Term
episodes of acute worsening of neurological function with some recovery and no progression in between
most common
1st attack = clinical isolated syndrome
attack frequency decreases with time
recovery and function good initially, declines with increasing attacks |
|
Definition
| Relapsing-Remitting MS (RRMS) |
|
|
Term
follows the relapsing-remitting course and is a steady progression of the disease
disability accumulates
less new lesions on MRI, but more atrophy and T1 holes |
|
Definition
| Secondary-Progressive MS (SPMS) |
|
|
Term
progressive worsening disease without distinct relapses
typically affects patients later in age
affect men and women equally |
|
Definition
| Primary-Progressive MS (PPMS) |
|
|
Term
progressive disease with occasional acute relapses
treat as if relapsing disease |
|
Definition
| Progressive-Relapsing MS (PRMS) |
|
|
Term
| appropriate treatments for an acute exacerbation in a patient with MS |
|
Definition
typically treated with steroids, PO or IV depending on severity of attack
decrease edema in area of demyelination
METHYLPREDNISOLONE IV is recommended (PO does not have data behind it)
DOSE: 500-1000 mg/day IV for 3-10 days
has not been shown to slow progression of disease but has been shown to delay repeat attacks for up to 2 years after optic neuritis
if cannot tolerate/refractory to steroids:
IV Immunoglobulin (IVIG)
plasmaphoresis every other day for 7 treatments if severe attacks/fail aggressive steroid therapy
adrenocorticotropic hormone (ACTH) (IM, subcutaneous, gel) -> release of adrenal steroids. Dose: 80-120 units/day in divided doses for 2-3 weeks |
|
|
Term
| How long should disease modifying therapy be continued in a patient with MS? |
|
Definition
|
|
Term
MOA of interferons
interferon-beta-1b (Betaseron and Extavia)
interferon-beta-1a (Avenox and Rebif) |
|
Definition
group of proteins that are normally produced by cells in the immune system in response to viral infection and other conditions
suppress T cell activity, decrease production of pro-inflammatory cytokines, decrease antigen presentation, decrease lymphocyte entry into CNS |
|
|
Term
indication for interferons
interferon-beta-1b (Betaseron and Extavia)
interferon-beta-1a (Avenox and Rebif) |
|
Definition
FIRST LINE
RRMS to decrease frequency of clinical exacerbation (and slow accumulation of disability - interferon-beta-1a)
first episode with features of MS on MRI (NOT Rebif) |
|
|
Term
| Dose of interferon-beta-1b (Betaseron and Extavia) |
|
Definition
do not shake upon reconstituting any product
0.25 mg SUBCUTANEOUSLY every other day
start at 0.0625 mg and increase over 6 weeks to 0.25 mg
prefilled diluent syringes and Betaseron vial that must be reconstituted - once mixed refrigerate, stable for ~3 hours |
|
|
Term
| Dose of interferon-beta-1a (Avonex) |
|
Definition
do not shake upon reconstituting any product
30 mcg IM weekly
DO NOT GIVE SUBCUTANEOUSLY -> decreased effectiveness, increased risk of injection site necrosis, atrophy, and hemorrhage
prefilled syringe - refrigerate, good at room temp for 7 days |
|
|
Term
| Dose of interferone-beta-1a (Rebif) |
|
Definition
do not shake upon reconstituting any product
22-44 mcg SUBCUTANEOUSLY 3x/week
start at 20% of dose and titrate over 4 weeks to desired dose
prefilled syringes - refrigerate, good at room temp for 30 days |
|
|
Term
| warnings/precautions to interferon products |
|
Definition
depression
injection site necrosis
hepatic disorders
anaphylaxis
history of seizure disorders
history of significant dardiac disease (CAD, CHF, arrhythmias) - due to flu-like syndrome, not direct toxicity
autoimmune disorders |
|
|
Term
| drug interactions with interferon products |
|
Definition
| caution with use of other hepatotoxic medications |
|
|
Term
| ADRs of interferon products |
|
Definition
depression
injection site reaction (necrosis rare, but serious)
limit this by rotating sites, hydrocortisone cream, use autoinjector
inject at room temp will decrease pain
flu-like symptoms (transient: fever, chills, myalgias)
last for ~24 hours post-injection and usually only occurs for the first 1-3 months of therapy
APAP or NSAIDs prior to and for 24 hours post-injection can alleviate sx
start at a lower dose and titrate up over a few months may also be helpful
lymphopenia
increased liver enzymes
retinal disorders (Rebif)
neutralizing antibodies may develop |
|
|
Term
| MOA of glatiramer acetate (Copaxone) |
|
Definition
mimic myelin basic protein (MBP or directly bind to MHC II receptors and inhibit binding of MBP peptides to T cell receptor complexes
induces Th2 cells -> decreased inflammation, demyelination, and axonal damage
suppress T cell activation
induces brain-derived neurotrophic factor (BDNF) |
|
|
Term
| indications for glatiramer acetate |
|
Definition
FIRST LINE
RRMS to reduce frequency of relapse
first episode with features of MS on MRI |
|
|
Term
| dose of glatiramer acetate |
|
Definition
20 mg SUBCUTANEOULSY daily (contains 40 mg mannintol)
prefilled syringe - refrigerate, stable at room temp for 30 days |
|
|
Term
| warnings/precautions to glatirmer acetate |
|
Definition
immediate post-injection reaction:
chest tightness, flushing, dyspnea, palpitations
begins several minutes after injection and lasting ~20 minutes
can occur more than once
chest pain
lipodystrophy/skin necrosis
immune response effects |
|
|
Term
| Pregnancy category of glatirmer acetate |
|
Definition
Category B - use only if clearly needed
unknown if excreted in breast milk |
|
|
Term
| ADRs of glatirmer acetate |
|
Definition
injection site reaction
dyspnea
rash
vasodilation
chest pain |
|
|
Term
| MOA of fingolimod (Gilenya) |
|
Definition
sphingosine-1 phosphate receptor agonist
sequesters lymphocytes into secondary lymph organs and decreases T cell and macrophage entry into CNS
converted to active metabolite by CYP4F2 (fingolimod-phosphate) |
|
|
Term
|
Definition
FIRST LINE/SECOND LINE
RRMS to delay disability progression, decrease frequency of exacerbations, and reduce T1 lesions on MRI scans |
|
|
Term
|
Definition
FIRST ORAL MEDICATION
0.5 mg PO daily |
|
|
Term
| warnings/precautions of fingolimod |
|
Definition
AV block, bradycardia
HTN
Immune suppression
respiratory SE
macular edema
caution in severe hepatic impairment |
|
|
Term
|
Definition
pronounced first dose bradycardia; AV block
REMS
BP and HR must be monitored during first dose
must watch patient for 6 hours post dose
if treatment stopped for >/= 2 weeks, must watch for 6 hours post dose again
headache
back pain
infection
macular edema
decreased FEV1
elevated LFTs
increased systolic and diastolic BP by 1-2 mmHg
lymphoma
if patient does not have history of exposure to varicella virus recommend patient get Zotstavax prior to starting treatment |
|
|
Term
| monitoring of patients on fingolimod |
|
Definition
baseline:
CBC, LFTs and bilirubin at least 6 months prior to starting therapy, eye exam and at 2-3 months, ECG, PFTs
first dose reaction |
|
|
Term
| drug interactions with fingolimod |
|
Definition
ketoconazole -> increased levels of fingolimod
caution use with class 1a and 3 antiarrhythmics -> torsades |
|
|
Term
| MOA of natalizumab (Tysabri) |
|
Definition
partially humanized monoclonal antibody
directed against VLA-1 (very-late antigen or alpha-4 beta-integrin), a cell surface adhesion antigen -> inability to adhere to VCAM-1 (vascular cell adhesion molecule) found on the endothelium of the CNS -> inability of activated lymphocytes to cross the BBB |
|
|
Term
| indication of natalizumab |
|
Definition
SECOND LINE
RRMS to delay accumulation of disability and reduce frequency of exacerbation
reserve for patient sunable to tolerate or who have failed other therapies |
|
|
Term
|
Definition
300 mg IV infusion over 1 hours monthly
monitor patient for 1 hour after infusion |
|
|
Term
| contraindications for use of natalizumab |
|
Definition
| current or history of progressive multifocal leukoenephalopathy (PML) |
|
|
Term
| warnings/precautions for natalizumab |
|
Definition
PML -> death or severe disability
rare brain infection caused by JC virus: mostly seen in immune compromised patients (HIV, transplant)
risk increases as duration of treatment inreases
treatment = plasma exchange
TOUCH program: pharmacy, provider, patient and infusion center must be registered
hepatotoxicity
immune reconstitution inflammatory syndrome (IRIS)
infection |
|
|
Term
| monitoring for natalizumab |
|
Definition
s/sx of PML
focal neurologic deficits - hemiparesis, visual field deficits, cognitive impairments, aphasia, ataxia, and/or cranial nerve deficits at 3-6 months after first infusion, then every 6 months
antibody, CSF analysis, and MRI as needed (suspected PML)
LFTs and bilirubin at baseline and periodically |
|
|
Term
|
Definition
headache
pain in the extremities/joint pain/abdominal pain
fatigue
infections (UTI, lung)
vaginitis
depression
diarrhea/nausea
antibodies can develop leading to decreased effectiveness of medication |
|
|
Term
| MOA of mitoxantrone (Novatrone) |
|
Definition
| inhibits B cell, T cell, and macrophage proliferation, impairs antigen presentation, and impairs secretion of INF-gamma, TNF-alpha, and IL-2 |
|
|
Term
| indications for mitoxantrone |
|
Definition
SECOND/THIRD LINE
reducing neurologic disability and relapse frequency in SPMS, PRMS, and worsening RRMS |
|
|
Term
|
Definition
12 mg/m^2 IV infusion over 5-15 minutes every 3 months
lifetime accumulative dose is 140 mg/m^2 |
|
|
Term
| warnings/precautions for mitoxantrone |
|
Definition
|
|
Term
|
Definition
cardiac toxicity - left ventricular function (LVEF) assessment and ECG must be done prior to each dose
nausea
alopecia
UTIs
blue-green urine ~24 hours after dose
bone marrow suppression
secondary acute myelogenous leukemia (AML) - risk higher for those people who have previously been treated with certain types of chemotherapy drugs |
|
|
Term
| monitoring for mitoxantrone |
|
Definition
CBC and LFTs prior to each dose
LVEF prior to each dose; yearly after DC of therapy |
|
|
Term
| treatment for secondary progressive MS (SPMS) |
|
Definition
|
|
Term
| treatment of primary progressive MS (PPMS) |
|
Definition
| no current therapy available |
|
|
Term
| treatment of progressive relapsing MS (PRMS) |
|
Definition
|
|
Term
| pathophysiology of amyotrophic lateral sclerosis (ALS) |
|
Definition
motor neurons in the brain (upper motor neurons) and spinal cord (lower motor neurons) degenerate or die due to excitotoxicity by glutamate or by free radicals due to mutation in SOD1 -> no signals to muscles -> muscle weakness, atrophy, and twitching
eventually there will be loss of voluntary movement |
|
|
Term
| pathophysiology of Huntington's disease |
|
Definition
chromosome #4:
GAC sequence is repeated much more frequently -> alterations in the N-terminus of Huntintin
mutation in the N-terminus may lead to inclusion within the nucleus of cells within the brain, which may lead to cell death upon entry into the nucleus or may produce substances that are detrimental to cells
huntintin controls the microtubule-assisted vesicle transport of the brain-devired neurotrophic factor (BDNF); BDNF is produced in the cortex but is released in the striatum, where it promotes cell survival
cAMP responsive element-binding protein (CREB) levels are decreased
damage occurs mainly in the caudate-putamen region and results in movement, cognitive, and psychiatric disorders |
|
|
Term
| disease/symptom management in ALS |
|
Definition
mainly symptom management
first and only FDA approved medication for treatment: Riluzole |
|
|
Term
|
Definition
glutamate inhibitor
inhibits glutamate release and inactivates voltage dependent Na Channels |
|
|
Term
|
Definition
| ALS - can extend survival or time to tracheostomy |
|
|
Term
|
Definition
50 mg PO BID
give 1 hour prior to or 2 hours after a meal
high fat meal decreases AUC |
|
|
Term
| warnings/precautions of riluzole |
|
Definition
CNS depression
pulmonary disease
neutropenia |
|
|
Term
| drug interactions with riluzole |
|
Definition
| strong CYP2A1 inducer and substrate |
|
|
Term
| monitoring and ADRs of riluzole |
|
Definition
monitoring: LFTs
ADRs:
respiratory depression
HTN
nausea
weakness |
|
|
Term
| disease/symptom management of Huntington's disease |
|
Definition
strictly treating symptoms, there is no treatment to alter the course of the disease
psychotherapy
speech therapy
physical therapy
occupational therapy
tetrabenazine |
|
|
Term
|
Definition
monoamine neurotransmitter (DA, 5HT, NE) interference and depletion in presynaptic vesicles (likely through actions on vesicle monoamine transporter)
also blocks CNS dopamine receptors |
|
|
Term
| indication for tetrabenazine |
|
Definition
suppresses chorea associated with Huntington's disease
may help with other movement disorders associated with Huntington's disease |
|
|
Term
|
Definition
initial:
12.5 mg daily
increase to 12.5 mg BID after 1 week
maintenance:
increase by 12.5 mg/day at weekly intervals
patients requiring doses > 50 mg/day: genotype for CYP2D6 |
|
|
Term
| contraindications for tetrabenazine |
|
Definition
suicidality
untreated or undertreated depression
hepatic impairment |
|
|
Term
| warnings/precautions of tetrabenazine |
|
Definition
depression
QT prolongation
esophageal dysmotility/aspiration
CNS deptression
orthostatic hypotension |
|
|
Term
| gold standard for diagnosis of MS |
|
Definition
MRI
brain lesions are separated by time and space
for diagnosis of MS: 2 attacks lasting at least 24 hours and are separated by at least 30 days |
|
|
Term
| symptom management of MS: ambulation/gait issues |
|
Definition
non-pharm: rehabilitation, mobility aids
pharm:
dalfampridine |
|
|
Term
|
Definition
| K channel blocker -> prolonged action potentials, delayed repolarization -> improved conduction in demyelinated neurons |
|
|
Term
| indication for dalfampridine |
|
Definition
| improve walking in patients with MS |
|
|
Term
|
Definition
|
|
Term
| contraindications to dalfampridine |
|
Definition
|
|
Term
| monitoring and ADRs for dalfampridine |
|
Definition
monitoring:
renal function
EEG
walking ability
ADRs:
headache
insomnia
seizures (dose dependent)
nausea
weakness |
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|
