ADVANCES IN MYGRAINE WAS PRESENTED IN BRIEF

1. PRESENTED BY
Dr. S P SRINIVAS NAYAK, PharmD, MSc.
Assistant Professor,
Sultan-ul-Uloom college of Pharmacy,
Hyderabad, Telangana, India

2. Migraine is a neurological disease that can
cause multiple symptoms, incapacitating and
affects 12% of the US population, including
children.
It typically manifests as severe throbbing pain
on one side of the head, but can be bilateral
in up to 1 in 3 adults and in a higher
proportion in children. Migraine attacks
generally last between 4 and 72 hours when
untreated or unsuccessfully treated.

3.  Until 30 years ago, migraine was believed to
be caused by dilatation of blood vessels, and
the aura of migraine, which affects about 20%
to 33% of patients, was thought to result
from vasoconstriction.

4.  Present studies says maigraine is dysfunction
that involves sensitization and activation of
trigeminovascular pathways.

5.  Stimulation of the trigeminal ganglion leads to
the release of vasoactive neuropeptides such as
substance P, calcitonin gene-related peptide
(CGRP), and neurokinin A.
 Release of these neuropeptides, in turn, has been
linked to neurogenic inflammation that may be
associated with migraine pain intensification and
prolongation. CGRP is a primary neurotransmitter
expressed in trigeminal ganglia nerves; it has
strong vasodilation effects of cerebral and dural
vessels.

6.  Stimulating the trigeminal ganglion causes
the release of CGRP, which can then cause a
migraine attack in persons with migraine.
 The role of serotonin (5-HT) in the
pathophysiology of migraine remains unclear,
but there is evidence that activation at
serotonin receptors is important in the acute
treatment of migraine. Triptans are highly
selective 5-HT1B/1D receptor agonists that
act to prevent the release of CGRP.

7. A 33-year-old man with a history of migraine
with aura. He reports migraine episodes
about once every month or two, preceded by
visual aura lasting 20 minutes.
His headache pain peaks within 90 minutes of
migraine onset. He reports being sensitive to
light, sound, and smell, and he experiences
nausea and vomiting at about 2 to 3 hours
after onset.

8.  He has already tried 3 different oral triptans
over the past few years without significant
success and is now frustrated. The pain and
vomiting during his most recent attack were
severe enough that his wife brought him to
the emergency department of a nearby
hospital where he was given fluids and an IV
opioid.
 This is Marshall’s first visit to this practice

9. A. Switch him to butalbital
B. Confirm that he is taking the oral triptan at the onset of the
attack
C. Switch him to a parenteral triptan
D. Recommend he begin preventive medications
E. Recommend an antiemetic suppository for the nausea and
vomiting

10.  B,C,D
 Answer Explanation: Triptans are most effective when taken early in
the migraine attack, before the development of cutaneous allodynia
(pain resulting from a non-noxious stimulus to normal skin), which
generally occurs within an hour of pain onset.
 Triptan treatment as early as the aura stage may even preempt the
headache phase.
 After ensuring that Marshall knows how and when triptans should be
taken, recommend the patient use an antiemetic suppository to prevent
nausea and vomiting. According to the Choosing Wisely Campaign,
non-steroidal anti-inflammatory drugs (NSAIDs) are recommended as
a first-line treatment for mild to moderate migraine, whereas butalbital-
containing compounds are not US Food and Drug Administration
(FDA)-approved for the treatment of migraine, only for tension-type
headache

11.  .The patient does not meet the criteria for
needing preventive medications unless he
prefers to take them. If he can successfully
treat his acute attacks, a preventive
medication is not needed. A parenteral
triptan offers the benefits of a more rapid
onset of action as well as bypassing the
gastrointestinal (GI) tract, which is
compromised by gastric status, nausea, and
vomiting during his migraine episodes,
impeding the absorption of a tablet.

12.  Marshall is counseled about the timing and
appropriate use of triptans, including when to
consider redosing.
 He is willing to try another nonoral route of
administration; therefore, he was prescribed
sumatriptan nasal spray. However, despite
appropriate timing of treatment initiation and the
nonoral route, he does not feel this option is
effective in pain reduction and requests a more-
effective medication. He’s heard about new
medications for acute migraine treatment. Are
they options for him?

13.  What can you tell him regarding older vs newer
migraine medications in light of the 2018 FDA
requirements to demonstrate efficacy in migraine
management?
 A. There is no difference between earlier and 2018
clinical trial requirements
 B. 2018 FDA guidance requires demonstration of
freedom from pain at 2 hours
 C. 2018 FDA guidance requires demonstration of an
effect on the most bothersome symptom (MBS)
 D. 2018 FDA guidance requires demonstration of
both freedom from pain at 2 hours and an effect on
the MBS

14.  Answer Explanation:
The 2018 FDA guidance notes that while it is
important for an acute treatment to
demonstrate its effect on the 4 coprimary end
points of pain, nausea, photophobia, and
phonophobia, it is also important to
demonstrate an effect on both freedom from
pain at 2 hours and on the patient’s MBS.

15.  Three novel agents have been approved by the FDA in
the past year using the FDA 2018 requirements for
the treatment of acute migraine
 The selective 5-HT 1F receptor agonist lasmiditan
and 2 small-molecule CGRP receptor antagonists,
ubrogepant and rimegepant. Another CGRP receptor
antagonist, intranasal vazegepant (BHV-3500), is
under investigation and has been shown to be
superior to placebo in a phase 2/3 study.
 In addition, 4 CGRP monoclonal antibodies
eptinezumab, erenumab, fremanezumab, and
galcanezumab have been approved by the FDA for
the prevention of migraine. These agents have all
been shown to be efficacious and safe for the
prevention of migraine in adults.

16.  The most common adverse effects associated with
lasmiditan were CNS-related, including dizziness,
somnolence, and paresthesia, and were mostly mild or
moderate in intensity.
 However, in light of the depressive effects of lasmiditan on
the CNS, patients should be counseled to avoid driving or
operating machinery for at least 8 hours after taking the
medication.
 Lasmiditan has been classified by the US Drug
Enforcement Agency as a Schedule V controlled substance
owing to its actions in the CNS and peripherally; however,
this classification indicates the agent has the least
addictive potential compared with agents classified as
Schedule I through IV.
 Consequently, lasmiditan has a driving restriction for 8
hours after taking the medication; however, many patients
already refrain from driving during a migraine attack.

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