Migraine | Pharmacology Assignment

Running head: HEALTHCARE
Pharmacology assignment
Name of the Student
Name of the University
Author Note

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Abstract
Introduction- Migraine refers to a neurological condition that is characterized by several
symptoms such as, debilitating and intense headache, vomiting, nausea, difficulty in speaking,
tingling and numbness, and sensitivity to sound and light.
Summary- Migraine has been found to affect individuals of all age groups. Sumatriptan is one
common medication that is administered for the management of migraine. Sumatriptan acts in
the form of an agonist of 5-HT1B and 5-HT1D. These agonistic actions result in constriction of
blood vessels located in the brain; thereby inhibiting the synthesis of pro-inflammatory
neuropeptides.
The drug has also found to decrease the flow of carotid arterial blood. Nonetheless, it increases
velocity of blood flow in the middle cerebral artery and the internal carotid artery. It is generally
administered in subcutaneous, oral, intranasal or rectal dosage, and sold under Imitrex brand
name. However, adverse effects that are associated with the administration of this include
arrhythmia, heart attack, stroke and sulfhemoglobinemia. Some lifestyle changes that decrease
frequency of migraine are consumption of healthy foods and drinks, physical exercise, reduction
of stress, and getting sufficient sleep.
Target population- The target population comprises of adults, living in Australia, who suffer
from migraine. Selection of the target population can be accredited to the fact that dissemination
of information on the mechanism of action of the drug, in addition to its precautions and side
effects will not only increase their health literacy, but also help in effective management of
migraine.

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Conclusion- To conclude, that sumatriptan should be administered in accurate dosage for
migraine management.
Keywords: migraine, triptan, sumatriptan, management

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Table of Contents
Homeostasis.....................................................................................................................................4
Pathophysiology..............................................................................................................................4
Pharmacology..................................................................................................................................6
Drug name...................................................................................................................................6
Pharmacodynamics......................................................................................................................6
Pharmacokinetics.........................................................................................................................7
Route of Administration..............................................................................................................7
Indications, contraindications, precautions and side effects........................................................7
Lifestyle changes.............................................................................................................................8
Implications.....................................................................................................................................9
Conclusion.......................................................................................................................................9
References......................................................................................................................................10

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Homeostasis
Homeostasis is maintained by the nervous system by regulating or controlling different
organs in the human body. Any kind of deviation from a threshold acts in the form of a stimulus
to the receptors, which in turn transmit nerve impulses to the regulating centres that are located
in the brain. The brain acts in the form of an effector, and leads to an adaptive response. This
response helps the body to return to its state of normalcy, following which the effectors,
receptors and the regulating centres cease their activities for a temporary period. Taking into
consideration the fact that the effector is under the influence of the conditions produced by it, the
procedure is often referred to as negative feedback control (Hall, 2016). This process of
maintaining normalcy leads to a fluctuation between extremities. Regulating centres are
predominantly present in the central nervous system that comprises of the brain and the spinal
cord. Homeostasis is particularly controlled by the hypothalamus that creates an impact on the
medulla oblongata, the pituitary gland, and the autonomic nervous system.
Pathophysiology
Migraine is considered to be neurovascular disorder, and research evidences support the
fact that the condition begins within the brain, following which it spreads to different blood
vessels. While some researchers postulate that neuronal mechanism is responsible for the onset
and progress of migraine, others establish a correlation with the blood vessels (Goadsby et al.,
2017). One particular theory is associated with an increase in excitability of cerebral cortex that
eventually results in abnormal pain management in the neurons that are particularly located in
trigeminal nucleus of brainstem. In the words of Leão, spreading depression or particle spreading
depression refers to a neuronal activity burst that is succeeded by a definite duration of inactivity,

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and thus particularly reported among patients who suffer from migraine with aura (Pietrobon,
2017).
NMDC receptor activation that results in an influx of calcium inside the cell is often
attributed for this particular feature. Following the birth of neuronal activity there occurs
decrease in the flow of blood to the cerebral cortex for the next six hours or more. Research
evidences state that transmission of depolarization on the brain most commonly activates the
nerves present in the neck and head that helps them sense the pain (Dodick, 2018). Evidences
also elaborate on the role of diencephalon and brainstem in the onset of head pain in migraine
(Gupta, 2019).
Other researchers also focus on the influence of peripheral activation through the sensory
nerves that are present around the blood vessels located in the neck and the head. Some of the
major blood vessels that are thought to be responsible for migraine are pial arteries, dual arteries
and extracranial arteries present in the human scalp (Charles, 2018). There is mounting evidence
for the association of the neuromodulator, adenosine. This neuromodulator gets released,
following progressive cleavage of ATP, it later on acts on the receptors, in order to make the
body and the brain attain a state of low activity (Haanes et al., 2018). This is triggered by dilation
of the blood vessels, following which the heart rate gets decreased. The role of caffeine in the
form of an inhibitor of adrenaline has also been explained, in relation to a decrease in
migraine. Additionally, researchers have established the strong correlation between calcitonin
gene related peptides (CGRPs) and the pathogenesis of migraine pain, owing to the fact that
CGRP levels increase at the time of a migraine attack (Iyengar, Ossipov & Johnson, 2017).

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Pharmacology
Drug name
The drug sumatriptan has the chemical formula C14H21N3O2S. It is also sold under the
proprietary name Imitrex, and is one of the most common medications administered for the
treatment of cluster headache and migraine (Drug Bank, 2020).
Pharmacodynamics
Sumatriptan belongs to the category of tryptamine based drugs that is used in the form of
innovative medication for migraine treatment. The drug shows structural similarity to serotonin
(5-HT), and acts in the form of a 5-HT receptor (type 5-HT1D and 5-HT1B) agonist. The action of
this particular drug can be accredited to its agonist activity on the aforementioned receptors that
are present in the blood vessels that bring about their construction. This can be attributed to the
fact that dilation of blood vessels occurs at the time of migraine (Araldi et al., 2017). While
promoting constriction of the blood vessels, these drugs are responsible for triggering a
subsequent inhibition of the release of proinflammatory neuropeptides such as, substance P and
CGRP.
Triptans have also been identified as selective agents, particularly for 5-HT1D and 5-
HT1B. The primary therapeutic effect of sumatriptan is associated to and inhibition of CGRP
release that is most commonly mediated through the 5-HT1D/1B receptor-agonist action. This in
turn is substantiated by effectiveness of novel CGRP antibodies and antagonists. Sumatriptan has
also been found to lesson activity of trigeminal nerve that predominantly contributes to efficacy
of the drug in the management of cluster headache (Venkatraghavan et al., 2016).

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Pharmacokinetics
A 6mg subcutaneous injection of sumatriptan is able to attain a Cmax of approximately
69.5ng/mL (95% CI of 62.8-76.9ng/mL) in addition to a Tmax of roughly 0.17h (95% CI of
0.08-0.33h), bioavailability of an estimated 100%, and AUC of approximately 9.0h*ng/mL (95%
CI of 7.5-10.9h*ng/mL). Oral administration of 25mg sumatriptan is able to reach Cmax of
16.5ng/mL (95% CI of 13.5-20.1ng/mL), in contrast to Tmax of around 1.50h (95% CI of 0.50-
2.00h). This is in contrast to 20 mg intranasal dosage and 25mg rectal dosage that reaches Cmax
of 12.9ng/mL (95% CI of 10.5-15.9ng/mL) and 22.9ng/mL (95% CI of 18.4-28.6ng/mL), besides
Tmax of 1.50h (95% CI of 0.25-3.00h) and 1.00h (95% CI of 0.75-3.00h), respectively (Drug
Bank, 2020). The drug has been identified to have a volume of distribution of approximately
50±8L for a subcutaneous dosage of 6mg, or 2.7L/kg. The drug has been associated with 14-21%
binding to protein in circulation. In terms of metabolism, monoamine oxidase A plays an
important role in metabolising the drug. Some of the principal metabolites are indole acetic acid
glucuronide and indole acetic acid. While 22±4% of the drug gets excreted in the form of urine
in an unchanged form, around 38±7% gets eliminated in urine in the form of indole acetic acid.
This is in contrast to 40% drug that gets eliminated in the fecal matter (NCBI, 2020).
Route of Administration
The drug can be administered by four different routes namely, mouth (oral), through
nasal spray (internasal), in the form of injection under skin (subcutaneous), or by suppositories
(rectal).
Indications, contraindications, precautions and side effects
A combination of naproxen tablet and sumatriptan is commonly indicated for the
management of migraines, with or in absence of aura, amongst patients who are aged 12 years or

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more. Sumatriptan nasal spray, nasal powder, tablet, and subcutaneous injections are primarily
indicated for the treatment of migraine amongst adults, with or without aura. In addition, one
subcutaneous formulation of sumatriptan is also generally indicated for the management of
cluster headaches amongst adults, while additional subcutaneous formulations are not (Drug
Bank, 2020). Some of the conditions which are contraindicated with the administration of
sumatriptan are serotonin syndrome, any disorder that is characterized by an increase in the level
of serotonin, heart attack, and angina (NCBI, 2020). Additionally, individuals suffering from
migraine headache that is concomitant with paralysis of one particular side of the body, coronary
artery disease, prinzmetal angina, stroke, cerebral ischemia, peripheral vascular disease, and
ischemic bowel are some other conditions that should be taken into consideration during
administration of this drug (Shao, Hughes & Eley, 2017).
An overdose of sumatriptan has been associated with other health conditions where
there occurs a change of the blood from red to green colour due to incorporation of sulphur in a
molecule of haemoglobin, commonly referred to as sulfhemoglobinemia (González-Hernández et
al., 2018). The drug is also associated with other adverse events, such as, myocardial infarction,
coronary artery vasospasm, ventricular fibrillation, ventricular tachycardia and transient
myocardial ischemia.
Lifestyle changes
Some common lifestyle modifications that might prove beneficial in the management of
migraine are maintenance of regular sleep pattern and engagement in physical exercise.
Adherence to a healthy diet, avoidance of particular triggers like skipping meals, pollution,

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weather changes, injuries and over-exertion is also necessary for migraine prevention and
management (Buse et al., 2020).
Implications
Relevance of the aforementioned findings to clinical practice and the target population of
migraine patients can be accredited to the fact that an estimated 6% Australians suffer from the
condition that accounts for approximately 1.2 million individuals (Shao, Hughes & Eley,
2017). Therefore, adequate knowledge on the mechanism of action of the commonly prescribed
medication and lifestyle changes would help in better management of migraine, thereby
enhancing health outcomes.
Conclusion
Thus, it can be concluded that migraine is an extremely prevalent neurological conditions
that affects majority of the general population, and often presents with or without aura.
Therefore, sumatriptan is an effective medication that can be administered for the management
of migraine. However, there are few contraindications and adverse effects of the drugs that
should be taken into consideration during its administration.

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References
Araldi, D., Ferrari, L. F., Green, P., & Levine, J. D. (2017). Marked sexual dimorphism in 5-HT1
receptors mediating pronociceptive effects of sumatriptan. Neuroscience, 344, 394-405.
https://doi.org/10.1016/j.neuroscience.2016.12.031
Brar, Y., & Saadabadi, A. (2019). Sumatriptan. In StatPearls [Internet]. StatPearls Publishing.
https://www.ncbi.nlm.nih.gov/books/NBK470206/
Buse, D., Penzien, D., Lake III, A., & Andrasik, F. (2020). Behavioral Approaches to Headache
and Migraine Management. The Medical Roundtable General Medicine Edition.
https://themedicalroundtable.com/article/behavioral-approaches-%E2%80%A8-
headache-and-migraine-%E2%80%A8management
Charles, A. (2018). The pathophysiology of migraine: implications for clinical management. The
Lancet Neurology, 17(2), 174-182. https://doi.org/10.1016/S1474-4422(17)30435-0
Dodick, D. W. (2018). A phase‐by‐phase review of migraine pathophysiology. Headache: The
Journal of Head and Face Pain, 58, 4-16. https://doi.org/10.1111/head.13300
Drug Bank. (2020). Sumatriptan. Retrieved from https://www.drugbank.ca/drugs/DB00669
Goadsby, P. J., Holland, P. R., Martins-Oliveira, M., Hoffmann, J., Schankin, C., & Akerman, S.
(2017). Pathophysiology of migraine: a disorder of sensory processing. Physiological
reviews, 97(2), 553-622. https://doi.org/10.1152/physrev.00034.2015
González-Hernández, A., Marichal-Cancino, B. A., MaassenVanDenBrink, A., & Villalón, C.
M. (2018). Side effects associated with current and prospective antimigraine

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pharmacotherapies. Expert opinion on drug metabolism & toxicology, 14(1), 25-41.
https://doi.org/10.1080/17425255.2018.1416097
Gupta, V. K. (2019). Migraine postdrome and pathogenesis.
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