ic4 + ic5 (tth, migraine)

Question 1

Clinical presentation of TTH

Answer 1

No prodromal symptoms, aura
Bilateral
Nonpulsatile tightness
mild-moderate

Question 2

What are the classifications of TTH?

What is the criteria?

Answer 2

Episodic infrequent: < 1 episode / month
Episodic frequent: 1-14 days / month
Chronic: ≥15 days / month

Question 3

Triggers of TTH (7 points)

Answer 3

Stress
Holding head in one position for a long time
Alcohol
Caffeine
Cold / flu, sinus infections
Dehydration
Hunger

Question 4

non pharm for TTH (5 points)

Answer 4

Patient education
Identify triggers via headache diary
CBT
Physical therapy
Lifestyle modification (improve sleep)

Question 5

Pharmacological acute treatment for TTH (3 points)

Answer 5

Paracetamol (with caffeine)
Aspirin
NSAIDs (Ibuprofen, Diclofenac, Naproxen, Ketoprofen)

Question 6

prophylactic treatment for TTH (3 points)

Answer 6

Amitriptyline (1st line, Tricyclic Antidepressants)
Mirtazapine
Venlafaxine

Question 7

Requirements for medication overuse headache (3 points)

Answer 7

1) Headaches for ≥ 15 days / month, with pre-existing headache disorder

2) Regular overuse of medications for > 3 months eg.
Ergotamine, triptans, opioids at least 10 days / month
Paracetamol, NSAIDs at least 15 days / month

3) Headache cannot be diagnosed as something else

Question 8

What are the phases of a migraine attack

Answer 8

Prodrome
Aura
Headache
Postdrome

Question 9

Symptoms of prodrome phase

Answer 9

Fatigue
Cognitive difficulties
Mood changes
Food cravings
Neck pain
Yawning

Question 10

symptoms of aura (2 points)

Answer 10

Visual aura
Speech, sensory disturbances

Question 11

headache phase symptoms (3 points)

Answer 11

Nausea with or without vomiting
Photophobia
Phonophobia

Question 12

postdrome symptoms (3 points)

Answer 12

Feeling weary
Difficulty concentrating
Neck stiffness

Question 13

Classification of migraine

Answer 13

episodic VS chronic migraine

episodic: at leat 5 attacks a lifetime

Chronic: At least 15 Monthly Headache Day (MHD), out of which is 8 migraine days for 3 months

Question 14

What is considered migraine without aura?

Answer 14

1) Headaches lasting up to 3 days when untreated / unsuccessfully treated

2) At least 2
- Unilateral location
- Pulsating
- Moderate - Severe intensity
- Aggravated or avoidance of routine physical activity

3) At least 1
- Nausea, vomiting
- Photophobia, phonophobia

Question 15

What is considered migraine with aura?

Answer 15

1) Fully reversible aura symptoms
- Visual
- Sensory
- Speech, language
motor

2) At least 3
- Aura spreads over 5 mins
- 2 or more aura symptoms occur in succession
- Aura lasts 1hr
- Aura is unilateral
- Aura is positive
- Aura is accompanied by headache

Question 16

what is the MOA of Migraines,

how do medications act on the pathway to relief headaches?

Answer 16

1) Vasodilation of intracranial, extracerebral (inside skull, outside brain) blood vessels
Cause 2) activation of trigeminal nerves to release vasoactive neuropeptides eg. CGRP to promote neurogenic inflammation

Cafergot and Sumatriptan acts on (1) vasodilation
Erenumab acts on (2) CGRP receptor

Question 17

What is the MOA of NSAIDs?

Answer 17

COX 2 inhibition inhibits prostaglandin synthesis
PGI2 causes neurogenically mediated inflammation in the trigeminovascular system

Question 18

MOA of Sumatriptan (3 points)

Answer 18

Selective vascular serotonin (1B and 1D) receptor agonist
1) Vasoconstriction of Intracranial Extracerebral BV
Does not affect cerebral blood flow (as it affects extracerebral (outside brain) blood vessels)

2) Inhibition of vasoactive peptide release by trigeminal neurons

3) Inhibit nociception neurotransmission within trigeminocervical complex

Question 19

If Sumatriptan does not work, what to do?

If there is a recurrence of migraine…

Answer 19

Can try another triptan (even though same class)

If have recurrence of migraine within 48hrs, take another dose of triptan

Question 20

DDI with sumatriptan

Answer 20

Concomitant MAO inhibitors
Take 2 weeks after MAOi

Concomitant Ergotamine / Ergot-type meds
Take 24hrs apart

Question 21

Adverse effect associated with Sumatriptan

Side effects (3 points)

Answer 21

Serotonin syndrome (transient BP increase, flushing)

Dysgeusia (unpleasant taste)
LFT disturbances
Sensation of pressure on chest

Question 22

MOA of cafergot

Answer 22

Ergotamine:
- Constrict vascular smooth muscles in intracranial extracerebral BV
- Lead to prolonged vasoconstriction by stimulating alpha adrenergic and serotonin receptors (1B and 1D receptors)

Caffeine:
- Adenosine A1, A2A, A2B receptor antagonist → vasoconstrict cerebral vasculature
- Enhance GI absorption of ergotamine by increasing solubility of ergotamine and decrease gastric PH

Question 23

PK differences between cafergot and sumatriptan

Answer 23

Plasma protein binding:
High -> Cafergot
Low -> Sumatriptan

Sumatriptan available nasal and IV, while Cafergot available oral and rectal

Question 24

DDI with Cafergot (2 points)

Answer 24

Vasconstrictor agents eg. ergots, sumatriptan

CYP3A4i eg. ritonavir, macrolides
Increases risk for vasospasm, leading to cerebral ischaemia

Question 25

Codeine and Tramadol place in therapy for migraines

Answer 25

should not be routinely used in migraine

Question 26

When should gepants and ditans be used?

Answer 26

1) Contraindicated or cannot tolerate triptans 2) Inadequate response to 2 triptans

Question 27

When should migraine prophylaxis be offered?

Answer 27

AHS: if migraine days at least 3 and degree of disability is severe EHF: migraine impairs QOL and disability on 2 days per month with optimised therapy OR risk of acute medication overuse

Question 28

Principles of preventative treatment (5 points)

Answer 28

Start low dose, titrate slowly Can combine different drug classes if partial response or have adverse effects Set a max target dose eg. Topiramate 100mg Minimum 8 weeks of oral treatment before lack of efficacy can be determined Set realistic expectations eg. - 50% reduction in frequency of headache, migraine days - Significant decrease in attack duration, severity - Reduction in migraine disability and improvements in lifestyle

Question 29

First line for migraine prophylaxis

Answer 29

4 types Candesartan Fovatriptan Beta-blockers MPT (Meto, Propra, Timo) Anti-epileptics (Topiramate, Sodium valproate)

Question 30

Which agent is first line for TTH prophylaxis but 2nd line for migraine prophylaxis

Answer 30

Amitriptyline

Question 31

Where is CGRP released? Where are CGRP receptors (4 points)

Answer 31

CGRP released from trigeminal neurons CGRP receptors found in 2nd order neuron in cortex, SM cells in cerebral artery, on mast cells, SM cells in meningeal BV

Question 32

Role of CGRP

Answer 32

1) Pain transmission (via 2nd order neuron in cortex) 2) Blood flow in cerebral blood vessels 3) Neurogenic inflammation (through release of inflammatory regulators by mast cells + dilate meningeal BV)

Question 33

What is the MOA of gepants?

Answer 33

CGRP receptor antagonist, bind to CGRP receptor and prevent signalling

Question 34

non pharm of migraine

Answer 34

Identify triggers, migraine diary adopt healthier lifestyle eg. eating habits, sleep early, regular exercise