Migraine Pharmacology Flashcards
How are tension HAs usually treated?
OTC NSAIDs by the patient
How are cluster HAs usually treated?
with nasal or SC triptans or ergots + a burst and taper steroid like prednisone
What is thought to initiate a migraine?
excitation of nociceptive nerve terminals in meningeal vessels
What does excitation of nociceptive nerve terminals in meningeal vessels lead to?
release neurotransmitters that vasodilate meningeal vessels locally and activate the trigeminal nucleus (creating the neurogenic inflammation that leads to migraine symptoms)
What leads to the throbbing in a migraine?
Dilation of meningeal blood vessels
What leads to N/V in a migraine?
activation of area postrema
What leads to hypersensitivity in a migraine?
activation of the hypothalamus
What leads to muscle spasm in a migraine?
activation of the cervical trigeminal system
What leads to head pain in a migraine?
activation of cortex and thalamus
What NSAIDs are used to treat mild to moderate migraine or menstrual migraine?
Ibuprofen
Nabumetone
Naloxone
Which NSAID is most likely to be overused?
Ibuprofen (take 4 per day)
What drug is useful if caffeine withdrawal is involved in HA?
NSAID (Acetaminophen) + Caffeine
What drug class is used as first line treatment for moderate to severe migraine?
Triptans
Which triptan has the fastest onset?
SC sumatriptan
Which triptans can be taken PO or nasally?
sumatriptan and zolmitriptan
What are other unique ways sumatriptan can be taken?
SC and patch
Which triptans have a longer action but slower onset?
Frovatriptan
Naratriptan
Which drug class for migraines is used in patients unresponsive to Triptans (because these are LESS effective)?
ergots
Which ergot can be given SC, IV, IM, and nasally?
ergotamine
Which ergot can be given orally or by suppository?
dihydroergotamine
What drug class should not be used (but can be used to treat allodynia) in migraines?
opiates
Which opiates are used (sometimes) to reduce the allodynia of migraine?
Hydrocodone
Oxycodone
Codeine
What should you use instead of opiates?
Want to use ketorolac instead (effective, not habit-forming)
Which drug class for migraines is contraindicated in pregnancy?
ergots
Which drug class is the mainstay of pregnancy migraines in the 1st trimester?
acetaminophen (avoid later in pregnancy due to patent DA, prolonged labor and delivery)
Which drug class can be used to treat migraines persisting into later trimesters?
opiates
Are triptans okay to take in pregnancy?
try to avoid
MOA: Thalamic GABA enhancement leads to sedative-hypnotic effects
Butalbital
When is butalbital used?
not really effective or important
MOA: Inhibit COX/ act on PGs to reduce production of inflammatory signals that would trigger MAPK upregulation & increased production of CGRP and SP
NSAIDs
MOA: Produce selective carotid (intracranial/extracranial) vasoconstriction (via 5-HT1B receptors) and presynaptic inhibiton of the trigeminovascular inflammatory responses implicated in migraine—inhibit CN V activation by vasoactive peptides and trigeminal cervical complex activation (via 5HT1D/5-HT1F receptors allowing for Ca2+ entry)
triptans
MOA: Block pre-synaptic Ca2+ receptors and open post-synaptic K+ receptors of pain fibers!
opiates
MOA: Vasoconstrictor that causes contraction of smooth muscle fibers (like those in small arteries). Central 5-HT vasoconst + peripheral α vasoconst + decreased amine reuptake
ergots
DDI: diuretics, beta blockers, ACEi’s, vasodilators, etc.
NSIADs
DDI: ETOH, porphyria and sedatives
butalbital
Triptan DDI: MAOIs
Sumatriptan
Zolmitriptan
Rizatriptan
Triptan DDI: propranolol
Zolmitriptan
Rizatriptan
Elitriptan
Triptan DDI: CYP3A inhibitors
Elitriptan
DDI: ergots
triptans
Interactions with triptans and SSRIs/SNRIs may lead to what?
5-HT syndrome
DDI: beta-blockers or DA? (potentiate vasoconst action), strong CYP3A4 inhibitors (increase persistence of ergot), Triptans (24 hr rule)
ergots
TOXICITY:
- Gastric irritation chronic use
- Additive nephrotoxicity (in the elderly)
- Potentiation of migraine-associated nausea
NSAIDs
TOXICITY:
- Cerebral vasoconstriction
- Postential CV interactions
NSAID (Acetaminophen) + caffeine
Deficiency in what enzyme may lead to problems with the metabolism of acetaminophen?
G6PD
TOXICITY:
- Drowsiness, sedation, diminished cerebral function
- CYP inducer and CNS/resp depressant
- Strongly linked to analgesic overuse syndrome
Butalbital
What drug class is contraindicated in heart disease, uncontrolled HTN or ischemic bowel disease due to coronary/peripheral vasospasm.?
triptans
What drug class is contraindicated in vasospastic predisposing conditions (CAP, PVD, sepsis, MI, uncont. HTN?
Ergots
TOXICITY:
- CNS effects ( dizziness, drowsiness, fatigue)
- Heaviness/tightness in chest.
Triptans
mostly SC sumatriptan
TOXICITY:
paralysis of motor nerve endings in sympathetic nervous system leading to mental disorientation, convulsions, muscle cramps, and dry gangreme of limbs
Ergotism due to too large a dose of ergots
TOXICITY: dependence & respiratory depression, low HR
Opiates
Patients with migraine + aura on OCP are at increased risk of what?
Oral contraceptives increases risk of stroke (especially when person smokes, has HTN or hyperlipidemia); patients with migraine + aura also at increased risk of stroke (MULTIPLICATIVE)
What is “analgesic overuse syndrome”?
Too frequent a use of anti-migraine drugs can lead to a paradoxical worsening of the clinical condition.
A patient with analgesic overuse syndrome is a candidate for what type of treatment?
prophylactic migraine treatment
How many days/month do you have to have headaches to meet criteria for analgesic overuse?
> 15 (and HA began or progressed in severity while taking medications + HA resolves or reverts to previous pattern within 2 months after stopping chronic drug administration)
How many months do you have to be overusing medication to meet criteria for analgesic overuse?
> 3 months
o Ergots, triptans, optiods and comginations= >10 days/month
o Simple analgesics = > 15 days per month
True or false: SHORT acting NSAIDs (least expensive) more likely to produce this than long-acting agents.
TRUE
Which drugs give the highest risk for developing analgesic overuse syndrome?
Aspirin/acetaminophen/caffeine
Butalbital-containing combinations
Opioids
How does analgesic overuse syndrome occur?
body’s adaptation to drug at the receptor—leading to changes in receptor density and transmitter synthesis.
Incomplete initial drug treatment for migraines can lead to what?
Trigeminovascular system sensitization
Trigeminovascular system sensitization leads to what?
- Reduced 5-HT levels and 5-HT2 receptor upregulation
- Cellular adaptation in an already aberrant signaling process.
- Free radical damage in PAG
What is the 3 faceted approach to transitioning patients away from overuse?
1) TRANSITION/BRIDGING:
2) BIOFEEDBACK
3) PROPHYLAXIS
What drugs are used in transition/bridging for analgesic overuse syndrome treatment?
- Control with ergotamine, prophylaxis with propranolol
- Tizanidine (antispasmotic alpha-2 agonist) + long-acting NSAID
What drugs are used in prophylaxis for analgesic overuse syndrome treatment?
TCA, SSRI, beta-blockers, anti-epileptics, and NSAIDs
List drugs used in migraine prophylaxis.
Amitriptyline Valproic Acid Propranolol Timolol Topiramate Botox
How is botox administered to treat migraines?
symmetrical injection into glabellar frontalis and temporalis muscles
What migraine prophylaxis medication is NOT FDA approved?
amitriptyline
What migraine prophylaxis medication is FDA approved in children?
propranolol
MOA: Na channel blocker with increased GABA activity
valproic acid
MOA: Decrease reuptake of NE and 5-HT + strong anticholinergic
Amitriptyline
MOA: Decreased arterial dilation and decreased NE-induced lipolysis
propranolol
MOA: Blocks NA and glutamate; increased GABA activity
Topiramate
MOA: possibly decrease release of mediators or decreased activation of nerves
Botox
TOXICITY: Aggressiveness, weight gain, dry mouth, sedation
amitriptyline
TOXICITY: Fatigue, exercise intolerance, problems with asthma, DM, AV block
propranolol
timolol
TOXICITY: none (not used in episodic migriane)
botox
TOXICITY: CAT X teratogen, hepatotoxic, sedation, nausea, weight gain, highly protein bound
valproic acid
List the anti-emetics used in migraines.
Prochlorperazine
Metoclopramide
Promethazine
Chlorpromazine
MOA: D2 block centrally; cholinergic and alpha-adrenergic blockade
Prochlorperazine
Chlorpromazine
MOA: D2 blockade centrally; prokinetic by increasing Ach effects
Metoclopramide
MOA: Cholinergic blockade**; H1 and weak D2 blockade
promethazine
TOXICITY: Dyskinesia, Hypotension, glaucoma, urinary retention, BPH
Prochlorperazine
Chlorpromazine
TOXICITY: Glaucoma, urinary retention, GPH, drowsiness, Parkinsonism
promethazine
TOXICITY: Increased prolactin levels→ gynecomastia
metaclopramide
What is the algorithm for migraine prophylaxis?
- First line drug
- If not successful after 2-3 months change dose
- If not affective still, try another first line drug
- If not affective still, combine 2 first lines
- If not affective, try alternate
What are externally generated signals that measure physciological process (ex. sweating, temperature, muscle tension)?
biofeedback
What is the replacement of inner thoughts with salutogenic script and frame of reference?
cognitive behavior therapy
What alternative therapy for migraine is associated with open mouth sores and upset stomach?
feverfew
What two alternative therapies have actually been proven to reduce migraine frequency?
feverfew
butterbur
