Headache Hozan Jaza

MSc. Clinical Pharmacy

College of Pharmacy

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Headache

Headache is a symptom that can be caused by many disorders for example, inflammation of pain-sensitive structures within the head, or it can be due to disorders of extracranial structures such as the eyes, ears, or sinuses.

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Classification of Headache Headache can be categorized on the basis of the

underlying etiology into two types.

Primary headache

Disorders are characterized by the lack of an identifiable and treatable underlying cause.

Classification of primary headache

Migraine

• Migraine without aura

• Migraine with aura

Tension-Type Headache

Cluster Headache

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Secondary headache Disorders are those associated with a variety of organic causes such as trauma, cerebrovascular malformations and brain tumors. Classification of secondary Headache

Headache Associated with Head and/ or neck trauma

Headache Associated with Vascular Disorders

• Intracranial hematoma

• Subarachnoid hemorrhage

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Headache Associated with Metabolic Disorder

(e.g., hypoxia, hypercapnia, hypoglycemia, dialysis)

Headache Associated with Nonvascular Intracranial Disorder (e.g. intracranial infection, or neoplasm)

Headache Associated with Substances or their Withdrawal (e.g., withdrawal from alcohol, caffeine, ergotamine, narcotics).

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Migraine Headaches

Clinical presentation of migraine headaches

It is characterized by recurring episodes of throbbing head pain, frequently unilateral.

It can be severe and associated with nausea, vomiting, and sensitivity to light, sound, and/or movement.

The migraine headache may occur at any time of day or night but usually occurs in the early morning hours on awakening.

Pain is usually gradual in onset, peaking in intensity over minutes to hours, and lasting between 4 and 72 hours untreated.

Pain is typically reported as moderate to severe and most often involves the frontotemporal region.

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The headache typically unilateral and throbbing or pulsating in nature, however, pain may be bilateral at onset or become generalized during the course of an attack.

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About 20% - 60% of migraineurs patient have premonitory symptoms(not to be confused with aura) in the hours or days before the onset of headache. Neurologic symptoms: ( phonophobia, photophobia,

hyperosmia , difficulty concentrating) . Psychological symptoms:(anxiety, depression,

euphoria, irritability & drowsiness, hyperactivity & restlessness) .

Autonomic symptoms: ( polyuria, diarrhea & constipation).

Constitutional symptoms( stiff neck, thirst, food cravings, anorexia)

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Migraine with aura

The migraine aura is experienced by approximately 31% of

migraineurs patient. The aura typically evolves over 5 to 20 minutes and lasts

less than 60 minutes. Headache usually occurs within 60 minutes of the end of

the aura. Visual auras can include both: positive features (e.g., scintillations, photopsia,

teichopsia, fortification spectrum) and negative features (e.g., scotoma, hemianopsia).

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Sensory and motor symptoms such as paresthesias or numbness of the arms & face, dysphasia or aphasia & weakness, may also occur.

Many patients seek a dark, quiet place for rest and relief.

Once the headache pain wanes, a resolution phase characterized by exhaustion, malaise, and irritability .

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DIAGNOSIS In the headache evaluation, diagnostic alarms should be identified, including: • “first” or “worst” headache ever, • onset of the headache • Is it associated with systemic illness ( fever,

nausea, vomiting & stiff neck) • focal neurologic symptoms or papilledema, • absence of daily headache • positive family history for migraine • presence of food triggers • menstrual association • improvement with sleep

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Check for abnormalities:

vital signs (fever, hypertension),

Fundoscopy (papilledema and hemorrhage),

neurologic examination (abnormalities or deficits in mental status)

Neuroimaging

(computed tomography or magnetic resonance imaging) Laboratory tests

In secondary headache presentation, serum chemistries, and other blood tests, such as a complete blood count, antinuclear antibody titer, ESR and thyroid function tests may be considered.

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Commonly Reported Triggers of Migraine

- Food triggers

• Alcohol

• caffeine withdrawal

• Chocolate

• Fermented foods

• Nitrate-containing foods (e.g., processed meats)

• Tyramine-containing foods

- Environmental triggers • Glare lights • High altitude • Loud noises • Strong smells and fumes • Tobacco smoke • Weather changes - Behavioral–physiologic triggers • Excess or insufficient sleep • Fatigue • Menstruation, menopause • Skipped meals • physical activity ( prolonged overexertion) • Stress or post-stress

TREATMENT

Non-pharmacologic therapy

Preventive management should begin with identification and avoidance of factors that provoke migraine attacks.

Application of ice to the head and periods of rest or sleep, usually in a dark, quiet environment.

Behavioral interventions (relaxation therapy) are preventive options for patients who prefer nondrug therapy or when drug therapy is ineffective or not tolerated.

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Abortive (acute) therapy Acute migraine therapies are most effective when

administered at the onset of migraine.

The frequent or excessive use of acute migraine medications can result in a pattern of increasing headache frequency and drug consumption known as medication-overuse headache or ( rebound headache). This occurs commonly with overuse of simple or combination analgesics, opiates, ergotamine tartrate, and triptans. This may be avoided by limiting use of acute migraine therapies to 2or 3 days per week.

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Analgesics and Nonsteroidal Antiinflammatory

Drugs

Simple analgesics and (NSAIDs) are effective as

first-line treatment for mild to moderate migraine attacks.

Aspirin, ibuprofen, naproxen sodium, tolfenamic acid, and the combination of acetaminophen plus aspirin and caffeine are effective.

In general, NSAIDs with a long half-life are preferred as less frequent dosing is needed.

Rectal suppositories and intramuscular analgesic are options for patients with severe nausea and vomiting. 17

Aspirin and acetaminophen are also available by prescription in combination with a short-acting barbiturate (butalbital).

Combination therapy with metoclopramide can speed absorption of analgesics and NSAIDs and alleviate migraine related nausea and vomiting.

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Opioids

Narcotic analgesic drugs (meperidine, oxycodone ad 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 failure to respond to conventional therapies.

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Antiemetics

A single dose of an antiemetic, such as metoclopramide, chlorpromazine, or prochlorperazine should be given15 to 30 minutes prior to administering oral acute migraine therapy.

Non oral treatments (rectal suppositories, nasal spray, injections) may be advisable when nausea and vomiting are severe.

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Corticosteroids

Corticosteroids may be an effective rescue therapy for status migrainosus, which is a severe migraine that may last up to 1 week.

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Ergot Alkaloids and Derivatives Ergot alkaloids are useful for moderate to severe

migraine attacks. Ergotamine tartrate

Ergotamine tartrate is available for oral, sublingual, and rectal administration.

Oral and rectal preparations contain caffeine to enhance absorption and potentiate analgesia. Because oral ergotamine undergoes extensive first-pass hepatic metabolism, rectal administration is preferred.

Dihydroergotamine (DHE)

Dihydroergotamine (DHE) is available for intranasal and parenteral (IM, IV & SC) administration.

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Nausea and vomiting are common adverse effects of ergotamine derivatives. Pretreatment with an antiemetic should be considered with ergotamine and IV DHE therapy.

DHE does not appear to cause rebound headache.

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Symptoms of severe peripheral ischemia (ergotism) include cold, painful extremities; continuous paresthesias; diminished peripheral pulses; and claudication.

Gangrenous extremities, myocardial infarction & bowel and brain ischemia have been reported rarely with ergotamine.

Contraindications include renal and hepatic failure; coronary, cerebral, or peripheral vascular disease; uncontrolled hypertension and women who are pregnant or nursing.

Ergotamine derivatives and triptans should not be used within 24 hours of each other.

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Serotonin Receptor Agonists (Triptans)

Sumatriptan, zolmitriptan ,naratriptan, ---- etc., are

appropriate first-line therapies for patients with moderate to severe migraine or as rescue therapy when non specific medications are ineffective.

Sumatriptanis available for oral, intranasal, and SC administration.

The SC injection is packaged as an autoinjector device for self-administration by patients. When compared with the oral formulation, SC administration offers enhanced efficacy and a more rapid onset of action (10 vs. 30 minutes).

Intranasal sumatriptan has a faster onset of effect (15 minutes) than the oral formulation.

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Approximately 30% to 40% of patients who

respond to sumatriptan experience headache recurrence within 24 hours; a second dose given at the time of recurrence is usually effective.

Side effects of triptans include paresthesias, fatigue, dizziness, flushing, warm sensations, and drowsiness. Minor injection site reactions are reported with SC use, and taste perversion and nasal discomfort may occur with intranasal administration.

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Up to 15% of patients report chest tightness, pressure, heaviness, or pain in the chest.

Isolated cases of myocardial infarction and coronary vasospasm with ischemia have been reported.

Contraindications include ischemic heart disease, uncontrolled hypertension, cerebrovascular disease.

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Triptans should not be given within 24 hours of ergotamine derivative administration.

Concomitant use of the triptans with selective serotonin reuptake inhibitors or the serotonin norepinephrine reuptake inhibitors and monoamine oxidase inhibitors can cause serotonin syndrome, apotentially life-threatening condition.

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Pharmacologic Prophylaxis of Migraine

Prophylactic therapies are administered on a daily basis to reduce the frequency, severity, and duration of attacks, as well as to increase responsiveness to acute symptomatic therapies. Prophylaxis should be considered in: Patient with recurring migraines that produce

significant disability. Those with frequent attacks requiring symptomatic

medication more than twice per week. Those with symptomatic therapies that are

ineffective, contraindicated, or produce serious side effects.

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Preventive therapy may also be administered intermittently when headaches recur in a predictable pattern (e.g., exercise-induced or menstrual migraine).

Prophylaxis should be initiated with low doses and advanced slowly until a therapeutic effect is achieved or side effects become intolerable.

Prophylaxis is usually continued for at least 3 to 6 months after headache frequency and severity have diminished, and then gradually tapered and discontinued, if possible.

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β-Adrenergic Antagonists

β-Blockers (propranolol, nadolol & timolol are the most widely used treatment for prevention of migraine.

Antidepressants

TCAs are usually well tolerated at the lower doses used for migraine prophylaxis, but anticholinergic side effects may limit use, especially in elderly patients or those with benign prostatic hyperplasia or glaucoma.

Evening doses are preferred because of sedation.

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Anticonvulsants

Valproic acid and divalproex can reduce the frequency, severity, and duration of headaches by at least 50%.

The extended release formulation of divalproex sodium is administered once daily and is better tolerated than the enteric-coated formulation.

Topiramate is recently approved by the FDA for migraine prophylaxis. Dose is initiated at 25 mg/day and increased slowly to minimize side effects, which may include paresthesias, fatigue & anorexia. 32

Calcium Channel Blockers

Verapamil provided only modest benefit in decreasing the frequency of attacks.

It has little effect on the severity of migraine attacks.

It is generally considered a second- or third-line prophylactic agent.

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Methysergide It is reserved for patients with refractory

headaches that do not respond to other preventive therapies.

Consequently a medication of free interval of 4-week, is recommended after each 6-month treatment period. Dosage should be tapered over 1 week to prevent rebound headaches.

Methysergide is best tolerated when taken with meals.

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Nonsteroidal Antiinflammatory Drugs NSAIDs are modestly effective for reducing the

frequency, severity, and duration of migraine attacks, but potential GI and renal toxicity limit daily or prolonged use.

They may be used intermittently to prevent headaches that recur in a predictable pattern (e.g., menstrual migraine).

Treatment should be initiated1 to 2 days before the time of headache and continued until attack is passed.

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Cluster Headaches

Cluster headaches derive their name from a characteristic pattern of recurrent headaches that are separated by periods of remission that last from months to even years. During those periods the headaches usually occur at least once daily.

The headache generally is unilateral, occurs behind the eye, reaches maximal intensity over several minutes, and lasts for <3hrs.

Unilateral lacrimation, rhinorrhea, and facial flushing may accompany the cluster headache.

During cluster periods, headache is commonly precipitated by alcohol, naps, and vasodilating drugs.

In contrast to migraine headaches, cluster headaches are more common in males than females.

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Treatment of cluster headache

Abortive therapy - Sumatriptan - Zolmitriptan - Oxygen Prophylactic therapy - Verapamil - Lithium - Suboccipital steroid injection - Topiramate

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Tension-Type Headaches It is the most common type of primary headache and is more common in women than men.

Pain is usually mild to moderate and non pulsating. It is also described as dull, persistent headache, occurring

bilaterally in a hatband distribution around the head. The headache may fluctuate in intensity throughout the day. Tension-type headaches often occur during or after stress,

but chronic tension-type headaches may persist for months even in the absence of recognizable stress.

Skeletal muscle over contraction, depression, and occasionally nausea may accompany the headache.

Mild photophobia or phonophobia occur in some patient.

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Treatment of Tension-Type Headaches

Abortive therapy

- Analgesics

Conventional analgesics, including NSAIDs are appropriate first-line treatments for tension headache.

Prophylactic therapy

- Amitriptyline

- Mirtazapine

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