Headache Disorders used for all pharmacy student

These materials useful for head ache disorder

1. Pharmacotherapy of Headache
Disorders
BY: Mubarik Fetu (B.Pharm, MSc, Clinical Pharmacy specialist)
Department of Pharmacy
College of medicine and health sciences
Wolkite University
E-mail: [email protected] [phone]

2. Introduction
Headache is a common medical complaint
Approximately 47% of the adult population
experiencing at least one headache per year.
Even when persistent or recurrent, headaches are
usually a benign primary condition;
Secondary headaches are caused by an underlying
medical disorder and may be medical emergencies.
Patients may seek headache care from multiple
providers.
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3. Introduction [2]
All clinicians should be familiar with:
The various types of headache,
Clinical indicators suggesting the need for urgent medical
attention and
Nonpharmacologic and pharmacologic options for
treatment
The International Headache Society (IHS) classifies
primary headaches as:
Migraine,
Tension-type,
Cluster and Other trigeminal autonomic cephalalgias
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4. Migraine headache
Epidemiology
In U.S 17.1% of women and 5.6% of men experience one
or more migraine headaches per year.
The prevalence of migraine varies considerably by age
and gender,
But the epidemiologic profile has remained stable over
the past 15 years.
Before the age of 12 years migraine is more common in
boys than girls,
The prevalence increases more rapidly in girls after
puberty.
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5. Migraine headache [2]
Gender differences in migraine prevalence have been
linked to menustration ,
However, these differences persist beyond menopause.
Prevalence is highest in both men and women between
the ages of 30 and 49 years.
The usual age of onset is 12 to 17 years of age for
females and 5 to 11 years for males.
About 93% of those with migraine reported some
headache-related disability,
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6. Migraine headache [3]
And 54% were severely disabled or needed bed rest
during an attack
A number of neurologic and psychiatric disorders as
well as CVD show increased comorbidity with migraine.
Whether this relationship is causal or representative of
a common pathophysiologic mechanism is unknown.
The economic burden of migraine is substantial;
The indirect costs from work-related disability far
exceed the direct costs associated with treatment.
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7. Migraine headache [4]
Etiology and Pathophysiology
 “Vascular hypothesis,” it was thought that focal
neurologic symptoms preceding or accompanying the
headache were caused by vasoconstriction and
reduction in cerebral blood flow.
The headache was thought to be caused by a
compensatory vasodilation with displacement of pain
sensitive intracranial structures.
Although blood flow is decreased during the aura of
migraine, other observations do not support the vascular
hypothesis
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8. Migraine headache [5]
Negative neuroimaging evidence for such vascular
changes and
The effectiveness of medications with no vascular
properties make this contention untenable.
A neuronal etiology has emerged as the leading
mechanism for the development of migraine pain.
More recent evidence suggests that the pain of migraine
is generated centrally
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9. Migraine headache [5]
Which involves episodic dysfunction of neural
structures that control the cranial circulation (the
trigeminovascular system)
This area may represent an endogenous “migraine
generator.”
Sporadic dysfunction of the nociceptive system and the
neural control of cerebral blood flow is hypothesized
These trigger migraine headache via their effects on
the trigeminovascular system
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10. Migraine headache [5]
It is believed that depressed neuronal electrical activity
spreads across the brain,
This produce transitory neural dysfunction.
Headache pain is likely due to compensatory
overactivity in the trigeminovascular system of the brain.
Activation of trigeminal sensory nerves leads to the
release of vasoactive neuropeptides :
Eg, calcitonin gene-related peptide, neurokininA,
substance P
These produce inflammatory response around vascular
structures in the brain, provoking the sensation of pain
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11. Migraine headache [5]
Continued sensitization of CNS sensory neurons can
potentiate and intensify headache pain as an attack
progresses.
Bioamine pathways projecting from the brainstem
regulate activity within the trigeminovascular system.
The pathogenesis of migraine is most likely due to an
imbalance in the modulation of nociception and blood
vessel tone by serotonergic and noradrenergic neurons
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12. Migraine headache [6]
Abnormalities in serotonin (5-HT) activity are also thought to
play a role in migraine headache.
Plasma 5-HT levels decrease by nearly half during a
migraine attack,
And a corresponding rise in the urinary excretion of 5-
hydroxyindoleacetic acid, the primary metabolite of 5-HT.
Also, reserpine, a drug that depletes 5-HT from body stores,
has been found to induce a stereotypical headache in
migraineurs and
It induce a dull discomfort in patients not prone to migraine
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13. Migraine headache [7]
In summary, the pathophysiology of migraine probably
involves dysfunction of the trigeminal neurons that
provide sensory innervation and modulate blood flow to
intracranial blood vessels.
The endogenous stimulus causing this dysfunction may
arise from a “migraine generator” in the brainstem.
Disturbances in 5-HT activity are also probably involved
It is this feature that serves as the target for many
migraine-specific therapies
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14. Migraine headache [8]
Clinical presentation
General
Migraine is a common, recurrent, severe headache that
interferes with normal functioning.
Symptoms
Migraine is characterized by:
Recurring episodes of throbbing head pain,
Frequently unilateral, with gradual onset
when untreated can last from 4 to 72 hours.
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15. Migraine headache [9]
IHS Diagnostic Criteria for Migraine
Migraine without aura
At least five attacks
Headache attack lasts 4-72 hours (untreated or
unsuccessfully treated)
Headache has at least two of the following
characteristics:
Unilateral location
Pulsating quality
Moderate or severe intensity
Aggravation by or avoidance of routine physical activity
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16. Migraine headache [10]
During headache at least one of the following:
Nausea, vomiting, or both
Photophobia and phonophobia
Not attributed to another disorder
Migraine with aura (classic migraine)
At least two attacks
Migraine aura fulfills criteria for typical aura, hemiplegic
migraine, retinal migraine or brainstem aura
Not attributed to another disorder
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18. Migraine headache [11]
Treatment
Desired Outcome
Treat migraine attacks rapidly and consistently without
recurrence
Restore the patient’s ability to function
Minimize the use of backup and rescue medications
Optimize self-care for overall management
Be cost-effective in overall management
Cause minimal or no adverse effects
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19. Migraine headache [12]
Non-pharmacologic therapy of acute migraine
headache is limited but can include:
application of ice to the head and periods of rest or sleep,
usually in a dark, quiet environment.
Preventive management of migraine should begin with the
identification and avoidance of factors that consistently
provoke migraine attacks in
Behavioral interventions, such as relaxation therapy, and
cognitive therapy, are preventive treatment options for
patients who prefer nondrug therapy
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20. Migraine headache [13]
Commonly Reported Triggers of Migraine
Food triggers : Alcohol Caffeine/caffeine withdrawal
Chocolate Fermented and pickled foods
Environmental triggers: Glare or flickering lights
High altitude, Loud noises ,Strong smells and fumes ,Tobacco
smoke
Behavioral–physiologic triggers: Excess or insufficient sleep,
Fatigue, Menstruation, menopause
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21. Migraine headache [14]
Non opiate analgesics
Simple analgesics and NSAIDs are effective
medications for the management of many migraine
attacks
They offer a reasonable first-line choice for
treatment of mild to moderate migraine attacks or
Severe attacks that have been responsive in the past
to similar NSAIDs or nonopiate analgesics.
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22. Migraine headache [15]
Of the NSAIDs, aspirin, ibuprofen, naproxen sodium,
tolfenamic acid, and the combination of acetaminophen plus
aspirin and caffeine have demonstrated the most consistent
evidence of efficacy.
Evidence for other NSAIDs is either limited or inconsistent.
Metoclopramide can speed the absorption of analgesics and
alleviate migraine-related nausea and vomiting.
NSAIDs should be avoided or used cautiously in patients with
previous ulcer disease, renal disease, or hypersensitivity to
aspirin.
Acetaminophen alone is not generally recommended for
migraine because the scientific support is not optimal
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23. Migraine headache [16]
Opiate Analgesics
Narcotic analgesic drugs (e.g., meperidine,
butorphanol, oxycodone, and hydromorphone) are
effective
But generally should be reserved for patients with:
moderate to severe infrequent headaches in whom
conventional therapies are contraindicated
or as "rescue medication" after patients have failed to
respond to conventional therapies.
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24. Migraine headache [17]
Corticosteroids
Can be considered as rescue therapy for status migrainous
Status migrainous is severe, continuous migraine that can
last up to 1 week.
Intravenous or intramuscular dexamethasone at a dose of
10 to 25 mg has also been used as an adjunct to abortive
therapy
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25. Migraine headache [18]
Ergot Alkaloids and Derivatives
Ergotamine tartrate ,dihydroergotamine
Can be considered for the treatment of moderate to
severe migraine attacks
Are nonselective 5-HT1 receptor agonists
Constrict intracranial blood vessels
Then inhibit the development of neurogenic inflammation in
the trigeminovascular system
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26. Migraine headache [19]
Ergotamine tartrate is available for oral, sublingual,
and rectal administration.
Oral and rectal preparations contain caffeine to
enhance absorption and potentiate analgesia.
Ergotamine use is limited because of issues of efficacy
and side effects.
Dihydroergotamine is available for intranasal and
parenteral administration.
Mixing with 1% or 2% lidocaine can reduce burning at
the injection site.
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27. Migraine headache [20]
Nausea and vomiting
Resulting from stimulation of the chemoreceptor trigger zone
Are among most common adverse effects of the ergotamine
derivatives.
Pretreatment with an antiemetic agent should be considered
Other common side effects include:
Abdominal pain, weakness, fatigue, paresthesias,
muscle pain, diarrhea, and chest tightness.
Rarely but severe Side effects:
Symptoms of severe peripheral ischemia (ergotism),
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28. Migraine headache [21]
Ergotamine derivatives are contraindicated in patients:
Renal or hepatic failure;
Coronary, cerebral, or peripheral vascular disease;
Uncontrolled hypertension; and sepsis; and
In pregnant or nursing women
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29. Migraine headache [22]
Serotonin Receptor Agonists (Triptans)
Introduction of the serotonin receptor agonists, or
triptans, represented a significant advance in migraine
pharmacotherapy.
The first member of this class, sumatriptan, and
The second-generation agents zolmitriptan,
naratriptan, rizatriptan, almotriptan, frovatriptan, and
eletriptan
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30. Migraine headache [22]
Are selective agonists of the 5-HT1B and 5-HT1D receptors.
The triptans are appropriate first-line therapy for patients
with mild to severe migraine
And are used for rescue therapy when nonspecific
medications are ineffective.
Selection of a triptan is based on characteristics of the
headache, convenience of dosing,
At all marketed doses, the oral triptans are effective and
well tolerated.
The triptans differ in their pharmacokinetic and
pharmacodynamic profiles
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31. 2/3/2023
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32. Migraine headache [23]
In general, triptans can be divided into:
faster onset and higher efficacy and slower onset and low
efficacy
Triptans like frovatriptan and naratriptan have the longest
half lives, the slowest onset of action, and less headache
recurrence.
This may make them more suitable for patients who have
migraine attacks of a slow onset and longer duration
Faster-acting triptans are more efficacious when a rapid
onset is necessary.
Subcutaneous, intranasal, or orally dissolving tablets may be
useful in patients with prominent early nausea or vomiting .
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33. Migraine headache [24]
Side effects to the triptans are common but usually mild
to moderate in nature and of short duration.
Adverse effects are consistent among the class and
include
paresthesias, fatigue, dizziness, flushing,
warm sensations, and somnolence.
One forth of patients receiving a triptan consistently
report “triptan sensations,”
These include: tightness, pressure, heaviness, or pain in
the chest, neck, or throat.
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34. Migraine headache [24]
The triptans are contraindicated in patients with:
History of ischemic heart disease
Uncontrolled hypertension
cerebrovascular disease
hemiplegic and basilar migraine
Should not be used routinely in pregnancy.
The triptans should not be given within 24 hours of the
ergotamine derivatives.
MAOIs use is not recommended with in 2 weeks of triptans
therapy
Concomitant use of SSRI may result in Serotonin syndrome
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36. Migraine headache [25]
Prophylactic drug therapy
Preventive migraine therapies are administered on a
daily basis to reduce the frequency, severity, and
duration of attacks
Preventive therapy should be considered in the setting
of:
Recurring migraines that produce significant disability
despite acute therapy;
Frequent attacks occurring more than twice per week with
the risk of developing medication-overuse headache;
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37. Migraine headache [26]
Symptomatic therapies that are ineffective or
contraindicated, or produce serious side effects
patient preference to limit the number of attacks
Preventive therapy also may be administered preemptively
or intermittently when headaches recur in a predictable
pattern
The evidence to support the various agents used for
migraine prophylaxis has recently been reviewed
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38. Migraine headache [27]
Beta -Adrenergic Antagonists
are among the most widely used drugs for migraine
prophylaxis.
drugs Propranolol, nadolol, timolol, atenolol, and metoprolol
They have proven efficacy in controlled clinical trials,
reducing the frequency of attacks by 50% in 60% to 80% of
patients
Selection of a -blocker can be based on -selectivity,
convenience of the formulation, and tolerability.
Can be considered in healthy or hypertension or angina
comorbidity
Used cautiously in : CHF, PVD, Asthma, DM
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39. Migraine headache [28]
Antidepressants
Amitriptyline, the most widely studied antidepressant for
migraine prophylaxis,
Has demonstrated efficacy in placebo-controlled and
comparative studies.
Use of other antidepressants is based primarily on clinical
and anecdotal experience
Especially in comorbid depression
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40. Migraine headache [29]
Anticonvulsants
Anticonvulsant medications have emerged as important
therapeutic options for migraine prophylaxis with
valproate, divalproex, topiramate, and gabapentin all
demonstrating efficacy.
Anticonvulsants are particularly useful in migraineurs with
comorbid seizures, anxiety disorder, or manic-depressive
illness.
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41. Migraine headache [29]
Nonsteroidal antiinflammatory drugs
Are modestly effective for reducing the frequency, severity, and
duration of migraine attacks,
But potential GI and renal toxicity limit the daily or prolonged use
of these agents.
Consequently, NSAIDs have been used intermittently to prevent
headaches that recur in a predictable pattern, such as menstrual
migraine.
Administration of NSAIDs in the perimenstrual period can be
beneficial in women with true menstrual migraine.
NSAIDs should be initiated up to 1 week prior to the expected
onset of headache and continued for no more than 10 days.
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42. Migraine headache [30]
Calcium Channel Blockers
The calcium channel blockers generally are considered
second or third-line options for preventive treatment
Used when other drugs with established clinical benefit are
ineffective or contraindicated.
Verapamil is the most widely used calcium channel blocker
for preventive treatment,
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43. 2/3/2023
43

44. Tension–type headache
Is the most common type of primary headache, with an
estimated 1-year prevalence ranging from 38% to 86%
peaks in the fourth decade and is higher among women
The incidence of tension type headache decreases with age
Only few sufferers seek medical attention, likely because
they have infrequent attacks
Risk factors associated with a poor outcome in tension-type
headache include
coexisting migraine, sleep problems, anxiety, poor stress
management, and the presence of chronic tension-type
headache 2/3/2023
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45. Tension–type headache [2]
Pathophysiology
The mechanism of pain in CTT headache is thought to
originate from myofascial factors and peripheral
sensitization of nociceptors.
Central mechanisms also are involved, with heightened
sensitivity of pain pathways in the CNS
The following may be initiating stimulus:
Mental stress, nonphysiologic motor stress,
a local myofascial release of irritants, or a combination of
these
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46. Tension–type headache [3]
Following activation of supraspinal pain perception
structures, a self-limiting headache results in most
individuals
CTT headache can evolve from ETT headache in
predisposed individuals due to a change in central
circuits and nociceptors
It is likely that other pathophysiologic mechanisms also
contribute to the development of tension-type headache
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47. Tension–type headache [4]
Clinical Presentation
The pain usually is mild to moderate in intensity
Often is described as a dull, nonpulsatile tightness or
pressure.
Bilateral pain is most common, but the location can vary
The pain is classically described as having a "hatband"
pattern.
Associated symptoms generally are absent, but mild
photophobia or phonophobia may be reported.
The disability associated with tension-type headache
typically is minor
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48. Tension–type headache [5]
Treatment
General Approach to Treatment
The vast majority of episodic tension-type headache
sufferers self-medicate with OTC medications
Simple analgesics and NSAIDs are the mainstay of acute
therapy.
Most agents used for tension-type headache have not been
studied in controlled clinical trials
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49. Tension–type headache [6]
Nonpharmacologic Therapy
Psychophysiologic therapy and physical therapy have
been used in the management of tension-type
headache.
Behavioral therapies can consist of reassurance and
counseling, stress management, relaxation training,
and biofeedback.
These therapies (alone or in combination) can result in
a 35% to 50% reduction in headache activity.
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50. Tension–type headache [7]
Pharmacologic Therapy
Simple analgesics (alone or in combination with caffeine) and
NSAIDs are effective for the acute treatment of most mild to
moderate tension-type headaches.
the following have demonstrated efficacy in placebo
controlled and comparative studies.
Acetaminophen, Aspirin,
Ibuprofen, naproxen,
ketoprofen, and ketorolac
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51. Cluster headache
Cluster headache, the most severe of the primary
headache disorders,
It is characterized by:
Attacks of excruciating, unilateral head pain
That occur in series lasting for weeks or months (ie, cluster
periods)
Separated by remission periods usually lasting months or
years.
Cluster headaches can be episodic or chronic.
Cluster headache is relatively uncommon among the
primary headache disorders
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52. Cluster headache [2]
The male-to-female ratio for cluster headache is
approximately 4:1
Age of onset typically in the third to fifth decade.
Up to 85% of patients with cluster headache are
tobacco smokers or have a history of smoking.
Tobacco cessation does not, however, seem to improve
the course of cluster headaches.
Recent genetic epidemiologic surveys support a
predisposition for cluster headache can exist in certain
families.
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53. Cluster headache [3]
Cluster headache is one of a group of disorders
referred to as trigeminal autonomic cephalalgias.
This autonomic nervous system dysfunction is
characterized by SNS underactivity coupled with PNS
activation
The pain is believed to be the result of vasoactive
neuropeptide release and neurogenic inflammation.
The exact cause of trigeminal activation in this
intermittently manifest syndrome is unclear
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54. Cluster headache [4]
Hypothalamic dysfunction, occasioned by diurnal or
seasonal changes in neurohumoral balance, may
responsible for headache periodicity
Serotonin affects neuronal activity and may play a role
in the pathophysiology of cluster headache.
The precipitation of cluster headache by high-altitude
exposure also implicates hypoxemia in the pathogenesis
Hypothalamus-regulated changes in cortisol, prolactin,
testosterone, growth hormone, leuteinizing hormone,
endorphin, and melatonin have been found during
periods of cluster headache attack.
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55. Cluster headache [5]
Neuroimaging studies performed during acute cluster
headache attacks have demonstrated activation of the
ipsilateral hypothalamic gray area,
Implicating the thalamus as a cluster generator.
Significant cranial autonomic activation occurs
ipsilateral to the pain
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56. Cluster headache [6]
Patients experiencing “cluster headache” may display
the following headache symptoms and characteristics:
At least one or more of the following symptoms:
Lacrimation
Nasal congestion and/or rhinorrhea
Eyelid edema
Forehead or facial sweating/flushing
Sensation of fullness in the ear
Miosis and/or ptosis
Or a sense of restlessness or agitation
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57. Cluster headache [7]
Duration of pain: 15–180 minutes (untreated)
Frequency of attacks: One every other day and/or
up to 8 per day for more than half the time the
disorder is active
Criteria for diagnosis: Five or more attacks
fulfilling the above criteria
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58. Cluster headache [8]
Treatment
As in migraine, therapy for cluster headaches involves
both abortive and prophylactic therapy.
Abortive therapy is directed at managing the acute
attack.
Prophylactic therapies are started early in the cluster
period in an attempt to induce remission.
Patients with chronic cluster headache can require
prophylactic medications indefinitely
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59. Cluster headache [9]
Abortive Therapy
Oxygen
The standard acute treatment of cluster headache is
inhalation of 100% oxygen by non breather facial mask at
a rate of 7 to 10 L/min for 15 to 30 minutes.
Repeat administration can be necessary because of
recurrence, as oxygen appears to merely delay, rather than
abort, the attack in some patients.
No side effects have been reported with the use of oxygen,
but caution should be used for those who smoke or have
COPD
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60. Cluster headache [10]
Ergotamine Derivatives
All forms of ergotamine have been used in cluster
headaches,
But no controlled clinical trials support their use.
In clinical use, intravenous dihydroergotamine results in the
quickest response,
Repeated administration for 3 to 7 days can break the cycle
of frequent attacks.
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61. Cluster headache [11]
Ergotamine tartrate also has provided effective relief
of cluster headache attacks when administered
sublingually or rectally,
But the pharmacokinetics of these preparations
frequently limit their clinical utility.
Dosing guidelines are similar to those for migraine
headache therapy
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62. Cluster headache [12]
Triptans
The quick onset of subcutaneous and intranasal triptans make
them safe and effective abortive agents for cluster
headaches
Subcutaneous Sumatriptan (6 mg) is the most effective agent.
Nasal sprays are less effective but may be better tolerated
in Some patients.
Adverse events reported in cluster headache patients are
similar to those seen in migraineurs.
Orally administered triptans have limited use in cluster
attacks because of their relatively slow onset of action;
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63. Cluster headache [13]
Prophylactic Therapy
Verapamil, the preferred calcium channel blocker for the
prevention of cluster headaches,
It is effective in approximately 70% of patients.
The beneficial effects of verapamil often appear after 1
week of therapy.
A typical suggested dosage range is from 360 to 720
mg/day,
Some patients requiring up to 1,200 mg/day.
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64. Cluster headache [13]
Lithium
Lithium carbonate is effective for episodic and chronic
cluster headache attacks
Can also be used in combination with verapamil.
A positive response is seen in
Up to 78% of patients with chronic cluster headache,
And in up to 63% of patients with episodic cluster
headache.
The usual dose is 600 to 1,200 mg/day, with a
suggested starting dose of 300 mg twice daily..
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65. Cluster headache [14]
Initial side effects are mild and include :
Tremor, lethargy,
Nausea, Diarrhea, and
Abdominal discomfort.
Thyroid and renal function must be monitored during
lithium therapy
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66. Cluster headache [15]
Ergotamine
Is efficacious for prophylactic as well as abortive therapy of
cluster headaches.
A 2-mg bedtime dose is often for the prevention of nocturnal
headache attacks.
Daily use of 1 to 2 mg ergotamine alone or in combination
with verapamil or lithium
Can provide effective headache prophylaxis in patients
refractory to other agents
Risk of ergotism or rebound headache little with this regimen
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67. Cluster headache [16]
Corticosteroids are useful for inducing remission.
Therapy is initiated with 40 to 60 mg/day prednisone
and tapered over approximately 3 weeks.
Relief appears within 1 to 2 days of initiating therapy.
To avoid steroid-induced complications, long-term use
is not recommended.
Headaches can recur when therapy is tapered or
discontinued
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68. Therapeutic outcome evaluation
Patients should be monitored for:
Frequency, intensity, and duration of headaches,
Change in the headache pattern.
Patients should be encouraged to keep a headache
diary
Careful monitoring is essential to:
Initiate the most appropriate pharmacotherapy,
Document therapeutic successes and failures,
Identify medication contraindications, and
Prevent or minimize adverse events.
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69. Therapeutic outcome evaluation [2]
Patients using acute therapies should be monitored to
identify potential medication-overuse headache.
Patient counseling is necessary to allow for proper
medication use
Strict adherence to dosing guidelines should be stressed
to minimize potential toxicity.
Patterns of abortive medication use can be documented
to establish the need for prophylactic therapy.
Prophylactic therapies also should be monitored closely
(every 3-6 months until stable)
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70. Thanks
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