Pharm management of HA Flashcards
Tension HA
Abortive treatment
NSAIDs +/- acetaminophen
Add caffeine if unresponsive
can add muscle relaxants
Tension HA
Prophylaxis
Amitryptiline (TCA)
SNRIs
SSRIs
Anticonvulsants
Migraine
Abortive treamtent
1) triptan
2) ergots = ergotamine or DHE
3) NSAIDs
4) Tramadol
5) isometheptene
Migraine
Prophylaxis
1) Antihypertensives (beta blocker or CCB)
2) anticonvulsants (topiramate and valproate)
3) antidepressants (amitryptiline)
4) NSAIDs
5) 5-HT2 receptor antagonists (methysergide)
Cluster HA
abortive treatment
1) ergots (DHE and ergotamine)
2) glucocorticoids (interrupt chain)
3) lidocaine
4) oxygen
5) triptans (sumatriptan)
Cluster HA
Prophylaxis
1) lithium
2) methysergide
3) verapamil (CCB)
Current model of migraine HA
1) neuropetpide trigger cascade of neuroinflamm
2) Phase 1 = 5HT release from neurons and platelets periph on to vessels causes vasoconstriction and ischemia
3) Phase 2 = cerebral vasodilation and pain regul by trigeminal neurovasc system
how do agonists of serotonin reduce pain in migraine
via release of pain inducing neuropeptides (CGRP)
5-HT1A
Location
Physiology
CNS
decr camp
5-HT1A
effects
1) neuronal inhib
2) sleep
3) anxiety
5-HT1A
agonists
antago
agonist= buspirone
antag = ergotamine
5-HT1B
Location
Physiology
CNS, blood vessel
decr camp
5-HT1B
effects
1) presynap inhib
2) pulm vasoconstriction
5-HT1B
agonists
ergotamine
5-HT1D
location
physiology
CNS, blood vessel
decr camp
5-HT1D
effects
cerebral vasoconstriction
5-HT1D
agonist
antagonist
sumatriptan
ergotamine
5-HT2A
location
physiology
CNS
5-HT2A
effects
1) behavior effects
2) contraction
3) aggregation
5-HT2A
agonist
antago
LSD
methysergide
5-HT2C
location
physiology
CNS
incr IP3/DAG
5-HT2C
effects
CSF secretion
5-HT2C
antagonist
methysergide
NSAIDs
Mechanism of action
COX1/2 inhibitors
interrupts inflamm mediator release caused by CGRP
NSAIDs
administration
duration
most OTC = oral
indomethacin = suppository
4-6 hrs to 8-12 hrs
NSAIDs
uses
sufficient for mild to moderate migrates without nausea or diability
used for short term prevention
NSAIDs
side effects
1) avoid in gastritis, peptic ulcers
2) affects platelet aggreg so avoid in bleeding disorders
3) avoid in renal insufficiency
tylenol = liver tox
NSAIDs
DDI
incr bleeding risk with antiplatelets or anticoags
Triptans
mechanism of action
5HT1B and 1D agonists
1) cerebral vasoconstriction
2) inhib release of neuropeptides causing vasodilation, inflamm
3) inhib trigeminal pain fibers
Triptans
administration
1) oral mainly, nasal, subq
2) sumatriptan = poor CNS distrib
short half life
Triptans
uses
first line for moderate-severe migraines
decr dilution-induced HA
Triptans
side effects
paresthesias, flushing, drowsiness, dizzy, chest tightness (worst with sumi)
rarely coronary vasospasm *ASSOC WITH DHE, MI, angina, arrhythmia, stroke, death (avoid with HTN and heart dz)
Triptans
DDI
additive constriction with ergot
incr risk of 5-HT syndrome with MAOIs (less with SNRI, SSRI)
Ergots
mechanism
5-HT1B and 1D
same as triptans
Ergots
administration
dihydroergotamine = oral, sublingal, rectal, incr abs with caffeine
DHE = intranasal and parenteral
Ergots
uses
less effective than triptans but also used in migraines
ergots
side effects
n/v (give with anti-emetics)
diarrhea, cramps, paresthesia
serious = vascular occlusion, gangrene via alpha 1 vasoconstriction
ergots
ddi
severe peripheral ischemia if used with beta blockers
additive constriction with triptans
avoid with CYP3A4 inhib = vaosspasm
when should you consider prophylaxis
1) severe, long last >12 hrs, frequent- more than 4 or disabling
prophylaxis
beta blockers
propranolol
timolol
causes side effect
first line for migraine prophylaxis
antihypertensive
causes fatigue, exercise intolerance, depression, ortho hypotension
prophylaxis
beta blockers
propranolol
timolol
contraindicated in
asthma
diabetes
conduction disturbances
prophylaxis
CCB
verapamil
third line for migraine prophylaxis
tolerance develops
prophylaxis
CCB
verapamil
contraindiction
don’t use with beta blocker= heart block
prophylaxis
ACEI/ARB
lisinopril
candesartan
2nd or 3rd line
TCA
amitryptiline
side effect
incr monoamine transmission, second line
sedation, dry mouth, tachy, weight gain, urinary retention
anticonvulsants
topiramate
side effect
effect similar to propranolol
side effect = paresthesias, weight loss, taste perversion, fatigue
pathophys of migraine
1) trigeminal neurovasc dysfunction
2) trigem neurovasc activ
3) release of vasoactive peptides
4) neuroinflamm and vasodilation of pial and dural vessels
5) pain
phase 1 of migraines
cerebral vasoconstriction and ischemia
cortical spreading depression (decr CBF from vasoconstrict –> aura)
activate trigem nerve afferents
phase 2 of migraines
cerebral vasodilation
trigeminal neurons release vasocactive peptides (substance P, CGRP) = vasodilation and neuroinflamm
role of sensitization
1) throbbing pain
2) worsening pain with coughing-bending-sudden head movements
3) hyperalgesia
4) allodynia
abortive treatment of migraine with n/v
SC sumatriptan
IV metoclopramide + diphenhydramine
abortive treatment of migraine with intractable HA
IV DHE
severe side effect of triptans, ergots esp DHE
vasoconstriction and vasooclusion
but more common in ergots and DHE due to alpha1 blockage
frontal lobe lesion causes urinary __
urgency
spinal cord lesions above S2-S4
spinal cord lesions of S2-S4 or injury to periph nerves innerv bladder
spastic bladder (think UMN) –> reflux up ureters
flaccid bladder (think LMN) –> overflow incontinence
