Headache - Ishmael Flashcards
What are the four main types of headaches?
- Sinus
- Migraine
- Cluster
- Tension
Which type of headache is more common in men, where the pain is centered behind the eye?
Cluster headaches
Which headache is characterized by pain, nausea, and visual changes most classically?
Migraine headache
Which headache is described by pain in the head similar to a hat band squeezing the head?
Tension headache
Which headache has pain behind the forehead and/or cheekbones?
Sinus headache
Which headache may be a secondary headache?
sinus headache is usually secondary to a bacterial infection
What differentiates migraines from other headaches?
The associated symptoms
What could be some causes of secondary headaches?
Infection Head injury Vascular condition Tumor Substance abuse/withdrawal GI disorders
What is the most common primary headache, and is normally associated with stress, anger, and fatigue?
The tension headache
With tension-type headaches, is pain usually associated with nausea, photophobia, or phonophobia?
Not usually nausea, but maybe photophobia or phonophobia (but not both).
Is a tension headache usually worse upon exertion?
No.
How long does a tension headache last if untreated?
30 minutes to days.
What non-pharmacologic treatments could be used for a tension headache?
- Palpation of muscles
- Stress management (behavioral treatment, relaxation training, biofeedback)
- 33-64% reduction in HA activity
What pharmacologic treatments are available for tension headaches?
- OTC simple analgesics (APAP, ASA, NSAIDS) with or without caffeine (may help analgesic be absorbed in the brain)
- high dose NSAIDS
- Combination with butalbital (barbiturate) or codeine (opiate)
How long should you use medications containing butalbital?
Less than 4 days a month
How long should you use combination analgesics?
Less than 10 days a month
How long should you use NSAIDS?
Less than 16 days a month
What symptoms must you have in order to have a migraine?
Recurrent attacks of pain plus associated symptoms during the pain: either 1) nausea and/or vomiting or 2) photophobia and phonophobia
What migraine and cluster headaches have in common?
They are vascular headaches (superficial vessel dilation)
How long do untreated and unsuccessfully treated headaches last?
From 4 to 72 hours
How are migraines described?
Unilateral pain that is pulsing, moderate to severe intensity, aggravated by routine physical stimuli.
How are hormone levels a factor in migraines.
They are more common in women than men, and up until puberty, they are just as prevalent in boys as girls. After puberty, they are three times higher than girls than boys. After menopause, symptoms may improve.
What would hormone therapy do to migraine prevalence in women, theoretically?
It would even out fluctuations and act as prophylaxis ..r reduce risk of migraines.
What is an aura?
- When symptoms preceded headache by 10-30 minutes (60 max) and include sensory warning signs.
At least one of the following symptoms must be included: - Reversible visual symptoms
- Reversible sensory symptoms
- Reversible speech disturbances
Usually composition of headache is similar from attack to attack.
In which part of the brain is the activity changing in an aura?
It is a cortical spreading depression, characterized first by transient waves of activity in the cerebral cortex (extensive glutamate release).
What are the four phases in a migraine attack?
Prodrome premonitory
Aura
Pain and associated symptoms
Postdrome
Which phase does the trigger occur in?
The prodrome phase. Irritability, fatigue, cravings, mood changes, muscle tension could all be factors.
What are the vascular and neurogenic components of a migraine?
The vasculature
The trigeminal nerve
Serotonin
Describe the pathway of a migraine from trigger to headache:
Trigger initiates a nociceptive response Causes dilation of blood vessels Causes neurogenic inflammatory response Pain Further nerve activation
What does a nociceptive response normally accomplish?
Activation of nociception usually warns and provide sensory information about tissue damage or inflammation
What is the term for a condition of disturbed ion transport?
Channelopathy
What is familial hemiplegic migraine? What mutation do they have? In what gene?
It is a rare, inherited form of a severe migraine with aura. The aura is characterized by a sudden attack of unilateral weakness that seems like a stroke.
They have a mutation in the alpha subunit of the voltage-gated P/Q type calcium channel. 15 mutations identified in the alpha subunit contribute to this disorder.
What medication would a person with familial hemiplegic migraines take prophylactically?
Verapamil, which is a calcium-channel antagonist
How is the Ca(V)2.1 related to migraines?
It is expressed in all areas implicated in the pathogenesis of migraine: trigeminal ganglia, brainstem nuclei involved in nociception, cerebral cortex.
What do the mutations in Ca(V)2.1 alpha subunit cause?
They have an inappropriate hyper excitability
What does the pain in a migraine headache come from?
It comes from the dilation and distention of cerebral blood vessels. There is a vein running through the subarachnoid space between the arachnoid and the pia mater (which lines the brain tissue). The innervation of these blood vessels is derived from the Trigeminal nerve (cranial nerve V). So the inflammation of the meninges at the level of the meninges is what causes the pain.
What are the three meninges?
Dura mater
Arachnoid
Pia mater
When information from the vessels within the meninges is collected, where does it go?
It is collected from within the meninges and the brainstem, and carried to the brain stem. The pain message is perceived by the thalamus and the cerebral cortex.
What stops the pain of the headache?
When the firing rate of the trigeminal nerve is reduced.
What explains the associated symptoms of a migraine?
The projection of the trigeminal nerve to other areas of the brain, which causes the nausea, photophobia, and phonophobia.
What part of the brain causes the aura?
The spreading cortical depression and initial excessive glutamate release causes an aura.
What condition is it when a sudden attack of facial pain occurs? What usually causes a response?
Trigeminal neuralgia. Carbemazepine (use-dependent Na+ channel blocker)
At what stage can a ligand bind to a voltage/frequency/use-dependent channel?
The ligand must bind in the open conformation, which stabilizes the inactive state. The channel must be in use for the ligand to bind and block the channel. Carbamazepine is an example of a use-dependent channel blocker.
What does the depolarization of the trigeminal nerve cause?
It causes the release of neuropeptide transmitters that cause vasodilation.
Which neurotransmitters are released by the trigeminal nerve?
Calcitonin gene-related peptide (CGRP) - most abundant
Substance P
Tachykinin
What types of things are in clinical trials right now regarding migraine medications?
CGRP antagonists and antibodies to the receptor
How many subunits are the human CGRP complex? What are they?
3
Calcitonin-like receptor
Receptor activity-modifying protein
Receptor component protein
What does vasodilation initiate? (caused by the activation of the trigeminal nerve and subsequent release of neuropeptides - especially CGRP)
Initiates a neurogenic inflammatory response
- Permeability of vascular endothelium increases
- Fluid and plasma proteins leak out
- Inflammation of meninges activates nociceptive response
- Neuropeptides maintain and amplify response
What heteroreceptors are on the trigeminal nerve the help regulate neuropeptide release?
5HT receptors
What do serotonin receptors on these intercranial blood vessels cause?
They mediate vasoconstriction of the blood vessels
Which serotonin receptors subtypes when activated inhibit adenylyl cyclase?
1A, 1B, 1D, 1E, 1F
Which serotonin subtypes are expressed in the trigeminal nerve and vasculature?
1B, 1D, 1F
What serotonin subtypes does the trigeminal nerve express that regulate the release of neuropeptides?
1D, 1F
What triggers the TGVS (trigeminovascular system) in the pain pathway?
The cortical spreading depression
What serotonin subtypes does sumatriptan target?
It is a selective agonist at the 5HT 1B and 1D receptors, and is essentially inactive at the other 5HT receptor subtypes.
What formulations does sumatriptan come in?
Injectable, tablet, and nasal spray
When during a migraine attack should sumatriptan be given?
It should be given to abort the current migraine (either late or early in the attack). It cannot be used prophylactically.
What migraine symptoms does sumatriptan control?
Nausea, vomiting, photophobia, phonophobia
What side effect of sumatriptan leads to a contraindication in a disease state?
It’s use as a vasoconstrictor (affinity for 5HT 1B receptors) makes it contraindicated in those with ischemic heart disease. (1B receptors regulate the constriction of cranial vasculature).
What are the actions of sumatriptan?
It is a mixed agonist, with actions at the 1B ad 1D receptor subtypes.
- 5HT 1D: decreases release of neuropeptides
- 5HT 1B: constricts cranial vasculature
Does sumatriptan have to get across the BBB to work at 5HT 1B receptors?
No, it works in the meninges, which is above the BBB.
Compare the second generation triptan drugs to sumatriptan:
- Have higher bioavailability and increased half-life
- All are selective 5HT 1B, 1D, 1F agonists
- Selective 1D agonists were not effective in clinical trials
What was the problem with sumatriptan?
It had a short half-life, so often it would be taken during the aura, and then would have cleared the body before the actual headache came on.
What would the medication in phase III trials (Lasmitidan) have as an advantage?
It is a selective 5HT 1F agonist, which would mean that it would act on the trigeminal nerve to decrease the release of neuropeptides, but would not be a vasoconstrictor and could be used in heart disease patients.
What side effects are reported in about 2% of those who use triptans?
It can cause paresthesias, atypical sensations, feeling of pressure or pain (chest, throat, jaw, neck), feelings of fatigue/malaise, vertigo. It may feel like a heart attack!
Triptan should not be used in what people?
- Cardiovascular disease/after stroke
- Within 24 hours of: 1) another triptan or 2) an ergot derivative
What kinds of medications would increase the risk of serotonin syndrome?
- SSRI
- SNRI
- Triptan
- concomitant use of these medications
- However, syndrome is very rare
How are ergot alkaloids useful in treating migraines?
They are a powerful vasoconstrictive agent, but have mixed action at dopamine and alpha-adrenergic receptors. These mixed actions contribute to side effects. They do have partial agonist actions at 5HT receptors.
What does ergot poisoning look like?
Mummified, blackened limbs. Abortive agent.
What are the main issues with ergotamine and dihydroergotamine?
They hit so many more receptor types than the triptans, that they end up causing side effects such as nausea and vomiting by stimulating the dopamine receptors, rather than reducing them.
Is efficacy enough to treat migraines?
No, the side effect profile is very important too.
How often can you dose ergotamine?
2mg sublingual dose can be repeated every 30 minutes up to 6mg/24 hours or 10mg/week.
Ergotamine has very poor oral availability. What can increase this when coadministered? What other effects does this have?
Caffeine. It can help the absorption of ergotamine, and also constrict arteries and has a stimulatory effect.
How often can you dose dihydroergotamine?
1mg injectable, IM, or SQ formulation can be repeated after 1 hour up to 2mg (IV) or 3mg (SQ or IM) in 24 hours or 6mg/week.
Which is more potent as a vasoconstrictor, ergotamine or dihydroergotamine?
Ergotamine, but it is also more potent as an emetic.
What kinds of side effects can be induced by ergot alkaloids? Are the SE’s tolerable?
Nausea, leg weakness, muscle pain, numbness, tingling. The side effects may lead to poisoning, and should in that case be withdrawn completely
When are ergot alkaloids contraindicated?
Pregnancy Cardiovascular disease Impaired renal or hepatic function Sepsis Triptans or other vasoconstrictors
When looking at a graph of persistent contractile response, what would the difference be between the ergot derivatives and the triptans in terms of % of initial coronary artery contraction after a wash?
The ergot derivatives are not changed at all, whereas the triptans immediately decrease their contractile response within 15 minutes.
What do nonspecific and specific migraine treatments aim to do?
The nonspecific treatments (analgesics, combo analgesics, caffeine) try to mask the pain, while the specific treatments aim go for vasoconstriction (1B) and decreased neurotransmitter release (1D, 1F)
Is caffeine an active or inactive component of nonspecific migraine treatment?
An active component, because it not only helps with absorption, but likely does something with adenosine receptors in pain and vasculature.
What is a medication overuse headache?
A rebound headache brought about by overmedication. only way to stop it is to decrease use of the medication. You cannot treat it with more medication, even prophylactic medication.
How long would it take to stop a MOH?
7-10 days of decreased use of the medication. Would probably need to use other coping strategies.
What kinds of meds could you get a MOH from?
Simple and combo pain relievers, triptan, ergot derivatives, opiates (all)
Will caffeine help a MOH?
It may exacerbate it.
When is a MOH the worst?
Usually in the morning. It is described as throbbing or a dull ache. It is different than the original headache.
Why is a complex migraine different from a regular migraine?
Because the migraine cannot be treated by a triptan medication. It is contraindicated because there is vasoconstriction going on in the brain that causes the symptoms. Symptoms may include speech disturbances, touch sensation, movement/weakness, vascular spasms. These symptoms are all reversible.
How do you treat a complex migraine?
With combination analgesics
When should you use medication like promethazine, metoclopramide, prochlorperazine, chlorpromazine, or trimetho-benzamide?
They are used for treating nausea, so use them as soon as possible. They do not treat the migraine headache.
When is a prophylactic medication usually prescribed to treat migraines?
When the acute treatment doesn’t work.
What is the goal of prophylactic treatment?
To reduce the severity, frequency, and length of the migraine attacks. Not clear how they work: they may prevent swelling of cranial vessels over time and control the underlying trigger. Will still require attack-abortive treatment.
How much do prophylactic medications help, and what types of medications are used?
- Effective 40% of the time
- Beta blockers, TCA’s, anticonvulsants/neurostabilizers
- Ca+ channel blockers (2nd line)
What is important in treating a migraine prophylactically?
To recognize the triggers.
What treatments may be better for children with migraines?
Riboflavin (B2)
Magnesium
Combination of riboflavin and magnesium
How long should you try a first-line migraine prophylaxis medication before switching to another first-line agent?
- 2-3 months at that dose, then adjust dose until effective
- If adverse effects, d/c and start other first-line agent
- After max dose has been reached without effectiveness, try other first-line agent.
- If no single first-line agent is effective, consider two first-line agents.
What symptoms go along with cluster headaches?
- unilateral pain behind the eye
- Can’t keep still, pacing, restless, and fidgety due to pain
- Associated symptoms include tearing on the same side of the face as the pain, runny/stuffy nose, droopy eyelid, sweating.
What gender are migraines more common in? Cluster headaches?
Cluster headaches are more common in men (20-40 year average onset) and migraines are more common in females.
How common are cluster headaches?
Rare, about 1% of the population (5% familial)
What medications can you use to acutely treat cluster headaches?
- High flow oxygen for 15-30 minutes (12 L/min)
- Triptans (SQ sumatriptan most effective)
- Ergotamines (IV dihydroergotamine, repeat for 3-7 days)
What is the prophylaxis treatment for cluster headaches?
- Corticosteroids (inducing remission/short-term relief)
- Verapamil (beneficial after 1 week of therapy)
- Lithium (can use instead of verapamil or in combo with)
What is the last resort for cluster headache prophylaxis?
Valproate + ergotamine
What percentage of people suffer a chronic daily headache?
4-5% estimate. Can be primary or secondary
Who tends to develop chronic daily headaches?
People who suffer from migraine or tension headaches for a long time often develop a daily headache. Initial migraine pain fades and changes. It becomes a chronic pain condition.
