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MIGRAINE, Detailed, 2, Originate, Triggers the release of, Fact: Serotonin…
MIGRAINE
Learning Issue 1: Risk Factors
Age
Migraine prevalence was highest between ages 30 and 39 years. Onset of migraine increases at menarche, with peaks in prevalence in the late 30s, and a rapid decline after menopause.
Gender
Females suffer from migraines at about twice the rate of men. It's presumably more common in women due to the influence of estrogen hormones, whereas testosterone hormones in men appear to protect against the headaches.
Stress & Depression
The presence of emotional symptoms like depression and stress may contribute to a higher prevalence of migraine due to increased levels of the stress hormone cortisol.
Hormonal fluctuation (Menstruation)
Low levels of estrogen and progesterone hormone just prior to menstruation may trigger headache attacks and influence onset and remission.
Lifestyle (Smoking)
Nicotine withdrawal may increases frequency of migraine attack.
Diet (Caffeine intake)
Caffeine may induce migraine attacks by dehydration and caffeine withdrawal.
Hereditary
Genetics may account for up to 60% of migraine sufferers. These genes may result in high sensitivity and susceptibility to environmental changes, including lifestyle factors and triggers which initiate an attack.
Hypertension
Elevated blood pressure may trigger migraine attack by causing a significant amount of arterial pressure, putting increased stress on the body.
Learning Issue 2: Sign & Symptoms
Frequency of migraines increase
the occurrence went from two migraines every month to 4 - 5 per month
Indicates that she's having a severe migraine
Onset of migraines
occurs in the morning
more frequent during her menses
psychological stress causes serotonin level to be decrease. as a result, production of cortisol increases which then leads to migraine
might also due to the stress of being a mother of 2 and does not have enough rest or sleep
Headaches
evolves within an hour
involves severe throbbing unilateral and temporal in distribution
preceded by an aura that consists of nausea and pastel lights flashing in her visual field
Results were strongest during the first six hours where decline in stress was associated with a nearly five-fold increased risk of migraine onset. The hormone cortisol, which rises during times of stress and reduces pain, may contribute to the triggering of headache during periods of relaxation."
also related with increase production of cortisol
physical examination
High BP (142/86mm Hg)
due to autonomic response to pain or stress and elevated diastolic blood pressure and increased susceptibility to migraine
Learning Issue 4: Drug Interactions
Abortive Therapies
(acute migraine treatment)
NSAID
front-line agents in acute migraine treatment
inhibiting prostaglandin (PGs) synthesis via the cyclooxygenase enzymes (COX-1 and COX-2)
toxicity: hypertension
increase blood pressure
Cafergot (ergotamine + caffeine)
ergot alkaloids class of drugs
a migraine-specific agent
To treat or prevent vascular headaches
used by patients with more severe symptoms
ergotamine act by lowering calcitonin gene-related protein (CGRP)
caffeine works synergistically with ergotamine by enhancing constricting cerebral vasculature or promote its GI absorption
used by patients that not responded to NSAIDs or combination analgesics
side effect: nausea and vomiting
Good efficacy until 3 months
higher frequency of use
decrease the brain's ability to inhibit pain
migraine becomes worsen
often throbbing headache in the early morning, sometimes accompanied by nausea that disappears within 1 hour (a minor withdrawal headache)
ergotamine is possible to change primary headaches pattern (transformed migraine)
migraine attacks
a withdrawal headache closely resembles a severe and prolonged attack with gradual return over weeks to the underlying headache pattern due to discontinued cafergot.
Narcotics
(Short-acting)
opioid analgesic
to treat moderate-to-severe migraine headache
intended for short-term use
The patient stop taking the medication because
"out of commission for days"
potential for promoting physical dependence, psychological addiction, or both
midrin
combination of dichloralphenazone, isomethepten and acetaminophen
To treat severe tension headaches
The patient stop taking the medication because
no efficacy
medication overuse headaches (MOH)
exceed of acetaminophen daily dosages
pain returns as each dose of drug wears off
high levels of painkillers for at least 3 months
naratriptan
first-line agents for treating acute migraine episodes with or without aura
Three distinct mechanisms of action
Vasoconstriction of painfully distended intracranial extracerebral arteries by a direct effect on vascular smooth muscle
Inhibition of nociceptive neurotransmission within the trigeminal nerve in the brainstem and upper spinal cord
Inhibition of the release of vasoactive neuropeptides by trigeminal nerve innervating the intracranial vessels and dura mater
Prophylactic Therapies
Valproic Acid 500mg
Valproic acid increases the level of gamma-Aminobutyric acid (GABA), an inhibitory neurotransmitter in the brain.
It does this by blocking the enzyme that normally breaks down GABA. This neurotransmitter reduces the nerve cell excitability and firing that normally leads to a seizure.
Belongs to anticonvulsants
Certain studies suggest that valproic acid have vasodilation effect
Thus, it reduces migraine frequency
Bupropion
Antidepressant that belongs to NDRI
weakly inhibiting the enzymes involved in the uptake of the neurotransmitters norepinephrine and dopamine from the synaptic cleft
Therefore prolonging their duration of action within the neuronal synapse and the downstream effects of these neurotransmitters.
Reduces the frequency of migraine
Propranolol
A non selective beta adrenergic receptor antagonist
Blocking of these receptors will prevent the dilation of blood vessels and stabilize serotonin levels.
Sertraline
An antidepressant that belongs to the SSRIs class
Sertraline selectively inhibits the reuptake of serotonin (5-HT) at the presynaptic neuronal membrane, thereby increasing serotonergic activity.
This results in an increased synaptic concentration of serotonin in the CNS, which leads to numerous functional changes associated with enhanced serotonergic neurotransmission.
Serotonin levels also drop during a migraine.
Thus, SSRIs are very helpful for migraine prophylaxis
Current Medications
Sertraline + Valproic Acid = Moderate Interaction
The efficacy of anticonvulsants may be diminished during co-administration with selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitor (SNRIs).
Naratriptan (triptan) + sertraline (SSRI)
Potential for significant interaction with absolute low risk, but need to be monitored closely
Pharmacodynamic interactions
Selective serotonin reuptake inhibitors (SSRIs) increase the amount of 5-HT (serotonin) at post-synaptic receptors. 5HT1 receptor agonists (triptants) may add to the effects of these increased amounts of serotonin
serotonin syndrome
mild cases: neuromuscular symptoms
severe cases: hyperthermia
1 more item...
metoclopramide (antiemetic) + sertraline (SSRI)
Serious interaction requires regular monitoring
Pharmacodynamic interactions
dopamine antagonism of metaclopramide
Serotonergic inhibition of the dopamine neurotransmission
SSRIs increase the serotonin activity, which inhibits the dopaminergic system, leading to severe extrapyramidal symptoms in combination with the antidopaminergic activity of metoclopramide.
serotonin syndrome
neuroleptic malignant syndrome
dystonia
Introduction
Pathophysiology
Overview
Multiple primary neuronal impairments
leads to
Intra- & Extracranial changes
causes
Migraine
Innervation of anterior structures by ophthalmic division of trigeminal nerve
cause pain @ anterior region of head
Convergence of fibers from upper cervical roots
Trigeminal nerve neurons
Trigeminal ganglion
Trigeminal nerve @ trigeminal nucleus claudalis
Neurogenic inflammation
Based on trigeminal system
Stimulation of trigeminal ganglion
Neurokinin A
All vasoactive neuropeptides
Calcitonin gene-related peptide
Substance P
Effect
sensitization (neurons become more responsive to stimulation)
Release of serotonin from brainstem serotonergic nuclei
Act directly either in
cranial vessels
central pain control pathways
cortical projections of brainstem serotonergic nuclei
Cause
Deficiency in serotonin pain inhibition system
Aids in activation of trigeminal system
Cortical spreading depression of Leão
Mechanism
Activates trigeminal afferents
These are activation of brain matrix metalloproteinases
Modify hematoencephalic barrier permeability
Causes aura
= Propagating wave of neuronal + Depolarization of glial
That triggers a cascade
In migraine w/o aura
cortical spreading depression at areas of depolarization that are not interpreted in a conscious manner
Mechansim
Release of proinflammatory mediators
Activation of NF-kB (nuclear factor kappa-B) & this spreading to trigeminal nerve fibers around vessels of pia meter
Activation of trigeminal afferents by neuronal pannexin-1 megachannel opening & subsequent activation of caspase-1
Example: Cerebellum
Effects
cortical, brainstem, and meningeal events
aggravates inflammation in meninges that cause headaches through central and peripheral mechanisms
Cortical depression (establish aura)
Prolonged activation of trigeminal nociception (leads to headache)
Abundance of calcitonin gene-related peptide in trigeminal ganglion neurons
Released from peripheral and central nerve terminal
from peripheral
initiation of excess nitric oxide synthesis & sensitization of trigeminal nerves
Calcitonin gene-related peptide = strong vasodilator of cerebral & dura mater vessels
involves in neurogenic inflammation
mediates the transfer of trigeminal pain from vessels to CNS
Secreted within the trigeminal ganglion
Conclusion
Prognosis
84% of the patients with migraine persisted with this diagnosis (migraine persistence)
10% of the patients had 1-year complete clinical remission
3% of the patients had partial remission
3% of the patients developed chronic migraine
Diagnosis
Migraine with aura (complicated migraine)
Headaches accompanied by an aura which consists of nausea and pastel lights flashing throughout the visual field.
Menstrual migraine
An increase intensity of migraine during menstruation.
Severe migraine
Migraine attacks lasting 3 days per month
Learning Issue 3: Lab investigation
all of the result turns out to be in the normal range
MIDAS questionnaire
used to evaluate the extent to which your migraines interfere with your ability to carry out your responsibilities and function in daily life.
It is composed of five questions which are scored to convert to a MIDAS disability grade, and two additional questions that focus on the frequency and severity of your migraines.
Learning Issue 5: Treatment
Non-Pharmacotherapy
SEEDS
Sleep
keep a consistent sleep schedule to manage the migraine
avoid using electronics in the two hours leading to bedtime as screen time may activate the brain.
Exercise
exercise may help in reducing the frequency, severity and duration of migraine attack
Exercise is thought to increase levels of beta-endorphins
Eat (Food and Hydration)
Dips in blood sugar that could set off a migraine attack can be avoided with meals that are heavy in protein, fibre, and healthy fats and low in processed foods.
to consume sufficient of water to offset the body's water loss from perspiration, urine, and other physiological activities.
For every caffeine-containing beverage you have, make sure to sip on an additional glass of water.
Diary
keeping a migraine journal can help you spot patterns that may indicate episodic, chronic, menstrual associated, or other forms of migraines,
keep a "stoplight" journal, which is a paper calendar we mark each night with a green, yellow, and red pen or sticker, next to toothbrush
Stress
Behavioural therapies
Biofeedback training
Patients can learn to manage their body's physical reactions to headaches through biofeedback training
cognitive behaviour therapy or stress management training
better understand their own behavioural risk/trigger factors for headaches (which frequently include stress, poor sleep, and skipping meals), as well as how to limit the effects of those factors
Relaxation training
assist patients in modifying physiological reactions linked to headaches, lessen nervous system activation, and soothe muscular tension
Smoking cessation
smoking may increase the levels of carbon monoxide in the blood and brain
stop smoking, encouraged to make the home and workplace smoke-free
Pharmacotherapy
Prophylactic therapy
A prophylactic is a drug or treatment intended to stop the development of a disease. It is targeting on prevention of migraine headache and menstrual migrain
Topiramate
oral, with starting dose: 25mg/day, later increase 25mg/week. Usual range 50-200 mg/day in divided dose
Anticonvulsant, replacing valproic acid; first line therapy
By enhancing GABA activity and lowering glutamate activity, topiramate reduces neural excitability, preventing migraines
Headache frequency significantly reduced
Naproxen sodium
oral, starting dose 550mg to 1100mg/day in divided dose
less severe headaches, less photophobia, shorter-lasting migraines
NSAIDs reduce the production of prostaglandins, which are involved in the pathophysiology of migraine headaches, by inhibiting cyclooxygenase
NSAIDs, second-line therapy. Modest efficacy for menstrual migraine
Abortive therapy
Is a is a type of treatment for migraine during onset and targets symptoms like head pain, nausea, and vomiting
Ibuprofen with lorazepam
200mg ibuprofen and 1mg lorazepam
Ibuprofen is an effective inhibitor of cyclooxygenase, resulting in the inhibition of prostaglandin synthesis.
photophobia, phonophobia, nausea as well as vomiting are improved
Lorazepam improve analgesic effect by increasing GABA activity on the GABA receptors
Almotriptan with metoclopramide
6.25mg almotriptan and 10mg metoclopramide
Among other triptan, almotriptan is having higher bioavailability of 70% with 65% response rate at 2 hours
Metoclopramide provides symptomatic relief & enhance absorption of triptan
Detailed
2
Originate
Triggers the release of
Fact: Serotonin levels are low between migraine attacks