migraine pharmacology and therapeutics Flashcards
1
Q
four factors thought to be involved in the cause of migraines
A
- serotonin system dysregulation
- trigeminal nerve
- vasodilation
- release of vasoactive and inflammatory peptides
2
Q
main vasoactive and inflammatory peptide
A
calcitonin gene related peptide
3
Q
what indicates trigeminal nerve in migraines
A
unilateral feature of migraines
4
Q
neuron pathway of the trigeminovascular system
A
- 1st order nociceptive fibers transmit signals from blood vessels in the dura
- 1st order neurons synapse with 2nd order in the trigeminocervical complex
- 2nd order neurons extend to the thalamus
- 3rd order neurons take the signal from the thalamus to the cortex
5
Q
peptides are released from where
A
nerve terminals
6
Q
neuropeptides cause
A
vasoconstriction
inflammation
7
Q
what activates pain receptors
A
sterile perivascular inflammation (in the dura)
8
Q
unified neural generator theory
A
in people with migraine headaches 2nd order neurons are hyperexcitable which increases perception of pain
9
Q
when migraine triggers occur what area of the brain appears to start the attack
A
hypothalamus
10
Q
pain processing center
A
periaqueductal gray
11
Q
Trigeminocervical complex excitability increases proportionally with
A
time to the next attack
12
Q
acute treatment for migraines concept
A
inhibit COX activity to decrease prostaglandin formation
13
Q
decreased prostaglandin activity does what
A
- decreased nociception
- decreased inflammation
- reduced vasodilation
- reduced transmission between 1st and 2nd order neurons
14
Q
benefits of caffeine in migraine treatments
A
- has intrinsic analgesic properties
- may promote uptake of drugs in the GI tract
15
Q
acute treatment combo drugs
A
- excedrin
- fiorinal
- fioricet
- midrin
16
Q
Midrin MoA
A
- Isometheptene vasoconstricts
- Dichloralphenazone is hypnotic and antipyretic
- acetaminophen
17
Q
Midrin adverse effects
A
- hepatotoxicity
- hypertension
- sedation
18
Q
Midrin contraindications
A
- glaucoma
- severe uncontrolled hypertension
- heart disease
- MAO-I
19
Q
triptan’s MoA
A
5-HT 1b/1d agonists (serotonin agonists)
20
Q
where is 5-HT1d serotonin receptor
A
- peripheral nociceptive fiber
- TCC
21
Q
where is 5-HT1b serotonin receptor
A
- cerebral and dural blood vessels
- TCC
22
Q
5-HT1b serotonin receptors cause
A
vasoconstriction
23
Q
5-HT1d serotonin receptors cause
A
decreased excitability of nociceptors by:
- reducing Ca influx
- increasing K conductance
24
Q
contraindications of triptans (5-HT1b/1d agonists)
A
- heart disease
- peripheral vascular disease
- uncontrolled hypertension
- ergot alkaloids w/i past 24 hr
- MAOI in last 2 weeks
25
when to use ergot alkaloids
in acute settings inside a hospital after other options have failed
26
ergot MoA
vasoconstriction
27
ergot basic adverse effects
- N/V
- abdominal pain
- weakness/fatigue
- muscle pain
- chest tightness
- peripheral ischema
28
ergot serious adverse effects
- gangrenous extremities
- myocardial infarction
- hepatic necrosis
- bowl/brain ischemia
29
what kind of migraine headaches can we treat prophylactically?
cyclical headaches, such as those tied with menstruation or seasons
30
generator location of cluster headache
hypothalamus
31
other symptoms of cluster headache
parasympathetic signs on the side of the face with pain
- lacrimation
- nasal congestion
- rhinorrhea
- sweating
32
pterygopalatine ganglion
reflex arch thought to be involved with the parasympathetic symptoms of cluster headaches
33
primary headache types
tension
migraine
cluster
34
secondary headache types
symptomatic of organic disease (ie drug induced)
35
pain description of migraines
- throbbing
- pulsating
- moderate to severe
- worsens with exertion
36
associated symptoms of migraine
- nausea
- vomiting
- photophobia
- phonophobia
- sometimes aura
37
pain description of tension headache
- dull
- non-pulsatile
- tightness
- pressure
- moderate
38
associated symptoms of tension headache
- mild photophobia
- mild phonophobia
- sometimes none
39
pain description of cluster headache
- occurs suddenly
- excruciating
- penetrating
- boring intensity
- severe
40
associated symptoms of cluster headache
- lacrimation
- nasal stuffiness
- rhinorrhea
- facial sweating
- eyelid edema
- miosis
- restlessness
- agitation
41
features of migraine
- unilateral
| - 4-72 hours long
42
features of tension headache
- bilateral, can extend down neck
| - variable length
43
features of cluster headache
- unilateral in the orbit
| - 15-120 mins, multiple times per day
44
migraine diagnosis
1. >= 5 attacks total
2. must last 4-72 hours
3. unilateral, pulsating, moderate/severe pain, activity avoidance (must have 2)
4. N/V, photophobia, phonophobia (must have 1)
45
migraine with aura diagnosis
1. >= 2 attacks
2. visual, sensory, and/or speech/language symtpoms
3. symptoms spread over 5 mins, last 5-60 mins, unilateral, headache within 60 mins
46
goals of acute migraine therapy
- treat rapidly and consistently
- restore ability to function
- minimize use of backup meds
47
goals of prophylactic migraine therapy
- reduce frequency, severity, disability
- reduce acute treatment
- improve QOL
48
nonpharm acute migraine therapy
- ice to the head
- rest or sleep
- dark quiet room
- avoid triggers
49
nonpharm prophylactic therapy
- regular sleep
- exercise
- smoking cessation
- reduce caffeine
- good eating habits
- relaxation therapy
50
food triggers for migraines
- alcohol
- caffeine
- chocolate
- aspartame
51
environmental triggers for migraines
- glare/flickering
- high altitude
- loud noises
- tobacco smoke
- weather changes
52
behavioral triggers of migraines
- excess/insufficient sleep
- fatigue
- menstruation/menopause
- sexual activity
- skipped meals
- strenuous physical activity
- stress
53
treatment of migraines with mild to moderate symptoms
1. NSAID
2. OTC combination (APAP, aspirin, caffeine)
3. triptan
54
NSAID side effect
nausea
55
longer half life, slower onset triptans
frovatriptan
| naratriptan
56
unique instruction of naratriptan use
repeat dose every 4 hours
57
triptan with fastest onset
sumatriptan SQ
58
triptan with interaction with propranolol
rizatriptan
59
repeating triptan doses
- after 2 hours for oral, nasal, ODT
- after 1 hour for SQ
- no more than 2-3 days per week
60
acute side effects of triptans
- flushing
- dizziness
- drowsiness
- paresthesias
61
precautions when using triptans
- ischemic heart disease
- stroke
- CAD
- pregnancy
- ergots
- serotonin syndrome
62
precautions in ergot use
- CAD or CVD
- uncontrolled hypertension
- renal/hepatic failure
- elderly
- pregnancy/lactating
63
ergots acute side effects
- N/V
- abdominal pain
- weakness/fatigue
- muscle pain
- peripheral ischemia
64
ergots serious side effects
- gangrenous extremities
- MI
- hepatic necrosis
65
opioid use in migraines
- last line
| - for moderate to severe migraine after other treatments fail
66
antiemetics for use in migraine
- metoclopramide
| - prochllorperazine
67
medication-overuse headache
- self-sustaining headache with prolonged use of medication
- daily or near daily
- discontinue offending agent by tapering
68
indications for migraine prophylaxis
- >2 migraines per week
- symptomatic therapy doesn't work
- symptomatic therapy causes AEs
- risk of permanent neurologic injury
- patient preference to limit attacks
69
prophylactic treatment strategy for predictable pattern headaches
nsaid or triptan at time of vulnerability
70
prophylactic treatment strategy for unpredictable pattern and healthy, has HTN, or angina
- beta-blocker
| - Ca channel blocker if beta-blocker contraindicated
71
FDA approved beta blockers for prophylaxis
propranolol
| timolol
72
side effects of beta-blockers
- fatigue
- dizziness
- bradycardia
- depression
- hypotension
73
precautions in beta-blocker use
- CHF
- peripheral vascular disease
- asthma
- hypoglycemic awareness
- depression
74
prophylactic treatment with comorbid depression or insomnia
TCA (amitriptyline)
| SNRI (venlafaxine)
75
prophylactic treatment with comorbid seizures or bipolar
topiramate
| valproic acid
76
time to see benefit with prophylactic medications
3-6 months
77
botulinum toxin in prophylaxis
- FDA approved for chronic migraine
| - injections into 31 sites every 12 weeks
78
first line therapy for tension headaches
OTC analgesics, limited to 2-3 days per week
79
acute therapy for cluster headache
- oxygen
- triptans
- ergots
80
prophylactic therapy for cluster headache
- suboccipital corticosteroid injection
- verapamil
- lithium
