Multiple Sclerosis - GK Flashcards by Megan Jacobson

An immunologic disorder marked by chronic inflammation of the central nervous system (CNS)

What disease is this?

Multiple Sclerosis

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In MS, mononuclear cells infiltrate the _______ space between arteries and veins and the pia mater, axons are _______ and destroyed, and immunoreactive changes in ______ cells result in the formation of ______ in multiple areas of the CNS.

perivascular

demyelinated

glial

plaques

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what is the key to the diagnosis of MS?

dissemination of these plaques in time and space

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What are the 4 types of MS?

relapsing-remitting RR
primary-progressive PP
secondary-progressive SP
progressive-relapsing or primary progressive with activity PR/PP

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MS tx falls into what 3 categories?

exacerbations: corticosteroids
Disease modifying therapies DMT
symptomatic therapies for spasticity, bladder and sensory sx, fatigue.

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What are the 5 FDA approved 1st gen agents used to tx MS?

Avonex
Rebif
Interferon-B1b
Pegylated Interferon-B1b
Glatiramer acetate

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MOA: alters expression and response to surface antigens enhancing immune cell activities

Dosage: IM

Avonex (Interferon-B1a)

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MOA: alters expression and response to surface antigens enhancing immune cell activities

Dosage: SQ

Rebif (Interferon B-1a)

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MOA:

Augments suppressor cell function and reduce IFN-γ secretion by activated lymphocyte
Macrophage-activating effect
Down regulates the expression of IFN-γ–induced class II MHC gene products on antigen-presenting glial cells
IFN suppresses T-cell proliferation and may decrease blood–brain barrier permeability

Dosage: SQ

Interferon B-1b

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MOA: alters expression and response to surface antigens enhancing immune cell activities

Dosage: SQ

Pegylated Interferon-B-1a

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MOA: mimics antigenic properties of myeling binding protein (MBP) and inhibits binding of MBP peptides to T-cell receptor complexes.

Dosage: SQ

Glatiramer acetate

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Indication and Dose: relapsing, orally

MOA: sequesters circulating lymphocytes into secondary lymphoid organs & reduces infiltration of T-lymphocytes & macrophages into the CNS.

Fongolimod

sequesters like a cowboy

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MOA: inhibits dihydroorotate dehydrogenase = prevent proliferation of peripheral lymphocytes (T&B cells). Reduces activation of lymphocytes in CNS, reduces inflammation and demyelination.

Dose & Indication: relapsing, orally

Which drug?

Teriflunomide

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Dose & Indication: relapsing, orally

MOA: Unknown-invitro nicotinic acid receptor agonist, invitro activator of Nrf2 pathway involved in cellular response to oxidative stress

Dimethyl Fumarate

“When you are di-ing, you need Oxygen and you fume if you don’t get it”

AKA

cellular response to oxidative stress

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Dose & Indication: RRMS, 1st dose: IV for 5 days 2nd dose: IV for 3 days. Administer 2nd dose 12 mo after 1st tx.

Which drug?

Alemtuzumab

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What kind of MS would you use Ocrelizumab for?

relapsing or progressive

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ADE: depression, flu-like sx, leukopenia, injection site rxn

Monitor: electrolytes, CBC, [LFT’s at baseline, 1 mo, and every 3 mo for a year, and every 6 mo thereafer], thyroid function, LVEF.

What drug is this?

Avonex (Interferon-B1a)

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Indication: Relapsing form of MS

**low potency

**avoid use in untreated severe depression**

What drug is this?

Avonex (Interferon B-1a)

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ADE: depression, flu-like sx, leukopenia, injection site rxn

Monitor: electrolytes, CBC, [LFT’s at baseline, 1 mo, and every 3 mo for a year, and every 6 mo thereafer], thyroid function, LVEF.

Rebif (Interferon-B-1a)

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Indication: Relapsing form of MS

_**high potency_

_**avoid use in untreated severe depression**_

What drug is this?

Rebif (Interferon-B1a)

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ADE: depression, flu-like sx, leukopenia, injection site rxn

Monitor: more frequent injection site rxns reported

What drug is this?

Interferon B-1b

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Indication: Relapsing form of MS

**high potency, pregnancy category C

What drug is this?

IFN Beta 1b

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ADE: depression, flu-like sx, leukopenia, injection site rxn

Monitor: electrolytes, CBC, [LFT’s at baseline, 1 mo, and every 3 mo for a year, and every 6 mo thereafer], thyroid function, LVEF.

What drug is this?

Pegylated IFN Beta 1a

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**Indication:** Remitting-Relapsing **\*\*avoid use in untreated severe depression\*\*** **Can premedicate or concurrently use an antipyertic/analgesic for flu-like sx** **What drug is this?**

Pegylated IFN B 1a

**ADE:** hypersensitivity, chest tightness, urticaria **Monitor:** MRI, tissue necrosis What drug is this?

Glatiramer Acetate

**Indication:** CIS, RRMS **Pregnancy category B** **What drug is this?**

Glatiramer acetate

**ADE:** macular r_etinal edema_, lymphocytopenia, AV block, infection, headache **Monitoring:** CBC, ECG, Varicella zoster antibody, BP, opthalmic exam, LFTs What drug is this?

Fingolimod ## Footnote **Sequesters like a cowboy**

Which drug requires **1st dose observation**?

Fingolimod ## Footnote **sequesters like a cowboy**

**Contraindications** for which drug? **DO NOT USE IN** pts receiving _class I & III antiarrhythmic drugs_ & those with _recent cardiac dz, 2nd & 3rd degree AV block._

Fingolimod ## Footnote **sequesters like a cowboy**

**ADE for which drug?** _Steven-Johnson Syndrome_, l_iver failure_, neutropenia, respiratory infection, _TB activation_, alopecia, neuropathy

Teriflunomide

Which drug would you monitor the following? CBC, **LFTs**, BO, pregnancy, **TB test**

Teriflunomide

\_\_\_\_\_\_\_\_\_ is an active metabolite of leflunomide.

Teriflunomide

\_\_\_\_\_\_\_\_ is contraindicated in **severe hepatic impairment.**

Teriflunomide

What is the main adverse effect of _Teri**flu**nomide_?

**_Stevens-Johnson syndrome_** \*\*begins with _**flu**-like symptoms_, followed by a **painful red or purplish rash** that spreads and blisters. The top layer of the skin then dies and sheds.

Which medication carries a **pregnancy category X rating**?

**Teriflunomide**

Which medication as an **active metabolite** and what is the name of the active metabolite and the medication?

**Medication:** Leflunomide **Active Metabolite:** Teriflunomide

**ADE:** _flushing_, rash, pruiritis, GI discomfort, lymphocytopenia, inc LFTs, _albuminuria_. **Monitoring:** CBC, LFTs

**Dimethyl Fumarate**

How do you minimize the **flushing** associated with **dimethyl fumarate**?

Take the medication with **food**

**MOA:** monoclonal antibody that **causes depletion of CD52-expressing** T, B, natural killer cells and monocytes. Which drug?

Alemtuzumab

**ADE:** _nasopharyngitis,_ UTI, _URI_, herpes viral infection, autoimmune dz, thyroid dz, _purpura, goodpastures syndrome_ **Monitoring:** CBC, thyroid fxn, antibodies to VZV, TB prior to tx, urinalysis

Aletuzumab

Premedicate w/**high dose corticosteroid** **immediately prior to infusion for 1st 3 days** You would do this before starting which drug?

Aletuzumab

Administer **herpes viral prophylaxis 1st day of tx** & continue for **atleast 2 mos** after completion of tx or **until CD4+ count atleast 200 cells/microliters** You would do this for which drug?

Ateluzumab

Use **birth control during tx** & for **4 months** following each tx course. You would do this for which drug?

Alezutumab

Which drug is contraindicated with HIV infection?

Alezutumab

Premedicate with **methylprednisolone and diphenhydramine 30-60 min prior** to each infusion before using this drug. Which drug?

Ocrelizumab

**ADE:** infusion rnx Infections: - nasopharyngitis - UTI - URI - Herpes viral infection - skin infections - neutropenia Which drug?

Ocrelizumab

Which ADEs does **Alemtuzumab have that separates it from Ocrelizumab**?

**autoimmune disorders** **thyroid disorders** **purpura** **goodpastures syndrome**

What would you screen for in a patient who is taking **Ocrelizumab**?

HBV, CNS changes

What drug is contraindicated in pts with HBV?

Ocrelizumab

Which drug has a risk for **progressive multifocal leukoencephalopathy (PML)**?

Ocrelizumab

MOA: **recombinant human anti-CD20 monoclonal antibody** that binds to the CD20 epitope _(different binding region on CD20 than rituximab)_ Which drug is this?

Ocrelizumab

Which drug is designed to **optimize B cell depletion by modification of the Fc region**, which **enhances antibody-dependent cell-mediated cytotoxicity** & **reduces complement-dependent cytotixicity** compared with rituximab?

Ocrelizumab

MOA: Inhibits _RNA and DNA synthesis_ **\*\*used in oncology for leukemias\*\*** Which drug is this?

Mitoxantrone

**ADE:** _bone marrow suppression_, neutropenia, _cardiotoxicity_, _AML_, nausea, vomiting, diarrhea, alopecia Which drug?

Mitoxantrone

What should you monitor for Mitoxantrone?

CBC, ECG, LVEF, LEFTs

There is a lifetime maximum dose to this drug due to the associated cardiac toxicity Which drug?

mitoxantrone

What **types of MS is mitoxantrone** indicated for?

SPMS, PRMS, worsening RRMS

MOA for which drug? ## Footnote **activated lymphocytes are denied entry past the blood-brain barrier**

Natalizumab

MOA for which drug? attaches to **VLA-1** and blocks its interaction with its ligand on CNS endothelium vascular cell adhesion molecule **(VCAM-1)**

Natalizumab

**ADE:** _PML,_ depression, fatigue, respiratory infection, _arthralgia_, _hepatotoxicity_ Which drug?

Natalizumab

What should you monitor in a patient taking Natalizumab?

JCV antibody infection MRI LFT

Which drug has a risk of IRIS when discontinued due to PML?

Natalizumab

a **first episode of neurologic sx** that lasts atleast **24 hrs**

CIS (clinically isolated syndromes)

What is the **"safety; tried & true" approach for relapsing-remitting** MS?

injection therapy with: **IFN B-1a (Avenox or Rebif)** OR **IFN B-1b** OR **glatiramer**

What is the **"convenience" approach for relapsing-remitting** MS?

oral therapy with **dimethyl fumarate, teriflunomide or fingolimide**

What is the **"efficacy" approach to relapsing-remitting** MS?

**Infusion monotherapy** with **natalizumab or ocrelizumab**

Exacerbations are the hallmark of early \_\_\_\_\_\_

RRMS

Relapses are based on ____ or ________ symptomatic presentations

**mono** or **poly**

What are signs of a relapse?

* Localization to the **optic nerve,** **spinal cord** or **brainstem** * **functional limitations** affecting daily life * **sx that continue to worsen over 2 weeks**

Exacerbations are treated with \_\_\_\_\_\_\_

high dose glucocorticoids

What high dose glucocorticoid is used to treat exacerbations? What is the response time of this drug?

**methylprednisolone IV** **3 to 5 days**

MOA: unknown but thought to improve recovery by **decreasing edema in the area of demyelination**

corticosteroids (methylprednisolone)

**T/F:** Corticosteroids have been shown to definitively affect dz progression

FALSE; they have **_NOT_** been shown to definitively affect dz progression.

When would you initiate methylprednisolone?

**Within 2 weeks of sx onset**

What are short term use ADE's of corticosteroids?

**sleep disturbance** **metallic taste**

What are ADE's of corticosteroids that would occur in pts with DM or those who have a predilection to DM?

elevation of blood sugar: would require the use of insulin

ADEs of l**onger durations of IV methylprednisolone**

**acne** **fungal infections** **mood alteration** Rare: GI hemorrhage

Which drug is also used for RA?

teriflunomide

If the pt **declines oral therapy**, what therapy option might provide the pt with a **safer alternative**?

IFN-Beta 1a/1b Galtiramer

What are the **1st line therapies** for MS?

**self-injected** medications IFN-Beta1a/1b **(Avonex, Rebif)** **Glatiramir Acetate**

1st line therapies decrease annualized relapse rate by about \_\_\_\_\_\_%

first line therapies decrease the formation of new \_\_\_\_\_\_\_\_\_

**white matter lesion**

Are first line DMT immediately efficacious for sx?

When is efficacy of first line DMTs noted?

1-2 years after starting therapy

All IFNs exert their actions in the ______ and at the ______ level

**periphery and blood-brain barrier**

What is the overall purpose of IFNs?

to **balance the expression of pro and anti-inflammatory agents in the brain**, and **reduce the # of inflammatory cells that cross the blood brain barrier**.

This drug is a mixture of 4 amino acids which is antigenically similar to myelin basic protein L: alanine glutamic acid lysine tyrosine

glatiramer acetate

**This drug induces Th2 lymphocytes (bystander suppression @ site of MS lesion)**

**glutiramer acetate**

This drug reduces **inflammation, demyelination and axonal damage**

glutiramer acetate

Recent studies suggest that this drug may be associated with a neuroprotective effect by inducing BDNF

gultiramer acetate

Which medication has an indication for CIS and RRMS?

glutiramer acetate

Which interferon is considered a low potency medication?

Avonex

Which drug is category B pregnancy?

Glutiramer acetate

Our pt reports a PMH of depression. Which meds would be considered a possible contraindication?

IFN-Beta 1a & 1b

What is appropriate monitoring parameters for the IFN meds?

electrolytes, CBC, LFT, thyroid fxn, LVEF, depression

Chest tightness can occur along with flusing with which med?

Glatiramer acetate

When would you use **fingolimod, natalizumab, alemtuzumab and mitoxantrone**? ## Footnote **MANF**

cases of inadequate response or intolerance to 1st line agents ## Footnote **MANF**

What are the limitations of **mitoxantrone**?

**life time limit dosage of 140** **preggo category D** **secondary leukemia**

When is fingolimod contraindicated?

pts receiving class I and III antiarrhythmuc drugs and those with recent cardiac disease, 2nd & 3rd degree AV block

What is PML and what is the dz process?

Progressive multifocal leukoencephalopathy A viral infection that targets cells that make myelin: material that insulates nerve cells (neurons)

When is John Cunninhgham virus activated?

When a person's immune system is compromised

When is mitoxantrone indicated?

SPMS PRMS worsening RRMS

Describe the drug interaction of fingolimod and ketoxonazole

ketoxconazole increases fingolimod serum concentration **(3A4 inhibition)**

What are possible starting treatments for RRMS?

IFN glatiramer acetate fingolimod teriflunomide dimethyl fumarate

Pt has experienced 3 exacerbations in the last 9 months and the sx are worsening with each exacerbation and his recovery is taking longer. What option is available if this pt is wanting a regimen that is convenient?

Teriflunomide or dimethyl fumarate (BG-12) Can be taken ORALLY

Multiple Sclerosis - GK Flashcards

(107 cards)