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TPX Neuro, Psych, & Sub abuse > Week 5: MS, Headache > Flashcards

Week 5: MS, Headache Flashcards

1
Q

What is a Primary Headache disorders

A

Not due to/related to other medical condition

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2
Q

Primary Headache Disorders: Migraine

Epidemiology

A

women>men

~12% of the population
second most disabling

condition globally

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3
Q

Primary Headache Disorders

Migraine W.O aura Diagnostic criteria

A

per internatinal classification of headache disorders 3r edition (ICHD-3)

A)atleast 5 attacks fulfilling critera B-D

B)Headache attacks lasting 4-72hrs (when untreated or unsuccessfully treated)

c) headache has atleast 2 of the following 4 characteristics
*unilateral location
*pulsating quality
*moderate or severe pain intensity
*aggravation by or causing avoidance of routine physical activity (e.g walking or climbing stairs)

D. during headache at least 1 of the following.
*nausea and/or vominting
photophobia or phonophobia

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4
Q

Primary Headache Disorders

different phases of migraines

A
  1. Premonitory (hours to days)
    *tiredness
    moodchange
    yawning
    thirst
    cravings
    urinary frequency
    light and sound sensitivity
    cranial autonimoic symptoms:conjunctival infection
    tearing
    rhinorrhoea,flushing and sweating

2.Aura phase

3.Headache Pain Phase (4-72 hrs)
*throbbing headache
*n&V
*light, sound and smell sensitivity

4.Post drome(up to 48hrs)
*tiredness
*difficulty concentrating

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5
Q

Primary Headache Disorders

Migraine patho

A

Premonitory phrase (prodrome): hypothalamus and other areas of brain triggered by alterations in homeostasis
*increased parasympathetic activity activates meningeal nociceptors

aura phase: cortical spreading depression

Headache pain phase: neuropeptides
cortical spread depression
sensitization
neuronal hyperexcitability

Seretonin

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6
Q

Primary Headache Disorders

Migraine triggers

A

stress

hormone changes/ menstruation

not eating

weather

sleep disturbance

perfume/ odor

neck pain

bright lights

alcohol

smoke

sleep late

heat

food

exercise

sexual ativity

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7
Q

Primary Headache Disorders

Migraine with aura diagnosis

A

Per ichd-3

A) atleast 2 attacks fulfilling criteria b and c

B) one or mor eof the following fully reversible aura symptoms

*visual
*sensory
*speech and/or language
*motor
*brainstem
*retinal

c)ateast 3 of the folloring 6 characteristics

*atleast 1 aura symptom spreads gradually over>5 min
*2 or more aura symptoms occur in succession
*each individual aura symptom lasts 5-60 min
atleast 1 aura symptom is unilateral
atleast 1 aura symptom is positive
the aura is accompanied, or followed within 60 min by headache

Visual»sensory>language

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8
Q

Primary Headache Disorders

Migraine vs TIA

A

migraine
*positive visual symptoms(may be followed by vision loss)
*gradual onset/evolution
*subsequential progression
*repetitive attacks of identical nature
*flurry of attacks midlife
*duration < 60 min
*headache follows ~50%

TIA
*visual loss
*abrupt onset
*simultaneous occurrence
*duration <15 min
*headache accompaniment uncommon

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9
Q

Primary Headache Disorders

General Migraine acute pharmacotherapy principles

A

abortive treatments are usually more effective if they are given early in the course of the headache

a large single dose tends to work better than repetitive small doses

counsel pts.on med overuse headache

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10
Q

Primary Headache Disorders

summary of acute migraine options for..

a)mild-mod. migraine attacks

b)mod.-severe migraine attacks

c)refractory mod-severe

A

a) mild-mod.
non opioid analgesics

NSAIDS
acetaminophen
ceffeinated analgesics combos

b)mod-severe
MIGRANE SPEC. AGENTS
*triptans (geenrally preffered over dha)
DHE
gepants(rimegepant, ubrogepant) or ditans (lasmiditan) can be considered if triptans are contraindicated or not tolerated

c)refractory
*combos of triptains+nsaids
*gepants
*ditans
*combos of analgesics w. codeine or tramadol can be considered, infused infrequently (not recommended for regular use)
*opioids (not recommended for regular use)

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11
Q

Primary Headache Disorders

General Considerations for NSAID use in Migraines

A

*acute treatment for mild-moderate migraines

*all nsaids are effective in migraine treatment

*can be combined w. triptans for more severe cases

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12
Q

Primary Headache Disorders

NSAIDs specifically indicated for migraines and considerations

A

Diclofenac Potassium oral solution (Cambia)
*indicated for migraine w. or w.o aura in >/=18 y.o
*must be added to 1-2 oz or 2-4 tbsp of water prior to administration

Celecoxib oral solution (Elyxyb)
*indicated for acute migraine treatment w. or w.o aura in adults

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13
Q

Primary Headache Disorders

Bubalbital/APAP/Caffeine (Fioricet, Bac, Esgic, Zebutal) considerations

A

non controlled substance

indication: tension -type headache, but also used in migraine

*reserved as a last resort for abortive migraine treatment

*CAN CAUSE MEDICATION OVERUSE HEADACHE IF USED MORE THAN 5X PER MONTH. limit use to </=3x per month

1 tablet/capsule contains:
50 mg butalbital
*300-325 mg APAP
*40 mg caffeine

*AE: CNS depression, stomach upset

BBW: hepatotoxicity (APAP)

available as oral solution (Vtol LQ), formulation w.o caffeine (Allzital, Bupap), and formulation w.c codiene (Fioricet/codeine: CIII)

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14
Q

Primary Headache Disorders

Butalbital/ASA/Caffeine considerations

A

CIII
indicated for tension type headache, but also used in migraine

CAN CAUSE MEDICATION OVERUSE HEADACHE

1 tablet/capsule contains:
50 mg butalbital
325 mg ASA
*40 mg caffeine

AE: cns depression, stomach upset

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15
Q

Primary Headache Disorders

Triptans

indication:
mao:
AE:
caution:
CI

A

indications: acute treatment of mod-severe migraine

MOA: 5HT1D AND 5-HT1B selective agonists. causes vasoconstriction and reduces neurogenic inflammation associated with antidromic neuronal transmission correlating with relief of migrating.

AE: flushing, chest pain, palpitations, dizziness, fatigue, xerostomia, serotonin syndrome

caution: in older adults

CI: hemiplegic migraines or mibrain w. brainstem aura, known or suspected ischemic heart disease
*Woldd-parkinson-white syndrome or arrythmias
cerebrovascular syndromes (stroke-TIA)
*uncontrolled HTN
*use w.i 24hrs of an ergotamine prep or a different triptain
MAO-Is.

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16
Q

Primary Headache Disorders

Triptans considerations

A

first line treatment in acute mod-severe migraines

administer earlr in the course of a migraine attack to improve response

limit use <10 days /month to avoid med overuse headache

*Avoid use in pts. w. high risk of cardiovascular events

*SQ

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17
Q

Primary Headache Disorders

Individual Triptan considerations

A

Almotriptan:
*

Eletriptan (Relpax):
*CI w. potent cyp3a4 inhibitors. do not adminster w.i 72hrs of cyp3a4 inhibitors (ketoconazole, nefazadone, clarithromycin, ritonivir)
*higher lipophilicity into brain

Frovatriptan (Frova)
*PO
*longest half life, may cause in prevention of migraines

Naratriptan (amerge)
*second longest t 1/2

rizatriptan
*PO,ODT

Sumatiptan
*PO
*intranasal formulation (15-30 min onset )
*SQ: 10 min onset
*AE occurs in 40% of pts. such as chest tightness and pressure, sob, PALPITATIONS, and anxiety after SQ. occurs shortly after and resolved w.i 30 min.
*try diff triptan if sumatriptan is intolerable

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18
Q

Primary Headache Disorders

Lasmiditan (REyvow)

A

controle substance : CV

indication: acute treatment of migraine w. or w.o aura in adults

moa: 5HT1F receptor agonists
dose: 50-200 mg once/day

AE: cns depression, seretonin syndrome, decreased HR, increased BP, palpitaions, dizziness, n&V

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19
Q

Primary Headache Disorders

Lasmiditan considerations

A

can cause profound cns depression

must wait atleast 8 hrs between dosing and operating heavy machinery or driving

currently a brand name so expensive

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20
Q

Primary Headache Disorders

Rimegepant(Nurtec) considerations

A

class: GEPANTS

moa: small molecule CGRP antagonists

indication: acute AND preventative treatment of migraines in headaches

Dose:PO ODT
*acute treatment: 75 mg PO qd: MDD 75mg
*prevention: 75 mg PO every other day

*AE: abdominal pain, dyspepsia, nausea

avoid use in Crcl<15mL/min

avoid use in severe hepatic impairment*onset of acion</= 2 hrs for acute treatment

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21
Q

Primary Headache Disorders

Ubrogepant (Ubrelvy) considerations

A

class: GEPANTS

moa:

indication: acute treatmnt of migraine w. or w.o aura in adutls

dose: 50 to 100 mg PO once. if persist, may repeat sode >/= 2 hrs/ mdd 200MG

AE: nausea, drowsiness, xerostomia

ci: strong CYP3A4 inhibitors

dose reduction in Crcl<30mL/min, avoid use in Crcl <15 ml/min (not studied

*do not eat with a highfat meal, delays absoprtion

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22
Q

Primary Headache Disorders

anti-migraine ergot class considerations

A

Examples: dihydroergotamine and ergotamine

MOA: activation of 5HT1D and 5HT1B receptors on the intrcranial blood vessels-> vasoconstiction
or acivation of 5HT1D receptors on sensory nerve endings of the trigeminal system-> inhibition of pro-inflammatory neuropeptide release

BBW: CI w.potent cyp3a4 inhibitors including protease inhibitors, macrolide abx, and azole antifungals

Serious AE: cardiac valvular fibrosis, ergotism, seretonin syndrome

AVOID USE IN PREGNANCY OR BREASTFEEDING

DO NO use w.in triptans, other seretonin agonists, or ergotamine containing or ergotamine like agents

monitoring: renal and liver function

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23
Q

Primary Headache Disorders

Ergotamine considerations

A

indication: acute trtmt of mod-severe migraine

other migraine trtments preffered unless

SL tabs

not recommended for use in older adults

AE: N&V, ecg changes, HTN, ischemia, vasospasm, numbness, paresthesia, gangrene, etc.

pearls: d/c after limited use can rsult in rebound headaches

grapejuice can increase ergotamine levels

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24
Q

Primary Headache Disorders

Dihydroergotamine (DHE) considerations

A

indications:
injection: acute treatment of cluster headaches
injection and nasal spray: acute treatment of migraine headaches w. or w.o aura

offlabel indicaions: medication overuse headache, status migrainosus

fewere AE than ergotamine

formulations; intranasal, injection (IV, IM,SQ)

CI: ischemic heart disease, vascular surgery,
nasal spray ci w. hemiplegic migraine or migraien w. brainstem aura.
use w.in 24hrs of triptan or other ergotamine preparation

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25
Q

Primary Headache Disorders

inpatient migraine treament

A

IV dexamethasone

SQ sumariptan

iv PROCHORPERAZINE OR metaclopramide OR chlorpromazine + diphenhydramine (combos of thes emore effective than SQ sumatriptan)

iv dhe+ANTIEMETIC

iv valproate

iv/im KETOROLAC

iv MG

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26
Q

Primary Headache Disorders

opioids and barbiturates in migraine treatment

A

avoid opioids and barbiturates for acute or preventative migraine treatment

can increase risk for dependence, addiction, or medication overuse headache

however can be lmited to use in pts. w. ci to other meds or in refractory pts.

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27
Q

Primary Headache Disorders

Preventative migraine treatment consideration

A

consider if..
attacks significantly interfere w. pts dail routines

frquent attacks

CI to failure or overuse of acut treatments

AE w. acute treatments

pt. preference

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28
Q

Primary Headache Disorders

Topiramate

A

indication: labeled: prevention of migraine headache in pts >/=12 y.o

off label: prevention of cluster headache

MOA: block voltage depdendant sodium channels
enhances GABA activity
antagonizes AMPA/ kainate glutamate rceptors
weakly inhibits carbonic anyhrase

AE:cognitive dysfunction, cns defects, nephrolithiasis, metabolic acidosis, angle closure glaucoma, aligohidrosis/hypothermia, suicidal ideation, weightloss, paresthesia

COUNSEL ON IMPORTANCE OF HYDRATION

AVOID IN PREGNANCY

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29
Q

Primary Headache Disorders

Valproic Acid considerations

A

moa: increases GABA or may enhance action of GABA

AE: cns effects, hematologic effects, hepatotoxicity, encephalopathy, TEN, SJS, DRESS

*BBW hepatotoxicity, patients w. mitochondrial disease, fetal risk, panceatitis

ci: PRVENTION OF MIGRAINE IN WOMEN AND WOMEN OF CHILDBEARING AGE WHO ARE NOT USING EFFECTIVE contraception

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30
Q

Primary Headache Disorders

beta blockers

A

propanolol, timolol specifically indicated for migraine prevention

moa: in migraine unknown. several different theories.
prop. and tim. have high affinity for 5HT2B and 5HT2C receptors and higher cns penetration inhibit nitrous oxide production

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31
Q

Primary Headache Disorders

Tricyclic Antidepressants

A

Amitrityline (tertiary), (nortriptyline (secondary)

BWW: suicidality

moa: increases the synaptic concentration of seretonin and/or norepinephrine in the CNS by inhibitino of their reuptake by presynaptic neuronal mebrane pump

considerations:
lower initial doses for migraine prevention than for MDD

AE: antihcolinergic, cardiac conduction abdnormalities, orthostatid hypotension, seretonin syndrome

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32
Q

Primary Headache Disorders

Venlafaxine

A

BBW: suicidality

MOA: SNRI

AE: CNS depression, weightloss, anorexia, increased bp, hepatotoxicity , hypnatremia, acute angle closure glaucoma, seretonin syndrome

adequate trial 1-2 mo. at therepeutic dose

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33
Q

Migraine secific Treatments

Atogepant (Qulipta)

A

clas: Gepant
PO tab
indication:PREVENTATIVE treatment of episodic migraine in adults

not recommended in severe hepatic impairment

AE: constipation, nausea, drowsiness, fatigue, weightloss.

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34
Q

Migraine Specific Treatments

CGRP monoclonal antibodies considerations

A

long half life: 28-32 days

caution in recent cv or cerebrovascular ischemic events

few drug interactions: efgartigimod

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35
Q

CGRP monoclonal

Eptinezumab (VYEPTI) considerations

indication:

Target

Admin:

adequate trial time:

AE:

A

CGRP monoclonal

indication: prvention of migraines

Target: CGRP ligand

Admin: IV q 3 mo.

adequate trial time: 6 mo.

AE:infusion reaction
nasopharyngitis
nausea

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36
Q

CGRP monoclonal

Erenumab(AIMOVIG) considerations

indication

Target

Admin:

adequate trial time

AE:

A

CGRP monoclonal

indication: prvention

Target: CGRP receptor

Admin: SQ q mo.

adequate trial time: 3 mo.

AE: injection site reaction
constipation

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37
Q

CGRP monoclonal

Fremanezumab (AJOVY) considerations

indication

Target:

Admin:

adequate trial time:

AE:

A

CGRP monoclonal

Fremanezumab (AJOVY) considerations

indication: prevention of migraines

Target: CGRP ligand

Admin: SQ q mo or q3mo (dosing dffers)

adequate trial time: 3 mo. for q mo. or 6 mo. for qurterly dosing

AE: injection site reaction

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38
Q

CGRP monoclonal

Galcanezumab considerations

indication

Target:

Admin:

adequate trial time:

AE:

A

CGRP monoclonal

indication: prevention of cluster headache during cluster.
prvention of migraines

Target: CGRP ligand

Admin: sq q mo. (dosing differs on indication)

adequate trial time: 3 mon.

AE: injection site reactions

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39
Q

Peripheral nerve blocks

A

intramuscular injections containing lidocaine and/ or bupivacaine and/ or methylprednisolone

indication:
migraine
cluster headaches
hemicrania continua and other headache disorders

ae: pt may report lightheadnessess or dizeeiness after injection

anesthetic nerve blocks safe in pregnancy, corticosteroid injec. not safe

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40
Q

nonpharm/ alternative migraine treatments

A

stress reduction techniques

dietatry changes

trigger avoidance

magneseium

vit. b2 (riboflavin

feverfew

butterbur

neuromodulation devices

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41
Q

FDA approved noninvasive neuromodulation devices

A

acute treatment of migraine w. or w.o aura
>/= 12.
savi DUAL
Nerivio/ Theanica
gamma core/electrocore

> /= 18. y.o
relivion mg/neurolief
cefaly dual enhanced cefaly/

preventative:
cefaly dual enhanced
gamma core

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42
Q

Migraine Preventative therapies and considerations

PO Mg

A

indication: PPX esp. in migraine esp. w. aura
PO F of mg citrate? mg oxide
AE: diarrhea, N&V

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43
Q

Migraine Preventative therapies and considerations
Vit. b2 Riboflavin

A

migraine ppx

well tolerates

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44
Q

Migraine Preventative therapies and considerations

feverfew

A

migraine ppx

avoid use in pregnancy may cause uterine cntractions and abortions

ae: gi. can counsel pts to titrate slowly

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45
Q

Migraine Preventative therapies and considerations

butterbur (Petasites)

A

migraine PPX
avois productz tht are not labeled as free from pyrrolizidine alkaloids (PA-free)

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46
Q

Dx of chronic migraine

A

migraines on >/= 15 days /months for > 3 mo.

47
Q

Chronic Migraine Pharm treatment considerations

Onabotulinumtoxin A (Botox)

A

neurotixin that prevents calcium dependent release of ach and produces a sttae of denervation

BBW: spread of toxin effect

AE: injection site pain, neck pain, myalgia, facial paresis

48
Q

Menstrual migraine

treatments

A

migraine occuring day 1_/- 2) of menstruation can be due to flucuating estrogen

treatments:
*frovatriptan (lonh half life): continue 6 days total
Naratriptan: continue for 6 days
others includ…

Colmitriptan
Mg

AVOID ESTROGEN CONTAINING CONTRACEPTIVES IN MIGRAINE W. AURA PTS

49
Q

considerations for contraceptives in migraines

A

2-2.5 x greater risk in females w. migraines w. aura

estrogen increases risk of ischemic stroke and should be avoided by woen w. migraine w. aura who already have an increased stroke risk

50
Q

migraine treatment for pts with cv or cerebrovascular diseases

A

gepants

lasmiditan

51
Q

Acute migraine trtment for pregnant pt

A

first line: apap
avoid NSAIDS in 3rd semester

52
Q

Tension headaches characteristics

A

last 30 min-7 days

atleast 2 of the following of 4 characteristics

bilateral
pressing or tighening pulsating quality
mild or mod intensity
not aggrvated by routine physical ctivity such as walking or climbing stairs

no more than 1 of photophobia, phonophobia, or mild nausea

neither modrate, severe, nor vomiting

53
Q

Tension type headache treatment

acute:
preventative

A

acute: simple analgesics (NSAIDS, apap)
combo analgesics w. caffeine (more effective then alone)
not preffered alternaitve: butalbital, venlafaxine

COUNSEL PT ON MED OVERUSE HEADACHE

Preventative:
AD: TCA’s, mirtazipine, venlafaxine

anticonvulsants: gabapentin, topiramate
trigger point injections

54
Q

Cluster Headache characterizations

A

severe or very severe unilateral orbital, supraorbital and/or temporal pain lasting 15-180 min when untreated

atleast 1 of the following signs or symtoms

conjunctival infection and or lacrimation
nasal congestion and/or rhinorrhea
eyelid edema
forhead facial sweating
miosis and or ptosis

occur with a frequency btw 1 q other day and 8 per day

55
Q

cluster headache etiology

A

prevalence <1%

male> female

onset 20-40 y.o

risk factors:
genetics
tobacco use
h/o head trauma

56
Q

acute treatment of cluster headache

A

oxygen

sq (preferred)or intransal(alternative) sumatriptan

intransal zolmitriptan

57
Q

preventative cluster headache treatment

A

verapamil (gold standard)
glucocorticoids
galcanezumab
lithium
topiramate
greater occipital nerve blocks

58
Q

hemicrania continua

A

unilateral headache that will not subside
present for >3 mo.

on same side of headache…
conjunctival infection and or lacrimation
nasal congestion and/or rhinorrhea
eyelid edema
forhead facial sweating
miosis and or ptosis

must respons absolutely to indomethacin

59
Q

hemicrania continua trt

A

indomethacin gold standard

alternatives:onabotulinumtoxin A
occipital nerve stimulation
vagus nerve stimulation
peripheral nerve blocks

60
Q

TRamatic brain injury headache

what is it

A

resembles clinincal features of migraines and or tension type headaches

associated w. postocncussive SS-fatigue, dizziness, insomnia, conc impairment, seizures, depression, anxiety

onset headache w.in 7 days if trauma

61
Q

pseudotumor cerebri

A

increased intracranial pressure causeing headache, papilledema, vision loss

effects women primarily of child bearing age

maybe med induced: growth hormone, tetracyclines, retinoids

trt: withdraw offending agent
weightloss
carbonic anhydrase inhibitors (Acetazolamide, topiramate)

furosemide

migriane preventative medications

62
Q

brain tumor headache

A

varying features dependent on tumor and type location

common phenotype is tension type headache

pain may be bilateral or on the side of the tumor

associated neurologic symptoms: seizures, fatigue, cognitive dysfunction, focal weakness

63
Q

brain tumor headache red flags

A

acute new usualy severe headache or headache tjay has changed from precvious patterns

new headache onset in an adult espin 50 y.o an dup

headache in older adults or in children

headahce one xertion onset at night or onset at early morning

headahce that is progrssive in nature

headache s.w fever or other systemic symptoms

headache w. meningismus

headache w. neurologic signs

precipiation of head pain with valsalva maneuver (by coughing, sneezing, or bending over

64
Q

RCVS (reversible multifocal narrowing of the cerebral arteries)

A

thunder clap headaches

neurologic deficits r/t brain edema, stroke, or seizure

meds associated w. it

ssri
triptans
ergots
cyclophsophomide
tacrolimus
nasal decongestants
illegal drugs
others

65
Q

subarrachnoid hemmorhage

A

sudden or thunderclap onset of headache

worst headache of my life

nausea

comiting

neck stiffiness

focal neurologic defecits

brief loss of conciousness

LIFE THREATENING EMERGENCY

66
Q

MEdication overuse headache

A

increased excitability of neurons in the cerbral cortex and trigeminal sysstem

vicious cycle of over use, more headaches, more medication

67
Q

Dx of medicaiton overuse headache

A

heaache occuring >/= 15 days/ month w. a pt with a preexisting headahce disorder

regular overuse for >3 mo. of one or more drugs that can be taken for acute and/or symptomatic trt

68
Q

medication over use headache risks for medicatoins

A

anti-‘migraine ergots >/= 10 days per month

triptans: 10 days/ month

opioids >/= 10 days per month

non opioid analgesics >/= 15 days / month

butalbitlal >/= 5 days per month: WORSE OFFENDER

69
Q

trt of medicaiton overuse headache

A

d/c / wean off overused headache

may consider bridge therapy during the initial period after d/c of overused medication

initiate preventative w. prn breakthoruh therapy

70
Q

substance withdrawal headache

A

caffeinw withdrawal headache: caffeine >200 mg/day for ?2 eeks

opioid wthdrawal headhache: opioids > 3 months

and many more
estrogen
TCA’s
SSRI

71
Q

Headahce hx and red flags

A

DO NOT OVERLOOK POTENTIALLY SERIOUS, LIFE THREATENING CAUSES OF HEADACHE

family hx , caffeine/ alcohol consumption, occupation, medical hx, current meds (frequency of NSAID use, etc)

hx: how lon ghav ethey been occuring

location: wheres is the pain and how does it radiate

frequency: how often do headaches occur

duration: how long does pai nlast

severity: how severe is the pain

type: what type of pain is it

triggers: any factors that precipitate and or worsen headache

accompanying symtpmos: any other symptoms accompany headache

significance: what impact does headache have on activities of daily living

relieveing factors- what relieves the headaches

72
Q

headache red flags: SNOOP

A

Systemic SS

ex: fever mylagias, weightloss

Systemic Disease
ex: malignancy, acquired immune deficiency syndrome

Neurologic symptoms/signs

Onset sudden (thunderclap headache)

onset after 40 years
Pattern change (progressive headache w. loff os ehadache free periods, chanhge in type of headache)

73
Q

MS

A

chronic autoimmune inflammatory disease that causes demyelantion of cns nerves

74
Q

etiology of MS

A

ENVIRONMENTAL+GENETIC

Environmental
*EBV
*Human Herpes Virus-6

Genetic
*HLA DR-2 (mutation)
* XX female (20-40 yo)

75
Q

PATHO OF MS

A

mutation / polymorphism in HLA DR-2 causes exaggerated autoimmune response when exposed to an antigen (such as viruss)

when T helper cell phagocytoses and presents part of antigen… it crosses the BBB, eventually binding to oligodendrocytes (oligodendrocytes myelainate axons in CNS)

interactions w. oligodendrocytes causes
increase in inflammatory markers (IL1, IL6, TNFa) which act on epithelial cells on BBB.

causes endotghelial cells to increase expression of WBC adhesion markers to inrease wbcs in area

  1. causes vasodilation in bbb
  2. increase capillary permeability between endothelial cells
  3. stimulate chemotaxis
  4. stimulate INF- gamma to activate macrophages to come to area.
  5. sntiobdy production of proteins expressed on opligodendrocytes
  6. macrophages phagocytose oligodendrocytes

eventually causes formation of plaqes (sclera) on axon, overtime becomes bultiple sclerosis

76
Q

symptoms of MS

A

muscle weakness

visual symptoms OPTIC NEURITIS (blurry double vision)

unstable gait or balance

pain/parathesias

emotional cognitive disturbances

fatigue

sexual dysfunction

speech

swallowing

abnormal sensations tingling, numbness

sensitivity to heat

bladder and bowel problems(frequency
,loss of control)

77
Q

Dx of MS

A

alternative diagnosis considered and excluded

atleast 2 documented clinical exacerbations seperated by time and space as well as 2 distinct mri lesions seperated by time and space

dissemination in space (DIS) distinctly diff anatomical lesions on imaging in areas known to be affected by MS

78
Q

clinically isolated syndrome

A

very first episode of neurologic symptoms lasting atleast 24hrs, caused by inflammation and demyelnination . pt may or may not go on to develop MS

1 exacerbatiom=n and 1 lesion while the clniician awaits a second exacerbartino AND LESION to make a dx of MS

79
Q

clniically deifnite MS

A

2 attacks and clniical evidence of 2 sep lesions

80
Q

labortatory definities MS

A

2 attacks, either para clinical or evidence of 1 lesion and CSF immunologic abnormalities

or

1 attack, clinical evidence of 2 sep lesions and CSF abnormalities 1 attack

or clniical evidence of 1 and paraclinical evidence of another seperate lesion, and CSF abnormalities

81
Q

MRI findings indicitave of MS

A

4 or more white matter lesions >3,,

3 white matter ;esions , 1 periventricular lesions 6 mm diameter ir >

ovoid lesions perpendicular to ventricles

corpus collosum lesions

open ring appearance

82
Q

CSF spinal fluid studies

strongly suggestive of MS

A

NORMAL RBC AND glucose

normal or mildly elevated protein

intrathecal igg synthesisw

increased Igg index or 24 hr synthesis rate

oligoclonal bands

83
Q

Relapsing Remitting MS RRMS

A

most commmon (85% of pts)

pts experience worsening of preexisting symptoms or onset of new symptoms fo rperiod >24hrs w.o concaminant fever, known as relapses, flare ups or exacerbations

contrasted by symptom free periods, where the pts SS partially or completely dissappear

84
Q

Secondary Progressive MS (SPMS)

A

progressino of RRMS

start out with clear cut relapses, turn into a steady progression

approx 50% of pts prougressed to SPMS after 10-15 years with RRMS

progression to spms was more common before advent of disease modifying meds

85
Q

primary progressive MS

A

realatively rare 10%

steayd decline w.o clear cut relapses.

med snmot generally effective at trwating this type

86
Q

Progressive Relapsing

A

most rare 5%

steady disease progression, in addition ro clear cut periods of exacerbation

87
Q

general trt of MS

A

NOT a known cure

trt aimed at controlling symptoms and maintaining function
*disease modifying and treatment of relapses

meds depending on symptoms

pbhysicla therapy

speech therapy

planned exercise programs in early course of sidease

88
Q

treatment of acute exacerbation of MS

A

HIGH DOSE corticosteroids: reduce release of inflammatory markers
1.Methylprednisoloine (Solumedrol): w. or w.o taper
a. h2/PPI for ulcer for ppx
b. monitor for glucose watch for infection

alternative:
2. corticotropin Acthar Gel: IM or SQ. for pts w. poor IV access

89
Q

Original ABCR Therapies

Interferon beta

MOA
indication
SE
monitoring
DDI
Forms
considerations:

A

Original ABCR Therapies

MOA: specific interferon induced proteins and mechanisms by which interferon beta exeters its effects in MS not fully defines

indication: relpasing forms such as CIS, RRMS, and SPMS

SE: flu like symtpms!!!!! in up to 60% of pts. pts can premedicate with APAP or ibuprofen to decrease symptoms, fevers, chills, headahce chest pain, injection site reactions, depression, myalgia, arthtralgia , asthenia, malaise, diaphoresis, myasthenia, abdominal pain

monitoring:
MONITOR LFTS . can increase during therapy

DDI

forms:
a. Avonex- interferon beta 1a
*IM injection qweek titrated

b.Rebif: subq injection given 3x a week titrated: interferon beta 1-a

c. Plegridy
SQ injection q2weeks
a. Pegylated version

BEtaseron, Exteavia (Interferon 1b)
*subq in jection q other day

considerations:
all category C
pts should have good injection site heigene
monitor lfts. if pt has elevated lft, dont premedicate with APAp, use NSAID

90
Q

Original ABCR Therapies

Glatiramer Acetate (Copaxone)

MOA
Form
indication
SE
monitoring
DDI
considerations:

A

Original ABCR Therapies

MOA: non fully knoen but could be related to alteration of t cell activation and differentiation
forms: Capaxone, Glatopa
subq inbjection once daily

indication: relapsing forms inclusing CIS, RRMS, SPMS

SE

INJECTION SITE REACTIONS, transient flushing, vasodilation, chest tightness and or chest pain, asthenia, N&V, pain , arthtralgia, anxiety, palpitations, dyspnea,constriction of throat (pt can feel like they are almost have a a heart attack)

monitoring
DDI

considerations: preg. category B

91
Q

Monoclonal AB in MS

NAtalizumab (Tysabri)
MOA
Form
indication
SE
monitoring
DDI
considerations:

A

MOA: prevents transmigration of leukocytes across the BB into inflames paranchmyal tissue

Form: Tysabri IV infusion once q4weeks

indication: relapsong forms including CIS, RRMS, and active SPSM

SE: Progressive Multifocal Leukoencephalopathy (PML) fatal viral opportunistic infection. activates in immunocompromised pts. massive brian inflammation. it is demyelanting, causing impoairment of transmission of nerve impulses. myelin casnnot be regained once lost in PML
*infusion reactions
deprssion
respiratory tract infection
UTI
depression
headache
fatigue
cholelithiasis
arthralgia

monitoring : PML

DDI

considerations:
preg category C
prescribed through REMS program. infusion centers must be registered to monitor for the development of this condition

92
Q

three factors that increase ones risk for having PML (Progressive Multifocal Leukoencephalopathy)

A

testing positive for antibodies to JCV, prior use to certain immunosuppressant meds such as fingolimod and dimethyl fumurate, and using natalizumab for more than 2 years

93
Q

Monoclonal AB in MS

Alemtuzamab (Lemtrada)

MOA
Form
indication
SE
monitoring
DDI
considerations:

A

Monoclonal AB in MS

MOA: targets cd52 on t and b lymphocytes, NK cells, MACROPHAGES AND MONOCYTES, CAUSING LONG-TERM REDUCTION OF CIRCULATING T CELLS. basically hitting the reset button on the immune system

Form
indication: RRMS, and SPMS, generally reserved for inadequate respononse to 2 or more medications

SE: development of autoimmmune thyroid disorders such as graves disease
rash in 90%
headache
pyrexia
fatigue
pruritis
N&V
chills
insomnia
chets dyscomfort
dyspnea
dyspepsia
flushing
uti, sinitis, uri, fungal infections

monitoring :monitor tsh q3 mo until 48hrs after last infusion
monitor cbc w. differential , Scr, and urinalysis w. urine cell counts at periodic intervals for 48 months after last dose
moinitor for 2 hours after infucsion
ECG prior to trt
no live vaccines, wait 6 weeks after VZV
annual hpv screen
SS PML
Baseline and annual skin exams
DDI

considerations:
BBW:
*can cause fatal autoimmune conditions such as immune thrombocytopenia and anti glomerular basement membrane disease
must premedicate with corticosteroids 3 days before trt.
*can also cause infusion rections.
* can increase risk for malignancy

administer antiviral ppx begiining on first day of trt
trt. for 5 days and then a 3 day course at month 12
Preg. category C

94
Q

Monoclonal AB in MS

Ocrelizumab

MOA
Form
indication
SE
CI:
monitoring
DDI
considerations:

A

Monoclonal AB in MS

MOA: binds to CD20 on surface of b cells and depeletes tgem form circulation. b cels make AB and may play role in immune mediated damage to brain and spinal cord

Form: IV . admin on day 1, then again 2 week slater, then subsequent doses admin. q6mo

indication: PPMS (only one indicated for this) as well as relapsing forms such as CIS, RRMS, and active SPMS

SE: infustion related reactions in up to 44% of pts, more common in higher dose and at first infusion, UTI, URI, headahce, nausea

CI: hx of lifethreatening infusion reaciton to the mab, active HBV infection

warning: hbv reactivation, screen for hbv
herpes infection
assess fo rinfection
malignancies can occur more frequently

monitoring
DDI
considerations:
significantly recuces relapse rate, disability and disease activity on mri with RRMS AND SPMS

95
Q

ORATORIO Phase III trial

A

first large scale trial to show positive results of Ocrelizumab in PPMS

96
Q

Monoclonal AB in MS

Ofatunamab (Kesimpta)

MOA
Form
indication
SE
monitoring
DDI
considerations:

A

Monoclonal AB in MS

MOA: binds to cd20 on b cells resulting in potent complement dependent cell lysis and ab-dependent cell mediated toxicity in cells that overexpress cd20

Form: SQ initially once weekly for 3 doses, maintenance once monthly start on week 4
indication can be taken @ home

SE: infectoins, local site reacitons, headache
warning:admin all live vaccines 2 weeks prior to theaspy

monitoring :
Serum quantitaive Immunoglobulins
consult liver specialist

DDI

considerations:
Store in fridge
before amdin, allow to reach to room temp for about 15-30 min
SQ initially once weekly for 3 doses, maintenance once monthly start on week 4
indication can be taken @ home

97
Q

Chemotherapy drugs in MS

Mitoxantrone (novantrone)

MOA
Form
indication
SE
monitoring
DDI
considerations:

A

Chemotherapy drugs in MS

MOA: inhibits DNA repair through topoisomerase II. affects rapidly dividin cells secondary ewffects on immune system

Form: IV Q3MO.
indication: SPMS, PRS, or worsening RRMS . NOT FOR PPMS

SE: cardio toxicity!!!, bone marrow suppresion, stomatitis, esophagitis , oral ulceration, nnv, alopecia, headache, fatigue, hepatic dysfuntion

monitoring
DDI
considerations:
category D
lifetime dose of 100mg/m2 due to cardiotoxicity

98
Q

Chemotherapy drugs in MS

Mavenclad (Clabridine)
MOA
Form
indication
SE
monitoring
DDI
considerations:

A

Chemotherapy drugs in MS

MOA: shut down of dna synthesis, leading to depletion of lymphocytes
Form: 10 mg tabs. over 2 year course, w. 2 cycles /year
indication: RRMS AND SOMS. NOT CIS

SE: HA, Nnv, lymphoctyopenia, bone marrow depression, decreased AHGA

monitoring : LFT
CBC
evaluate HIV, TB HBV, HVC, HZV, pregnancy test, MRI, SS acute infection

DDI: substrate of BCRP/ABCG2, PGPABCB1, myeLOSUPRESSIVE AGENTS, echinacea,

CI: in pts with current malignancy

considerations:
swallow whole
do not chew
cry hands for handleing
sep form other meds for 3 hours
no live vaccines
graft vs host disease
bone marrow supression
cardiotoxicity

BBW:
ci in pts with current malignancy
prior increased risk of pregnancy
CI in pregnancy women and use effective contraception during trt and atleast 6 mop. after last dose. teratogenic

99
Q

Other oral drugs

Fingolimod (Gilenya)
MOA
Form
indication
SE
monitoring
DDI
considerations:

A

Other oral drugs

MOA: acts on S1P receptors. depletes cd4+ and cd9 and t lymphocutes in the bloodstream, and inhibits release from lymphatic system
Form: 0.5 mg QD
indication: CIS, RRMS, and active SPMS in patients >10 y.o

SE: HA, lymphopenia, URI, macular edema, increase in ABP, abdominal pain, diarrhea, dose dependent transient HRa reduction
monitoring : need ECG prior to initiaiting, BP and HR taken. then checked qhr for 6hr. coontinue obserbing if bpm <45 or if hr is still at lowest after 6 hr. if it is, must continue

monitoring
baseline eye exam, can cause macular edema

CI: MI, unstable angine, storke, TIA, decompensated HF, type IIor iii av block
DDI

considerations:
Always requires 5 hrs first doe monitoring
reduced lymph count by 70%
heart rate decrease on day 1, attenuates over time
mild increase in FE1 at high dose
use contraception. teratogenic
stoered at roomt emp

100
Q

Other oral drugs

Mayzent / Siponimod

MOA
Form
indication
SE
monitoring
DDI
considerations:

A

Other oral drugs

MOA:S1P receptor modulator. decrease circulation lymphocytes and confines ot lymph system

Form

indication

SE: HA, HTN, INcreased transaminases, bradycardia, etc.

monitoring :
cbc, lfts, ecg @ bedtime, VZV antibodied, BP,

DDI: immunosupressants, qt prolonging agents, live vaccines

warnings: macualr edema, bradycardia, AV block, qt prolongation. PRES

ci:MI, unstable angine, storke, TIA, decompensated HF, type IIor iii av block

considerations:
unopened containers should be stored refrigerated. opened ok @ roop temp
pts must undergo genetic testing: cyp2c9 genotype 1/1,1/2,2/2 titration w. maintenance 2 mg

genotype 1/2,2/3: titration maintenance 1 mg
cyp2c9 : ocntraindicated
if therapy interupted, will need to retitrate

first dose 6 hour monitroing for pts w. preexistingcardiac conditions including sinus bradycardia

risk of rebound syndrome

use ocntrraceptive . can cardiac harm fetus

101
Q

Other oral drugs

Zeposia/ Ozonimod

MOA
Form
indication
SE
monitoring
DDI
considerations:

A

Other oral drugs

MOA: SP1 receptor modulator

Form:
indication

SE

monitoring : same as other sp1 modulators

DDI: SSRI’s, SNRI’s, MAOIs , tyramine

considerations:
new drug on ma rket
same as other sp1 receptor modulators
MAO-I restrictions
doesnt require first dose monitoring
Tyramine warnings

102
Q

Teriflunomide Considerations

A

moa: blocks pyridine synthesis in rapidly dividing cells. produces cytostatic effect on t and b lymphocyte pperiphery, reduced b cell proliferation

indicatin: relapsing forms

delayed absoprtion w. food. but can be taken w. or w.o food

se: HA, nasopharyngitis, alopecia, insomnia, etc.

monitoiring: cbc 6 mo. b4 starting, LFT and billlirubin

BBW: pregnancy category X. also decreases semen count in men

103
Q

Fumurate derivatives

Dimethyl fumarate (Tecfidra)

A

apaptosis in acitvated t cells by inducing t helper 2-like cytokines

AE: gi side effects!!!!! and flushing

deleayed absorption, do not crush

LFT monitor

104
Q

Fumurate derivatives

Diroximel fumerate (Vulmerity) considerstions

A

causes less gi irritation than dimethyl fumerate

BID dosing

105
Q

fumerate derivatives

Monomethyl fumerate (Bafiertam ) considerations’

A

has less GI side effects than Dimethyl fumarate

106
Q

Symptomatic Trtment of MS

Spasticity

A

abnormal increas ein muscle tone and stiffness
baclofen

dantrolene

diazepine, clonazepam

tizaidine

gabapentin, tiagabine, pregabline

botox

dalfampridine

107
Q

Symptomatic Trtment of MS

Bladder

A

80% of pts have OAB or urinary retention

propantheline

oxybutniin

dicyclomine, bentyl

DDAVP

vatheritization

imipramine

prazosin

botox

solifenacin

darifenacin

trospium

mirabegron

108
Q

Symptomatic Trtment of MS

sensory (Parathesias, neuropsthic pain)

A

55% of ms pts have some clinical pain

carbamezapine

phenytoin

TCA

gabapentin

lamotrigine

pregablin

duloxetine

109
Q

Symptomatic Trtment of MS

fatigue, cognitive issues, emotional issues

A

amantadine

SSRI/SNRI/ modafinil
methylphenyldate
destroamphetamine

110
Q

Symptomatic Trtment of MS

pseudobulbar affect

A

occurs in ppl with ALS, AD, MS, PD, stroke TBI

uncontrollable episodes of crying or laughing

treatable w. Neudecta (Dextromethrophan and quinidine)

moa unkown

111
Q

Symptomatic Trtment of MS

walking

A

dalfampridine

111
Q
A
112
Q

Cannabinoids in MS

A

TPX Neuro, Psych, & Sub abuse (7 decks)

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