = .05). No increased rate of adverse events was noted in the combination group in comparison to the single-therapy group.31 However, in a recent review examining changes in the use of nonbiologic DMARDs in Japan, use of BUC alone appeared to be decreasing and use of MTX appeared to be increasing. BUC was also being more often used in combination with MTX.32 Adverse effects Proteinuria is reported to be the most frequent adverse effect of BUC. In one report, 10 cases of nephrotic syndrome were noted. Most cases occurred within the first 4 months of use. Discontinuation led to resolution of this complication within 1 year. In patients with BUC-induced proteinuria and membranous nephropathy, immediate withdrawal of BUC resulted in complete resolution of the proteinuria without any deterioration in renal function. Thus, monitoring of urinary protein is important when using this agent.33 BUC-induced yellow nail syndrome (a triad of yellow nails, lymphedema, and pulmonary manifestations) was recently described in a review of 36 cases reported mostly in Japanese medical journals.34 Most of these patients (90%) showed improvement in their yellow nails after discontinuation of BUC, but the lymphedema and pulmonary manifestations improved only in 31% and 35% of patients, respectively. Other rare side effects include skin disorders manifested as a rash, which can be vesicular or involve swelling of the lips. Less frequently reported adverse effects include hepatitis35 and bone marrow suppression.36 At least 15 cases of BUC-induced pulmonary injury have been reported. Advanced age was associated with the development of severe interstitial pneumonia, and pulmonary complications were reported to be resistant to corticosteroids and life-threatening, especially in the elderly.37,38 One case of bronchiolitis obliteransorganizing pneumonia has been reported during treatment with BUC.39 Dosage and monitoring Typical doses of BUC range from 100 to 300mg daily. Monitoring should include regular assessment of blood counts and urinalysis for proteinuria. Patients should be evaluated for efficacy by 3 months to determine their response to this therapy. Metal antagonists R.H.B. Meyboom, in Side Effects of Drugs Annual, 2009 Comparative studies In a retrospective 12-month review of the medical records of 348 patients with rheumatoid arthritis (ACR classification) bucillamine and methotrexate were compared (30CR). There were 74 adverse events in 71 patients; none was life-threatening. Skin rashes were the most common (47%) followed by proteinuria (25%). One patient had nephrotic syndrome for about 6 months; bucillamine was withdrawn and the patient made a good recovery. Other adverse events were stomatitis, glossitis, cough, and raised transaminase activities. Rashes mainly occurred in the first 3 months of use, while proteinuria often developed after a longer interval. The authors concluded that the effectiveness of bucillamine can usually be judged within 3 months of use and that it is indicated in the treatment of rheumatoid arthritis of moderate severity, either before or after methotrexate. Immune-Mediated and Other Glomerular Diseases Meryl Waldman, ... John R. Sedor, in Seldin and Giebisch's The Kidney (Fourth Edition), 2008 Membranous Nephropathy Drug-induced membranous nephropathy (MN) has been described most commonly with medications prescribed for rheumatoid arthritis, such as oral and parenteral gold, d-penicillamine, and bucillamine (27, 311, 568, 823, 854, 871). These drugs have also been linked to minimal change disease (243, 265, 311), though less frequently than with MN. Rare case reports of anti-GBM disease and vasculitis due to D-penicillamine have also been reported (243, 513). D-Penicillamineinduced MN has been associated with HLA-B8/DR3 antigen (311, 554, 757), suggesting a genetic predisposition. MN from gold or d-penicillamine generally develops within 6 to 12 months of starting the drugs (30, 361). Decreased GFR is usually not observed. Gold and D-penicillamine are often discontinued when MN is diagnosed, resulting in resolution of proteinuria within 12 months (311, 554). However, in a retrospective series of 53 patients with biopsy-proven nephropathy from gold or d-penicillamine, 21 subjects continued therapy for up to 11 months, without adverse effects on GFR, peak proteinuria values, or resolution of proteinuria (310). Mercury-containing substances, such as older, infrequently prescribed diuretics, some skin creams, and industrial exposure to mercury, have been associated with the nephrotic syndrome due to MN and minimal change disease (58, 330, 404, 528, 605, 809). When captopril was initially released, several case reports were published, demonstrating that high-dose captopril was associated with MN (115, 339, 767, 788). Substitution of enalapril for captopril results in resolution of nephropathy (841), suggesting that sulfhydryl groups unique to captopril may be a stimulus. Lithium has been associated with a variety of glomerular diseases, including MN and FSGS (622, 700), though the most common glomerular lesion is minimal change disease (660, 780). Penicillamine In Meyler's Side Effects of Drugs (Sixteenth Edition), 2016 Nails The peculiar yellow nail syndrome [365], characterized by dystrophy of the nails, lymphedema, pleural effusion, and bronchial involvement, has occasionally been reported in association with penicillamine and also with bucillamine [366369]. It has been suggested that penicillamine and bucillamine, because of their structural similarity to cysteine, might disturb nail growth by interfering with keratin synthesis. Although the nail changes and injury to other organs probably develop by different mechanisms, in patients with nail changes a careful search for possible systemic disorders is needed. Monosymptomatic nail changes, with longitudinal ridging, transverse or longitudinal defects of the nail plate, absence of lunulae, and a tendency toward onychoschizia, can also occur as adverse reactions to penicillamine [370]. 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