Migraine Drugs Flashcards
What are the 9 Abortive Drugs for Migraines?
serotonin 5 HT, Ergot, Dopamine, Analgesics
Specific serotonin 5-HT agonists
1) sumatriptan
2) zolmitriptan
Ergot Alkaloids
3) dihydroergotamine
Dopamine Antagonists
4) Metoclopramide
5) Prochlorperazine
6) Chlorpromazine
Analgesics
7) Aspirin
8) Acetaminophen
9) Ibuprofen
Name 7 Prophylactic Drugs for Migraines
Beta-blockers
1) propranolol
2) metoprolol
3) timolol
Antidepressants
4) Amitriptyline
Anticonvulsant
5) Topiramate
6) Calcitonin gene-related peptide (CGRP) ligand or receptor antagonists - newer drugs
7) Botulinum toxin type A
Explain oral absorption of drugs during migraines, what route is preferred and what therapeutic strategies to use.
Oral absorption of drugs is slowed during migraine:
Deceased GI motility – caffeine helps to reduce this
Nausea/vomiting (90%)
Parenteral routes of administration should be used
High variability with individual response to drug therapy, therapeutic strategies must be customized
What are the 4 phases of a migraine?
1) Prodrome
2) Aura
3) Headache
4) Postdrome
Characteristics of prodromes.
≤ 60%; changes in mood (depression, irritability,
etc…) & appetite (food cravings) that occur
hours to days before the migraine
Characteristics or Aura Stage
with / without aura, incidence
Migraine without aura (Common Migraine)
Migraine with aura (Classic Migraine)
≤ 25 % of people with migraine
Characteristics of headache phase of migraine?
pain, location, other symptoms, duration, symptom improvement
Progression from a dull ache to intense pulsations
Usually unilateral and occur in the frontotemporal
region and may extend to the neck and back of skull
Accompanied by nausea and vomiting (~90%)
Photophobia and Phonophobia
Migraine Lasts 4 -72 hours
Symptoms improve with resting in a dark room and
worsen with physical activity
More common in women versus men
What frequency of migraines determines whether to use abortive therapy v. prophylactic therapy?
≤ 2 attacks per week;
Abortive therapy
≥ 3 attacks per week;
Prophylactic therapy
What are rebound headaches, and what is associated with their occurance?
Rebound headaches are characterized by an increase in
headache frequency and an increase in drug consumption
Combination analgesics, opiates, ergotamine tartrate
and triptans are associated with rebound headaches
What should be done to avoid rebound headaches? What is the only drug useful in relieving medication overuse headaches?
To avoid the problem of rebound headaches abortive
therapy should be used ~ 2 times a week
Only botulinum toxin is useful relieving medication
overuse headaches
NSAIDs for Abortive Therapy: Efficacy, MOA and contraindications
Relative efficacy of the different NSAIDs for treating
migraine has not been clearly established
Mechanism of action: block prostaglandin synthesis and prevent inflammation in the trigeminovascular system
Use with caution in patients with peptic ulcer disease,
renal disease or hypersensitivity to aspirin.
Describe usefulness in treating migraines with acetaminophen
Acetaminophen – efficacious in treating migraine pain and symptoms including photophobia and phonophobia
Ergotamine route, t1/2 and dosage.
Route: Oral, sublingual and suppository
Dosage: The maximum oral/sublingual dose should not exceed 6 mg/attack or 10mg/week .
The biological half life of ergotamine is ~2 hrs, however ergotamine-induced vasoconstriction (duration of action) can last ~24 hrs
Pharmacodynamics of Ergotamine: What receptors, how does it reduce neurogenic inflammation?
Ergotamine is a dirty drug and interacts with serotonin,
dopamine and adrenergic receptors.
Activation of 5-HT1B receptors causing vasoconstriction
Reduce neurogenic inflammation by decreasing the release of vasodilator/proinflammatory neuropeptide transmitters (e.g. substance P, neurokinin A, CGRP)
Ergot Alkaloid contraindications, drug interactions and side effects
what adjunct therapy can help alleviate side-effects
Powerful vasoconstrictor –
Partial agonist at alpha-adrenoceptors and 5-HT2
receptors, contraindicated in patients with peripheral
vascular disease and pregnancy (category X).
Beta-blockers may potentiate vasoconstriction caused
by ergotamine. Patients on both medications should
be closely monitored
Side-effects: Nausea, vomiting and anorexia
Occurs in 10% of patients due to activation of central dopamine receptors
May require adjunct therapy with antiemetic (10mg Metoclopramide)
Dihydroergotamine: Route, pharmacodynamics, toxicity and adverse reactions
Incompletely absorbed form the GI tract and is
administered parenterally (IM,SQ) or via a nasal
spray (Migranol)
Pharmacodynamics – similar to ergotamine
Toxicity, adverse reactions, and contraindications
similar to ergotamine except dihydroergotamine
causes vasospasm less than ergotamine
Triptans: Route, metabolized by, contraindications.
How long after onset of migraine can the still be effective?
subcutaneous injection, oral tablets, nasal spray or transdermal patch
Metabolized by MAO-A, contraindicated with the use of a
MAO inhibitor within a 2 week time span after discontinuing
MAO therapy
Triptans can be administered up to 4 hrs after the onset of a
headache and still be effective
Sumatriptan pharmacodynamics
receptor, symptoms treated
Sumatriptan is an agonist at type 1 serotonin receptors, similar action as the ergot alkaloids
Relieves nausea/vomiting and photophobia/phonophobia
Triptans: Toxicity, adverse reactions and contraindications
what route should not be used to administer?
Cardiovascular (coronary spasm, myocardial infarction,
ventricular arrhythmias)
Several fatalities reported with subcutaneous sumatriptan
due to myocardial infarction
Do not give by IV due to due to the risk of vasospasm
Use of sumatriptan is contraindicated within 24 hrs of
treatment with an ergot due to the risk of additive vasospastic effects.
Triptan side-effects
Common with sumatriptan and newer triptans:
chest and throat tightness, difficulty breathing, panic/anxiety,
paresthesia, feeling of heaviness
2nd gen Triptans (zolmitriptan)
locations of action, other areas of action, oral absorption
Like sumatriptan these drugs act at the peripheral
components of the trigeminovascular system
Due to greater lipid solubility they also act centrally to
inhibit pain transmission in the trigeminal nucleus
(see Figure 1)
Better oral absorption versus sumatriptan (Imitrex
Dopamine antagonists: Name 3 kinds, what they are useful for, route and what they do.
Metoclopramide
Prochlorperazine
Chlorpromazine
These dopamine antagonists are useful for the
treatment of acute migraine attacks that are
unresponsive to sumatriptan, DHE or oral analgesics
Given by IV when administered in emergency
department
Relieve headache pain and have anti-emetic activity
Prophylactic Therapy: When to use them, how long until they are considered ineffective. What to do after 3-6 months for effective patient.
Consider prophylactic therapies with patients
who don’t respond to acute therapies or who
have ≥ 3 migraines per week.
Patients need to try these therapies for 2-3
months before they are considered ineffective.
If effective patient should stay on the drug for 3
- 6 months, after this time, try to remove the
drug to determine if remission has occurred.
Which two B-blockers are FDA approved for migraine? What is one other that is also effective?
Propranolol and timolol are FDA approved for migraine
Metoprolol is also effective
Prophylactic Drug Therapy – β Blockers: MOA and what should be avoided
Mechanism of action is not clear but these drugs do have some affinity for serotonin receptors
Beta-blockers with intrinsic sympathomimetic activity (partial agonist) e.g. acebutolol, pindolol, and penbutolol are not effective and should not be used for migraine therapy
Amitriptyline: Type, MOA, side-effects
Antidepressant prophylactic drug
Mechanism of action of amitriptyline is unknown, independent of antidepressant action, may involve
down-regulation of central 5-HT2 and adrenergic
receptors
Sedation and anticholinergic side-effects (dry mouth,
blurred vision, urinary retention, cardiac arrhythmia)
Fluoxetine (Prozac) has fewer anticholinergic side
effects
Topiramate: Type, MOA, side-effects
Type: Anti-seizure drug for Migraine treatment
MOA: – unknown for migraines, facilitate GABA neurotransmission, modulate glutamate, inhibit sodium and
calcium channels
Side-effects: paresthesia, fatique, anorexia/nausea, diarrhea,
weight loss, memory problems (cognitive slowness)
Calcitonin gene-related peptide: Type, clinical trial effectiveness
Type: Prophylactic Drug Therapy
Drugs with – “mab” suffix are human monoclonal antibodies; rimegepant and atogepant are small-molecule drugs given PO
All have been approved since 2018
Clinical trials show modest but significant effects – no “magic bullets” here
Botulinum Toxin A: MOA, route, length of action
Anti-migraine effect is not well understood
Injection of 70 – 100 units into a number of possible
sites (frontalis, glabellar, temporalis, masseter, splenius
capiti, paraspinal cervical, and trapezius muscles)
The anti-migraine effect can potentially last for up to 3
months and is only medication for rebound headaches
