Multiple Sclerosis Flashcards
What type of disease is MS
Chronic autoimmnune, inflammatory disease that destroys myelin sheath and impairs the ability to send electrical impulses
What is though to have an effect on MS
Higher Vitamin D levels reduce the disease activity in MS patients
The Epstein-Barr virus triggers MS in
How is MS graded on a scale and how is severity determined?
On the Kurtzke scale and low is better
What are some symptoms of MS?
muscle weakness, blurry vision, bladder problems, cognitive disturbances, sensitivity to heat
How do you diagnose MS?
2 documented clinical exacerbation separated by time and space
2 distinct MRI lesion separated by time and space (DIS - on areas known to be affected by MS)
What MRI findings are consistent with MS?
- 4 white matter lesions (>3mm)
- 3 white matter lesions, 1 periventricular (>6mm)
- Ovoid lesions perpendicular to ventricles
- Open ring appearance gadolinium enhancements
- Corpus callosum lesions
How can you describe CIS
1st episode of neuro symptoms lasting 24 hours due to inflammation and demyelination.
Patient may or may not develop MS
What is the most common form of MS?
Relapsing Remitting Multiple Sclerosis
How can you described RRMS?
Worsening or new onset of symptoms lasting >48 hours contrasted by symptoms free periods (remission)
How can you describe SPMS?
Progression of RRMS and is steadily progressing with or without clear-cut relapses
How can you describe PPMS?
Rare with a steady decline without clear cut relapses. Meds also aren’t generally effective at this point.
How can you describe PRMS?
Rare with steady progression with clear-cut MS exacerbations. Can use steroids but disease will still progress.
What is the treatment for MS?
No known cure. Can only treat symptoms
How to treat symptoms of an acute severe attack?
- Methylprednisolone
- Corticotropin (Acthar gel)
- H2 blocker/PPI (ulcer prophylaxis)
- Monitor blood glucose
- Watch for infection
What are your Original ABCR Injectables
Interferon Beta 1a
- Avonix
- Rebif
- Plegridy
Interferon Beta 1b
- Betaseron
What Interferon Beta used for?
Relapsing forms of MS: CIS, RRMS, active SPMS
What are the interferon beta side effects?
- Flu like symptoms!!!!!
- Injection site reaction
- Depression
- Myalgia
- Mayasteria
What is Glatiramer Acetate?
may alter T cell activation/differentiation.
Available as Copaxone
What is Copaxone used for?
Relapsing forms: CIS, RRMS, actve SPMS
What are the side effects of Copaxone?
Injection site reaction
Transient flushing
Chest tightness/pain
What are the monoclonal antibodies used ins MS?
- Natalizumab
- Alemtuzumab
- Daclizumab
- Ocrelizumab
- Ofatunumab
What does Natalizumab do?
Prevent transmigration of leukocytes across endothelium into inflamed parenchymal tissues
*crossing BBB
What is Natalizumab also known as?
Tysabri
How is Natalizumab dosed?
300 mg IV every 4 weeks
What is Natalizumab used for?
Relapsing forms: CIS, RRMS, active SPMS
What is fatal side effect of Natalizumab?
PML - rare, fatal viral infection that is activated by the latent JC virus and is demyelinating
What program is Natalizumab under and for what?
TOUCH prescribing program due to PML
Who must be registered under the TOUCH program?
Patients
Prescribers
Infusion centers
What are the side effects of Natalizumab?
- Infusion site reaction
- Resp Tract Infection
- Urinary Tract Infection
- Cholelithiasis
- Depression
- PML
What does Alemtuzumab do?
Decrease of T cell circulation
What is Alemtuzumab indicated for?
Relapsing forms of MS and reserved for inadequate response to 2 or more medications.
What should you do to initiate Alemtuzumab?
Premedicate with corticosteroids for the first 3 days and antiviral prophylaxis (herpes) on the first day till 2 months post alemtuzumab
What is the side effect of Alemtuzumab?
- Autoimmnue Thyroid Disorder (GRAVES)
- Rash
- Neuro problems
- Musculoskeletal pain
- Shortness of Breath
What is Alemtuzumab Black Box Warning?
autoimmnue condition: thrombocytopenia and antiglomerular basement membrane disease
Infusion Reaction
Malignancy
How should you monitor Alemtuzumab?
Monitor TSH levels at baseline and every 3 months
Monitor CBC w/ differential, SCr, urinalysis periodically for 48 mos post alemtuzumab
Baseline and yearly skin exams
ECG prior each treatment
Protocol for initiating Alemtuzuamb
Admin in setting with appropriate equipment and personnel (anaphylaxis or infusion reaction) - life threatening
Observe for 2 hours
How does Ocrelizumab work?
May play a role in immune system mediated damage to brain and spinal cord tissues
Are there any medications that can help treat PPMS?
Yes. Ocrelizumab is the first to show results during the ORATORIO trial
What does Ocrelizumab do?
It reduces relapse, disease progression and disease activity on MRI in RRMS, SPMS
What is Ocrelizumab indicated for?
PPMS, relapsing forms: CIS, RRMS, active SPMS
What are your side effects or precautions while on Ocrelizumab?
- decrease in IgG levels (monitor levels for opportunistic infection)
- Increase risk in URTI and UTI
- Systemic and local injection reaction
- PML
- Use contraception in reproductive females during and 6 months post
What are your immunomodulator drugs?
- Mitoxantrone
- Mavenclad
How does Mitoxantrone work?
It causes DNA strand breaks and inhibits repair via topoisomerase II. It affects rapidly dividing cells.
What is mitoxantrone indicated for?
SPMS, PRMS, worsening RRMS
- to reduce neuro disability and relapse frequency
- reserve for rapid advancing/refractory
What are the side effects of Mitoxantrone?
- Cardiotoxicity
- Hepatic dysfunction
- Alopecia
- Bone marrow suppression (CBC)
- Stoma/esophagitis, oral ulceration
What is Mavenclad?
Immunomodulator that is a purine nuceloside analog. It is a prodrug and it helps deplete lymphocytes by DNA breakage and repair synthesis shutdown
What is Mavenclad indicated for?
RRMS, active SPMS (when response is inadequate)
How to dose Mavenclad?
3.5 mg/kg over a 2 year course
1.75 mg/kg/year
4 - 5 consecutive days
Available as 10 mg tablets
Max daily dose is 20 mg/day
What should you do if you miss a dose?
Admin missed dose next day and extend treatment by number of missed doses
What is the precaution with taking Mavenclad?
Lymphocyte must be within normal limits before initiating treatment
What is the precaution with of Mavenclad administering Mavenclad?
NIOSH says its hazardous so wear gloves during handling, admin, disposal of Mavenclad
What is the BBW associated with Mavenclad?
- Malignancies
- Teratogenicity
What is Mavenclad Contraindicated with?
- Hypersensitivity
- Breastfeeding
What MS drug requires first dose monitoring?
Fingolomod
Siponimod
How long does Fingolomod first dose monitoring last?
6 hours
-ECG and monitor hourly for bradycardia
What are the side effects of Fingolomod?
- Lympho/Leukopenia
- URTI
- macular edema
- Increased BP and Hypertension
- Increased LFTs
What are your precautions in Fingolomod usage?
Use contraceptives
What is Mayzent/Siponomod?
It is an MS drug; S1P receptor modulator that decrease the amount of lymphocytes available to the CNS; blocks from leaving lymph nodes
What is Mayzent/Siponomod indicated for?
CIS, RRMS, active SPMS
What is the protocol for initiating Mayzent/Siponomod therapy?
CYP2C9 Gentotype testing
What genotypes to test for Mayzent/Siponomod?
1/1, 1/2, 2/2; I: 0.25 - 1.25, M: 2
1/3, 2/3; I: 0.25 - 0.75, M: 1
What genotype is contraindicated in Mayzent/Siponomod therapy?
CYP2C9 3/3
What is the protocol for Mayzent/Siponomod therapy intitation?
First dose monitoring for pre-existing cardiac conditions (6 hours)
What are the contraindications of Mayzent/Siponomod?
CYP2C9 3/3
MI/TIA/stroke/ADHF (hospitalized)/3rd degree heart block/Class III/IV HF
What are the warnings/precautions of Mayzent/Siponomod?
Infections
Immunization (test VZV antibodies)
PML
Macular edema
Bradycardia (transient decrease in HR)
Atrioventricular conduction delays
QT prolongation
Cardio disease
Respiratory effects
Hepatic effects
HTN
Neurotoxicity
Malignancy
D/C of therapy (rebound syndrome)
What are Mayzent/Siponomod DDIs
Immunosuppresants
Bradycardia causing agents
AV blocking agents
QT prolonging agents
2C/3A4 inducers may decrease conc
2C/3A4 inhibitors may increase concM
What are the monitoring parameters for Mayzent/Siponomod?
ECG
CBC
Hepatic (baseline bilirubin/transaminase)
Ophthalmogic exam
Respiratory function
VZV antibodies
Sinus bradycardia
1st/2nd degree AV block
h/o MI or HF
How does Zeposia/Ozonimod work?
Binds to S1P 1&5 receptors and blocks lymphocytes from emerging from lymph nodes
What is contraindicated in Zeposia/Ozonimod therapy?
MI/unstable angina/TIA/ADHF (hospitaliztion), Class III/IV, 2nd or 3rd degree AV block, use of MAOBi
What is your diet precaution with Zeposia/Ozonimod?
High tyramine food may cause hypertensive crisis
What is Teriflunomide?
It blocks pyrimidine synthesis and decreases the ability of APC’s to activate T cells
How does Teriflunomide work?
selectively produces a cytostatic effect on proliferating T and B cell lymphocytes in periphery and reduces B cell proliferation
What is Teriflunomide indicated for?
For relapsing forms of MS
What are the side effects of Teriflunomide?
Nasopharyngitis
URTI/UTI
Alopecia
Sensory disturbances
Nasopharyngitis
Increased LFTs
What are the fumerates used in MS?
Dimethyl Fumerate (Tecfidera)
Diroximel Fumerate (Vulmerity)
Monomethyl fumerate (Bafiertam)
How do the fumerates work?
reduce migration of lymphocytes
What are the side effects of a fumerate?
GI side effects (food; due to MMF)
Flushing (admin aspirin)
What is the difference between the fumerates?
Vulmerity rapidly converts MMF - less GI effects
Bafiertam lower dose needed - lower GI effects
What are the treatable symptoms of MS?
Spasticity
Bladder problems
Sensory issues
Fatigue/cognitive issue/emotional issues
Walking
Pseuldobulbar Affect
How can you treat spasticity in MS?
Baclofen
Dantrolene
Benzo (diazepam, clonazepam)
Tizanaidine
Gabentin, pregabalin, tiagabine
Botox
Dalfampridine
How to treat bladder problems in MS?
Propantheline
Oxybutinin
Dicyclomine
Desmopressin
Mirabegron (Mybetriq)
**Antimuscarininc
**Anticholinergic
How to treat sensory issues in MS?
Gabapentin
Pregabalin
Carba/Oxcarbazepine
TCAs
Lamotrigine
Duloxetine
How to treat Fatigue/Cognitive/Emotional issue in MS?
Amantadine
SSRI/SNRI
Modafanil
Methylphenidate
Dexamphetamine
What is pseudobulbar affect?
uncontrollable laughing or crying in MS, AD, ALS patients
How can we treat pseudobulbar affect?
Nuedexta
What are the contents of Nuedexta?
Dextromethorphan and Quinidine
What does Dextromethorphan in PBA in MS?
Inhibit glutamate at NMDA receptor
What does Quinidine do in PBA in MS?
Boosts Dextromethorphan (blocks its metabolism)
What helps with walking in MS?
Dalfampridine
What is Dalfampridine contraindicated in?
It is contraindicared in moderate or severe renal impairment
