Therapy of Migraines Flashcards by Sarah Assaf

Mechanism behind migraines?

Vasodilation of intracranial extracerebral blood vessels = activation trigeminal nerves = release vasoactive neuropeptides that interact with dural blood vessels = promote vasodilation and dural plasma extravasation = neurogenic inflammation.

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Which neuropeptides are implicated in migraines?

1) Calcitonin gene-related peptide (CGRP)
2) Neurokinin A
3) Substance P

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__ receptors are also implicated in the pathophysiology of migraine headache.

5-HT

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What is Pizotifen?

5-HT2 antagonist

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What does Pizotifen do?

Prevents migraine attack from starting

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Specific antimigraine drugs (ergot alkaloids and triptans) are agonists at vascular and neuronal __ receptor subtypes.

5-HT1

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What do specific antimigraine drugs (ergot alkaloids and triptans) cause?

1) Vasoconstriction of meningeal blood vessels
2) Inhibition of vasoactive neuropeptide release and pain signal transmission

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What are some nonpharmacologic migraine therapies?

1) Rest or sleep in a dark, quiet environment

2) Regular sleep, exercise, and eating habits, smoking cessation, and limited caffeine intake

3) Identification and avoidance of migraine triggers

4) Behavioral interventions such as relaxation therapy, biofeedback, and cognitive therapy, are preventive treatment options.

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Commonly Reported Triggers of Migraine Include:

1) Food triggers
2) Environmental triggers
3) Hormones
4) Behavioral/Physiologic triggers

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Which food might trigger migraines?

1) Alcohol
2) Caffeine/caffeine withdrawal
3) Chocolate
4) Fermented and pickled foods
5) Monosodium glutamate [MSG] (in Chinese food, seasoned salt, and instant foods)
6) Nitrate-containing foods (processed meats)
7) Saccharin/aspartame (diet foods or diet sodas)
8) Tyramine-containing foods

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Which environmental triggers might cause migraines?

1) Glare or flickering lights
2) High altitude
3) Loud noises
4) Strong smells and fumes
5) Tobacco smoke
6) Weather changes

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Which Hormones changes might trigger, intensify, or alleviate migraines?

Changes in estrogen levels (menarche, menstruation, pregnancy, menopause, and OCPs)

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A drop in ___ precipitates migraine attacks.

Estrogen

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Which behavioral/physiologic triggers might cause migraines?

1) Excess or insufficient sleep
2) Fatigue
3) Menstruation, menopause
4) Sexual activity
5) Skipped meals
6) Strenuous physical activity (prolonged overexertion)
7) Stress or post-stress

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What are the goals of acute migraine treatment?

1) Terminate migraine attacks rapidly
2) Reduce recurrence rate significantly
3) Restore the patient’s ability to function normally
4) Cause minimal or no therapy-related adverse effects

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What are the goals of long-term migraine treatment?

1) Reduce migraine frequency, severity, and disability
2) Reduce reliance on poorly tolerated, ineffective, or unwanted acute pharmacotherapies!
3) Improve quality of life
4) Prevent headache
5) Avoid escalation of headache-medication use!
6) Educate and enable patients to manage their disease
7) Reduce headache-related distress and psychological symptoms

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____ is the mainstay of treatment for most migraine patients.

Drug therapy

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Acute (Abortive) therapies can be divided into:

1) Migraine-specific
2) Migraine non-specific

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What are some migraine-specific drugs?

1) Ergots
2) Triptans

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What are some migraine non-specific drugs?

1) Analgesics
2) Antiemetics
3) NSAIDs
4) Corticosteroids

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When are migraine drugs most effective?

When administered at the onset of migraine

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Initial treatment of migraines is based on:

1) Headache-related disability
2) Symptom severity

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It is advised to use ___(specific/nonspecific) agents for mild - moderate headache NOT causing disability.

Non-specific

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The absorption and efficacy of orally administered drugs can be compromised by ___that accompany migraine.

1) Gastric stasis
2) Nausea and vomiting

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What should you do when nausea and vomiting accompanying migraines are severe?

Pretreatment with antiemetic agents or the use of non-oral treatment (suppositories, nasal sprays, or injections)

What are the classes of migraine therapies?

1) Analgesics 2) NSAIDs 3) Ergot alkaloids 4) Serotonin agonists (Triptans) 5) Miscellaneous

Which analgesics are used for migraines?

Acetaminophen

Which NSAIDs are used for migraines?

1) Aspirin 2) Ibuprofen 3) Naproxen 4) Diclofenac

Which Serotonin agonists (Triptans) are used for migraines?

1) Sumatriptan 2) Zolmitriptan 3) Rizatriptan 4) Almotriptan 5) Frovatriptan 6) Eletriptan

Which Ergot alkaloids are used for migraines?

1) Ergotamine/caffeine 2) Dihydroergotamine

Which Miscellaneous drugs are used for migraines?

1) Metoclopramide 2) Prochlorperazine

The frequent or excessive use of acute migraine medications can result in:

Medication-overuse headache (Rebound headache)

What happens in rebound headache?

The headache returns as the medication is eliminated, leading to use of more drug for relief

How do rebound headaches present?

The patient experiences a daily or near-daily headache with superimposed episodic migraine attacks.

What happens when you discontinue a drug during rebound headaches?

Gradual decrease in headache frequency and severity and a return of the original headache characteristics

Is drug detoxification done on an outpatient or inpatient basis?

Outpatient

Regulation of nociceptive systems and renewed responsiveness to therapy usually occur within __ following medication withdrawal for rebound headaches.

2 months

It is recommend to limit the use of acute migraine therapies to ____ to avoid the development of medication-overuse headache.

<10 days per month

Preventive migraine therapies are administered on a __ basis to reduce the frequency, severity, and duration of attacks and improve responsiveness to symptomatic migraine therapies.

Daily

What are the first-line choices for treatment of mild-to-moderate migraine attacks?

Simple analgesics and NSAIDs

The combination of ___ have demonstrated the most consistent evidence of efficacy in migraines.

Acetaminophen + Aspirin/Caffeine

Is Acetaminophen alone recommended for migraines?

How do NSAIDs prevent inflammation in the trigeminovascular system?

Through the inhibition of prostaglandin synthesis

How does Metoclopramide help with migraines?

It increases the absorption of analgesics and alleviates migraine-related nausea and vomiting.

What are NSAID's adverse reactions

1) GI (previous ulcer disease) 2) CNS (somnolence, dizziness), 3) Renal disease 4) Hypersensitivity reactions 5) Cardiovascular (hypertension, heart failure)

When should you administer an antiemetic when taking oral abortive migraine drugs?

15 - 30 minutes before ingestion

Metoclopramide is useful for:

1) Nausea & Vomiting 2) Reversing gastroparesis 3) Improving absorption from the GI tract

___ can be used in moderate-to-severe migraine attacks.

Ergot Alkaloids and Derivatives

Oral and rectal preparations of Ergot Alkaloids and Derivatives contain ___ to enhance absorption and potentiate analgesia.

Caffeine

___ is available for intranasal, intramuscular, subcutaneous, and IV routes.

Dihydroergotamine

Adverse effects of Ergot Alkaloids and Derivatives?

1) Nausea and vomiting!!!!! 2) Abdominal pain 3) Weakness 4) Fatigue 5) Paresthesias 6) Muscle pain 7) Diarrhea 8) Chest tightness 9) Severe ischemia!!!!

Why do Ergot Alkaloids and Derivatives cause nausea and vomiting?

From stimulation of the chemoreceptor trigger zone

Ergotamine derivatives are contraindicated in which patients?

1) Renal or hepatic failure 2) Coronary, cerebral, or peripheral vascular disease 3) Uncontrolled hypertension 4) Sepsis 5) Women who are pregnant or nursing

What are the signs of severe ischemia?

1) Cold, numb, painful extremities 2) Continuous paresthesias 3) Diminished peripheral pulses 4) Claudication and gangrenous extremities 5) Myocardial infarction 6) Hepatic necrosis 7) Bowel and brain ischemia

Rebound headache in Ergot alkaloids and derivatives occur more with __.

Ergotamine tartrate

Triptans are selective agonists at:

The 5-HT1B and 5-HT1D receptors

Are triptans selective or non-selective?

Selective

___ are appropriate first-line therapy for patients with mild to severe migraine.

Triptans

Which drugs are used for rescue therapy when nonspecific migraine medications are ineffective?

Triptans

Relief of migraine headache is the result of three key actions:

1) Normalization of dilated intracranial arteries through enhanced vasoconstriction 2) Inhibition of vasoactive peptide release from perivascular trigeminal neurons 3) Inhibition of transmission through second-order neurons ascending to the thalamus

__(Oral/Subcutaneous) Sumatriptan has a more rapid onset of action.

Subcutaneous

___(Oral/Intranasal) Sumatriptan has a faster onset of effect.

Intranasal

Triptans can be divided into:

1) Those with a faster onset and higher efficacy 2) Those with a slower onset and lower efficacy

Compared with other triptans, ___ and ___ have the longest half-lives, the slowest onset of action, and less headache recurrence.

Frovatriptan and Naratriptan

Compared with other triptans, Frovatriptan and Naratriptan have:

1) The longest half-lives 2) The slowest onset of action 3) Less headache recurrence

What is your next step if one Triptan fails?

The patient can be switched successfully to another triptan

Major adverse effects of Triptans?

1) Local adverse effects: a) Subcutaneous injection site reactions b) Taste perversion c) Nasal discomfort after intranasal use 2) “Triptan sensations,” including tightness, pressure, heaviness, or pain in the chest, neck, or throat 3) Medication-overuse headache

Contraindications of Triptans?

1) History of ischemic heart disease, uncontrolled hypertension, cerebrovascular disease, and hepatic diseases 2) Hemiplegic and basilar migraine 3) Pregnancy

Which patients should receive a cardiovascular assessment prior to triptan use and have initial doses administered under medical supervision?

1) Postmenopausal women 2) Men older than 40 years of age 3) Patients with uncontrolled risk factors

The Triptans should NOT be given within 24 hours of the ___.

Ergotamine derivatives

Administration of Sumatriptan, Rizatriptan, and Zolmitriptan within 2 weeks of therapy with ___ is NOT recommended.

Monoamine Oxidase Inhibitors (MAOIs)

MAOIs __(increase/decrease) Triptan’s metabolism.

Decrease

Administration of _____ within 2 weeks of therapy with Monoamine Oxidase Inhibitors (MAOIs) is NOT recommended.

1) Sumatriptan 2) Rizatriptan 3) Zolmitriptan

___ should NOT be administered with cytochrome P450 and CYP3A4 inhibitors such as macrolide antibiotics, antifungals, and some antiviral therapies.

Eletriptan

Concomitant Triptan therapy with SSRIs or SNRIs can potentially cause:

Serotonin syndrome

Which drug classes can be given to prevent migraines?

1) β-Adrenergic antagonists 2) Anticonvulsants 3) Antidepressants 4) NSAIDs 5) Serotonin agonists (Triptans)

Which β-Adrenergic antagonists can be given to prevent migraines?

1) Propranolol 2) Atenolol 3) Metoprolol XL 4) Nadolol

Which Anticonvulsants can be given to prevent migraines?

1) Topiramate 2) Valproic acid

Which Antidepressants can be given to prevent migraines?

1) Amitriptyline 2) Venlafaxine

Which NSAIDs can be given to prevent migraines?

1) Ibuprofen 2) Ketoprofen 3) Naproxen

Which Serotonin agonists (Triptans) can be given to prevent migraines?

1) Frovatriptan 2) Naratriptan 3) Zolmitriptan

Preventive migraine therapy should be considered in the following cases:

1) Recurring migraines that produce significant disability despite acute therapy. 2) Frequent attacks occurring more than twice per week with the risk of developing medication-overuse headache. 3) Symptomatic therapies that are ineffective or contraindicated, or produce serious adverse effects. 4) Uncommon migraine variants that cause profound disruption and/or risk of permanent neurologic injury (hemiplegic migraine, basilar migraine, and migraine with prolonged aura) 5) When headaches recur in a predictable pattern (exercise-induced migraine or menstrual migraine) 6) Patient’s preference

Which migraine prevention drugs have established efficacy?

1) Propranolol 2) Timolol 3) Divalproex sodium 4) Topiramate

The selection of a migraine prevention agent is typically based on:

1) Its adverse effect profile 2) The patient’s coexisting comorbid conditions

___ are needed to achieve clinical benefit when using migraine prevention agents, but some reduction in attack frequency can be evident by the first month of therapy; but maximal benefits are typically observed by ___ of treatment.

2 - 3 months; 6 months

Migraine drug therapy should be initiated with __(high/low) doses.

Low

Drug doses for migraine prophylaxis are often __(higher/lower) than those necessary for other indications.

Lower

Overuse of acute headache medications will interfere with:

The effects of preventive migraine treatment

Prophylactic migraine treatment usually is continued for at least ___ after the frequency and severity of headaches have diminished, then gradual tapering or discontinuation may be reasonable.

6 - 12 months

Which drugs are among the most widely used drugs for migraine prophylaxis?

β-Adrenergic Antagonists

Which β-Adrenergic Antagonists reduce the frequency of migraine attacks by 50% in greater than 50% of patients?

1) Metoprolol 2) Propranolol 3) Timolol