Psych/Nuero Final: Dez MS, ALS, MG

Multiple Sclerosis (MS)

-autoimmune process targeted against ___ and ___ (the cells that make myelin)

-end result = stripping of the myelin sheath surrounding CNS axons

myelin, oligodendrocytes

What is myelin?

-plasma membrane wrapped around a nerve axon and serves as an "___" for electrical conduction

insulator

4 Forms of MS

1. Relapsing Remitting (most ___)

2. Primary Progressive

3. Secondary Progressive

4. Progressive Relapsind

common

MS Exacerbations more common in what season?

spring

MS Primary Symptoms (complications from the disease itself)

-__ complaints (optic neuritis)

-___ problems

-___, tremor

visual, gait, spasticity

MS Secondary Symptoms (complications from primary symptoms)

-recurrent ___

-___ calculi

-Decubiti and ___

infections, urinary, osteomyelitis

MS Diagnosis

-generally a diagnosis by __ (we do MRI and look at lesions)

exclusion

The following are __ disease-modifying agents:

-Interferon β

-Glatiramer Acetate

-Mitoxantrone

-Natalizumab

-Fingolimod

-Terifluonomide

-Dimethyl Fumarate

-Alemtuzumab

-Daclizumab

-Ocrelizumab

-Cladribine

-Siponimod

-Ofatumumab

-Ponesimod

-Ublituzimab-xiiy

chronic

Interferon β

-efficacy is seen ___-__ years after initiation

-this medication decreases relapse rate by about 30% and decreases formation of new white matter lesions (mildly effective)

1-2

Interferon β ADEs

-flu-like symptoms

-injection site reactions

-depression

-____ (decreased WBC)

leukopenia

Interferon β Products

-Avonex (low potency)

-Rebif, Betaseron, Extavia (high potency)

-Plegridy (pegylated form; dosed every ___ days)

14

Interferon β

-administration = __ or __ injection

SQ, IM

Glatiramer Acetate

-efficacy is seen ___-__ years after initiation

-this medication decreases relapse rate by about 30% and decreases formation of new white matter lesions (mildly effective)

-administration = SQ injection

1-2

Glatiramer Acetate ADEs

-injection site reactions (chest tightness, flushing, dyspnea) (10% of patients; occurs at any time/dose)

-___ with chronic use

lipodystrophy

Mitoxantrone

-__ agent

-Pregnancy category __

-administration = IV

chemotherapy, D

Mitoxantrone ADEs

-___ ___ suppression, neutropenia

-____

-acute myeloid leukemia

-GI-N/V/D

bone marrow, cardiotoxicity

Natalizumab

-first mAb that came to market --___ efficacious!!

-administration = IV

highly

Natalizumab

-after getting approved, it was removed from market in 2005 after reports of progressive multifocal leukoencephalopathy (___)

PML

PML Risk Factors

-__+ months of treatment

-history of ___ infection

-prior use of ___

24, JCV, immunosuppressants

Since we know Natalizumab is associated with PML, it is important to test for ___ against the JCV virus at baseline and every 6 months

antibodies

Natalizumab

-returned to market in 2006 in a ___ program called __

REMS, TOUCH

Natalizumab ADEs

-___ (Immune Reconstitution Inflammatory Syndrome)

-Depression

-Fatigue, ____ infection, arthralgia

IRIS, respiratory

Fingolamide

-first __ product approved

oral

Fingolamide

-___ and ___ can occur

bradyarrythmias, bradycardia

Fingolamide

-Due to risk of bradyarrythmias and bradycardia, requires ___ (6-24 hours) and ___ monitoring for 1st dose

observation, cardiac

Fingolamide Contraindications

-concombinant ___ disease states (eg antiarrhythmics, MI, stroke, HF, QTc ≥500msec)

cardiac

Fingolamide ADEs

-____

-macular retinal ___

-__ block

-infection

lymphocytopenia, edema, AV

Terifluonide

-administration = oral

-very long half life

-pregnancy category ___

X

Terifluonide Drug Interactions

-inhibits CYP2C8 and induces CYP1A2

-substrate of __ __ resistant protein (BCRP)

breast cancer

Terifluonide ADEs

-___ (rare)

-neutropenia, respiratory infection

-activation of ___

-___ failure

-alopecia

SJS, tuberculosis, liver

Dimethyl Fumarate

-administration = ___

oral

Dimethyl Fumarate ADEs

-flushing, rash, pruritis (take with ___ to decrease flushing)

-GI discomfort, increased ___

-albuminuria

-lymphocytopenia

food, LFTs

Alemtuzumab

-administration = IV

-have to be enrolled in __ program to receive medication due to side effects

REMS

Alemtuzumab ADEs

-idiopathic ____

-autoimmune ___ ___

thrombocytopenia, thyroid disease

Alemtuzumab ADEs

-___ (tumor)

neoplasm

Alemtuzumab ADEs

-___ infections

-___ reaction

opportunistic, infusion

Alemtuzumab

-Due to risk of opportunistic infections, patients require antiviral ___ (acyclovir 200mg BID) for 2 months after completing regimen and until CD4 >__

prophylaxis, 200

Alemtuzumab

-Due to risk of infusion reaction, patients are premedicated with ___ 3 days before starting medication and given ___ and ___ prior to infusion

corticosteroids, antihistamines, acetaminophen

Ocrelizumab

-administration = IV

-patients must be screened for ___ __

hepatitis B

Cladribine

-approved for relapsing remitting and secondary progressive

-___ chemotherapy given in 2 treatment courses

-ADRs= lymphopenia, upper __ tract infection, __ injury

oral, respiratory, liver

Siponimod

-approved for secondary progressive

-same mechanism as fingolaminde, also an oral agent

-requires ___ genetic testing and additional work up

-oral dose __ for initation based on genetic testing result

CYP2C9, titration

Ofatumumab

-weekly SQ injection

-patients have to be screened for __ __ and __ __

-ADEs = upper respiratory tract infection, headache, injection related and site reactions

-very expensive

hepatitis B, serum immunoglobulins

Ponesimod

-approved for relapsing-remitting and secondary progressive

-oral therapy with starter pack and dose ___

titration

Ponesimod ADEs

-bradyarrythmias (__ hour monitoring needed after first dose)

-increased risk of __ infections

-hepatotoxicity

4, HSV

Ublituximab-xiiy

-approved for secondary progressive and relapsing remitting

-__ infusion x 2 doses, then every 24 weeks

IV

Ublituximab-xiiy ADEs

-infusion ___ (premedicate with methylprednisolone, diphenhydramine, and APAP)

-upper respiratory infections

-__ injury (monitor AST/ALT, bilirubin, etc)

reactions, liver

Ublituximab-xiiy

-Contraindicated in patients with active ___ ___ (patients have to be screened before starting)

hepatitis B

Ublituximab-xiiy

-severe ___ risk (females should be counseled and advised to take contraception during and at least 6 months after therapy)

fetal

There is no agent __ over one agent over another for relapsing remitting MS

recommended

If patient has highly active MS, use an agent that is highly efficacious (___, ___, ___)

alemtuzumab, fingolimod, natalizumab

If patient has primary progressive MS, use ____

ocrelizumab

We don't know if combination therapy would be ___ (plus it would be rlly expensive)

effective

Most of the time, if a medication is safer, it is less ___

effective

The following are to treat MS ___:

-corticosteroids

-IV immunoglobulin (rarely used)

-plasmapheresis

exacerbations

Corticosteroids

-HUGE dose of ___ for 3-10 days after MS exacerbation depending on clinical reponse

methylprednisolone

IV immunoglobulin

-given for MS exacerbation

-___ and ___ should be given before each infusion due to infusion related ADEs

diphenhydramine, acetaminophen

IV immunoglobulin ADEs

-infusion related (headache, fever, chills)

-acute __ injury

-___ (rare)

kidney, thrombosis

Plasmapheresis

-"standard in addition to corticosteroids" for MS exacerbations as ___ care to speed recovery

supportive

Myasthenia Gravis (MG)

-autoantibodies against the post-synaptic ___ ___

neuromuscular junction

Myasthenia Gravis (MG)

-85% of patients have anti-___ antibodies, which leads to neuromuscular transmission failure and muscle weakness

acetylcholine

Myasthenia Gravis (MG)

-15% of patients have anti-___ antibodies (or against another unidentified receptor)

MuSK

MG Diagnosis

1. Edrophonium (not rlly used in practice)

-edrophonium, a acetylcholinesterase inhibitor, is given to patient

-if improvement of muscle weakness occurs, this is a ____ result

positive

MG Diagnosis

2. Quantified Myasthenia Gravis Score

3. Testing for ___ (STANDARD! this can tell us if MG is anti-Ach or anti-MuSK)

The following are to treat MG ___:

-pyridostigmine

-efgartigimod

-thymectomy

chronically

1st line therapy for MG = ___

Pyridostigmine

Pyridostigmine

-acetylcholinesterase inhibitor

-will have to __ medication up (bc there is no cure for MG, so as disease progresses you will have to either increase dose or frequency)

titrate

Pyridostigmine Formulations

-Injection

-Syrup

-IR Tablet

-ER tablet (sometimes just used at ___)

bedtime

Pyridostigmine Adverse Effects

-think ___ toxicity (fluid coming out)

cholinergic

Pyridostigmine Adverse Effects

-cholinergic activity- SLUDGE (___, ___, ___, ___, ___ __, ___)

salivation, lacrimation, urination, defecation, GI upset, emesis

Pyridostigmine Adverse Effects

-___ toxicity (can cause muscle fasciculation and cramps)

nicotinic

Efgartigimod Alfa-Fcab

-approved for adult patients with ___-___ receptor antibody positive

anti-acetylcholine

Efgartigimod Alfa-Fcab

-administered as weekly __ infusion x 4 doses

IV

Efgartigimod Alfa-Fcab

-shown to improve ___ of daily living (not shown to slow progression)

-may increase risk of ___

activities, infections

Thymectomy

-used in patient has a ___ (tumor on epithelial cells of the thymus gland) to slow disease progression

thymoma

The following are to treat MG ___:

-corticosteroids

-plasmapheresis

-IV immunoglobulin (rarely used)

exacerbations

Corticosteroids

-HIGH dose ___ IV or ___ PO

methylprednisolone, prednisone

There are medications you need to AVOID in MG because they interact with__ or with __ ___

acetylcholine, neuromuscular transmission

medications you need to AVOID in MG

1. Antibiotics

-___ (amikacin, gentamycin, tobramycin)

-____ (levofloxacin, moxfloxacin, ciprofloxacin)

-____ (azithromycin, clarithromycin, erythromycin)

-metronidazole

aminoglycosides, fluoroquinolones, macrolides

medications you need to AVOID in MG

2. ___ blockers

3. ___ ___ blockers

4. magnesium

5. ____ (chlorpromazine, fluphenazine, perphenazine, prochlorperazine)

beta, calcium channel, phenothiazines

Amyotrophic Lateral Sclerosis = ___

ALS

ALS

-average age of diagnosis is 55 years (___)

-life expectancy is 2-5 years (worst __ rate)

older, survival

ALS Pathophysiology

-a lot we do not know

-progressive degeneration of upper and lower motor neurons in the brain and spinal cord

-"brain works fine but ___ does not"

-think wheelchair, intubated, PEG tube

body

ALS Symptoms

-Initially presents as nonspecific ___ signs - weakness, muscle wasting, stiffness, muscle twitching

neuromuscular

ALS Diagnosis

Most important test for diagnosing ALS = ___

electromyography

ALS Diagnosis

-other disease states that mimic signs of ALS should be ___ (often involves MRI)

excluded

ALS Forms

1. 90% of cases are ___ ___

2. 10% of cases are ___ (linked to mutation on chromosome 21)

classical sporadic, familial

ALS has no known cure and involves disease management:

-nutrition (pt may need feeding tube)

-respiratory (pt may need ventilation)

-____ (trouble speaking, pt may need communication devices)

-____ (excessive drooling, pt may need anticholinergic)

dysarthria, sialorrhea

ALS Agents:

-ruluzole

-edaravone

-tofersen

Standard of Care in ALS to slow disease progression = ___

riluzole

Riluzole

-take med on empty stomach

-common ADEs = nausea, neuromuscular weakness

-serious ADEs = __ injury, neutropenia, interstitial __ disease

liver, lung

Edaravone

-shown to decline loss of __

-administration = IV

-ADEs= headache, abnormal gait

function

Tofersen

-approved in 2023 via accelerated pathway

-indicated for patients with __ gene mutation

SOD1

Tofersen

-shown to decrease plasma neurofilament light chain (marker of disease ___)

-administration = IV

-ADEs = fatifue, arthralgia, myalgia, increase in __ in CSF

progrssion, WBC

ALS Agents for ___ care:

-Quinidine/Dextromethorphan

-Glycopyrrolate, Hyoscyamine

supportive

Quinidine/Dextromethorphan

-antiarrhythmic + cough suppressant

-only use for patients with symptoms of ___ ___ (___)

psuedobulbar affect (PBA)

PBA Symptoms = involuntary, sudden, and frequent episodes of ____/___

laughing/crying

Quinidine/Dextromethorphan

-DO NOT USE with concomitant ___, prolonged ___, or CYP__ substrates

MAOI, QT, 2D6

Quinidine/Dextromethorphan

-ADE = ___ (nausea/vomiting), dizziness, asthenia, peripheral ___

GI, edema