Multiple myeloma
John M Barrett, Jennifer G Treleaven in Clinical Practice of Stem-Cell Transplantation, 1999
Although numerous studies have documented tumour responsiveness to both chemotherapy and radio-therapy, multiple myeloma remains an incurable disease. The standard treatment for myeloma for more than three decades has remained a combination of oral melphalan and prednisolone [1]). Various other combinations such as ABCM, VMCP/VBAP and MOCCA [2-5] have been used, but with the exception of ABCM no other treatment strategy has shown a benefit over melphalan and prednisolone. A recent meta-analysis of combination chemotherapy versus melphalan and prednisolone by Gregory et al. [6] of 3814 patients concluded that both treatments were equally effective. A subgroup analysis in this same study revealed melphalan and prednisolone to be superior for patients with intrinsically good prognosis disease, while combination chemotherapy was beneficial for poor prognosis myeloma. This meta-analysis, however, excluded the important MRC V trial [7] which documented the benefits of ABCM combination chemotherapy over oral melphalan, because the control arm was treated with melphalan alone.
Side-effects, interactions and pharmacokinetics
Roger Mcfadden in Introducing Pharmacology, 2009
This chapter explains the cellular origins and pathophysiology of common cancers and the pharmacological action of anti-cancer drugs. Most anti-cancer drugs inhibit the cell division so the people need to understand the process of cell division in order to understand how these drugs work. An ideal anti-cancer drug would kill all cancer cells while leaving normal, healthy cells untouched but targeting the cancerous cells is difficult because differences from other body cells are small. The prednisolone is not an anti-cancer drug but it recruits resting cancer cells from G 0 phase into G 1 phase of the active cell cycle where they are targeted by other drugs in the R-CHOP regime. Anti-cancer drugs target cells that are dividing rapidly, with the intention of either stopping cell division or damaging the cell to the extent that it either self-destructs or is destroyed by the body's own immune cells.
Examination A Questions
Anthony Warrens, Malcolm Persey, Michael Fertleman, Stephen Powis in A Guide to the MRCP Part 2 Written Paper 2Ed, 2005
A 32-year-old renal transplant recipient presents with dyspnoea 6 weeks after transplantation. She had required transplantation after a rapid and irreversible deterioration in renal function due to type I diabetes mellitus. She had had one episode of acute rejection 10 days after transplantation which had been reversed with high-dose corticosteroids. She was discharged 3 weeks after transplantation on prednisolone, azathioprine and cyclosporin A with a plasma creatinine of 119 μmol/L. She had failed to present for regular review for 2 weeks before the present assessment.
Prednisolone Pharmacokinetics and Protein-Binding in Patients with Portosystemic Shunt
Published in Scandinavian Journal of Gastroenterology, 1983
H. Bergrem, S. Ritland, I. Opedal, A. Bergan
The pharmacokinetics and protein-binding of orally administered prednisolone have been studied in seven patients with chronic liver disease and portosystemic shunts. The peak prednisolone serum concentration and the time of peak prednisolone concentration were similar to those found in normal subjects, indicating that there is no clinically significant first-pass metabolism of prednisolone. The elimination half-time and the extent of bioavailability of total prednisolone tended to be lower in the patients, and the extent of free, unbound prednisolone higher, but the differences were not statistically significant. The patients had a significantly lower serum protein-binding of prednisolone than the controls. Despite the decreased protein-binding in the patients, however, the results indicate that changes occur in the pharmacokinetics of prednisolone that tend to reduce the bioavailability of free, biologically active prednisolone towards that seen in healthy subjects. Reduction of the prednisolone dose is therefore not indicated in patients with portosystemic shunt and chronic liver disease, even in the presence of hypoalbuminemia.
Is AL-438 likely to have fewer side effects than the glucocorticoids?
Published in Expert Opinion on Investigational Drugs, 2003
The glucocorticoids are effective anti-inflammatory agents but their use may be limited by systemic side effects. AL-438 and prednisolone inhibit binding to glucocorticoid and mineralcorticoid receptors with similar potency. In rat models of acute and chronic inflammation, AL-438 was effective but less potent than prednisolone. In fasted overnight rats, prednisolone was hyperglycaemic but AL-438 was not. Prednisolone also inhibited bone formation in rats, whereas AL-438 did not. The differing profile of AL-438 relative to prednisolone may be due to altered interactions between the receptor and selected co-activators. AL-438 may have lesser side effects than prednisolone.
Bioavailability of Prednisolone in Patients with Intestinal Malabsorption: The Importance of Measuring Serum Protein-Binding
Published in Scandinavian Journal of Gastroenterology, 1983
The effect of intestinal malabsorption on the oral bioavailability of prednisolone has been studied in six patients with celiac disease and in six patients with malabsorption of various etiologies, five of whom had undergone gut resections. The serum protein-binding of prednisolone was measured in five patients with celiac disease and hypoalbuminemia and in eight healthy controls. Compared with the controls, patients with celiac disease had a 22% lower peak serum prednisolone concentration (p < 0.05) and a 16% smaller area under the time-concentration curve of total prednisolone (NS). The proportion of free prednisolone was 79% greater in patients with celiac disease (p < 0.01), and the area under the time-concentration curve of free, biologically active prednisolone 53% larger (p < 0.05). There were no significant differences in peak prednisolone concentration or area under the time-concentration curve between the controls and the other patients with malabsorption, who all had normal serum albumin concentrations. These results indicate that the absorption of prednisolone in patients with malabsorption is normal and that the apparently reduced bioavailability in celiac disease patients is more likely to be due to an increased volume of distribution secondary to hypoalbuminemia and reduced protein-binding.
Related Knowledge Centers
- Active Metabolite
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- Corticosteroid
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