Ariane B.

Aquino February 12, 2020

ClinPhar 5A

Headache:

Migraine and Tension-Type Headache

Headache is a general term that refers to a persistent or lasting pain in the head
region.

Primary Headache

Migraine Tension-Type Headache

 A disorder of recurrent attack  most ubiquitous headache and is

the most common reason (one of)
Affect 10-15% of adults in US
why OTC analgesics are purchased
Children <12yrs - Male
 common in adult females
>12 yrs - shifts to Female

Location: bilateral
Location: unilateral (70%)
Character: pressure or tightness which
Characteristic: gradual onset, crescendo waxes and wanes
pattern (increasing in intensity and
Duration: variable (30minutes to 7days)
frequency), moderate to severe intensity
Associated symptoms: none
Duration: 4-72 hours(treated or not
treated)

Associated symptom: nausea, vomiting, Episodic TTH- the mean frequency of

photophobia, phonophobia, aura attacks is 3 days per month

Chronic TTH - is defined as 15 or more

attacks in a 1-month period

Cluster Headache Sinus headache

 A group of idiopathic headache  Associated with sinusitis

entities and trigeminal neuralgia
 Location: always unilateral

Character: pain begins quickly, deep

continuous pain, excruciating and
Hormonal Headache
explosive in quality
 Associated with low estrogen
Duration: 30mins- 3hours
concentration
Associated symptom: symptoms of
 Beginning of menstrual cycle
some trigeminal nerve problems (pain,
Horners Syndrome, lacrimation, nasal  Withdrawal of hormone therapy
discharge)

Secondary Headache

 “Red Flag”

 Result of serious underlying disease or other conditions

 Ex. Intracranial hemorrhage, internal carotid artery

Pathophysiology of Headache Disorders

Migraine Headache

Vascular hypothesis
 tissue pain generated by vascular reactivity

 suggests that intracerebral vasoconstriction leads to neural ischemia and is

followed by reflex extracranial vasodilation and pain

Neuronal etiology

 tissue pain generated by neuronal imbalance accompanied by trigeminovascular

system overactivity

 leading mechanism of the development of migraine

 depressed neuronal electrical activity spreads across the brain, which produces
transitory neural dysfunction

 activation of trigeminal sensory nerves leads to the release of vasoactive

peptides [e.g., calcitonin gene-related peptide (CGRP), neurokinin A, and
substance P] that produce a sterile inflammatory response around vascular
structures in the meninges of the brain, which leads to pain

 continued sensitization of central nervous system sensory neurons can

potentiate and intensify headache pain as an attack progresses.

 the pathogenesis of migraine may be due to an imbalance in the modulation of

nociceptors and blood vessel tone by serotonin and norepinephrine neurons

Tension-Type Headaches

 the pain is thought to originate in the myofascial tissues of the head, but central
brain processing is believed to be an important modulator of pain perception.

 Chronic TTH syndromes may evolve from recurrent episodic headaches as

central nociception becomes sensitized.

Clinical Presentations and Diagnosis

Migraines

Migraine with aura Migraine without aura

Aura is defined as a transient focal neurologic symptom.

(+)visual perception of flickering lights, spots, or wavy

lines

(-)partial loss of vision

Tension-Type Headache
 A comprehensive headache history is essential and includes age at onset;
frequency, timing, and duration of attacks; possible triggers; ameliorating
factors; description and characteristics of symptoms; associated signs and
symptoms; treatment history; and family and social history.

 Neuroimaging should be considered in patients with unexplained abnormal

neurologic examination or atypical headache history.

Treatment

The goal is to achieve consistent, rapid headache relief with minimal adverse effects
and symptom recurrence, and minimal disability and emotional distress, thereby
enabling the patient to resume normal daily activities.

• Limit use of acute migraine therapies to fewer than 10 days per month to avoid
development of medication-misuse headache.

Treatment algorithm for migraine headaches.

Nonpharmacologic Treatment

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

 Identify and avoid triggers of migraine attacks.

 Behavioral interventions (relaxation therapy, biofeedback, and cognitive

therapy) may help patients who prefer nondrug therapy or when drug therapy is
ineffective or not tolerated.

Pharmacologic Treatment of Acute Migraine

 Administer acute migraine therapies at the onset of migraine.

 Pretreatment with an antiemetic (emetoclopramide, chlorpromazine, or

prochlorperazine) 15 to 30 minutes before oral or nonoral migraine treatments
(rectal suppositories, nasal spray, or injections) may be advisable when nausea
and vomiting are severe. In addition to its antiemetic effects, metoclopramide
helps reverse gastroparesis and enhances absorption of oral medications.
 Frequent or excessive use of acute migraine medications can result in increasing
headache frequency and drug consumption known as medication-overuse
headache.

 Limit use of acute migraine therapies to 2 or 3 days per week.

ANALGESICS AND NONSTEROIDAL ANTIINFLAMMATORY DRUGS

 firstline treatments for mild to moderate migraine attacks

 Aspirin, diclofenac, ibuprofen, ketorolac, naproxen sodium, tolfenamic acid

 prevent neurogenically mediated inflammation in the trigeminovascular system

by inhibiting prostaglandin synthesis.

 Rectal suppositories and intramuscular (IM) ketorolac are options for patients
with severe nausea and vomiting.

 The combination of acetaminophen, aspirin, and caffeine is approved for

relieving migraine pain.

 Midrin, a proprietary combination of acetaminophen, isometheptene mucate (a

sympathomimetic amine), and dichloralphenazone (a chloral hydrate derivative),
may be an alternative for patients with mild to moderate migraine attacks.

ERGOT ALKALOIDS AND DERIVATIVES

Ergot alkaloids

 useful for moderate to severe migraine attacks

 They are nonselective 5HT1 receptor agonists that constrict intracranial blood
vessels and inhibit the development of neurogenic inflammation in the
trigeminovascularsystem.

 Venous and arterial constriction occurs.

 They also have activity at dopaminergic receptors.

 Ergotamine tartrate

 Dihydroergotamine (DHE)

 Do not use ergotamine derivatives and triptans within 24 hours of each other.
SEROTONIN RECEPTOR AGONISTS (TRIPTANS)

 first-line therapies for patients with mild to severe migraine or as rescue therapy
when nonspecific medications are ineffective

 selective agonists of the 5HTreceptors. Relief of migraine headache results from

(1) normalization of dilated intracranial arteries

(2) inhibition of vasoactive peptide release

(3) inhibition of transmission through secondorder neurons ascending to the

thalamus.

 Sumatriptan

OPIOIDS

 Reserve opioids and derivatives (meperidine, butorphanol, oxycodone, and

hydromorphone) 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.

 Closely supervise opioid therapy.

Pharmacologic Prophylaxis of Migraine

 Only propranolol, timolol, divalproex sodium, and topiramate are Food and
Drug Administration (FDA) approved for migraine prevention.

 Frovatriptan is effective for prophylaxis of menstrual migraine, and naratriptan

and zolmitriptan are probably effective.

TENSION-TYPE HEADACHETREATMENT

 Nonpharmacologic therapies include reassurance and counseling, stress

management, relaxation training, and biofeedback. Physical therapeutic options
(eg, heat or cold packs, ultrasound, electrical nerve stimulation, massage,
acupuncture, trigger point injections, and occipital nerve blocks) have
performed inconsistently.

 Simple analgesics (alone or in combination with caffeine) and NSAIDs are the
mainstay of acute therapy.
 The TCAs are used most often for prophylaxis of tension headache, but
venlafaxine, mirtazapine, gabapentin, and topiramate may also be effective.

Patient Care/Counseling

 Instruct the patient to keep a headache diary to identify potential causes of

headaches and responses to therapy

 Provide the patient specific information regarding actions to take if therapy is

ineffective or adverse effects develop

 Educate the patient on the importance of adherence to the individualized

pharmacologic regimen to prevent headache and to diminish pain upon
recurrence.

 Educate the patient on the warning symptoms and signs of headache

complications, and when to seek emergency medical attention.

Reference:

Pharmacotherapy Principles and Practice, Marie A. Chisholm-Burns et. al.,2008

Pharmacotherapy Handbook 9th Edition,Barbara Wells et. al.,2015

http:// armandoh.org

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0224285
 Intranasal lidocaine for acute migraine: A meta-analysis of
randomized controlled trials

Pei-Wen Chi ,Kun-Yi Hsieh ,Kuan-Yu Chen,Chin-Wang Hsu,Chyi-Huey Bai,Chiehfeng Chen,

Yuan-Pin Hsu 

Published: October 23, 2019

Background

Intranasal lidocaine has been shown to be effective in treating patients with acute
migraines; however, its efficacy is still controversial. In this study, we intend to
assess the efficacy and safety of intranasal lidocaine compared with a placebo or an
active comparator for the treatment of migraines.

Method

PubMed, EMBASE, Cochrane library, and Scopus databases were searched from their
inceptions to November 2018. Randomized controlled studies investigating the
efficacy of intranasal lidocaine compared with a placebo or an active comparator
were selected. Two reviewers independently extracted and synthesized data using a
random-effects model. The primary outcome was pain intensity. The secondary
outcomes were success rate, the need for rescue medicine, and relapse occurrences.
We registered the study at PROSPERO with an ID of CRD42018116226.

Results

Six studies (n = 613) were eligible for the meta-analysis. Overall, the results revealed
that the study population who was administered intranasal lidocaine had a lower
pain intensity at 5 min (standardized mean difference (SMD) = -0.61; 95% CI = -1.04
to -0.19) and 15 min (SMD = -0.72; 95% CI = -1.14 to -0.19), had a higher success rate
(RR = 3.55; 95% CI: 1.89 to 6.64) and a less frequent need for rescue medicine (RR =
0.51; 95% CI = 0.36 to 0.72) than the control group. These beneficial effects were not
observed when an antiemetic was administered. Furthermore, intranasal lidocaine
use had no significant influence on the relapse rate (RR = 0.89; 95% CI = 0.51–1.56),
regardless of the use of antiemetics. Using lidocaine caused local irritation in up to
49.4% of the patients in one report but did not cause major adverse events.

Conclusion

Intranasal lidocaine can be considered a useful option for patients with an acute
migraine. It yields a high success rate, a low pain intensity, an infrequent need for
rescue medicine, and tolerable adverse events. The administration of antiemetics is
an important confounding factor.