Migraines Flashcards
what is primary headaches?
what does primary headache include ?
- primary headache are headaches not caused by another medical condition
primary headache include :
-migraine
-tension- type headache
-cluster headache
-other primary headache
what is secondary headache
Secondary headaches are caused by problems elsewhere
what is episodic migraine?
occurs on less than 15 days per month and can be further subdivided into low frequency (1-9 per month) and high frequency (10-14 days per month)
what is chronic migraine
occurs on 15 or more days per month
what is two major sub-types for migrane
- migraine without aura
-migraine with aura
migraine without aura
-most common
-higher attack frequency
-usually more debiliating
migraines with aura
-headaches classed as for without aura
-additional visual and/or sensory disturbances
what is the Diagnostic Criteria: Migraine
> 5 headache attacks lasting between 4-72 hours
Headache must have at least two of the following characteristics
- Unilateral location
- Pulsating quality
- Moderate or severe pain intensity
- Aggravated by or causes avoidance of routine physical activity (e.g., walking or climbing stairs)
During headache at least one of the following
- Nausea and/or vomiting
- Photophobia and phonophobia
Headache not attributed to another disorder
what are the Diagnostic Criteria: Migraine With Aura
At least two headache attacks (as characterized for without aura) lasting between 4-72 hours
Patients must have no motor weakness
the aura consists of :
- Fully reversible positive or negative visual symptoms e.g., flickering lights, spots or lines or loss of vision
- Fully reversible positive or negative sensory symptoms including positive features e.g., pins and needles or numbness
- Fully reversible dysphasic speech disturbance
what is the complications of migraines?
- Status migrainosus - >72 h attack
- Migrainous infarction (stroke) - Aura >1 h, blood vessels narrow O2 drops
- Persistent aura without infarction - Aura >1 week
- Migraine aura-triggered seizure - Seizure follows a migraine
What Triggers Migraine Attacks?
Migraine is an inherited tendency to headache and cannot be cured
Migraine can be modified and controlled by life-style adjustment and the use of medicines
triggers include:
chocolate
alcohol
caffeine
sleeping late
what is migraine pathophysiology?
Migraine is a complex genetic disorder
Likely a polygenic multifactorial inheritance
Genome-wide association studies have identified potentially interesting genes
Present understanding derived from familial hemiplegic migraine (FHM): a rare monogenic, autosomal dominant form of migraine with aura
Three genes identified are either ion channels or transporters
(many genes involved so its hard to target)
what is the Current Migraine Theory
Migraine is a neurovascular disease
Activation and sensitization of the trigeminovascular pain pathway
Innervates cranial tissues, in particular the meninges and their large blood vessels
A phenomenon called “Cortical Spreading Depression” is the neurophysical correlate of migraine aura
Cortical Spreading Depression is a slowly propagating wave of strong neuronal and glial depolarization
what are common prescriptions for migraineurs
Used for : hypertension
beta blockers
calcium channel blockers
used for : Pain
norcotic analegesics - codiene
Used for : antidepressants
- Tricyclic antidepressants, monoamine oxidase inhibitors, Selective Serotonin Reuptake Inhibitors, Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs
Used for : Discovered in 1920s; originally used to stop bleeding after a woman gave birth
- Ergots
used for antiwirnkle
botox
used for: A migraine drug! in 1990s
triptans
Currently very few drugs specifically for the treatment of migraine
what is the first line acute treatments for migraine
Aspirin (900 mg): first-line treatment for patients with acute migraine.
Ibuprofen (400 mg): first-line treatment for patients with acute migraine. If ineffective, the dose should be increased to 600 mg.
Triptans: first-line treatment for patients with acute migraine. The first choice is sumatriptan (50–100 mg), but others should be offered if sumatriptan fails. (NOT used for longterm)
Combination therapy using sumatriptan (50–85 mg) and naproxen (500 mg).
Often prescribed with anti-emetics e.g., Metoclopramide (10 mg) or prochlorperazine (10 mg).
what do triptans act on the targets ?
5-HT was first proposed to be involved in the pathophysiology of migraine as levels decrease during attacks
Slow intravenous infusions of 5-HT could abort a migraine attack
Lead to the discovery of “Triptans”: 5-HT1D/B/F receptor agonists
- e.g., Sumatriptan (1st generation)
-e.g., Zolmitriptan, Rizatriptan, Naratriptan (2nd generation)
have higher oral bioavailability and longer plasma half-life
Triptans are effective in approximately 70% patients
Do not prevent migraines-provide relief
what is the mechanism of action of triptans?
Proposed mechanisms of action of triptans include:
- constriction of cranial arteries
-inhibitory actions on the CNS
- inhibition of presynaptic TG neurons
agonists of 5-HT
what patients is triptans contraindicated in?
Contraindicated in patients with coronary or cardiovascular disease, hypertension or that are pregnant
what can overuse of triptans do?
Overuse can cause severe rebound attacks-medication-overuse headaches - when they stop taking it
what is the Migraine Medications: Prophylactic Treatment
how long do you have to suffer with migranes to start?
Considered for patients suffering 4+ attacks per month
Preventive medications aim to reduce the frequency, severity and length of migraines and may increase the effectiveness of symptom-relieving medicines used during migraine attacks
b-blockers e.g., propranolol (80-160 mg, daily): unclear how they work as they cause dilation of blood vessels
Topiramate (50-100 mg daily): blocks voltage-dependent sodium and calcium channels; mechanism of action for migraine unclear
Tricyclic anti-depressants e.g., amitriptyline, (25–150 mg at night),thought to work by preventing reuptake of 5-HT and antagonizing 5-HT2 receptors
Anti-convulsants e.g., sodium valproate (400–1500 mg daily); voltage-dependent sodium channels
Candesartan (16 mg daily); angiotensin II receptor antagonist
Botulinum toxin A is recommended for the prophylactic treatment of patients with chronic migraine where medication overuse has been addressed and patients have been appropriately treated with three or more oral migraine prophylactic treatments
Molecular Mediators of Migraine: Calcitonin Gene-Related Peptide (CGRP) what is it?
CGRP is a multifunctional 37 amino acid neuropeptide; derived from alternative processing of the calcitonin gene
CGRP is a potent vasodilator and is involved in neurogenic inflammation and nociception
CGRP receptors are present at sites relevant to migraine - pheripheral and central
Injection of CGRP into migraineurs can cause delayed migraine-like headaches
when does CGRP increase?
Increased levels of CGRP in serum and saliva of migraineurs during attacks
CGRP Receptors as Molecular Targets for the Treatment of Migraine
what were the possible developments and their drawbacks
CGRP receptor antagonists the so-called “Gepants” have been promising in clinical trials
Olcegepant: first CGRP receptor antagonist to enter trials
Efficacious in Phase II clinical trials: i.v. only, poor oral availability
Telcagepant: reached Phase III trials before termination due to high liver transaminases
Additional drawbacks include short duration of effect
in development stage:
Monoclonal Antibodies to Treat Migraine:
problems?
Monoclonal antibodies must be injected (intravenous or subcutaneous)
Must be humanized or fully human antibodies
Long-term consequences of injecting antibodies, unknown
what are the current prophylactic treatment
No cure
Erenumab (Aimovig): CGRP Receptor
Galcanezumab (Emgality): CGRP
Fremanezumab (Ajovy): CGRP
Eptinezumab (Vyepti): CGRP
used for Episodic and chronic migraine (preventative only)
Current Status: New Treatments
Gepants (CGRP receptor antagonists)
- Ubrogepant (Ubrelvy): The first-in-class oral CGRP antagonist; approved by FDA (December 2019)
-Rimegepant (Nurtec ODT): FDA & EU approved
- Atogepant: FDA approved Sep 2021 (episodic)
Gepants: No evidence for rebound headaches
Ditans (5-HT1F receptor agonists)
- Only affects nerves, not blood vessels
- Lasmiditan (Reyvow): FDA approved (October 2019)
