Question

Case Study 3 Glucocorticoid Agents A 40-year-old woman has had rheumatoid arthritis for 5 years. She has been on multiple NSAIDS with some symptomatic relief. On a few occasions she has taken corticosteroids for severe exacerbations. She feels that her disease is getting worse. She has more stiffness and swelling in her hands and wrists. She is currently taking the recommended maximum dosage of ibuprofen, but admits to taking more than she should on bad days. On examination, the nurse notes active synovitis of both wrists and all of her metacarpal joints. There is a subtle ulnar deviation of all of her fingers. The Physician assesses her as having an acute exacerbation of rheumatoid arthritis, prescribes a short course of corticosteroids and starts her on methotrexate . What is the mechanism of the immune response mediated by glucocorticoids? (25 pts.) 2. What is the mechanism of action of methotrexate (25pts.) 3. Why is methotrexate helpful in this situation? (25pts.) What would the nurse teach this woman regarding glucocorticoid drugs? (25pts.)

Answer 1

1, Glucocorticoids used for the treatment of antiinflammatory effects in Auto immune disease..It prevent graft rejction..It was acting as a glucocorticoid mediated immunosuppression..It has both negative and positive effects on various limbs with a dynamic and bi- directional spectrum of activities and components of immune response..Glucocorticoids induce specific antigens influencing deudrific cells maturation and function and promoting the development of regulating high IL-10-producing T cells..It was used in cell therapy treatment..It has inhibitory effects on multiple type of immune cells..it manage many acute diseases symptoms of inflammatory and autoimmune disorder..They are more widely used to treat both acute and chronic inflammation like Rheumatoid arthritis,inflammatory bowel disease,psoriasis ans aczema,some leukemia,immunosuppressive regimens following organ transplant..Main charecteristics of the glucocorticoids receptors(GR) as a DNA binding protein that regulates transcription initiation,the clowning of GR and the action of immuno suppression glucocorticoids mediated by interference and signaling by the inflammatory transcriptional regulator: NF-KB and AP-1 glucorticoids inhibits the vasodialtion and increase vascular permeability happen in inflammation and they decrease leukocyte emigration into inflamed sites..
2, Methotrexate irreversibly and competitively inhibitss dihydrofolate reductase that enzymes participates in tetrahydrofolate synthesis..Di hydrofolate reductase catalyses the conversion of dihydrofolate into active tetrahydrofolate..folic acid for de novo synthesis of the nucleosides,thymidine needed for DNA synthesis..Glutamate residues to methotrexate to produce methotrexate polyglutamate..These glutamate residues to methotrexate increases the affinity for more enzymes and enzymes of the de novo purine..Synthesis pathway of the enzymes indirectly affect by methotrexate like 5.10-methotrexate hydrofolate reductase and dehydrogenase..methotrexate inhibit the synthesis of DNA,RNA, and proteins..
3,Methotrexate (MTX) is a folate analogue to inhibit dihydrofolate reductase..Less folate is the proximal single carbon donor in several reactions involved in denovo systhesis patheays for pyrimidine precursors and purine of DNA and RNA need cell proliferation..Tetrahydrofolate in methionine -homocystemic cycle needed for methyl group reaction of methylation of DNA,RNA and protein..It is useful for the treatment of neoplastic disease..In rheumatoid arthritis it inhibit proliferation of the lymphocytes and other cells responsible for inflammation in the joints ..It does not act as a cytotoxic agent to the cell responsible for the joint inflammation..It reduce the inflammation by preventing the proliferation of immune cells ,it works as a effective concentration in very short time..This mechanism responsible for antiinflammatory effects..