Headache and Facial Pain 1

Question 1

How can head pain be elicited?

Answer 1

1) Inflammation or traction (έλξη) of pain sensitive structures
2) Vasodilation
3) Muscle Contraction

Question 2

Pain-Sensitive Structures

Answer 2

1) Venous sinuses and their tributaries (κλάδοι)
2) Dural and meningeal arteries, arteries at the base of the brain
3) Portions of the meninges
4) Upper cervical nerve roots
5) Scalp muscles and aponeurosis

Question 3

Main pain-sensitive intracranial structure’s innervation

Answer 3

Trigeminovascular neurons mainly of the opthalmic division

Question 4

Migraine Without Aura Criteria

Answer 4

• At least five attacks
• Headache attacks lasting 4-72 hours (unless succesfully treated)
• At least two of the following pain characteristics
  i) Unilateral loccation
  ii) Pulsating quality
  iii) Moderate to severe intensity
  iv) Aggrevated by or causes avoidance of routine physical activity
• During headache at least one of the following
  i) Nausea or vomiting
  ii) Photophobia and phonophobia

Question 5

Migraine With Aura Criteria

Answer 5

Question 6

Percentage of migraine with and without aura

Answer 6

Migraine with aura 20%
Migraine without aura 80%

Question 7

Migraine prevalence

Answer 7

Women 18%
Men 6%

Question 8

Which is the most sensitive criterion for migraine?

Answer 8

Headache worsening with activity

Question 9

Pathogenesis of migraine (1) pain (2) aura

Answer 9

1)
A) Cortical spreading depression:
Cortical spreading depression is a self-propagating wave of neuronal and glial depolarization that spreads across the cerebral cortex.
Cortical spreading depression is hypothesized to:
●Cause the aura of migraine
●Activate trigeminal nerve afferents
●Alter blood-brain barrier permeability

The activation of trigeminal afferents by cortical spreading depression in turn causes inflammatory changes in the pain-sensitive meninges that generate the headache of migraine through central and peripheral reflex mechanisms
(prolonged activation of trigeminal nociception, generates the pain of the migraine headache)

It has been suggested that migraine without aura may be caused by the occurrence of cortical spreading depression in areas of the brain (eg, cerebellum) where depolarization is not consciously perceived

B) Trigeminovascular system
The pathophysiology of migraine involves activation of the trigeminovascular system, which consists of small caliber pseudounipolar sensory neurons that originate from the trigeminal ganglion and upper cervical dorsal roots. These sensory neurons project to innervate large cerebral vessels, pial vessels, dura mater, and large venous sinuses. Most of the innervation of the anterior structures is via the ophthalmic division of the trigeminal nerve with a greater contribution of upper cervical roots to posterior structures.

From the trigeminal nucleus caudalis, fibers that are involved in the localization of pain ascend to the thalamus (mostly to the ventroposterior medial nucleus of the thalamus) and to the sensory cortex.

C) Stimulation of the trigeminal ganglion results in release of vasoactive neuropeptides, including substance P, calcitonin gene-related peptide (CGRP), and neurokinin A. Release of these neuropeptides is associated with the process of neurogenic inflammation. The two main components of this sterile inflammatory response are vasodilation (CGRP is a potent vasodilator) and plasma protein extravasation.

D) A self-sustaining process of further pain, inflammation, and sensitization of central trigeminal neurons occurs, with sensitization of glial cells in the periaqueductal gray, for which there appears to be a central generator, located in the rostral brainstem.
By the time these central structures become sensitized, they are activated independently of peripheral stimuli.

2) Migraineurs have a hyperexcitable cerebral cortex, which probably underlies migraine auras and the frequent comorbid depression, mania, and anxiety

Question 10

Role of CGRP in migraine

Answer 10

CGRP appears to mediate
i) trigeminovascular pain transmission from intracranial vessels to the central nervous system
ii) the vasodilatory component of neurogenic inflammation

Question 11

Why triptans are not effective in later stages of migraine?

Answer 11

In later stages, sensitization of glial cells in the periaqueductal gray (for which there appears to be a central generator located in the rostral brainstem) occurs.
By the time these central structures become sensitized, they are activated independently of peripheral stimuli.
Triptans do not enter the central nervous system and therefore at this point are ineffective.

Question 12

Is there genetic contribution in migraine?

Answer 12

Yes
8 percent of migraineurs have first-degree relatives with migraine.
Identical twins are twice as likely to have migraine

3 migraine genes have been identified all associated with familial hemiplegic migraine (rare)
The first three types of familial hemiplegic migraine (FHM) are channelopathies.
FHM1 is caused by variants of the CACNA1A gene,
FHM2 by variants of the ATP1A2 gene, and
FHM3 by variants of the SCN1A gene.
Variants of the PRRT2 gene also cause some cases of familial hemiplegic migraine.

Question 13

Migraine prevention (non pharmacologic)

Answer 13

• Avoid oversleeping/ undersleeping
• Antimigraine diet
• Adequate hydration
• Avoid missing meals
• Minimize caffeine intake
• Control stress and psychiatric comorbidities

Question 14

Can migraine cause neck pain or lacrimation/ rhinorrhea?

Answer 14

Yes

Question 15

Migraine variants

Answer 15

Question 16

Complications of migraine

Answer 16

Prolonged symptoms may last for the entire headache, for several days or weeks, or in some cases leave a permanent neurologic deficit.

1) Status migrainosus is a debilitating migraine attack lasting for more than 72 hours. The median attack duration is approximately five days.
It is more common among females than males and may occur in patients with migraine either with or without aura.

2) Persistent aura without infarction is defined by aura symptoms persisting for one week or more with no evidence of infarction on neuroimaging.

3) Migrainous infarction is defined by a migraine attack, occurring in a patient with migraine with aura, in which one or more aura symptoms persist for more than one hour and neuroimaging shows an infarction in a relevant brain area.

4) Migraine aura-triggered seizure is a seizure triggered by an attack of migraine with aura.

Question 17

Vestibular migraine criteria

Answer 17

Question 18

chronic migraine diagnostic criteria

Answer 18

Question 19

Migraine: acute attack treatment

Answer 19

1) nonsteroidal anti-inflammatory drugs (NSAIDs)
2) acetaminophen
3) triptans
4) antiemetics
5) calcitonin gene-related peptide (CGRP) antagonists
6) lasmiditan
7) dihydroergotamine

Noninvasive neuromodulation devices are typically used for patients who do not respond to or tolerate drug treatments and those who wish to avoid medications.

The selection of a specific agent depends on patient-specific factors including the severity and character of symptoms, comorbid conditions, and prior response to treatment.

Question 20

Risk of medication overuse headache

Answer 20

• Highest with opioids, butalbital-containing combination analgesics, and aspirin-acetaminophen-caffeine combinations.
• The risk with triptans is considered intermediate by some experts but high by others.
• MOH may be avoided with some CGRP antagonists, which are effective for preventive as well as acute treatment of migraine
• The risk is lowest with NSAIDs, which may even be protective against the development of chronic migraine for patients who have less than 10 headache days per month.

Question 21

Why is parenteral treatment prefered in acute migraine?

Answer 21

oral agents are less effective because of poor absorption secondary to migraine-induced gastric stasis and vomiting.

Question 22

Symptomatic treatment of acute mild migraine attack

Answer 22

• Initial treatment with nonopioid analgesics, including nonsteroidal anti-inflammatory drugs (NSAIDs) and/or acetaminophen
• For patients unresponsive to nonopioid analgesics, we add a triptan
  The combined use of an NSAID with a triptan is more effective than either agent alone.

Question 23

Symptomatic treatment of moderate to severe migraine attack

Answer 23

• treatment with a triptan with or without a nonopioid analgesic (eg, naproxen sodium)
  The combined use of a triptan and a nonopioid analgesic appears to be more effective than using either class alone
• When attacks are associated with severe nausea or vomiting, we add an antiemetic and/or switch to a nonoral migraine-specific medication.
• Alternative options include calcitonin gene-related peptide (CGRP) antagonists, lasmiditan, an antiemetic drug, and dihydroergotamine

Question 24

Management of severe migraine in the emergency department

Answer 24

combination treatment that includes:

*Subcutaneous sumatriptan 6 mg and/or a parenteral antiemetic agent.

*Adjunctive diphenhydramine 25 mg, if IV metoclopramide or prochlorperazine are used, to prevent akathisia and other dystonic reactions.

*Adjunctive dexamethasone 4 mg (IV or IM) to reduce the risk of early headache recurrence

Alternative options include IV dihydroergotamine (DHE 45) combined with IV metoclopramide (for patients who have not receive a triptan within 24 hours), IV sodium valproate, or IM/IV ketorolac.

Question 25

Status migrainosus management

Answer 25

a combination of intravenous fluids plus parenteral medications, including ketorolac and a dopamine receptor blocker (eg, prochlorperazine, metoclopramide, chlorpromazine)

Other options include valproate and/or dihydroergotamine; some patients may require admission for persistent disabling symptoms

Question 26

non- modifiable and potentially modiafiable factors for transformation of episodic to chronic migraine

Answer 26

A) Nonmodifiable risk factors for the transformation from episodic to chronic migraine include the following:

●Female sex
●Genetic makeup
●History of head or neck injury
●Low education level
●Low socioeconomic status
●Stressful life events (eg, divorce, job loss)
●Younger age
●Presence of cutaneous allodynia
●Comorbid pain disorders

B) Potentially modifiable risk factors for this transformation include:

●Higher baseline headache frequency
●High frequency use or overuse of abortive headache medications
●Depression
●Habitual snoring
●High caffeine consumption
●Obesity
●Sleep disorders
●Low efficacy of acute migraine treatment
●Persistent, frequent nausea
●Asthma

Question 27

NSAIDS in the treatment of acute migraine attack: 1) type 2) risks

Answer 27

Risks
1) Gastrointestinal bleeding
2) Hepatic disease
3) Serious cardiovascular thrombotic events (myocardial infarction, stroke)
4) New-onset hypertension or exacerbation of hypertension

+++ Naproxen: Higher dose (eg, 500 mg twice daily) may have less cardiovascular toxicity than comparable doses of other NSAIDs

Question 28

Triptans in the treatment of acute migraine attack: 1) Types 2) Mechanism of action

Answer 28

• serotonin 1b/1d agonists
• inhibit the release of vasoactive peptides
• promote vasoconstriction
• block pain pathways in the brainstem
• inhibit transmission in the trigeminal nucleus caudalis, thereby blocking afferent input to second order neurons; this effect is probably mediated by reducing the levels of calcitonin gene-related peptide (CGRP)
• may also activate 5-HT 1b/1d receptors in descending brainstem pain-modulating pathways and thereby inhibit dural nociception

Question 29

Triptans in the treatment of acute migraine attack: route of administration

Answer 29

• Sumatriptan can be given as a subcutaneous injection (usually administered by autoinjector in the thigh), as a nasal spray, as a nasal powder, or orally.
• Zolmitriptan is also available for both nasal and oral use.
• The others are available for oral use only

Question 30

In which case must the dose of rizatriptan be adjusted downward

Answer 30

The dose of rizatriptan must be adjusted downward in patients who take propranolol, since propranolol increases rizatriptan levels by 70 percent

Question 31

Triptans: Limitations to use

Answer 31

• All triptans should be limited to no more than 10 days of use per month to avoid medication overuse headache
• It is still recommended that triptans be avoided in patients with hemiplegic migraine, basilar migraine, ischemic stroke, ischemic heart disease, Prinzmetal’s angina, and uncontrolled hypertension
• Combination with monoamine oxidase inhibitors is relatively contraindicated with triptans because of the risk of serotonin syndrome.
• Triptans should not be used within 24 hours of the use of ergotamine preparations or a different triptan medication
• Eletriptan is primarily metabolized by cytochrome P-450 enzyme CYP3A4. Therefore, eletriptan should not be used within at least 72 hours of treatment with other drugs that are potent CYP3A4 inhibitors, such as ketoconazole, itraconazole, nefazodone, troleandomycin, clarithromycin, ritonavir, and nelfinavir.

Question 32

Can triptans be combined with NSAIDS?

Answer 32

The combined use of a triptan and NSAID to treat acute migraine appears to be more effective than using either drug class alone.

The best-studied combination is sumatriptan with naproxen.

Question 33

CGRP antagonists in acute management of migraine 1) mechanism of action 2) types, dosage and route of administration 3) contraindications 4) use in pregancy 5) adverse effects

Answer 33

1) block neurogenic inflammation, decrease blood flow in meningeal vessels, inhibit pain transmission
δράση κυρίως στην περιφέρεια σε επίπεδο μηνίγγων, τριδυμικών απολήξεων στα μηνιγγικά αγγεία, μέχρι το επίπεδο του τριδυμικού γαγγλίου
πολύ ασθενέστερη δράση κεντρικότερα (επίπεδο νωτιαίου πυρήνα του τριδύμου και άνω)
2)
Rimegepant 75 mg as a single oral dose (κυκλοφορεί στην Ελλάδα)
Συνδέεται στον υποδοχέα για το CGRP, μειώνοντας έτσι την ικανότητα του CGRP να συνδέεται επίσης στον υποδοχέα
Χρησιμοποιείται για την αντιμετώπιση και την πρόληψη των κρίσεων ημικρανίας σε ενήλικες.

Ubrogepant 50 to 100 mg orally, may repeat dose in two hours; maximum dose 200 mg per 24 hours
calcitonin gene-related peptide receptor antagonist indicated for the acute treatment of migraine with or without aura in adults
Zavegepant 10 mg given intranasally as a single spray
calcitonin gene-related peptide receptor antagonist indicated for the acute treatment of migraine with or without aura in adults

3)
Το VYDURA δεν συνιστάται:

• σε ασθενείς με σοβαρή ηπατική δυσλειτουργία
• σε ασθενείς με νεφρική νόσο τελικού σταδίου (CLcr <15 ml/λεπτό)
• για συγχορήγηση με ισχυρούς αναστολείς του CYP3A4
• για συγχορήγηση με ισχυρούς ή μέτριους επαγωγείς του CYP3A4

4) it is preferable to avoid

5) most common adverse effects: upper respiratory infections, dizziness, nausea

Question 34

Antiemetics in migraine treatment 1) mechanism of action 2) types and dosage 3) contraindications 4) significant adverse reactions 5) use in pregnancy

Answer 34

1) dopamine receptor antagonists

2) Intravenous (IV) metoclopramide 10 mg once
IV or intramuscular (IM) prochlorperazine 10 mg once

3)
- Gastrointestinal haemorrhage, mechanical obstruction or gastro-intestinal perforation for which the stimulation of gastrointestinal motility constitutes a risk
- Confirmed or suspected phaeochromocytoma, due to the risk of severe hypertension episodes
- History of neuroleptic or metoclopramide-induced tardive dyskinesia
- Epilepsy (increased crises frequency and intensity)
- Parkinson’s disease
- Combination with levodopa or dopaminergic agonists
- Known history of methaemoglobinaemia with metoclopramide or of NADH cytochrome-b5 deficiency.
- Metoclopramide should not be used during breast-feeding

4)
- CNS depression
- extrapyramidal symptoms
- hyperprolactinemia

5) may be considered for adjunctive treatment of nausea and vomiting in pregnant patients when symptoms persist following initial pharmacologic therapy

Question 35

Lasmiditan: 1) mechanism of action 2) dosage and route of administration 3) contraindications 4) significant adverse events 5) pregnancy

Answer 35

1) Lasmiditan is a high-affinity, highly selective serotonin 5-HT1F receptor agonist.
Selective targeting of the 5-HT1F receptor is hypothesized to decrease stimulation of the trigeminal system and treat migraine pain without causing vasoconstriction

2) Oral: 50 to 100 mg as a single dose
Maximum: One dose per 24 hours

3) Use is not recommended in patients with severe hepatic impairment

4)
- CNS depression
- Οι ασθενείς θα πρέπει να καθοδηγούνται να μην οδηγούν ή να μην επιδίδονται σε άλλες δραστηριότητες που απαιτούν ιδιαίτερη προσοχή για τουλάχιστον 8 ώρες μετά τη λήψη κάθε δόσης λασμιδιτάνης
- Serotonin syndrome

5) not recommended

Question 36

ergots: 1) mechanism of action 2) types and route of administration 3) contraindications 4) pregnancy

Answer 36

1) bind to 5HT 1b/d receptors (just as triptans do)

2) Dihydroergotamine IV, IM, Intranasal, Subcutaneous
Ergotamine Sublingual

3)
- uncontrolled hypertension
- ischemic heart disease
- angina pectoris
- history of MI
- silent ischemia, or coronary artery vasospasm including Prinzmetal angina
- peripheral vascular disease
- sepsis
- severe hepatic or renal dysfunction
- following vascular surgery
- concurrent use of peripheral and central vasoconstrictors
- concurrent use of potent inhibitors of CYP3A4 (includes protease inhibitors, azole antifungals, and some macrolide antibiotics)

4) not indicated

Question 37

Can ergots be administered with other antimigraine treatment

Answer 37

avoid use within 24 hours of 5-hydroxytryptamine-1 (5-HT1) receptor agonists (triptans), other serotonin agonists, or ergotamine-containing or ergot-like agents

Question 38

Dexamethasone in migraine treatment: 1) indication 2) dosage

Answer 38

1) to reduce the risk of early headache recurrence for patients who are treated with standard abortive therapy for migraine headache in the emergency department or clinic

2) single dose of parenteral dexamethasone 4mg

Question 39

Neuromodulation in migraine treatment: 1) indication 2) types

Answer 39

1) These treatments stimulate the central or peripheral nervous system with an electrical current or a magnetic field.
They are options for patients who prefer nonpharmacologic treatments or who have an inadequate response, inability to tolerate, or contraindications to drug treatments for migraine.

2)
Transcutaneous supraorbital nerve stimulation
Remote electrical neuromodulation
Transcranial magnetic stimulation
Noninvasive vagus nerve stimulation

Question 40

Peripheral nerve blocks in migraine treatment: 1) indication 2) types

Answer 40

1) are options for the acute treatment of migraine in patients who have severe and prolonged migraine attacks, and in patients who are refractory to or have contraindications to standard migraine treatments

2)
Occipital nerve blocks
Sphenopalatine ganglion blocks

Question 41

Indications for preventive treatment in migraine

Answer 41

• Frequent (eg, ≥4 per month) or long-lasting (eg, ≥12 hours) migraine headaches
• Migraine attacks that cause significant disability or diminished quality of life despite appropriate acute treatment
• Contraindication to acute therapies
• Failure of acute therapies
• Serious adverse effects of acute therapies
• Risk of medication overuse headache
• Menstrual migraine

Question 42

1) First and 2) Second line agents for the prevention of migraine

Answer 42

1) First-line agents – For most patients with episodic migraine (≤14 headache days per month) who have an indication for preventive therapy initial treatment with amitriptyline, venlafaxine, one of the beta blockers (metoprolol or propranolol), or topiramate is suggested

Approximately half of patients given any of these drugs will have a 50 percent reduction in the frequency of headache, but the doses required may lead to intolerable side effects

2) Second-line agents – For patients with a contraindication to or inadequate response (after at least eight weeks at a therapeutic dose) of two or more first-line drugs
These include other antihypertensives, the calcitonin gene-related peptide (CGRP) antagonists, valproate, and gabapentin.

++ Σύμφωνα με ελληνική εταιρεία κεφαλαλγίας τα CGRP πρέπει να θεωρούνται επίσης πρώτης γραμμής

Question 43

b-blockers in migraine prevention: type and dosage, duration of treatment before deeming a failure, contraindications

Answer 43

Metoprolol, propranolol, and timolol are established as effective for migraine prevention

●Propranolol in two divided doses starting at 40 mg daily; dose range 40 to 240 mg daily

●Metoprolol in two divided doses starting at 50 mg daily; dose range 50 to 200 mg daily

It can take several weeks for headache improvement to accrue with these drugs; the dose should be titrated and maintained for at least three months before deeming the medication a failure.

Using beta blockers as initial therapy for migraine prevention in patients over age 60 and in smokers is not suggested. Compared with other antihypertensive drugs in the primary treatment of hypertension, beta blockers may be associated with a higher rate of stroke and other cardiovascular events.

The use of beta blockers may be also limited in patients with erectile dysfunction, peripheral vascular disease, Raynaud phenomenon, and patients with baseline bradycardia or low blood pressure.
They must be used cautiously as well in patients with asthma, diabetes mellitus, or depression, and in those with cardiac conduction disturbances or sinus node dysfunction.

Question 44

Topiramate in migraine prevention: dosage, mechanism of action, contraindications, side effects

Answer 44

1) Initial: 25 mg once daily; increase dose in 25 to 50 mg increments at intervals ≥1 week based on response and tolerability, up to 100 mg/day in 1 to 2 divided doses based on chosen formulation.

2) Antiseizure activity may be due to a combination of potential mechanisms: Blocks neuronal voltage-dependent sodium channels, enhances GABA(A) activity, antagonizes AMPA/kainate glutamate receptors, and weakly inhibits carbonic anhydrase.

3) Immediate release: There are no contraindications listed in the manufacturer’s labeling.

4)
- CNS effects/cognitive dysfunction
Sedative: dizziness, drowsiness, fatigue
Cognitive: short-term and long-term cognitive dysfunction in both children and adults, including disturbance in attention, memory impairment, and language problems, declines in verbal fluency, attention/concentration, processing speed, language skills, perception, working memory, reduced IQ, poor verbal fluency, abnormal thinking, and word-finding deficits.
Psychiatric: aggressive behavior, mood disorder, anxiety, depression, Paresthesia
- Metabolic acidosis
- Nephrolithiasis
- Ocular effects (acute myopia with secondary angle-closure glaucoma, choroidal effusion and visual field defect, scotoma, and maculopathy)
- Oligohidrosis/hyperthermia
- Suicidal ideation/tendencies
- Weight loss/anorexia

Question 45

Amitriptyline in migraine prevention: dosage, mechanism of action, contraindications, adverse effects

Answer 45

amitriptyline (starting dose 10 mg at bedtime, dose range 20 to 50 mg at bedtime)

mechanism of action: Increases the synaptic concentration of serotonin and/or norepinephrine in the central nervous system by inhibition of their reuptake by the presynaptic neuronal membrane pump.

contraindications: coadministration with or within 14 days of MAOIs, acute recovery phase following myocardial infarction

adverse effects:
- Anticholinergic effects (constipation (including fecal impaction), xerostomia, blurred vision, and urinary retention)
- Bleeding risk
- Cardiac conduction abnormalities (most commonly QRS prolongation, atrioventricular conduction disturbance, and cardiac arrhythmias, including sinus tachycardia. QT prolongation and ventricular arrhythmias may also occur)
- CNS depression
- Fragility fractures
- Hyponatremia
- Ocular effects (acute angle-closure glaucoma)
- Orthostatic hypotension
- Serotonin syndrome
- Suicidal thinking and behavior
- Withdrawal syndrome

Question 46

Venlafaxine in migraine prevention: dosage, mechanism of action, contraindications, adverse effects

Answer 46

Venlafaxine (starting at 37.5 mg once a day, dose range 75 to 150 mg once a day)

Mechanism of action: inhibitors of neuronal serotonin and norepinephrine reuptake and weak inhibitors of dopamine reuptake
Venlafaxine functions like an SSRI in low doses (37.5 mg/day) and as a dual mechanism agent affecting serotonin and norepinephrine at doses above 225 mg/day

Contraindications: use of monoamine oxidase inhibitors (MAOIs) (concurrently or within 14 days of discontinuing the MAOI); initiation of MAOI within 7 days of discontinuing venlafaxine; initiation in patients receiving linezolid or IV methylene blue.

Adverse effects:
Activation of mania or hypomania
Bleeding risk
Blood pressure elevations
Fragility fractures
Hepatotoxicity
Hyponatremia
Ocular effects (acute angle-closure glaucoma)
Serotonin syndrome
Sexual dysfunction
Suicidal thinking and behavior
Withdrawal syndrome

Other:
Dermatologic: Diaphoresis
Endocrine & metabolic: Weight loss
Gastrointestinal: Anorexia, nausea , xerostomia
Nervous system: Asthenia, dizziness, drowsiness, insomnia

Question 47

CGRPs in the prevention of migraine: mechanism of action

Answer 47

CGRP antagonists are reasonable options for patients with marked disability from frequent migraine who do not respond to or cannot tolerate other options.
They may provide earlier benefit than other preventive agents, and the formulations given by injection may also be helpful for those who have difficulty complying with preventive medications that require daily pills.
However, high cost and barriers to insurance approval may limit their access.

Erenumab: δεσμεύεται στον υποδοχέα του σχετιζόμενου με το γονίδιο της καλσιτονίνης πεπτιδίου (CGRP) (το μοναδικό)

Galcanezumab, Fremanezumab, Eptinezumab: δεσμεύουν το σχετιζόμενο με το γονίδιο της καλσιτονίνης πεπτίδιο (Calcitonin Gene-Related Peptide-CGRP) και με αυτόν τον τρόπο προλαμβάνουν τη βιολογική δράση του

Rimegepant

Atogepant

Question 48

CGRP antagonists in migraine prevention dosage

Answer 48

Large molecules in the form of monoclonal antibodies directed against the CGRP receptor or ligand are given by injection for migraine prevention.
Small-molecule CGRP antagonists (“gepants”) are oral agents first shown effective for acute migraine treatment.

• Atogepant έγκριση από ΕΜΑ με την προυπόθεση ότι οι ασθενείς θα έχουν τουλάχιστον 4 μέρες ημικρανίας τον μήνα / το μόνο gepant μέχρι στιγμής που υπάρχει μελέτη για την πρόληψη της χρόνιας ημικρανίας

Question 49

Rimegepant indications and dosage

Answer 49

Acute treatment of migraine
The recommended dose is 75 mg rimegepant, as needed, once daily.
Prophylaxis of migraine
The recommended dose is 75 mg rimegepant every other day.

** The maximum dose per day is 75 mg rimegepant

Question 50

CGRP mAbs contraindications

Answer 50

None

προσοχή όμως σε παθήσεις μικρών τριχοειδών όπως Raynaud
(το CGRP είναι η πιο αγγειοδιασταλτική ουσία στο σώμα και η καταστολή του μπορεί να έχει επίπτωση)

Question 51

Calcium channel blockers in migraine prevention: type and dosage

Answer 51

verapamil (in three divided doses starting at 120 mg daily, dose range 120 to 240 mg daily).
If there is no response at lower doses, or if tolerance develops, verapamil can be increased to 480 mg per day in divided doses as tolerated; increased vigilance for bradycardia and heart block is mandatory with higher verapamil doses.

Flunarizine (sibelium) 5 to 10 mg daily

Tolerance may be overcome by increasing the dose of medication, or by switching to a different calcium channel blocker.

Question 52

ACE inhibitors/ARBs in migraine prevention: type and dosage

Answer 52

lisinopril (10 mg/day for one week, then 20 mg/day)

Candesartan 16 mg once daily.

(the small size and single-center crossover design of trials prevent definitive conclusions regarding the effectiveness of lisinopril and candesartan for migraine prevention)

Question 53

Valproate in migraine prevention: dosage, mechanism of action, contraindications, adverse effects

Answer 53

1) Initial: 500 mg once daily (ER) or in 2 divided doses (DR or ER); increase dose gradually based on response and tolerability in increments of 250 mg/day at intervals >3 days, up to 1 g/day in 1 to 2 divided doses based on chosen formulation (DR or ER). Based on clinical experience, some patients require doses up to 1.5 g/day for sufficient response

2) Causes increased availability of gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter, to brain neurons or may enhance the action of GABA or mimic its action at postsynaptic receptor sites. Also blocks voltage-dependent sodium channels, which results in suppression of high-frequency repetitive neuronal firing.

3) Contraindications: hepatic disease or significant impairment; urea cycle disorders; prevention of migraine in pregnant women and women of childbearing potential who are not using effective contraception; mitochondrial disorders

4)
- CNS effects
CNS depression (including dizziness and drowsiness)
nervous system stimulation (eg, nervousness, insomnia, tremor) Delirium and hallucinations
Parkinsonism and cognitive dysfunction (In general, valproate appears to have less effect on cognitive abilities compared to other older antiseizure medications)
- Hematologic effects (thrombocytopenia)
- Hepatotoxicity/hepatic failure
- Hyperammonemia and encephalopathy
- Hypersensitivity reactions (delayed)
- Pancreatitis
- Suicidal ideation/tendencies

Question 54

Botulinum toxin indication in migraine

Answer 54

there is evidence that botulinum toxin type A (onabotulinumtoxinA) injection is effective for the treatment of chronic migraine (ie, headache on ≥15 days per month for at least three months, with at least 8 of the 15 headaches per month fulfilling criteria for migraine)

Question 55

Neuromodulation for migraine prevention

Answer 55

●Transcutaneous supraorbital nerve stimulation

●Transcranial magnetic stimulation

●Vagal nerve stimulation (additional studies needed)

Question 56

Factors favouring and factors avoiding drugs in migraine prevention

Answer 56

Question 57

Choice of migraine preventive treatment for patients:

1) with hypertension who are nonsmokers and ≤60 years of age
2) with hypertension who are smokers or are >60 years of age
3) with depression or mood disorder
4) with epilepsy
5) with insomnia
6) with obesity
7) with Raynaud phenomenon

Answer 57

1) reasonable options include metoprolol, propranolol, or timolol in the absence of contraindications to beta blockers.

2) options include verapamil or flunarizine.
Beta blockers as initial therapy for migraine prevention in these patients are not suggested, because they may be associated with a higher rate of cardiovascular events compared with other antihypertensive drugs in the primary treatment of hypertension

3) reasonable options include amitriptyline or venlafaxine.

4) reasonable options include valproate or topiramate.

5) amitriptyline is a reasonable option.

6) topiramate is a reasonable option.

7) reasonable options include verapamil or flunarizine.

Question 58

First-line prophylactic medications for chronic migraine

Answer 58

●Propranolol
●Amitriptyline
●Topiramate
●Valproic acid and its derivatives (for males and for females who do not have childbearing potential)

Question 59

Second-line prophylactic medications for chronic migraine

Answer 59

*OnabotulinumtoxinA
*Calcitonin gene-related peptide (CGRP) antagonists (erenumab, fremanezumab, galcanezumab, eptinezumab, atogepant)
*Occipital nerve block (ONB)
*Venlafaxine
*Verapamil
*Other beta blockers (atenolol, nadolol, metoprolol)
*Gabapentin
*Magnesium
*Riboflavin
*Candesartan
*Other tricyclic antidepressants (nortriptyline, protriptyline)

Question 60

Which triptan is effective in symptomatic treatment of cluster headache

Answer 60

Injectable sumatriptan, 2–6 mg, is highly effective, but its use is limited to a maximum of 12 mg daily.
Because these attacks are more rapid in onset but shorter in duration than migraines, no other form of sumatriptan or other triptan tends to be effective.

Question 61

Medication overuse headache diagnostic criteria

Answer 61