Week 5: MS, Headache Flashcards
What is a Primary Headache disorders
Not due to/related to other medical condition
Primary Headache Disorders: Migraine
Epidemiology
women>men
~12% of the population
second most disabling
condition globally
Primary Headache Disorders
Migraine W.O aura Diagnostic criteria
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
Primary Headache Disorders
different phases of migraines
- 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
Primary Headache Disorders
Migraine patho
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
Primary Headache Disorders
Migraine triggers
stress
hormone changes/ menstruation
not eating
weather
sleep disturbance
perfume/ odor
neck pain
bright lights
alcohol
smoke
sleep late
heat
food
exercise
sexual ativity
Primary Headache Disorders
Migraine with aura diagnosis
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
Primary Headache Disorders
Migraine vs TIA
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
Primary Headache Disorders
General Migraine acute pharmacotherapy principles
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
Primary Headache Disorders
summary of acute migraine options for..
a)mild-mod. migraine attacks
b)mod.-severe migraine attacks
c)refractory mod-severe
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)
Primary Headache Disorders
General Considerations for NSAID use in Migraines
*acute treatment for mild-moderate migraines
*all nsaids are effective in migraine treatment
*can be combined w. triptans for more severe cases
Primary Headache Disorders
NSAIDs specifically indicated for migraines and considerations
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
Primary Headache Disorders
Bubalbital/APAP/Caffeine (Fioricet, Bac, Esgic, Zebutal) considerations
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)
Primary Headache Disorders
Butalbital/ASA/Caffeine considerations
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
Primary Headache Disorders
Triptans
indication:
mao:
AE:
caution:
CI
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.
Primary Headache Disorders
Triptans considerations
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
Primary Headache Disorders
Individual Triptan considerations
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
Primary Headache Disorders
Lasmiditan (REyvow)
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
Primary Headache Disorders
Lasmiditan considerations
can cause profound cns depression
must wait atleast 8 hrs between dosing and operating heavy machinery or driving
currently a brand name so expensive
Primary Headache Disorders
Rimegepant(Nurtec) considerations
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
Primary Headache Disorders
Ubrogepant (Ubrelvy) considerations
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
Primary Headache Disorders
anti-migraine ergot class considerations
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
Primary Headache Disorders
Ergotamine considerations
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
Primary Headache Disorders
Dihydroergotamine (DHE) considerations
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
Primary Headache Disorders
inpatient migraine treament
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
Primary Headache Disorders
opioids and barbiturates in migraine treatment
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.
Primary Headache Disorders
Preventative migraine treatment consideration
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
Primary Headache Disorders
Topiramate
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
Primary Headache Disorders
Valproic Acid considerations
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
Primary Headache Disorders
beta blockers
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
Primary Headache Disorders
Tricyclic Antidepressants
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
Primary Headache Disorders
Venlafaxine
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
Migraine secific Treatments
Atogepant (Qulipta)
clas: Gepant
PO tab
indication:PREVENTATIVE treatment of episodic migraine in adults
not recommended in severe hepatic impairment
AE: constipation, nausea, drowsiness, fatigue, weightloss.
Migraine Specific Treatments
CGRP monoclonal antibodies considerations
long half life: 28-32 days
caution in recent cv or cerebrovascular ischemic events
few drug interactions: efgartigimod
CGRP monoclonal
Eptinezumab (VYEPTI) considerations
indication:
Target
Admin:
adequate trial time:
AE:
CGRP monoclonal
indication: prvention of migraines
Target: CGRP ligand
Admin: IV q 3 mo.
adequate trial time: 6 mo.
AE:infusion reaction
nasopharyngitis
nausea
CGRP monoclonal
Erenumab(AIMOVIG) considerations
indication
Target
Admin:
adequate trial time
AE:
CGRP monoclonal
indication: prvention
Target: CGRP receptor
Admin: SQ q mo.
adequate trial time: 3 mo.
AE: injection site reaction
constipation
CGRP monoclonal
Fremanezumab (AJOVY) considerations
indication
Target:
Admin:
adequate trial time:
AE:
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
CGRP monoclonal
Galcanezumab considerations
indication
Target:
Admin:
adequate trial time:
AE:
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
Peripheral nerve blocks
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
nonpharm/ alternative migraine treatments
stress reduction techniques
dietatry changes
trigger avoidance
magneseium
vit. b2 (riboflavin
feverfew
butterbur
neuromodulation devices
FDA approved noninvasive neuromodulation devices
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
Migraine Preventative therapies and considerations
PO Mg
indication: PPX esp. in migraine esp. w. aura
PO F of mg citrate? mg oxide
AE: diarrhea, N&V
Migraine Preventative therapies and considerations
Vit. b2 Riboflavin
migraine ppx
well tolerates
Migraine Preventative therapies and considerations
feverfew
migraine ppx
avoid use in pregnancy may cause uterine cntractions and abortions
ae: gi. can counsel pts to titrate slowly
Migraine Preventative therapies and considerations
butterbur (Petasites)
migraine PPX
avois productz tht are not labeled as free from pyrrolizidine alkaloids (PA-free)