Multiple Schlerosis Flashcards

Question

Interferon beta - Drug Class and MoA

Answer 1

ABCR Injectables MoA: not fully defined. It may augment suppressor T-cell function; may decrease interferon gamma secretion by activated lymphocytes; may decrease macrophage activating effect; may down-regulate expression of major histocompatibility complex gene production on antigen presenting glial cells. May also suppress T cell proliferation and decrease blood brain barrier permeability

Answer 2

RELAPSING forms of MS including clinically isolated syndrome, RRMS, and “active” SPMS

Answer 3

Interferon beta-1a 30mcg IM injection dosed weekly Can titrate to 30mcg to avoid flu-like symptoms

Answer 4

Interferon beta-1a SubQ injection TIW 22 or 44 mcg dose

Answer 5

Interferon beta-1a SubQ injection every 14 days Dose titration up to 125mcg Plegridy® is pegylated interferon which refers to polyethylene glycol attached to interferon molecules to allow them to maintain their biologic effects in the body for a longer period of time

Answer 6

Interferon beta-1b SubQ injection QOD 250mcg dose after titrating over 6 weeks

Answer 7

Interferon beta-1b SubQ injection QOD 250mcg dose after titrating over 6 weeks

Answer 8

**FLU LIKE SYMPTOMS** - up to 60% of patients. Pre-medicate with Tylenol/ibuprofen to alleviate Generally worse in females and those with lower body weight **Depression (not best agent if pt has uncontrolled depression) Injection site reactions, HA, fever, myalgia, malaise, etc.

Answer 9

Mechanism of Action = Not fully known, thought to be related to alteration of T-cell activation and differentiation. Glatiramer acetate-specific suppressor T-cells are induced and activated in the periphery (potential MoA). May mimic antigenic properties of myelin basic protein; May bind to Major histocompatibility complex class II receptors and inhibit binding of myelin basic protein peptides to T cell receptor complexes; May induce Th2 antiinflammatory lymphocytes and decrease inflammation, demyelination, and axon damage. Available as Copaxone,® Glatopa – Subcutaneous injection given once daily

Answer 10

RELAPSING forms including clinically isolated syndrome, RRMS, and active SPMS Side note: Is NOT an interferon beta agent, is an ABCR injectable

Answer 11

Some neurologists don’t believe in relapsing nature of SPMS. Active denotes those with SPMS that relapse

Answer 12

Murine complement sequence only

Answer 13

Murine antigen binding domain and complement sequence (See image in notes)

Answer 14

Tysabri Mechanism of Action = Antagonizes α4-integrin of the adhesion molecule very late activating antigen (VLA)-4 on leukocytes. Binds to the α4-subunit of α4β1 and α4β7 integrins expressed on the surface of all leukocytes except neutrophils, and inhibits the α4- mediated adhesion of leukocytes to their counter-receptor(s). **Prevents transmigration of leukocytes across the endothelium into inflamed parenchymal tissue. Think of patho of MS (“leaky BBB” that allows body’s natural immune response to target myelin) Even more effective than interferon beta agents for efficacy

Answer 15

Natalizumab • A humanized monoclonal antibody. • Intravenous infusion given once every 4 weeks • Dose = 300 mg

Answer 16

Natalizumab=sztn biosimilar to Tysabri

Answer 17

RELAPSING forms including clinically isolated syndrome, RRMS, and active SPMS

Answer 18

**Progressive Multifocal Leukoencephalopathy (PML) = a sometimes fatal viral opportunistic infection – Results from activation of the latent John Cunningham polyomavirus in immunocompromised pts – PML is a demyelinating disease similar to MS, causing impairment of the transmission of nerve impulses, however **once myelin is lost in PML, it cannot be regained.** TOUCH Prescribing Program - MRI and symptom monitoring required due to PML risk Other SEs: infusion rxn, UTI, respiratory tract infection, depression, HA, fatigue, etc.

Answer 19

1. Natalizumab 2. Fingolimod 3. Dimethyl Fumarate

Answer 20

1. testing positive for antibodies to JCV (John Cunningham Virus, human polyomavirus 2) 2. prior use of certain immunosuppressant medications 3. using natalizumab for more than 2 years

Answer 21

Lemtrada Mechanism of Action = humanized monoclonal antibody. Targets CD52 on T and B lymphocytes, natural killer cells, macrophages and monocytes, causing long-term reduction of circulating T-cells

Answer 22

Lemtrada Indicated for RELAPSING forms of MS, generally reserved for inadequate response to 2 or more (disease modifying) medications

Answer 23

Lemtrada “A reset on the patient’s immune system” 12 mg infused *IV daily over 4 hours for 5 days, then a 3 day course at month 12; patients are observed 2 hours after infusion. Patients can be re-treated again for another 3 days after 12 months *Premedicate with corticosteroids (methylprednisolone 1,000 mg or equivalent) * Antihistamines and/or antipyretics may also be considered. Administer antiviral prophylaxis (for herpetic viral infections (16% vs 3% interferon)) beginning on the first day of treatment and continue for at least 2 months after completion of alemtuzumab and until CD4+ lymphocyte count is ≥200/mm3

Answer 24

Lemtrada *DEVELOPMENT OF Autoimmune THYROID DISORDERS  Including GRAVES’ DISEASE requiring thyroid ablation  In 1/3 of patients  For MS, monitor TSH at baseline and every 3 months until 48 months after last infusion or longer or at any time during therapy if clinically indicated. *Rash in 90% of patients Others: infections, dizziness, HA, N/V/D, etc.

Answer 25

Lemtrada BBW: - autoimmune conditions, such as immune thrombocytopenia and anti-glomerular basement membrane disease. - ischemic/hemorrhagic stroke within 3 days of dose admin - Infusion reactions (Lemtrada): Alemtuzumab causes serious and life-threatening infusion reactions (92%). must be administered in a setting with appropriate equipment and personnel to manage anaphylaxis or serious infusion reactions. Monitor patients for 2 hours after each infusion. - Malignancy

Answer 26

Lemtrada CBC with differential prior to initiation then monthly until 48 months after last infusion; serum creatinine prior to initiation then monthly until 48 months after last infusion or at any time during therapy if clinically indicated; Urinalysis with urine cell counts (prior to initiation then monthly); signs/symptoms of infection; TSH at baseline and every 3 months until 48 months after last infusion or longer or at any time during therapy if clinically indicated; Observe for at least 2 hours after each infusion, longer if clinically indicated; ECG prior to each treatment course No live vaccines, wait 6 weeks after VZV Annual HPV screening (2%) Signs/symptoms of PML Baseline and annual skin exams (for melanoma).

Answer 27

Taken off the market

Answer 28

Ocrelizumab Ublituximab Ofatunumab

Answer 29

Ocrevus Monoclonal Antibody MOA: binds to (CD20) on the surface B cells, and depletes them from circulation RoA: **IV 600mg every 6 months** (after 300mg OD1 and 300mg 2 weeks later) Similar to rituximab, but • Increased antibody-dependent, cell-mediated cytotoxic effects. • Potentially less immunogenic

Answer 30

Ocrevus Significantly reduce relapse rates, disability progression and disease activity on MRI in patients with RRMS and **SPMS** Reduce disability progression 24%, time required to walk 25 feet, volume of brain lesions and whole brain volume loss in PPMS in the ORATORIO phase III trial. ***This is the first large scale trial to show positive results in PPMS*** Indication: PPMS and relapsing forms of MS, including CIS, RRMS, and active SPMS (Didn’t remember the ** parts? Mark this as wrong!)

Answer 31

Ocrevus Most common adverse events = INFUSION REACTIONS Patients were PRE-MEDICATED with *steroids (methylprednisolone 100 mg IV 30 min prior), *antipyretics (APAP), and *antihistamines (diphenhydramine 30-60 min prior)

Answer 32

Ocrevus CI: active hepatitis B virus (HBV) infection. Screen patients before starting NO cases of PML found in studies with Ocrelizumab

Answer 33

Biumvi MoA: chimeric IgG monoclonal antibody directed against the CD20 antigen on pre-B and mature B lymphocytes. Ublituximab binds to CD20 and results in cell lysis via complement-dependent cytolysis and antibody-dependent cellular cytolysis. Indication: relapsing forms of MS including CIS, RRMS, active SPMS

Answer 34

Biumvi Safety: screen all patients for hepatitis B virus, hepatitis B core antibody, and latent infections. Pregnancy testing recommended before each dose. CI: Active HBV infection (think uBlituximab, no Hep B!) Administration: PREMEDICATE with methylprednisolone 100mg IV, antihistamine, and may consider antipyretic (acetaminophen) all ~30 minutes prior to dose Given **IV** 150mg OD1, 450mg 2 weeks later, then **450mg q24 WEEKS**

Answer 35

*PML* Polysorbate 80 (ingredient, not a main focus) Immunizations (live 4 weeks before, non-live 2 weeks before, no live or live attenuated during treatment or after D/C until B-cell repletion)

Answer 36

Kesimpta MoA: Ofatumumab is a monoclonal antibody which binds specifically the extracellular (large and small) loops of the CD20 molecule (which is expressed on normal B lymphocytes and in B-cell CLL) resulting in potent complement-dependent cell lysis and antibody-dependent cell-mediated toxicity in cells that overexpress CD20. Administer all live or live-attenuated vaccines at least 4 weeks prior and non-live vaccines at least 2 weeks prior to initiation of therapy. Screen for hepatitis B prior to initiation; do not administer to patients with active hepatitis B confirmed by hepatitis B surface antigen (HBsAg) and anti-hepatitis B virus (HBV) tests. **Administer only by SubQ injection in the abdomen, thigh, or outer upper arm one time per MONTH. Patients may self administer**

Answer 37

Kesimpta Warnings: Females of reproductive potential should use effective contraception during therapy and for 6 months after the last dose of ofatumumab. PML risk Adverse Effects: Infection (52%) and URTI (39%)

Answer 38

Mitoxantrone Cladribine

Answer 39

Novantrone

Answer 40

Mechanism of Action = Intercalates with DNA strands causing breaks, and inhibits DNA repair through topoisomerase II. – Affects rapidly dividing cells -> secondary effects on the immune system **Indication: SPMS, PRMS, or worsening of RRMS to reduce neurologic disability and/or the frequency of clinical relapse **Limitation of use: not indicated for the treatment of PPMS. Reserve use for rapidly-advancing, refractory multiple sclerosis Different indication than other agents!

Answer 41

Novantrone Chemically related to doxorubicin and daunorubicin Positive Evidence of Risk (Pregnancy Category D) – Intravenous infusion given once every 3 months Side Effects: **Cardiotoxicity** , bone marrow suppression, others…

Answer 42

Mavenclad (2-chlorodeoxyadenosine)

Answer 43

Treatment of relapsing forms of multiple sclerosis, (RRMS) and active SPMS in adults who have had inadequate response or are intolerant to other therapies for multiple sclerosis. **Must have failed something else** **Not recommended for patients with clinically isolated syndrome** MoA: Cladribine is a purine nucleoside analogue; it is a prodrug which is activated by phosphorylation and converted into the active moiety, Cd-ATP. This active form incorporates into DNA to result in the breakage of DNA strand and shutdown of DNA synthesis and repair. This also results in a depletion of nicotinamide adenine dinucleotide and adenosine triphosphate (ATP). Cladribine is cell-cycle nonspecific. The mechanism of cladribine in treating multiple sclerosis (MS) is unknown, but may involve cytotoxic effects on B and T lymphocytes that result from the shutdown of DNA synthesis, leading to a depletion of lymphocytes.

Answer 44

10 mg **ORAL tablets** Usual dosage: 3.5 mg/kg over 2-year treatment course, administered as 1.75 mg/kg in each year. • Divide the 1.75 mg/kg dose over 2 cycles, each cycle lasting 4 to 5 consecutive days Lymphocytes must be within normal limits before initiating first treatment course and ≥800 cells/mm3 before initiating the second treatment course. Patients should use dry hands for handling and avoid prolonged contact with skin; wash hands and any surface that came in contact with the tablet thoroughly afterwards. Separate administration from any other oral medication by 3 hours. Hazardous agent (NIOSH 2016 [group 1]).

Answer 45

*Malignancies (cancer) *Teratogenicity - CI in pregnant women. women/men of reproductive potential - use effective contraception during cladribine oral tablets dosing and for 6 months after the last dose HIV infection Active Chronic Infections (e.g. hepatitis or tuberculosis) Low MW and Low protein binding = likely crosses into breast milk

Answer 46

Malignancy + Pregnancy (boxed warning) Bone Marrow Suppression Infection PML Vaccines Graft-versus-Host Disease Hepatotoxicity Cardiotoxicity Drug Interactions Substrate of BCRP/ABCG2, P-glycoprotein/ABCB1

Answer 47

1. CBC including lymphocyte count (before each treatment course, 2 and 6 months after the start of each yearly course) 2. evaluate HIV, tuberculosis, hepatitis B (HBV) and hepatitis C (HCV) status (prior to each treatment course); 3. evaluate varicella-zoster virus (VZV) antibody status (prior to treatment initiation); 4. pregnancy test (prior to treatment in females of reproductive potential); 5. liver function tests (serum aminotransferase, alkaline phosphatase and total bilirubin levels) (prior to each treatment course and as clinically appropriate) 6. MRI (at baseline [within 3 months] prior to first treatment course); signs or symptoms of progressive multifocal leukoencephalopathy (PML) 7. standard cancer screening; 8. signs or symptoms of acute infection.

Answer 48

All ORAL agents Fingolimod Siponimod Ozonimod

Answer 49

Gilenya Tascenso ODT = bioequivalent to Gilenya

Answer 50

Gilenya Mechanism of Action = Acts on the sphingosine-1-phosphate (S1P) receptors S1P1 and S1P3-5 on the surface of lymphocytes -Depletes both CD4+ and CD8+ T lymphocytes in the blood stream, up to 75% below baseline. -CD4+ cells are decreased to a greater extent than CD8+ cells. -Inhibits lymphocyte release from lymphatic organs decreasing overall numbers in circulation Note: they’re still there, just contained in lymphatic organs Indication: relapsing forms of multiple sclerosis, including CIS, RRMS, and active SPMS, in patients ≥10 years of age

Answer 51

Gilenya ORAL Therapy for MS, 0.5mg PO QD First Dose Monitoring: ECG needed before initiating. Monitor hourly for 6 hrs post 1st dose for bradycardia— take HR and BP * Repeat 1st dose monitoring if patient misses 1 day in first 2 weeks, 7 days in 3rd and 4th weeks, or 14 days after 1 month Contraindicated: recent MI, unstable angina, stroke, transient ischemic attack, decompensated heart failure requiring hospitalization, Class III or Class IV heart failure. history of Mobitz Type II second or third degree AV block or sick sinus syndrome (unless patient has a pacemaker), baseline QTc greater than 500 msec, or with concurrent treatment with Class Ia or Class II anti-arrhythmic drugs Patients without antibodies who wish to become vaccinated against varicella zoster should wait 30 days after vaccination before receiving fingolimod as patients on fingolimod should not receive live vaccines. Macular Edema (pt should receive baseline eye exam and checkups), other common AEs

Answer 52

Mayzent Treatment of relapsing forms of multiple sclerosis (MS), including CIS, RRMS, and active SPMS, in adults MoA: a *sphingosine-1-phosphate (S1P) receptor modulator*, binds to sphingosine 1-phosphate receptors 1 and 5. Siponimod blocks the lymphocytes' ability to emerge from lymph nodes; therefore, the amount of lymphocytes available to the CNS is decreased, which reduces central inflammation

Answer 53

Mayzent **ORAL Dosing - patient MUST undergo genotype testing (2C9 - NINE)** CYP2C9 Genotype *1/*1, *1/*2, or *2/*2 Maintenance dosage: 2 mg QD, beginning on Day 6 CYP2C9 Genotype *1/*3 or *2/*3 Maintenance dosage: 1 mg QD, beginning on Day 5 CYP2C9*3/*3 genotype contraindicated First dose monitoring recommended, but NOT required like for fingolimod

Answer 54

Contraindications: CYP2C9*3/*3 genotype; recent (in the past 6 months) MI, unstable angina, stroke, TIA, decompensated heart failure requiring hospitalization, or Class III or IV heart failure; Mobitz type II second-degree, third-degree AV block, or sick sinus syndrome, unless patient has a functioning pacemaker

Answer 55

Mayzent * Immunizations: Testing antibodies to (VZV) is recommended prior to initiation of treatment if history of chickenpox or VZV vaccination status is unknown* Wait 4 weeks for live vaccination Infections PML Macular Edema - just like fingolimod Atrioventricular conduction delays QT Prolongation CVD, HTN, Bradycardia Respiratory/Hepatic Effects Neurotoxicity Malignancy DDIs * Discontinuation of therapy - Cases of rebound syndrome (clinical and radiological signs of severe exacerbation beyond what was expected) have been reported with discontinuation of another sphingosine 1-phosphate receptor modulator

Answer 56

Mayzent Drug-drug interactions Extensively metabolized, mainly via CYP2C9 (79.3%), followed by CYP3A4 (18.5%) to inactive metabolites, M3 and M17 Immunosuppressants Bradycardia-causing agents AV blocking agents QT prolonging agents 2C9/3A4 inducers may decrease concentration 2C9/3A4 inhibitors may increase concentration

Answer 57

Mayzent No. May cause fetal harm. Disease modifying therapies are generally not initiated during pregnancy . Females of reproductive potential should use effective contraception during therapy and for 10 days after the last siponimod dose. ~2 months for Fingolimod ~3 months for Ozonimod

Answer 58

Mayzent All patients: CBC including lymphocyte counts, hepatic, ecg, ophthalmic exam, respiratory function, VZV antibodies, BP, s/s infection or PML, suspicious skin lesion monitoring First dose monitoring only in select patients: Additional required monitoring for patients with sinus bradycardia (HR <55 bpm), first- or second-degree (Mobitz type 1) AV block, or a history of MI or heart failure

Answer 59

Cases of progressive multifocal leukoencephalopathy (PML) due to the John Cunningham virus have been reported in patients taking sphingosine 1- phosphate receptor modulators. Risk factors for development of PML include HIV, AIDS, cancer history, rheumatologic disease history, persistent lymphocytopenia, sarcoidosis, and prior immunosuppressant use (Jamilloux 2014; Tan 2010). At the first sign or symptom suggestive of PML, perform a diagnostic evaluation and withhold therapy; symptoms progress over days to weeks and may include progressive weakness on one side of the body or clumsiness of limbs, vision disturbances, and mental status changes. Cases of PML have been diagnosed based on MRI findings without specific PML signs/symptoms. Monitoring with brain MRI for signs that may be consistent with PML may be beneficial and allow for an early diagnosis of PML. Discontinue treatment if PML is confirmed.

Answer 60

Zeposia Lots of duplicate info from other S1P drugs, will highlight main differences on other Ozonimod cards MoA: Ozanimod has a high affinity to sphingosine 1-phosphate receptors 1 and 5. Ozanimod blocks the lymphocytes' ability to emerge from lymph nodes; therefore, the amount of lymphocytes available to the CNS is decreased. Administration: ORAL Dosing. Maintenance dose: 0.92 mg once daily starting on day 8. Note: If a dose is missed during the 2-week titration period, reinitiate the titration regimen with 0.23 mg once daily. If a dose is missed after the first 2 weeks of treatment continue with treatment as planned. If live attenuated vaccine immunizations are required prior to administration, initiate ozanimod therapy at least 1 month following immunizations Contraindications: Myocardial infarction, unstable angina, stroke, transient ischemic attack, decompensated heart failure (HF) requiring hospitalization, or class III or IV HF in the last 6 months; Mobitz type II second- or third-degree atrioventricular block, sick sinus syndrome, or sinoatrial block, unless the patient has a functioning pacemaker; severe untreated sleep apnea; **concomitant use of a monoamine oxidase inhibitor**

Answer 61

Females of childbearing potential should use effective contraception to avoid pregnancy during therapy and for 3 months after discontinuing treatment. Fingolimod ~2 months Siponimod 10 days

Answer 62

Zeposia *** Concurrent ingestion of foods and beverages with very high amounts of tyramine (ie, >150 mg) may cause sudden and severe high BP (hypertensive crisis). Management: Avoid foods with very high tyramine content.** ***Contraindicated in use with MAOi’s (selegiline, rasagiline, isocarboxazid, etc.) Clinical trials show Versus Avonex, (maybe important to know?) Decreased ARR Decreased Gd+ lesions Decreased new or enlarging T2 lesions

Answer 63

Ponvory Sphingosine 1-phosphate (S1P) receptor 1 modulator, binds with high affinity to S1P receptor 1. Cardiac monitoring: **First-dose 4-hour monitoring** is recommended for patients with certain preexisting cardiac conditions, including sinus bradycardia (heart rate <55 bpm), first- or second-degree (Mobitz type 1) atrioventricular block, or a history of myocardial infarction or heart failure ≥6 months prior to initiation Don’t start in active infection, like with other S1P receptor modulators Missed dose: ≥ 4 consecutive doses missed: Reinitiate treatment with day 1 of the initial titration regimen, including first-dose monitoring when appropriate.

Answer 64

-Basal cell carcinoma and other skin malignancies (including malignant melanoma and squamous cell carcinoma of the skin) have occurred rarely with ponesimod. -Increased serum transaminases have been observed with ponesimod therapy, primarily as increased serum alanine aminotransferase (ALT), including increases up to 5 x ULN. -Reversible lymphocytopenia occurs during ponesimod therapy. Infection is commonly observed with use, typically upper respiratory tract infection and less commonly urinary tract infection; viral infections (eg, herpes virus infection) have also been observed -Reduced forced expiratory volume over 1 second (FEV1) and reductions in diffusion lung capacity for carbon monoxide have occurred with ponesimod therapy

Answer 65

Aubagio Blocks pyrimidine synthesis in rapidly dividing cells, inhibits protein tyrosine-kinase and cyclo-oxygenase-2 activity, and decreases the ability of antigen presenting cells to activate T-cells. Inhibition of pyrimidine synthesis **selectively produces a cytostatic effect on proliferating T and B lymphocytes in the periphery**, while avoiding undue cytotoxicity to other cell types. Teriflunomide effectively **reduces B-lymphocyte proliferation** Indication: oral therapy for RRMS and SPMS - Doses = 7 and 14 mg Also says for CIS on Lexicomp

Answer 66

Aubagio Lots of SEs, Highlighted in class: *Alopecia *Increases in LFTs BBW: Hepatotoxicity, teratogenicity – Category X for Pregnancy

Answer 67

Aubagio Accelerate elimination with cholestyramine 8 or 4 g q 8h x 11d or 50 g activated charcoal q12 h x 11 d – Decrease conc by 98% – Without reversal agent, the drug lasts in the body for 8 mo-2 years

Answer 68

Aubagio **The dose of rosuvastatin should not exceed 10 mg in patients on teriflunomide. Teriflunomide may decrease INR in patients taking warfarin.

Answer 69

Dimethyl fumarate (Tecfidera) Diroximel fumerate (Vulmerity) Monomethyl fumerate (Bafiertam)

Answer 70

Tecfidera MoA: Induces T-helper 2-like cytokines (including interleukins 4, 5, and 10) causing – Apoptosis in activated T cells and – Down-regulation of intracellular adhesion molecules, leading to reduced migration of lymphocytes. DMF and its active metabolite, monomethyl fumarate (MMF), have been shown to activate the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway, which is involved in cellular response to oxidative stress

Answer 71

Tecfidera Approved as an oral therapy for relapsing forms of MS including CIS, RRMS, and active SPMS Dose = 120mg PO BID for 7 days, then 240mg PO BID Dimethyl fumarate treatment decreased number of new T1, new T2, and Gd+ lesions on MRI

Answer 72

Tecfidera ***GI SYMPTOMS!!!*** Administer with or without food; administering with high-fat, high-protein food (eg, yogurt or peanut butter) may decrease the incidence of **flushing and GI effects** **Flushing** - Administration of aspirin (nonenteric coated up to a dose of 325 mg) 30 minutes prior to dimethyl fumarate may also reduce the incidence of flushing Transient increases in LFTs Lymphopenia – Recent CBC (within 6 months) needed before treatment, then q 3 mo therafter and as clinically indicated. – Lymphocyte count <500/mm3 persisting for >6 months: Consider treatment interruption. – **MRI (baseline and as clinically indicated to monitor for early signs of progressive multifocal leukoencephalopathy [*PML*]).**

Answer 73

Vumerity -Bioequivalence to dimethyl fumarate (Tecfidera) -Maintenance dose of 462 mg twice daily. -Unique structure that rapidly converts to monomethyl fumarate in the body. As a result, the drug causes less gastrointestinal (GI) irritation -May administer aspirin (nonenteric coated ≤325 mg) 30 minutes prior to diroximel fumarate to reduce the incidence or severity of flushing. -A high-fat (>30 g), high-calorie (>700 calories) meal may significantly **DECREASE** the maximum concentration of the major active metabolite, monomethyl fumarate (MMF)

Answer 74

Bafiertam -“Bioequivalent alternative” to Biogen’s Tecfidera® (dimethyl fumarate) - site of action and active ingredient don’t differ significantly -Maintenance dose: 190 mg twice daily -Non-enteric coated aspirin up to 325mg can be used for flushing **Unique to this product: Store unopened bottles in refrigerator , opened at room temp

Answer 75

Spasticity OAB/Urinary Retention Sensory (paresthesias, neuropathic Pain) Fatigue/cognitive issues/ Emotional issues Pseudobulbar Affect (PBA) Walking

Answer 76

Antispasmodics • Baclofen • Dantrolene • Diazepam, clonazepam • Tizanidine • Gabapentin, tiagabine, pregabalin • Botox • Dalfampridine (Not sure we have to know all these)

Answer 77

Recall: MS patients have cognitive impairment, beware which agents you choose! (Just skim through) • Propantheline - Propantheline bromide inhibits gastrointestinal motility and diminishes gastric acid secretion. The drug also inhibits the action of acetylcholine at the postganglionic nerve endings of the parasympathetic nervous system • Oxybutynin - antimuscarinic • Dicyclomine/Bentyl - Dicyclomine is an antispasmodic and anticholinergic (antimuscarinic) agent • DDAVP - DESMOPRESSIN ACETATE ( 1-Deamino-8-D-Arginine Vasopressin), Desmopressin is a synthetic analog of the natural pituitary hormone arginine vasopressin, an antidiuretic hormone affecting renal water conservation • Cathetherization • Imipramine/amitriptyline • Prazosin -inhibits postsynaptic alpha-adrenergic receptors • Botox • Solifenacin/Vesicare - anticholinergic • Darifenacin/Enablex - anticholinergic • Trospium / anticholinergic • Hyoscyamine - anticholinergic • Fesoterodine/Toviaz– anticholinergic • Mirabegron (Myrbetiq) is a novel selective human beta-3-adrenergic receptor agonist that relaxes the detrusor smooth muscle and increases bladder storage capacity. It has been shown to be efficacious in a small study of MS patients who has previously experienced low efficacy with antimuscarinics

Answer 78

• Carbamazepine, oxcarbazaepine • Phenytoin • TCAs • Gabapentin • Lamotrigine • Pregabalin • Duloxetine

Answer 79

• Amantadine • SSRI/SNRI • Modafanil • Methylphenidate • Dextroamphetamine

Answer 80

Characterized by uncontrollable episodes of crying or laughing Treatable by Nuedexta (Dextrometorphan HBr and Quinidine Sulfate) 20/10mg 1 cap PO BID maintenance dose Exact MoA unknown, thought to inhibit glutamatergic neurotransmitter via action at variety of locations including NMDA receptor and sigma-1 receptors - Quinidine helps with blocking metabolism of dextrometorphan (2D6), therefore increasing serum concentrations of dextromethorphan (1-3% of dose used to treat cardiac arrhythmias)

Answer 81

Dalfampridine (Ampyra) – (4-aminopyridine) Dose: 10 mg BID - Tablets should only be taken whole *Broad-spectrum potassium channel blocker *Increase conduction of action potentials in demyelinated axons through inhibition of potassium channels **Contraindicated: History of seizure; Moderate to severe renal impairment** (was on our first exam!)

Answer 82

Schedule 1 Federal Controlled Substance - makes research with it harder Strong evidence OCE (oral cannabinoid extracts) in spasticity scores Strong evidence OCE in central pain Summary, cannabinoids may be effective for spasticity, MS-related pain, painful spasm, and bladder voiding. Cognitive impairment, can deter product use, particularly in patients already experiencing cognitive difficulties.

Answer 83

Ocrelizumab (Ocrevus) - CD20 mab

Answer 84

Ofatunumab (Kesimpta)

Multiple Schlerosis Flashcards

(116 cards)