migraine medications

Question 1

anti-migraine targets pathophysiology of migraine

Answer 1

• Vasodilation of intracranial extracerebral blood vessels –> activation of perivascular trigeminal nerves –> release vasoactive neuropeptides (CGRP) and promote neurogenic inflammation
• Central pain transmission may activate other brainstem nuclei
  sx: NV, photophobic, phonophobia

Question 2

vasoactive neuropeptides
incr lvl of excitatory aa/ ECF K+ lvls

Answer 2

1) incr CGRP: incr vasoconstriction

2) Incr excitatory aa (glutamate) & alteration in ECF K affect migraine threshold
□ incr 5HT, serotonin
= Vasoconstriction of meningeal blood vessels
= Inhibit vasoactive neuropeptide release and pain signal transmission

Question 3

NSAID

Answer 3

• Analgesic, anti-inflam, anti-pyretic properties
• Inhibit COX enzyme, inhibit PG synthesis
• Also have vasoconstrictive effect
  ○ eg: aspirin (paracetamol if CI)
  ○ Suitable for lower pain experienced

Question 4

Triptans MOA

Answer 4

1) 5HT1B, 5HT1D agonist receptor, meningeal blood vessels
○ Vasoconstrict cerebral blood vessels
○ selective constrict carotid arterial circ, not affect cerebral blood flow

2) inhibitors trigeminal nerve activity
○ Inhibit vasoactive, pro-inflamm neuropeptide (CGRP)
○ Inhibit nociception

Question 5

triptans indicated for

Answer 5

1) Mod/severe: Acute tx of migraine with or w/o aura
2) cluster headache (sc inj)

• Pain relief within 2hrs (prevent pathway)
• When OTC don’t relieve

Question 6

PK of triptans

Answer 6

PO, IV, nasal
Rapidly absorbed, low plasma protein binding

Eliminated primarily by oxidative metabolism mediated by monoamine oxidase (MAO)

Question 7

triptans CI

Answer 7

(vasoconstriction):
- arterial HTN, CHD, MI, IHD, Raynaud’s disease
- hist IS/ TIA
- severe hepatic impairment

• hypersensitivity to triptans

Question 8

triptans caution in pop

Answer 8

1) pt with seizure/ lowered seizure threshold
2) elderly >65yo, not recomm
3) preg (not teratogenic)
4) lactation (excreted in BF, avoid for 12hrs)

5) no renal adj
6) mild-mod: max dose 50mg PO. (CI in severe)

• 50-100mg, repeat after 2hrs (max 200mg/day)

Question 9

DDI with triptans

Answer 9

MAOi (will incr suma dose, not within 2wks of therapy

ergotamine & its derivatives , within 24hrs
- cafergot, methysergide, dihydroergotamine

other triptans within 24hrs

Question 10

SE of triptans

Answer 10

Common:
- dysgeusia (unpleasant taste)
- transient BP incr
- flushing, sensation of cold
- pressure, tightness in throat/ jaw
- dizzy, tired, vertigo

Rare:
- minor disturbances in LFT

Question 11

rare but serious SE of triptans

Answer 11

1) drug allergy (swollen, SOB, rashes)

2) serotonin syndrome (agitated, restless, HR, sweat, twitch, NVD)

3) heart attack (SOB, chest pain / fullness, squeeze)

Question 12

PK of sumatriptan

Answer 12

A: 30mins for PO > IN > sc
D: protein bind 14-21%
M: extensive 1st pass, MAO (A isoenzyme)
E: t1/2 = 2hrs

Question 13

Ergotamine (older meds < triptans)

Answer 13

a-adrenergic blocking agent (smooth muscle peripheral and cranial blood vessels)

CI in CVD, CHD, CBV, uncontrolled HTN
Worst SE, less efficacy at 2hrs < triptans

Question 14

cafergot = caffeine + ergotamine MOA

not available in SG (in PO, suppository -NV)

Answer 14

1. Tonic action on vascular smooth muscles in external carotid network
2. Vasoconstriction by stimulating a-adrenergic and 5HT receptors (5HT1B, 5HT1D)
3. caffeine: further enhance vasoconstrictive effect

Question 15

cafergot indicated for

Answer 15

1) Mod/severe Acute tx, given at 1st sx of attack
2) vascular headaches

Question 16

cafergot PK

Answer 16

PO, rectal
Rapidly absorbed (max plasma conc reached in 1.5-2hr)

High plasma protein binding, low bioavailability (2-5%)
- metabolised by hepatic enzymes, 1st pass M
- t1/2 = 2~2.5hrs

Inhibits liver CYP3A4 **

Question 17

DDI of cafergot

Answer 17

1) CYP3A4I
(macrolides abx)
- incr exposure to ergot toxicity = vasospasm, tissue ischaemia

2) vasoconstrictors (ergot alkaloids, sumatriptan) other 5HT1 agonists

Question 18

SE of cafergot

Answer 18

Ergot toxicity (vasospasm, tissue ischemia)

Common: NV, dizzy, rebound headache (MOH), vision,numb, vertigo

Rare: hypersensitive, MI, ergotism

Question 19

opioids

Answer 19

• Abusable drugs, opioid overuse linked to worse outcomes, med-overuse headache
• Widespread effect of opioid signaling
  ○ Hyperalgesia
  ○ Allodynia
  ○ Worsen N in pts

Question 20

anti CGRP examples

Answer 20

Anti-CGRP Ab: prevent CGRP interaction
(eptinezumab, fremanezumab, galcanezumab)

Anti CGRP receptor Ab: bind to receptor to prevent CGRP interact with receptor and prevent signalling
(erenumab)

Gepants: Antagonist of CGRP receptors, prevent signalling
(atogepant, rimegepant, ubrogepant)

Question 21

Anti-CGRP Ab considerations

Answer 21

○ Recomm: pt with episodic or chronic migraine who have not responded to at least 2 tx

OR cannot use other preventive tx due to comorbidities, SE, poor compliance

OR moderate effect on QOL, disabilitating (MIDAS > 11, HIT > 50)

○ Clinical study: middle age, no high risk stroke/ infarction

Question 22

Anti CGRP receptor Ab considerations

Answer 22

• LT safety risk: mild, transient ischaemic events as no CGRP hypertension vasodilator effect in ischemia

Question 23

erenumab (anti CGRP-R Ab)

Answer 23

• blocks CGRP receptor

Decr CGRP effect of = Nociceptive neuropeptide at trigeminal ganglion
1) Vasodilator
2) Leaky - allow more neuropeptide to enter
3) Nociceptive trigger - pain sensation

Question 24

erenumab indicated for

Answer 24

Mod/severe
Prophylaxis of migraine in adults =/> 4days/ mnth

Not for acute tx

Question 25

PK of erenumab

Answer 25

SC inj (mnthly)
Clinical benefit within 3mnths

Linear kinetics at therapeutic doses (CGRP receptor binding saturated)

Question 26

SE of erenumab

Answer 26

hypersensitive rxn
inj site rxn
constipation
pruritis

Question 27

how to take to prevent MOH

Answer 27

limit to 9-10d/ mnth = avoid MOH

when to take?– aucte or prophylaxis
what to avoid?
what to monitor – migraine headache (severity, onset, duration, sx)