Headache (Chapter 52). Background Headache is the 4th most common symptom of outpatient visits Costs between $1 - $17 billion annually Prevalence highest.

Headache (Chapter 52)

Background

• Headache is the 4th most common symptom of outpatient visits

• Costs between $1 - $17 billion annually

• Prevalence highest in adolescents and early adulthood and decreases with age

Classification of Headache (Table 52-1)

• Migraine-primary

• Tension Type-primary

• Cluster-primary

• HA from structural lesion (secondary), HA w/trauma (secondary), HA w/vascular disorders, HA w/nonvascular intracranial disorder, HA w/substance or withdrawal

Migraine

• F>M• Idiopathic, recurring HA disorder manifesting in

attacks lasting 4 to 72 hrs, develops over minuutes to hours

• Typically - Unilateral (may be bilateral), pulsating (progresses from dull ache to pulsating pain), moderate or severe intensity, aggravated by routine physical activity and associated w/ nausea, photo & phonophobia,

Migraine

• Usually begins in frontotemporal region and radiates to occiput and neck

• May have N/V (90%) and last 72 hrs• Alleviated by relaxation in dark room and sleep, • Complicated migraine - less common, neurologic symptoms

are more pronounced or disabling– Aura symptoms may outlast the migraine

• Permanent neurologic sequelae not common with migraine• Subclassified to Aura or No Aura

Aura• Occurs with Migraine about 30% of cases

• Complex of focal neurologic symptoms – alterations in vision or sensation

• Usually begin 10 minutes to 1 hr prior to onset of head pain

• Light headedness and photophopsia (unformed flashes of light)

• Scotoma- Isolated area within the visual field where vision is absent (30% of cases)

• Scintillating scotoma- looks like silvery kaliedoscope

Cluster Headaches (HA)• M>F (5:1), usually 20-40 years old • Recurrent HA separated by periods of remission (months to yrs)• During the “cluster”time -HA occur >1/day• Unilateral, occurs behind eye, reaches MAX intensity over few

minutes, lasts for <3hrs • Unilateral lacrimation, rhinorrhea, and facial flushing may

accompany cluster• HA is commonly precipitated by alcohol, naps, stress, missed

meals and vasodilating drugs - (Avoid during cluster period)

Cluster Headaches (HA)• No Aura

• Pathophysiology remains elusive– May have to do with vasodilation, but intracranial

blood flow studies are not consistent with this mechanism

– Abnormal level of melatonin, growth hormone, testosterone have been found in cluster HA, possible hypothalamic connection

– Has been found in monozygotic twins, may be genetic?

Tension-Type Headaches (TTHA)• Lifetime prevalence of 88% (F) and 69% (M)• Highest prevalence in women, age 30-39, with higher

education• Dull, persistent HA• Bilateral “hatband” distribution• Usually NOT debilitating and intensity may fluctuate

throughout the day• Usually intermittent, however can have Chronic TTHA(2%

of population), Continuos HA for months or years

Tension-Type Headaches (TTHA)• Often occur during or after stress

• Skeletal muscle overcontraction, depression, and nausea may accompany HA

• No prodrome

• May be associated with depression, repressed hostility, resentment

• Patients with recurrent TTHA may not experience more stressful events than those without TTHA, but may have less effective coping strategies

Tension-Type Headaches (TTHA)• Pathophysiology elusive

– was felt to be caused by excessive muscle contraction with constriction of pain-sensitive extracranial structures

• However, no correlation between muscle contraction and presence of TTHA

– Vascular reactivity felt to play a role• However, temporal muscle flow is unaltered compared to

controls

– Platelet 5HT is lower in patient with TTHA• some overlap with pathophysiology of migraine

Secondary Headache (HA) Disorders• Associated with trauma, vascular disorders, Central

Nervous System (CNS) infections, HIV, metabolic disorders

• >300 disorders can produce HA

• Watch out for HA especially if– New for patient and Severe in nature, may be sudden

onset (Acute HA) or over days to months (subacute HA)• may be a sign of destructive cause for HA

Acute Headache (HA) • May be symptomatic of

– subarachnoid hemorrhage (SAH), stroke, meningitis, intracranial mass lesion (e.g. brain tumor, hematoma, abscess)

• SAH HA - “worst HA of my life”, may also see alteration in mental status and focal neurologic signs

• Meningitis HA - usually bilateral, develops over hrs to days, may also see fever, photophobia, positive meningeal signs (Kernigs’s Brudzinski)

Subacute Headache (HA) • May be symptomatic of

– increased intracranial pressure, intracranial mass lesion, temporal arteritis, sinusitis or trigeminal neuralgia

• Trigeminal neuralgia - >40, F>M, characterized by sudden intense pain that recurs paroxysmally, occurs along the second or third division of trigeminal nerve and lasts only moments, triggered by talking, chewing, shaving , etc.

Pathophysiology• Brain itself is insensitive to pain• HA Pain can be produced by nociceptors (peripheral

pain receptors), injury to CNS or peripheral nervous system, or displacement of pain sensitive structure below

• Pain sensitive structures– proximal portions of cerebral arteries, large veins, and venous

sinuses – Also may be referred pain from inflammation of frontal or

maxillary sinus or refractive error of the eye

Pathophysiology (cont)• Traditionally

– Vascular Disturbance - migraine and cluster

– Muscular Lesion - Tension type

• However, now we think that migraine and cluster may be disturbance in brain function– neurovascular hypothesis

• HA is triggered by disturbance in central processing pathways and lead to release of potent neuropetides (calcitonin gene-related peptide (CGRP), substance P, and neurokinin A) and then vasodilation

Pathophysiology (cont)• Serotonin also plays a role in migraine

pathogenesis • Serotonin agonists are effective in migraine and cluster HA

• Plasma 5HT levels decrease by 1/2 during a migraine

• Reserpine - depletes 5HT from body stores can induce migraine

• 5HT(1b) & 5HT(1d) subtypes are largely distributed in blood vessels and nerves and are target of triptan and ergot

Drug Therapy• Abortive Therapy

– relief during an acute attack

• Prophylactic Therapy– prevent or reduce severity of recurrent HA

• Infrequent tension-type HA - just need abortive therapy with OTC analgesics

• Migraine and Cluster HA- may need prophylactic therapy – HA that impact patients life despite abortive therapy (>2xmonth),

disabling HA unresponsive to abortive tx, pts in whom abortive agents contraindicated, migraines which are severe in nature

Drug Therapy (cont)• Abortive

– Ergot alkaloids (ergotamine& dihydroergotamine) • used to be popular for migraine/cluster HA

– Triptans (sumatriptan, zolmitriptan, naratriptan, rizatriptan, almotriptan, frovatriptan, eletriptan)

• more favored, efficacious and fewer ADR

• Prophylactic for migraine– Antidepressants (e.g. amitriptyline), Beta blockers (e.g. propranolol),

valproate, calcium channel blockers (e.g. verapamil), NSAIDs

• Prophylactic for cluster - verapamil, prednisone, valproate

Section 1 • What % males and females suffer from migraines?

• What is typical age of onset of migraine?

• Is the pain of migraine always unilateral?

• If it is unilateral, does it always recur on same side?

• How long does the pain usually last?

• What is the typical frequency of migraine?

• How often do “aura” symptoms occur?

Section 1 • What is a “scotoma”, a “scintillating scotoma”

• How often do nausea and vomitting occur?

• What other neurologic symptoms can occur with migraine?

Section 2 • Why are KLs HA not too worrisome of some

more malignant disease?

Section 3 • How often should patients expect to get relief

from pharmacologic intervention?

• Give pharmacologic examples of abortive therapy

• Give examples of aggravating factors for migraine (table 52-3)

Section 4 • Is there a link between oral contraceptives (OC)

and migraine?

• Which hormone of the OC is felt to be the likely culprit?

• What are 2 action plans if you suspect the OC to be related to migraine?

• If you D/C OC, what % of women notice improvement in migraine symptoms?

Section 5 • Name the specific triptans (#7).

• Before triptans, what was the drug of choice when analgesics didn’t work?

• How does the administration of ergot differ from that of triptans?

• Which is more expensive, triptan or ergot?

• Which receptors do the triptans and ergot affect?

• Name the 3 proposed mechanisms of action for triptans efficacy

• What are 2 specific contraindications to triptan use?

Section 5 (cont)• How is dosage form for triptan (oral, Subcut, nasal spray)

selected?• How quickly should pt expect relief after triptan administered?• What are the adverse effects of triptans• How often does chest pain occur after use of triptans• When should triptan not be used?• How often does migraine recur?• What is the serotonin syndrome?• Review dosing of sumatriptan.

Section 5 (cont)

• How does the second generation triptan differ from first generation?

• What important drug interactions exist between triptan and other medications?

• What should we tell person with prescription for Maxalt MLT, Zomig ZMT and wet hands?

Section 6

• Does tolerance develop with use of triptans?

• What are alternatives for patients not getting relief from 50mg of sumatriptan?

•

Section 7

• Describe ergotamine – when first used– Advantages of ergot– How often is ergot effective– Where does ergot have its effect?– How does ergot work?

Section 8

• What is the purpose of caffeine in ergot products?

Section 9

• What are the different forms of ergot available?

• Which works more quickly, sublingual or oral ergot?

Section 10

• Contraindications to use of ergot?

• Is hypertension a contraindication to ergot use?

Section 11

• What are adverse effects of patients receiving ergotamine?

• What technique can be taken to minimize GI upset of ergotamine?

• What are the peripheral vasoconstrictive effects of ergotamine?

Section 12

• What is the antiemetic of choice in migraine? and why?

Section 13

• What other agents are available as abortive agents?– How effective is Isometheptene (Midrin)

compared to oral ergotamine?– Usual dose of midrin?

• Have NSAIDS shown efficacy in migraine

• How is DHE spray administered?

Section 14

• Treatment of intractable migraine– DHE - – Sumatriptan - – Prochlorperazine– Chlorpromazine– Narcotic Analgesics- place in therapy?– Corticosteroids - – Table 52-5

Section 15

• What is the usual criteria for establishing prophylactic therapy?

• How effective is propranolol therapy?

• How does propranolol work?

• Can we use alternative B-blocker such as atenolol, metoprolol?

• Table 52-6

Section 16

• What dose of propranolol should be used?

• How long before benefit is realized?

Section 20• What are 3 first-line therapies for migraine

prophylaxis?

• In what patient would amitriptyline be a first choice?

• What dose of amitriptyline is used for migraine prophylaxis?

• Does fluoxetine work as well as amitriptyline?

•

Section 20 (cont)• What was the efficacy of valproate in blinded

trials?

• What is dose of valproate for migraine prophylaxis?

• What are most common Side effects of amitriptyline and valproate?

Section 21

• How does the effectiveness of NSAIDs compare to propranolol, valproate, amitriptyline for prevention of migraine?

• When would NSAID be reasonable choice as prophylaxis?

• Which calcium channel blocker has shown most evidence to support its use in migraine prophylaxis?

• What is the usual dose of verapamil for prophylaxis?

Section 21 (cont)• When should we expect benefit from

verapamil?

• What is the expected benefit from verapamil?

• In what patients would verapamil be a reasonable choice?

• Is verapamil felt to be better than valproate, propranolol, or amitriptyline?

Section 22• What are the characteristics of “analgesic-induced HA”?• What is another term for “analgesic-induced HA”?• What is treatment for “analgesic-induced HA”?• What should LD be told about frequency of HA during

treatment for “analgesic-induced HA”? • In treatment for “analgesic-induced HA”, which medications

should be D/C first?• Which medication should be considered for LD during

withdrawal of her medications?

Section 24• What is the treatment of choice for cluster HA? (see

figure 52-8)

• How effective is sumatriptan in treatment of cluster HA?

• What is recommended maximal daily use of sumatriptan?

• When is O2 therapy preferred for treatment of cluster HA?

• How quickly does O2 therapy work?

• How effective is ergotamine in treatment of cluster HA?

Section 25• What is the drug of choice for prophylaxis of cluster

HA?

• What is the efficacy of verapamil in prophylaxis of cluster HA?

Section 26• What are main methods of treating Tension Type HA

(TTHA)?

• What is the drug of choice for acute TTHA?

• Which is better for TTHA, APAP 1000mg or Ibuprofen 400mg?

• When should sedatives (e.g. butalbital), anxiolytics (e.g. diazepam), muscle relaxants (e.g. cyclobenzapirine) be used for TTHA?

• What are nondrug techniques useful for TTHA?

Section 27• How efficacious is amitriptyline in prophylaxis of

Tension Type HA (TTHA)?

• What is the usual amitriptyline dose for TTHA?

• How long does it take for amitriptyline to show benefit in TTHA?

• Is citalopram effective in prophylaxis of TTHA?