IC5

Question 1

what is the SNOOP10 guide? list the guide

Answer 1

red flags for secondary headaches:
SN2O2P10
systemic symptoms eg fever
neoplasm (abnormal mass)
neurologic deficit/dysfunction
onset sudden or abrupt
old age >50y/o
pattern change
positional headache
precipitated by sneezing, coughing, exercise
papilledema
progressive w/ atypical presentation
pregnancy/puerperium
painful eye w/ autonomic features
post traumatic onset
pathology of immune system (HIV/immunocompromised)
painkiller overuse/new drug.

Question 2

history taking for headache

Answer 2

LOTAARRRP
location
onset
type
associated = any weakness, dizziness, FEVER?
recurring = frequency? quality
precipitating = exercise, sneezing, coughing? recent injury? painkiller use?

get history of painkiller use.

Question 3

distinguishing features of primary headache (tension-type)
include pain location ,type, intensity, QOL, other symptoms, duration

Answer 3

bilateral pain
tightening
mild-moderate
does not affect/affected by daily activities
no other symptoms
30min to 7 days

Question 4

distinguishing features of primary headache (migraine)
include pain location ,type, intensity, QOL, other symptoms, duration

Answer 4

unilateral pain
throbbing
moderate-severe
affects/affected by daily activities
nausea/vomiting, sensitivity to light, sight, aura
4-72hours

Question 5

distinguishing features of primary headache (cluster headache)
include pain location ,type, intensity, QOL, other symptoms, duration

Answer 5

unilateral pain
variable
severe-VERY severe
restless/agitation
cranial autonomic symptoms on the side of the headache (runny nose, congestion, watery/swollen/red eye)
15-180min

Question 6

what is the clinical presentation of TTH?

Answer 6

NO premonitory symptoms and aura

bilateral

non-pulsatile tightness or pressure

mild-moderate

pericranial/cervical muscle tenderness

Question 7

ICHD3 classification for infreq ETTH?

Answer 7

frequency of atleast 10 headache episodes occuring on avg <1 day/month (<12days/year)

duration 30min-7 days

and any of the following:
1) two of the following:
- bilateral
- pressing/tightening non pulsatile
- mild-moderate
- not aggravated by routine phy activity

2) both of the following
- no N/V
- no more than one of photophobia/phonophobia

3) not better accounted for by another ICHD3 diagnosis

Question 8

ICHD3 classification for frequent ETTH?

Answer 8

frequency of atleast 10 headache episodes occuring on avg 1-14 days/month (12-180days/year)

duration 30min-7 days

and any of the following:
1) two of the following:
- bilateral
- pressing/tightening non pulsatile
- mild-moderate
- not aggravated by routine phy activity

2) both of the following
- no N/V
- no more than one of photophobia/phonophobia

3) not better accounted for by another ICHD3 diagnosis

Question 9

ICHD3 classification for CTTH?

Answer 9

frequency of ≥15 days/month on avg >3 months (≥180days/year)

duration hours to days, or unremitting

and any of the following:
1) two of the following:
- bilateral
- pressing/tightening non pulsatile
- mild-moderate
- not aggravated by routine phy activity

2) both of the following
- neither moderate or severe N/V
- no more than one of photophobia/phonophobia/mild nausea

3) not better accounted for by another ICHD3 diagnosis

Question 10

triggers for TTH?

Answer 10

physical emotional stress
activities where head is held in one position for a long time
alcohol
caffeine
cold/flu or sinus infections
dehydration
hunger

Question 11

TTH pathophysiology?

Answer 11

myofascial mechanisms? = due to head being in the same position for long?

vascular mechanisms? = increased or abnormal blood flow in the cerebral arteries

= both peripheral sensitisation

genetic disposition/polymorphism?

central mechanisms? = altered pain perception and dysfunction in descending pain modulation?

Question 12

goals of therapy for TTH?

Answer 12

pain relieve

prevent progression to chronic TTH

consider patient education to identify triggers, eg. a headache diary

Question 13

acute phx management for TTH?

Answer 13

paracetamol (alone or with caffeine)
aspirin
NSAIDs: ibuprofen, naproxen, diclofenac, ketoprofen

Question 14

prophylactic phx management for TTH

Answer 14

amitriptyline (1st line) (TCA)

mirtazapine, venlafaxine

Question 15

non phx management for TTH?

Answer 15

cognitive behavioural therapy, biofeedback, relaxation

physical and/or occupational therapy

lifestyle modification (include sleep hygiene)

Question 16

proposed phases (and duration) of migraine attack?

Answer 16

prodrome
- hours to days

aura
- 5-60min

headache
- 4-72 hours

postdrome
- <12-24h

Question 17

what are some prodrome symptoms in migraine

Answer 17

fatigue
cognitive difficulties
mood changes
food cravings
neck pain
yawning

Question 18

aura symptoms in migraine

Answer 18

related to cortex and cortical spreading
- visual aura
- sensory and speech disturbance
- motor symptoms.

Question 19

headache symptoms in migraine

Answer 19

nausea with or without vomitting
photophobia
phonophobia

Question 20

post-drome symptoms in migraine

Answer 20

tired or weary

difficulty concentrating

neck stiffness

Question 21

ICHD3 criteria for migraine without aura

Answer 21

A. At least 5 attacks fulfilling criteria B-D

B. Headache attacks lasting 4–72 hours (when untreated or unsuccessfully treated)

C. Headache has at least 2 of the following 4 characteristics:
1. Unilateral location
2. Pulsating quality
3. Moderate or severe pain intensity
4. Aggravation by or causing avoidance of routine physical activity (e.g., walking or climbing stairs)

D. During headache at least 1 of the following:
1. Nausea and/or vomiting
2. Photophobia and phonophobia

E. Not better accounted for by another ICHD-3 diagnosis

Question 22

ICHD3 criteria for migraine with aura

Answer 22

A. At least 2 attacks fulfilling criteria B-C

B. At least 1 of the following fully reversible aura symptoms:
1. Visual
2. Sensory
3. Speech and/or language
4. Motor
5. Brainstem
6. Retinal

C. At least 3 of the following 6 characteristics:
1. At least 1 aura symptom spreads gradually over ≥5 minutes
2. 2 or more aura symptoms occur in succession
3. Each individual aura symptom lasts 5–60 minutes
4. At least 1 aura symptom is unilateral
5. At least 1 aura symptom is positive
6. The aura is accompanied, or followed within 60 minutes, by headache

D. Not better accounted for by another ICHD-3 diagnosis

Question 23

ICHD3 classification for chronic migraine

Answer 23

≥15 monthly headache days (MHD)
≥8 monthly migraine days (MMD)
for >3 months

criteria for MMD
≥2 migraine characterics: unilateral, pulsating, mod/severe, aggravated by QOL
AND if no aura, ≥1 of following
- photophobia/phonophobia, N/V

Question 24

nonphx management of migraine

Answer 24

patient education and empowerment
- identify triggers
- headache diary
- adopt a healthy lifestyle (regular eating, sleep, exercise habits).

Question 25

acute treatment goals for headache

Answer 25

rapid, consistent freedom from pain and associated symptoms, without recurrence

restored ability to function

minimal need for repeat dosing/resuce meds

optimal self care and reduced subsequent use of resources

minimal or no adr

cost-effective tx

Question 26

what are the drugs with established efficacy for migraine

Answer 26

triptans

ergotamine derivatives

gepants

lasmiditan

nonspecific: NSAIDs (eg diclofenac, ibuprofen, naproxen), paracetamol+caffeine

Question 27

principles for acute treatment of migraine

what to consider for tx of acute migraine, eg treatment plan?

Answer 27

acute treatment should be taken as early as possible. =should have significant beneficial response in 2h, 24h pain free sustained response, and reduced disabiltiy during attacks

stratified approach by starting with simple analgesics. (parecetamol > nsaids > triptans)

consider anti emetics with N/V symptoms

choose appropriate dosage forms and formulation
eg nausea exacerbated with water= choose orally disintegrating tablets
eg severe n/v or full-blown symptoms = parenteral formulation

Question 28

MOA of NSAIDs for migraine

Answer 28

inhibit prostaglandin synthesis

= prevent subsequent neurogenically mediated inflammation in the trigeminovascular system.

Question 29

indication for NSAIDs in migraine (and ones with established efficacy)

Answer 29

aspirin
diclofenac
ibuprofen
naproxen
celecoxib

Question 30

adr of NSAIDs in migraine

Answer 30

hypersx, GI (dyspepsia, N/V/D), CNS (drowsy/dizzy)

Question 31

c/i or caution for nsaid in migraine

Answer 31

previous PUD, renal disease, severe CVD, hypersx

Question 32

triptans MOA

Answer 32

5ht1b and 5ht1d selective receptor agonist
- vasoconstriction of intracranial extracerebral blood vessels
- inhibit vasoactive peptide released by trigeminal neurons
- inhibit nociception transmission within trigeminocervical complex.

Question 33

C/I for triptans

Answer 33

stroke/TIA
ischemic CAD
coronary artery vasospasm
uncontrolled HTN
PVD
GI ischemia
history of hemiplegic/basilar migraine

Question 33

how to use triptans for migraine

Answer 33

take early in course of attack
pain intensity is mild

if there is lack of response, switch to another triptan

some patients experience recurrence within 48h = take an additional dose

Question 34

ADR triptans

Answer 34

pressure on chest
nausea
fatigue
distal paraesthesia

Question 35

DDI for triptans

Answer 35

concurrnet ergotamine/ergot type medication within 24h

concurrent MAOi or within 2 weeks of discontinuation of MAOi therapy (sumatriptan broken down by MAOi)

Question 36

ergotamine MOA and locally available drug

Answer 36

local: ergotamine1mg/caffeine100mg

ergotamine:
1) 5ht1b/1d on intracranial vessel vasoconstriction
2) inhibit NE uptake at alpha-adrenoreceptor = prolonged vasoconstriction (more concern with ischemic ADR)

caffeine: adenosine A1, A2A, A2B receptor antagonist = vasoconstriction cerebral vasculature
may also enhance GI absorption of ergotamine by increase solubility of ergotamine and decrease GI pH.

Question 37

ADR of ergotamine

Answer 37

N/V
cramps
insomnia,
transient lower limb muscle pain

Question 38

Contraindications of ergotamine

Answer 38

stroke/TIA
ischemic CAD
coronary artery vasospasm
uncontrolled HTN
PVD
GI ischemia
history of hemiplegic/basilar migraine

Question 39

DDI or ergotamine (and outcome)

Answer 39

concurrent triptans 24h

potent cyp3a4 inhiibtors

increases the risk for vasospasm = cerebral ischemia AND/OR schema of extremities

Question 40

opiod use in migraine?

Answer 40

not recommended due to lack of evidence, risk of dependence/abuse/withdrawal syndrome

Question 41

criteria for initiating gepants and ditans for migraine?

Answer 41

prescription from licensed clinician

patients atleast 18 y/o

diagnosis by ICHD3 migraine with aura, migraine without aura, chronic migraine.

either of the following: contraindicated to/unable to tolerate triptans, inadequate response to ≥2 triptans.

Question 41

criteria for medication overuse headache

Answer 41

occuring ≥15days/month in patients with pre-existing headacheh and developing as consequence of regular overuse of acute or symptomatic hradahce medication

paracetamol or ≥1 nsaid on ≥15 days/month for >3 months

triptan or ≥1 opioid on ≥10 days/month for >3months

Question 42

criteria for preventive treatment

Answer 42

AHS guideline
prevention should be offered if
≥6 MHD, no degree of disability
≥4 MHD, some degree of disability
≥3 MHD, severe degree of disability

EHF guideline
prevention offered if
1) migraine impairs quality of life
AND either
2a) attack cause disability on ≥2 days per month and optimised acute therapy does not prevent the above
2b) risk of over frequent use of acute therapy and patient willing to take daily medication.

Question 42

what is CGRP involvement in migraine?

Answer 42

CGRP neuropeptide rises during migraine episodes = contribute to inflammatory processes, neurogenic inflammation, blood flow in the cerebral (smooth muscle) blood vessels, and pain transmission

Question 42

what are the antiCGRP therapies

Answer 42

gepants
anti-CGRP antibodies
anti-CGRP receptor antibodies

Question 42

medications with evidence of efficacy for preventive migraine treatment

Answer 42

parenteral: eptinezumab, erenumab, fremanezumab, galcanezumab

oral:
heart drugs:
candesartan,
metoprolol, timolol, propanolol

anti seizure:
valproate sodium, divalproex sodium

antimigraine:
frovitriptan

Question 43

what is the mechanism of action of gepants

Answer 43

CGRP receptor antagonists, which bind to CGRP receptor and prevent signalling

Question 43

what is the mechanism of action of antiCGRP antibodies and examples?

Answer 43

prevent CGRP from interacting with the receptor

includes monoclonal antibodies like eptinezumab and other -nezumab drugs.

Question 44

what is the MOA of antiCGRP receptor antibodies and any examples?

Answer 44

bind to CGRP receptor and prevent signalling

monoclonal antibody = erenumab

Question 45

what are some ADRs of CGRP blockade (including clinically reported and animal studies)

Answer 45

clinically reported:
GASTRO: constipation, nausea
BLOOD: raynaud (decreased blood flow to finger), hypertension
BONE: joint pain
THROAT: nasopharyngitis.

animal studies
- delayed wound healing
- block cardiopulmonary protective effect
- decreased survival in sepsis model
- bone loss
- reproductive toxicity

Question 46

studies on long term use of CGRP receptors?

Answer 46

unknown. may not want to use long term because effects are unknown?

Question 47

role of CGRP in the body

Answer 47

endogenous CGRP has multiple protective roles in CNS, immune, skin, GI, bone, pregnancy, endocrine, cardiovascular.

Question 48

criteria for initiating CGRP mABs

Answer 48

meet 1 and 2 + either 3-5
1) prescribed by licensed clinician
2) ≥18 y/o
3) diagnosis of ICHD3 migraine with or without aura + inability to tolerate/inadequate RESPONSE to 8 WEEK trial dose to the other meds/treatment (4-7MMDs)
4) - ICHD3 migraine with or without aura …. (MIDAS or HIT)
5) ICHD3 chronic migraine and…

contraindication or inability to tolerate 2 or more oral triptans

Question 49

what is the criteria for continuing CGRP mABs

Answer 49

either
1) reduction in mean MHDs or headaches of at least moderate severity of ≥50% relative to the pretreatment baseline

2) clinically meaningful improvement in any specific outcome measureMENTS
eg MIDAS decrease ≥5pts if 11-20
by 30% if >20

Question 50

principles for preventive treatment of migraine

Answer 50

4S 1O

1) start low and titrate
- if there is partial but suboptimal response or dose limiting ADR= consider combining preventive drugs from diff classes.

2) reaching therapeutic dose
- set initial target dose and stop titration once maximal dose reached, efficacy optimal, AE become intolerable.

3) set adequate trial
- minimum 8 wks at target therapeutic dose before effectiveness can be determined = switch if no response after the 8 weeks.
- min 3 months for monthly injectable cgrp dosing and 6 months for quarterly dosing.

4) set realistic expectations
- define treatment success for the patient: 50% reduction in freq, significant decrease in attack duration? severity? improved response to acute treatment? reduction in disability and improve in QOL? psychological distress?

5) optimise drug selection and maximise adherence
- tolerability, headache subtype, concomitant meds, weight, ease of use, contra VS patient preferences… comorbis, preg, response, cost, insurance coverage.

Question 51

how to assess treatment efficacy

Answer 51

headache diary

disability assessment eg MIDAS
grade: 0-5, 6-10, 11-20, 21+

ADR

Question 52

migraine pathophysiology in depth (relate to prodromal symptoms):

Answer 52

prodrome
- neuropeptides, hypothalamus activation
- hypothalamus affects homeostatic functions resulting in changes in appetite, fatigue..

aura
- cortical spreading depression.
- due to hyperexcitation (depolarisaiton wave that inhibits cortical actvity = reduced blood flow) followed by depression in brain activity.

headache
- CGRP invovlement = sensitisation of peripheral/central trigeminovascular system= pain

prodrome
- similar to prodrome.