Cohen: Headaches + Pharm Flashcards
Sumatriptan
“Imetrex” - Seratonin 5-HT Agonist
MOA: activates 5-HT receptor on presynaptic trigeminal nn. endings inhibiting release of vasodilating peptides;; stimulates vasoconstriction
– duration of use is often shorter than h/a
- given oral, nasal, subcu a couple hours after start of migraine
USE: ** first line ** tx of migraine attacks that are severe
ADR’s: mild - tingling, warmth, dizziness, mm. eakness, fatigue, flushing, nausea, sweating, neck pain
CI: CAD and cerebral vascular disease!
relative CI: angina, ischemic heart disease, HTN - d/t slight vasoconstriction
DDI: DO NOT USE w/in 24 hours of ergotamine which have severe vasoconstriction
Dihdroergotamine (DHE)
Ergot Alkaloids
MOA: constriction of peripheral and cranial blood vessels - may also affect peptide release and act as agonist at 5HT1 (act on agonists and antagonists on MANY different receptors, thus have more SE’s)
USE:
- migraines
- DHE used specifically for intracatible severe pain
Caution: vasoconstriction is long-lasting and cumulative when doses are repeated!
ADR’s: GI problems, prolonged vasospasm, gangrene, bowel infarction, severe vasoconstriction, weakness, fatigue, pareshtesias
CI: obstructive vascular diseases, collagen diseases, uncontrolled HTN, hepatic/renal dysfunction
Ergotamine
Ergot Alkaloids
MOA: constriction of peripheral and cranial blood vessels - works on multiple receptors other than 5HT1… may also affect peptide release and act as agonist at 5HT1 (act on agonists and antagonists on MANY different receptors, thus have more SE’s)
USE:
- migraines
Caution: vasoconstriction is long-lasting and cumulative when doses are repeated! can raise BP
ADR’s: GI problems, prolonged vasospasm, gangrene, bowel infarction, severe vasoconstriction, weakness, fatigue, pareshtesias
CI: obstructive vascular diseases, collagen diseases, uncontrolled HTN, hepatic/renal dysfunction
“analgesics”
- aspirin, acetaminophen, caffeine (excedrin)
- ibuprofen (advil)
analgesics: MOA: prevent neurogenic mediated inflamation in the trigeminovascular system through inhibition of PG synthesis
USE:
- common headaches - reasonable first choice for mid/moderate migraine attacks
ADR’s: ** GI problems **
- dyspepsia, nausea, vomiting, diarrhea
- somnolence, dizziness
CI: ulcer disease, renal dysfunction, hypersensitivity to aspirin
metoclopramide
= reglan - antiemetic
MOA: block D2 like dopamine receptors in the chemoreceptor trigger zone and solitary tract nucleus
USE: adjuncts for nausea/vomiting that accompany migraine h/a
- single dose given 15-30 mins prior to abortive therapy
ADRs: drowsinness, dizziness
propanolol
beta antagonist - migraine prophylaxis
MOA: may raise migraine threshold by modulating adrenergic/ serotenoergic NT in cortical and subcortical pathways
USE: most widely used drugs for migraine prophylaxis
ADRs: drowsiness, fatigue, sleep disturbances
CI: CHF, PVD, asthma, depression, DM
verapamil
CCB - migraine prophylaxis
MOA: inhibits Ca2+ entry from select voltage sensitive areas of vascular smooth mm. produces relaxation of vascular smooth mm. and vasodilation
use: migraine prophylaxis - off label use
amitriptyline
antidepressant - migraine prophylaxis
MOA: bneficial effects may result from down regulation of central 5HT2 receptors, increased levels of synaptic NE and enhanced opioid receptor actions
ADRs: sedating d/t being antidepressant, weight gain
topiramate
anticonvulsant - migraine prophylaxis
MOA: enhance GABA mediated inhibition, modulate excitatory NT glutamate, inhibit sodium and calcium ion channel activity
** particularly useful in pts. w/ migraines and comorbid seizures, anxiety disorders, or bipolar disorders **
ADRs: paresthesia, fatigue, anorexia, diarrhea, w/l, taste perversion
common vs. classic migraine?
classic = has aura which may involve nausea, scotomas, speech problems - aura followed by severe throbbing unilateral h/a
common = lacks aura phase
migraines:
- involve trigeminal nn. – nerves release peptides and promote vasodilation
migraine criteria **
> = 5 attacks lasting 4–72 hours
> = 2 of the following
Unilateral , Pulsating, Moderate or severe intensity , Aggravation by routine physical activity
> = 1 of the following
- Nausea and/or vomiting
- Photophobia and phonophobia (sensitive to light or sound)
No evidence on history or examination of disease that might cause headaches
when to do migraine prophylaxis?
for patients with 3+ migraines per month
Great! Amitriptyline, propanalol, topiramate
Fair: verapamil
- are only ones approved by FDA
tx of cluster h/a?
sumatriptan injection, high dose O2, nasal lidocaine
preventative: verapamil, lithium, prednisone
other options: deep brain stimulation or occipital nn. stimulator
tx of trigeminal neuralgia?
carbamazepine, may require radiological or surgical ablation as well
primary vs. secondary h/a?
Primary Headaches: No obvious pathological cause, but a well-known syndrome of headaches, such as migraine, tension-type, cluster, etc.
- migraine, tension, cluster h/a
Secondary Headache, or Headaches: A pathological cause can be found, such as tumor, hemorrhage, infection, etc.
–> warning signs: single h/a, sudden onset, onset after age 50, recent onset <6 mos, systemic disease (malignancy, AIDs), change in h/a pattern, abnormal neuro exam
testing for h/a?
- imaging: MRI or CT
- imaging NOT needed for recurrent migraine - only get for recent change in pattern or focal neuro signs
- MRI is more likely to show cause for h/a, but CT is faster and will show SA hemorrhage - CSF: always do if you’re not sure! (when ICP is elevated can ddx pseudotumor cerebri or idiopathic intracrnail HTN)
Migraines
Features:
- nauseating, photosensitivity, worse with activity
- build up in intensity over 30-60 mins
- last 1 day on average (4hours - 3 days)
- 15-20% of pts. get an AURA 20-30 min before pain begins (visual changes, sensory changes, speech changes)
Epidemiology:
- more common in women, whites, familial
- many have psych disorders
- hormones play a role
Causes:
- environmental triggers
- fasting, meds, weather, fragrances, hormones, pregnancy, stress
pathology of migraines?
Neurogenic Theory:
Aura- Cortical spreading depression occurs during a migraine aura: see brief depolarization of cortical neurons followed by a prolonged reduction in neuronal depolarization and synaptic transmission along w/ small decreased blood flow
Pain - regions of pons and brainstem become very active electrically up to 30 mins before there is increased blood flow to brain — at beginning of pain phase pons sends increased frequency of depolarization to trigeminal nn - CN V
1. increased activity of CNV –> vasodilation and inflammation of dura mater
(trigeminovascular activation)
2. input from cerebral hemispheres and thalmus may trigger a migrain to start in the migraine center of the pons
*** Release of serotonin occurs in a migraine, from neurons in the pons and the trigeminal nerves, as well as other released chemicals, including Calcitonin Gene Related Peptide (CGRP), Substance P and nitric oxide
** migraine is eventually stopped by over stimulation of serotonin autoreceptors
what are possible sites of triptan action?
- vasoconstriction of meningeal blood vessels
- trigeminal inhibition of neuropeptide release
- interruption of pain transmission from cranial structures
anatomy of migraine?
triggered in the cortex and pons initates aura
goes to brian stem, where nausea/vomiting are triggered
eventually goes to CN V, neuropeptide release, vasodilation, inflammation and pain sign generation
CGRP
calcitonin gene related peptide is released — antagonists of CGRP DO stop migraine and cause virtually no vasoconstriction (evidence that migraine isn’t only vascular)
tension h/a
features: bilateral, dull, squeezing, tight, non-pulsating
- no vomiting or no more than one: nausea, photophobia, phonophobia
- exercise doesn’t aggravate pain
- moderate/severe pain is less common
- MSK component
* * medication seldom necessary
CTTH - chronic tension type h/a
Average frequency > 15 days/month, with average duration > 4 hours/day if untreated and a history of > 6 months
History of episodic tension-type headache (ETTH)
Gradual increase (evolution) over > 3 months
First of all, these patients must not take ANY analgesics more than once a week
** look for comorbidities **
HTN, depression, anxiety, insomnia, DM, neck pain or analgesic abuse
medication overuse h/a
“rebound headache” taking any pain pill more than once per week increases frequency of headaches!
cluster h/a
features:
-more common in men
- brief, 15 min-2 hr attacks, one sided, in or around eye, often 1 hour after falling asleep
- occur daily for weeks to months at time
** intense pain which peaks rapidly!
autonomic features- lacrimation, congestion, rhinorrhea, swelling, miosis, ptosis, eyelid edema
Pathology unknown: maybe hypothalamic or PS
idiopathic intracranial HTN
“Psuedotumor cerebri”
- Progressive diffuse headaches with intermittent loss of vision in one or both eyes, especially with eye movements
- Almost all patients are OBESE YOUNG WOMEN, rarely found in men; some association with estrogen and possibly progesterone supplements, Acutane for acne
- Increased intracranial pressure: due to overproduction of CSF? Brain swelling?
- nearly ALL have papilledema w/ increased ICP **
- however have small ventricles with greatly elevated CSF pressure
gradual sometimes irreversible loss of vision if not ddx early
tx: WEIGHT LOSS, corticosteroids, carbonic anhydrase inhibitors, topiramate
- If persistent, with visual loss, defenestration of the optic nerve sheath, or a lumbar-peritoneal shunt, to improve drainage and lower ICP
trigeminal neuralgia
“tic douloureux”
A very brief, shooting pain lasting only seconds; may be triggered by facial contact
Occurs in one of the branches of CN V, usually maxillary or mandibular, rare in ophthalmic branch; many attacks per day, even in sleep
Pain is often “triggered” by touching face, eating, shaving, applying lipstick or makeup
Idiopathic, with no pathology normally, or vascular irritation of CN V nucleus or fibers
Uncommon under age 50, unless a brainstem vascular lesion, multiple sclerosis, tumors
giant cell arteritis
“temporal arteritis”
vasculitis, or a non-infectious inflammation of arteries, leading to gradual occlusion at some locations
Involves the superficial temporal artery, a branch of the external carotid artery, on one and rarely both sides
May spread to the adjacent internal carotid artery, reaching the ophthalmic artery and causing COMPLETE VISUAL LOSS via ischemia
sx:
- have pulsing superficial temporal artery, often times seen sticking out
- over age 50, accompanied by fatigue, difficulty chewing, pain in neck and shoulders
“50/50 Rule” over age 50, ESR more than 50
Diagnosis suggested by elevated Erythrocyte Sedimentation Rate (ESR) and C-Reactive Protein, and confirmed by superficial temporary artery biopsy
tx: ** curable w/ prednisone** w/in first weeks of onset
