CDM 4 Exam 2 Review I MS A Inflammatory demyelinating disease of CNS B Deyelinated lesions sclerosis C Cause of MS is unkown II Epidemiology Etiology A Environmental genetic factors B Risk is higher for 1 Women 2 1 1 Possibly combination of genetic susceptibility and a non genetic trigger a Smoking low Vitamin D levels infections Epstein Barr mono a Women are usually diagnosed at an earlier age b Men usually have the more severe progressive form 2 Whites with scandanavian ancestry 3 Blacks more likely to have progressive form 4 1st degree relative with MS 5 Above 37th parallel C Diagnosis peak in 4th decade D Risk can change depending on geography and age 1 Young children 15 yo take on the risk of the area they live in III Pathophysiology A Myelin speed of AP along neuron B MS is an autoimmune response which causes inflammation of myelin eventually leading to demyelination destruction of myelin s sx based on area of nerve demyelination s sx may last for days months may come and go so very hard to diagnose IV Clinical Presentation A Primary s sx 1 Visual complaints optic neuritis 2 Gait problems 3 Paresthesias tingling pricking tickling or burning of skin 4 Pain 5 Spacisity SKM paralysis tendon reflex hypertonia muscle tone of symptomatic muscles 6 Weakness 7 Ataxia unsteady gait 8 Speech difficulty 9 Psychological cognitive change 10 Lhermitte s sign barber chair phenomenon an electrical sensation that runs down the back and into the limbs 11 Fatigue 12 Bowel bladder dysfunction B Secondary symptoms 1 Recurrent UTIs 2 Urinary Calculi 3 Decubiti 4 Depression 5 URIs 6 Poor Nutrition C Tertiary Symptoms 1 Financial 2 Personal 3 Social 4 Vocational 5 Emotional 1 D Disease Courses 1 Relapsing remitting MS RRMS what we will focus on 2 Primary Progressive MS 3 Secondary progressive MS 4 Progressive relapsing MS PPMS SPMS PRMS Indicator Age at onset Gender Initial symptoms Attack frequency in early disease Course of disease Favorable Prognosis 40 years Female Low Relapsing remitting Unfavorable Prognosis 40 years Male High Progressive Optic neuritis or sensory Motor or cerebellar E Relapse remitting MS Inflammatory attacks on myelin and the nerve fibers themselves 1 2 During attacks activated immune cells cause localized areas of damage creating the symptoms 3 Relapses followed by partial or complete recovery periods remissions a No disease progression occurs b 85 of people are initially diagnosed with relapsing remitting MS c Progression to SPMS occurs in 80 of patients V Treatment of acute exacerbations A Methylprednisolone 2 1 Shortens duration of attack 2 May delay repeat attacks for up to 2 years after optic neuritis IV ONLY PO will not 3 Dose 500 1000mg IV daily 4 Duration 3 10 days with improvement in 3 5 days 5 ADE sleep disturbance metallic taste BG GI upset hyperactivity depression CRAZY VI FDA approved disease modifying agents Brand Avonex Rebif Plegridy Betaseron Extavia Copaxone Aubagio Dimethyl Fumarate Gilenya Lemtrada Tysabri Novantrone A Goals of therapy Generic Interferon beta 1a Interferon beta 1a PEGinteferon beta 1a Interferon beta 1b Interferon beta 1b Glatiramer acetate Teriflunomide Tecfidera Fingolimod Alemtuzumab Natalizumab Mitoxantrone 1 Reduce inflammation and axonal damage 2 Decrease relapse rate best outcome with newer agents 3 Reduce progression of disability longer we can keep them walking the better the outcome 4 Slow accumulation of lesions on MRI B Ms and pregnancy 1 Relapse rate usually reduced during 3rd trimester with increase postpartum 2 MS meds Most without adequate studies in pregnancy mitoxantrone Class D teriflunomide class X Importance of contraception and communication with MD 3 C MS pipeline immunomodulators phase 3 trials 1 Daclizumab monthly SQ injection for RRMS reduce annual relapse rate DECIDE trial cut relapse rates and disability progression in MS pts more effectively than Avonex in phase III trial hepatotoxicity remained an issue 2 Laquinimod PO once daily for RRMS reduce relapses disability progression and brain volume loss may be neuroprotective VII MS take home points A MS is a progressive disease with no cure goals of tx are to slow disease progression treat exacerbations and manage symptoms B The majority of tx are injections or infusions and education on proper administration and expected ADE is important 3 C Pharmacists can play an important role in terms of pt education and recommendations on managing VIII Considerations for determination of MS disease modifying therapy failure or loss of efficacy specific symptoms A Patient factors 1 Drug tolerability 2 Drug toxicity 3 Adherence to dose regimen 4 Adherence to monitoring requirements B Clinical factors C MRI factors 1 Comparison of pretreatment and on treatment relapse rates 2 On treatment relapse rate 1 year severity and degree of recovery 3 4 5 Presence of NABs for interferon Beta drugs and natalizumab Increased neurological impairment ex EDSS score increase by 1 point in 1 y Increased cognitive dysfunction Increase in brain lesion serial MRI scans 1 2 Occurrence of on treatment active adolinium enhancing lesions 3 4 5 Development or worsening of cerebral atrophy Increase in brain stem or spinal cord lesions Increase in brain MRA TI black holes marker of irreversible axonal loss D Questions to be answered 4 Ideal time for initiation of therapy 1 Biomarkers to assist in defining tx failure 2 3 No studies comparing all four ABC R drugs 4 No role for combination Disease modifying therapy IX Pharmacist s role in MS and ALS A Muscle Pain 1 Management carbamazepine PHT amitriptyline nortriptyline gabapentin 2 Comments consider NSAIDS for resulting joint pain TCA anticholinergic effects B Muscle spasticity 1 Management tizanidine baclofen diazepam cyclobenzaprine dantrolene botulin toxinA 2 Comments Titrate to effect dantrolene and intrathecal baclofen used in severe cases C Excessive saliva or drooling sialorrhea ALS only 1 Management glycopyrrolate benztropine atropine PO IM SC IV hyoscyamine scopolamine patch 2 Comments consider route of admin when selecting agent D Fasciculation cramps 1 Management quinine sulfate CBZ PHT Mg Vit E verapamil 2 Comments quinine is first line despite lack of data in this pt population E Weight loss malnutrition F Depression and anxiety G Insomnia 1 Management chloral hydrate diphenhydramine flurazepam 2 Comments use with caution H Pathological laughing or crying Pseudobulbar affect a neurological condition characterized by episodes of crying