1MULTIPLE SCLEROSIS MULTIPLE SCLEROSIS Q. 1 Tysabri augments the risk of a unusual type of brain infection known as progressive multifocal leukoencephalopathy (PML) that can lead to mortality or severe disability (Lichtenstein et al., 2012). Using Tysabri can cause this rare brain infection and the risk of getting PML get higher if the patient is infected with the John Cunningham virus. As per the report byFernĂĄndezet al., (2012) a large portion of the patients under Tysabri are becoming positive to the antibodies for the JC virus. John Cunning ham virus can become prevalent in patient if the immune system of the person is compromised due to a disease or due to the sage of the immunosuppressive medications(Palazzo & Yahia, 2012). This virus can affect the brain. This affects the white maters of the brain and attacks the cells in making the myelin sheath that normally protects the nerve cells (Torkildsen et al. 2014). This is related to multiple sclerosis as it is a disease of the central nervous system where the myelin sheath is attacked by the immune system (Loma & Heyman, 2011). The underlying nerve fibers might get damaged due to this. The myelin sheath may get infected and is gradually destroyed developing sclerosis or lesions. Natazulimabisquiteeffectiveinreducingtherelapsesanddelayingthedisease progression of multiple sclerosis. However it does so by suppressing the immune system. Tysabri does so by binding to the alpha subunit of the integrin present on the surface of the
2MULTIPLE SCLEROSIS lymphocytes (Fernåndez et al., 2012). This action obstructs the subunit binding of the receptors. This prevents the entry of the lymphocytes in the central nervous system, which reduces the pathological processes of multiple sclerosis. This suppression of the immunity increases the chance of infection by the JC viruses (Fernåndez et al., 2012). Question 2 Relapsing remitting Multiple sclerosis can be defined as attacks of new neurologic symptoms. The attacks or the relapses or the exacerbations are followed by period of partial or complete recovery. At the time of remissions all the symptoms can disappear and some of the symptoms may persist and can even become permanent. RRMS can be further classified in to active or inactive and worsening or non worsening range. The new lesions formed are de- myelinating reacting with the myelin sheaths directly in the presence of the infiltrating T cells. As perHøglund & Maghazachi, (2014), RRMS is caused by some genetic, environmental factors or infectious agents. There are generally two types of immune responses that is the innate and the adaptive immune response. The initiation of the innate immune response is brought about by the microbial product that activates the specific receptors mainly the toll receptors. Activation of the toll like receptors by the pathogens initiates the adaptive immune response. This helps in the progression of the MS by affecting the effector function of the B and the T cells (Høglund & Maghazachi, 2014). The initiation of the adaptive immune response is again promoted by the presentation of the antigen to the T- lymphocyte by the Antigen presenting cells like the dendritic cells, microglia and the macrophages (Høglund & Maghazachi, 2014). This interaction initiates the adaptiveimmuneresponseinMS.TheTcellsproduceseveralcytokinesthatpromote
3MULTIPLE SCLEROSIS inflammation and the chronic MS plaques. The presence of the T cells in the perivascular cells and the parenchyma triggers the staffing of more T cells as well as the B cells, microglia and the dendritic cells. The cytokines released by them damages the surrounding tissues (Høglund & Maghazachi, 2014). Opsonisation and the complement deposition can cause de-myelination of the neurons and cause neuronal damage. Axonal damage can also occur. A crucial finding in the pathogenesis of MS is the interference in the blood brain barrier. The blood brain barrier of the brain is the basic anatomical barrier that separates the blood from the neurons (Goldenberg, 2012). MS lesions occur due to the migration of the leukocytes to the brain and thus the inflammation occurs. (Goldenberg, 2012). The symptoms of RRMS includes the blurred vision, numbness or tingling, bowel or bladder problems that can be linked to the clinical manifestations shown by the Mrs. Jane Robertson, who is a 34 years old female. It is revealed from the case study that the patient was suffering from temporary blindness in one eye. This may happen in case the optic nerves of the eye gets inflamed. People with multiple sclerosis might have bowel problem due to the nerve damage or the aggravation caused by constipation. It is also caused by the action of certain medications. Any individual suffering from long time physical complications might suffer from depression. Apart from this MS can itself cause depression (Induruwa et al., 2015). According to Siegert & Abernethy, (2015), MS is associated with the presence of the type of lesions in particular regions of the central nervous system, such as lesions in the temporal lobe. Studies have found that that the rate of depression is greater in patients with lesions than those without lesions. This is how the pathophysiology is linked to the patientâs symptoms. Question 3
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4MULTIPLE SCLEROSIS Interferon Beta (Avonex) IM 30mg once a week- Use: It is a cytokine in the interferon that is used to treat multiple sclerosis. Mode of action: Beta interferons (IFNβ) achieves its anti-inflammatory effects by inhibiting the activation of the T-cells and the proliferation, apoptosis of the auto-reactive T cells and induction of the regulatory T-cells, inhibiting the migration of the leucocytes across the blood brain barrier, modulation of the cytokine and the potential antiviral property (Shirani et al., 2013). Methotrexate (Methoblastin) 7.5mg once a week Use- It is a toxic anti-metabolite that helps in the control of the autoimmune disease. It helps to delay the progression of MS. Mode of action- It helps by inhibiting the T cell activation and, inhibiting the enzyme that is responsible for the purine metabolism and suppression of the intercellular adhesion molecular expressions for inhibiting the immune attack. Teriflunomide (Aubagio) Use- It provides a therapeutic benefit in MS not causing clinical suppression of the immune system. Mode of action- Teriflunomide inhibits the dihydro-orotate dehydrogenase, which is a key microbial enzyme used in the de novo pyrimidine synthesis pathway, resulting in the reduction of the T cell proliferation without cell death (Bar-Or et al., 2014). Natalizumab (Tysabri) injection 20 mg/mL, 15mL once a week
5MULTIPLE SCLEROSIS Use- It is a monoclonal antibody that is used in multiple sclerosis by preventing the immune cells in the CNS. Mode of action- It inhibits the transmission of the lymphocytes in the central nervous system by interfering with the ι4 subunit of ι4β1 integrins expressed on the leukocytes surface (except neutrophils). Question 4. One of the issues regarding her medication is that the doctor had put her on a course of Methotrexate and has suggested that she commences with Natalizumab. According to several studies these two drugs may interact and can cause adverse drug reaction and hence are not taken together usually (Hoepner et al., 2014). Natazulimab is a monoclonal antibody that weakens the immune system, hence if taken with an immunosuppressant weakens the immune system further and increase the chance of JC virus infection. Natazulimab (Tysabri) class of the drug should be stopped immediately as she had already developed PML and use of natazulimab with an immunosuppressant may further aggravate the situation. Question 5 The seven rights of medication involved right medication. In this case study it seems that the pharmacist has delivered her a wrong mediation as it was written Avonexover the package. Avonex belongs to the class interferon beta 1-a. whereas Teriflunomide is an active metabolite that blocks the pyrimidine synthesis (He et al., 2012). Hence these two drugs are different hence the pharmacist has prescribed a wrong medicine.Furthermore, with the name printed on the
6MULTIPLE SCLEROSIS package it seemed that the medication had been delivered to the wrong patient as the name printed in the package was Mrs. Jayne Roberts. The route of administration via orally has been correct. Patient was given the right dosage of medicine. No report of documentation has been mentioned in the case study. Question 6 Goals-The goal is to reduce the symptoms of the relapsing remittig form of the multiple sclerosis and to relive the neurologic deficients such that the patient can resume to her normal life (Torkildsen et al., 2016). Drug dosage form, route and schedule and duration therapy for the treatment- Alemtuzumab Dosing- 12mg/day 5 consecutive days which is followed by 12 mg/day for 3 consecutive days one year later. Route - Intravenous. Avonex Dosing- 30 mcg weekly Route- Intramuscular. Aubagio Dosing- 7.0 mg and 14.0 mg; qd Route- Orally.
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7MULTIPLE SCLEROSIS Adjustments in the drug therapy-One of the major adjustments in the drug therapy is to stop the therapy of Tysabri along with other immunosuppressant, as the patient has already been diagnosed JC virus. Non pharmacological therapies-Non pharmacological treatment in Multiple sclerosis involves physical therapies such as acupunctire, yoga or relaxation by meditations. Herbal remedies can also ne applied. Proper nutritional assessment can alleviate the MS symptoms. People with MS having regular massage therapy can be helpful for getting rid of the stress and depression (Heine eta al., 2012). According toTorkildsen et al.,( 2016) evening primrose oil has ben found to be effective in reducing the MS symptoms.
8MULTIPLE SCLEROSIS References Bar-Or, A., Pachner, A., Menguy-Vacheron, F., Kaplan, J., & Wiendl, H. (2014). Teriflunomide andItsMechanismofActioninMultipleSclerosis.Drugs,74(6),659â674. http://doi.org/10.1007/s40265-014-0212-x FernĂĄndez, O., GarcĂa-Merino, J. A., Arroyo, R., Ălvarez-CermeĂąo, J. C., Arbizu, T., Izquierdo, G., ... & Oreja-Guevara, C. (2012). Spanish consensus on the use of natalizumab (TysabriÂŽ)â2011.NeurologĂa (English Edition),27(7), 432-441. Goldenberg, M. M. (2012). Multiple sclerosis review.Pharmacy and Therapeutics,37(3), 175. He, D., Xu, Z., Dong, S., Zhang, H., Zhou, H., Wang, L., & Zhang, S. (2012). Teriflunomide for multiple sclerosis.Cochrane Database Syst Rev,12. Heine, M., Rietberg, M. B., Van Wegen, E. E., Port, I. V. D., & Kwakkel, G. (2012). Exercise therapy for fatigue in multiple sclerosis.Cochrane Database Syst Rev,7. Hoepner, R., Faissner, S., Salmen, A., Gold, R., & Chan, A. (2014). Efficacy and side effects of natalizumab therapy in patients with multiple sclerosis.Journal of central nervous system disease,6, JCNSD-S14049. Høglund, R. A., & Maghazachi, A. A. (2014). Multiple sclerosis and the role of immune cells. World journal of experimental medicine,4(3), 27. Induruwa, I., Constantinescu, C. S., & Gran, B. (2012). Fatigue in multiple sclerosisâa brief review.Journal of the neurological sciences,323(1), 9-15.
9MULTIPLE SCLEROSIS Lichtenstein, G. R., Hanauer, S. B., & Sandborn, W. J. (2012). Risk of Biologic Therapy- Associated Progressive Multifocal Leukoencephalopathy: Use of the JC Virus Antibody Assay in the Treatment of Moderate-to-Severe Crohnâs Disease.Gastroenterology & Hepatology,8(11 Suppl 8), 1â20. Loma, I., & Heyman, R. (2011). Multiple Sclerosis: Pathogenesis and Treatment.Current Neuropharmacology,9(3), 409â416.http://doi.org/10.2174/157015911796557911 Palazzo, E., & Yahia, S. A. (2012). Progressive multifocal leukoencephalopathy in autoimmune diseases.Joint Bone Spine,79(4), 351-355. Shirani, A., Zhao, Y., Karim, M. E., Evans, C., Kingwell, E., van der Kop, M. L., ... & Tremlett, H. (2012). Association between use of interferon beta and progression of disability in patients with relapsing-remitting multiple sclerosis.Jama,308(3), 247-256. Siegert, R. J., & Abernethy, D. A. (2015). Depression in multiple sclerosis: a review.Journal of Neurology, Neurosurgery & Psychiatry,76(4), 469-475. Taylor, K. L., Hadgkiss, E. J., Jelinek, G. A., Weiland, T. J., Pereira, N. G., Marck, C. H., & van der Meer, D. M. (2014). Lifestyle factors, demographics and medications associated with depression risk in an international sample of people with multiple sclerosis.BMC psychiatry,14(1), 327. Torkildsen, Ă., Myhr, K. M., & Bø, L. (2016). Diseaseâmodifying treatments for multiple sclerosisâa review of approved medications.European journal of neurology,23(S1), 18- 27.