Exam 3 - Migraines L30 Flashcards
Classes of drugs used for abortive therapy
1) Serotonin receptor agonists
2) Ergot alkaloids
3) Dopamine Receptor antagonists
4) Calcitonin gene-related peptide receptor antagonists
5) Analgesics
Classes of drugs used for prophylactic therapy
1) beta-blockers
2) antidepressants
3) anticonvulsant drugs
4) calcitonin gene-related peptide ligand inhibitor
5) botulinum toxin type a
6) calcium channel blockers
Migraine background information
-about 44.5 million Americans suffer from migraines
-more women than men
-genetically linked
-costs American economy due to lost productiveness and healthcare costs
what are the GI aspects of migraines?
-decreased GI motility and nausea/vomiting symptoms slow the oral absorption of drugs during a migraine
-parental routes of administration should be used
Due to the high variability of individual response to migraine drugs…
therapeutic strategies must be customized to each patient
what are the phases of a migraine?
1) prodrome
2) aura
3) headache
4) postdrome
describe the prodrome phase
-present in less than 60% of patients
- changes in mood and appetite (cravings) that occur hours to days before migraine
describe the aura phase
-aura classified as visual disturbances (fortification spectrum)
-occurs in less than 25% of people
-migraine without aura called common migraine
-migraine with aura called classic migraine
describe the headache phase
-progression from dull ache to intense pulsations
-accompanied by GI symptoms (nausea and vomiting)
-photophobia and phonophobia sometimes present
-lasts 4-72 hours
describe postdrome phase
characteristics of this phase differ among all people with migraines
what are some other less common types of migraines?
-menstrual migraine
-tension type headache (not as bad as migraine, less symptoms)
-cluster headaches (very rare, intense pain, more common in males)
what are the proposed mechanisms of migrains
-vascular theory
-spreading depression
-serotonergic abnormalities
-p/q calcium channel mutations
describe the vascular theory
aura is caused by vasoconstriction of vessels, and pain is caused by the vasodilation
describe the spreading depression theory
migraines caused by the spreading decrease in cortical electrical activity
describe the serotonergic abnormalities mechanism
-mechanism not known, however it is known that IV injection of serotonin can abort a spontaneous or drug induced migraine
-some drugs work at serotonin receptors
what are rebound headaches?
-migraines that are actually caused by increase use of drugs meant to treat migraines
-to avoid, abortive therapy drugs should only be used 2 times a week
-botox is only medication that can relieve these
what are the analgesics drugs used in migraine treatment
-NSAIDS (aspirin, acetamenophen, ibuprofen)
-opiates (butorphanol)
describe NSAID use in migraine treatment
-over the counter
-efficacy not clearly established
-mechanism of action appears to be related to blocking of prostaglandin synthesis and preventing inflammation
-use with caution in patients with renal problems and ulcers
which symptoms is acetaminophen very effective in treating?
photophobia and phonophobia
describe opiates in migraine treatment
-not often used, high abuse potential
-many adverse affects
describe ergot alkaloids
-naturally occurring compounds found in grains contaminated by fungus
-historically the drug of choice for treatment
-oral, sublingual, suppository dosage form
-half life is 2 hours, but duration of action (vasoconstriction) is 24 hours
-sometimes mixed with caffeine or other alkaloids to avoid side effects
what are the pharmacodynamics of ergot alkaloids
-activation of 5-HT1b receptors cause vasoconstriction
-activation of 5-HT1d reduces inflammation by decreasing release of substance P, neurokinin A, CGRP
contraindications of ergot alkaloids
-cant be used in pregnant women or patients with peripheral vascular disease
-vasoconstriction can be potentiated by beta blockers in patients taking ergot alkaloids
ergot alkaloid adverse reactions
-upsetting GI symptoms
-occurs in 10% of patients due to activation of dopamine receptors in chemoreceptor trigger zone
-may require adjunct therapy with antiemetic (10mg oral metoclopramide)
ergot alkaloid prototype
-dihydroergotamine (DHE 45)
-administered parenterally or via nasal spray
chemistry and pharmacokinetics of triptans
-subcutaneous injection, oral tablets,
nasal spray/powder or transdermal patch
-metabolized by MAO-A, contraindicated with use of MAO inhibitor within 2 week time span
-can be administered up to 4 hrs after onset of headache and still be effective
Triptan drugs
-first line drugs used for migraines
-sumatriptan (1st gen, 1b/1d agonist)
-zolmitriptan (2nd gen 1b/1d)
sumatriptan
-triptan drug
-can be subcutaneous injection, oral tablet, nasal spray/powder, transdermal patch
-type 1 serotonin receptor agonist (similar to to ergot alkaloid)
-relieves nausea/vomiting and photo/phonophobia
toxicity and adverse reactions of triptans
-adverse cardiovascular symptoms
-several fatalities reported due to subcutaneous injection of triptans resulting in MIs
-do NOT give IV
-Do not give within 24 hours of ergot alkaloid
describe 2nd gen triptans
-act at the peripheral components of the trigeminovascular symptoms (like 1st gen)
-greater lipid solubility leads to them acting centrally to inhibit pain transmission in trigeminal nucleus
-better oral absorption
describe dopamine receptor antagonists
-metoclopramide, prochlorperazine, and chlorpromazine
-useful when triptans, DHE, and analgesics don’t work
-given by IV in emergency departments
-relieve headaches and have anti-emetic activity
when to consider prophylactic drug therapy
-when patients don’t respond to acute therapies and have more than 3 migraines a week
-need to be tried for 2-3 months before being considered ineffective
-should only use for 3-6 months then stop
beta blockers
-propanolol, metoprolol, timolol
-prophylactic drugs
-mechanism of action not clear (serotonin related?)
-b-blockers with intrinsic sympathomimetic activity not effective
antidepressants
-amitriptyline
-prophylactic drug
-mechanism of action unknown, but independent from antidepressant action
-sedation and anticholinergic side effects present
anticonvulsants
-topiramate
-prophylactic drugs
-mechanism of action unknown, perhaps GABA transmission?
-topiramate has some side effects (paresthesia, fatigue, anorexia/nausea, diarrhea, weight loss, cognitive problems)
CGPR ligand inhibitors
-prophylactic drugs
-rimegepant is also used for acute treatment
-mab suffix denotes human monoclonal antibodies
-modest effects shown in clinical trials
botulinum toxin A
-prophylactic drug
-also used for cosmetics
-only medication for rebound headaches
-anti migraine effect can last for up to 3 months
calcium channel blockers
-prophylactic drugs
-less effective than other drugs, last resort
migraines in children
-shorter duration of pain (30 min)
-1st step is to eliminate possible food triggers
