Migraine Flashcards
(25 cards)
Define primary and secondary headaches
Primary headaches are headaches not caused by another medical condition
Secondary headaches are caused by problems elsewhere
What headaches are primary?
Migraine
Tension-type headache
Cluster headache
How many people does migraine affect? which gender? Age group?
1 in 7 people in the UK
More common in women than in men
Affects people during their most productive years 18-55 years
What is a migraine?
a complex neurological disorder with no known cause or cure
Ranked #19 by WHO among all diseases world-wide causing disability
What are the two major sub types of migraine?
Migraine without aura:
most common
higher attack frequency
usually more debilitating
Migraine with aura:
classed same as without aura in addition to visual and /or sensory disturbances
What is the diagnositic criteria for migraine without an aura?
At least five headache attacks lasting between 4-72 hours (untreated or unsuccessfully treated
Headache must have at least two of the following characteristics:
1. unilateral location
2. pulsating quality
3.moderate or severe pain
4. aggravation by or causing avoidance of routine physical activity e.g walking
During the headache at least one of the following:
- nausea and/or vomiting
- photophobia and phonophobia (fear of loud sounds)
Headache not attributed to another disorder
What is the diagnositic criteria for migraine with an aura?
At least two headache attacks (as characterized for without aura)lasting between 4-72 hours
Patients must have no motor weakness and have aura consisting of:
1. fully reversible visual symptoms including positive features e.g., flickering lights, spots or lines
2. fully reversible visual symptoms including negative features e.g., loss of vision
3. fully reversible sensory symptoms including positive features e.g., pins and needles
4. fully reversible sensory symptoms including negative features e.g., numbness
5. fully reversible dysphasic speech disturbance
At least two of the following: 1. visual symptoms and/or unilateral sensory symptoms 2. at least one aura symptom develops gradually over ≥5 minutes and/or different aura symptoms occur in succession over ≥5 minutes 3. each symptom lasts ≥5 and ≤60 minutes
Migraine without aura begins during the aura or follows aura within 60 minutes
Headache not attributed to another disorder
When can migraines kill? (4)
1. Status migrainosus >72 h attack; rule out stroke 2. Migrainous infarction Aura >1 h; rule out stroke 3. Persistent aura without infarction Aura >1 week; rule out stroke 4. Migraine aura-triggered seizure Seizure follows a migraine
What Triggers Migraine Attacks?
Migraine is an inherited tendency to headache and cannot be cured Over 100 triggers identified Chocolate Caffeine Sleeping late Alcohol Environmental e.g strip lighting
What is the current migraine theory?
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
What is cortical spreading depression?
Cortical Spreading Depression is a slowly propagating wave of strong neuronal and glial depolarization
What is Familial Hemiplegic Migraine Type 1?
Mutation of neuronal Cav2.1 channel
Mutated channels have a gain of function-increased open probability
Shifted activation to more negative voltages
Higher propensity to propagate CSD
What are the common prescriptions for migraines although usually used for something else?
Beta Blocker/Calcium channel blockers
Narcotic analgesics e.g. codeine
Tricyclic antidepressants
Ergots (Discovered in 1920s; originally used to stop bleeding after a woman gave birth)
Triptans - an actual migraine drug
How are 5-Hydroxytryptamine used in treatment?
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. sumitriptan (1st gen)
Zolmitriptan, Rizatriptan (2nd gen)
What makes 2nd gen triptans different to 1st gen?
have higher oral bioavailability and longer plasma half-life
What is the proposed mechanism of action of triptans?
constriction of cranial
arteries - 5-HT1B/D
receptors
inhibitory actions
on the CNS - 5-HT1B/D
receptors
inhibition of
presynaptic TG
neurons - 5-HT1B/D/F
receptors
What are triptans contraindicated in?
Contraindicated in patients with coronary or cardiovascular disease, hypertension or that are pregnant
What is the caution with using triptans?
Overuse can cause severe rebound attacks-medication-overuse headaches
What additional treatments are there?
Simple analgesics
Anti-emetics e.g. metoclopramide are often taken with other medications to hasten absorption
Ergots e.g., ergotamine, dihydroergotamine also act on 5-HT1 receptors but are only partial agonists
Opioid medications e.g., codeine can be used for patients with contraindications for triptans and ergots. Can be habit forming used a last resort
What sort of prophylactic treatments are there?
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., metoprolol, propranolol: unclear how they work as they cause dilation of blood vessels
Tricyclic anti-depressants e.g., amitriptyline, nortriptyline work by preventing reuptake of 5-HT and antagonizing 5-HT2 receptors
Anti-convulsants e.g., sodium valproate, gabapentin
Non-steroidal anti-inflammatory drug (NSAID) e.g., Naproxen
Calcium channel blockers e.g., verapamil
What additional treatments are there? part 2
Anti-serotonergic (Anti 5-HT) drugs e.g., Pizotifen, Methysergide work by antagonizing 5-HT2 receptors
Methysergide is a semi synthetic ergot alkaloid. It should only be administered under hospital supervision because of the side effects (retroperitoneal fibrosis and fibrosis of heart values and pleura)
Botulinium toxin A (Botox®) licensed for the treatment of chronic migraine (15+ attacks per month)
Mechanism of action is yet unknown, but thought to work by relaxing muscles and by inhibiting the release of peripheral nociceptive neurotransmitters e.g., CGRP
What role does calcitonin gene-related peptide play?
Molecular mediator of migraine
What is calcitonin gene-related peptide?
a multifunctional 37 amino acid neuropeptide
a potent vasodilator and is involved in neurogenic inflammation and nociception
Increased levels of CGRP in serum and saliva of migraineurs during attacks
Injection of CGRP into migraineurs can cause delayed migraine-like headaches
Using the CGRP receptors as molecular targets, what drugs are out there in trials?
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
