Headache Pharmacotherapy Flashcards
Headache disorders
epidemiology
Overall highest incidence in early adulthood
66% of women and 57 % of men report one headache per month
67% of people use OTC for treatment
Prevalence of migraine increased in last 20 yrs by 60%
Common chars of primary headache disorders
Migraine/tension/cluster
Prevalence/frequency/severity
Migraine
Prevalence: 10-15%
Frequency: 1-4/month
Severity: Mod-severe
Tension
Prevalence: 40%
Frequency: 1-15/month
Severity: Mild-mod
Cluster
Prevalence: 0.007%
Frequency: Qday x 1-2 month
Severity: severe
Common chars of primary headache disorders
Migraine/tension/cluster
Unilateral/duration/pain type/assoc sx
Migraine Unilateral: 60% Duration: 4-72 hours Pain type: Throbbing Assoc sx: Aura, n/v
Tension Unilateral: Rarely Duration: 15-180 minutes Pain type: Dull Assoc sx: Stiffness
Cluster Unilateral: Always Duration: Variable Pain type: Sharp Assoc sx: Autonomic (lacrimation, nasal stuffiness)
Chronic daily headache
Many pts have headache >15 day/mon and suffer from CDH which can be secondary to tension-type, migraine
Many CDH are a result of analgesic overuse (analgesic rebound headache/drug-induced headache)
Mechanisms of headache
Vascular hypothesis
HA due to alteration in blood flow
HA due to compensatory vasodilation
Many effective drugs dont effect bld vessels
Mechanisms of headache
Neurovascular hypothesis
Implicates trigeminovascular system
complex interaction between trigeminal nerve and the cranial blood vessels
Mechanisms of headache pain
Trigeminovascular system
trigeminovascular system is a network of nerve fibers that innervate cranial vessels
Sensitization of vessels is likely to produce headache
regulated partly by seretonin (5HT) which may decrease in acute attack (migraine?)
Calcitonin G related peptide
5HT-1D receptors on trigeminal nerve
5HT-1B receptors on cranial vessel
Principles of headache pharmacotherapy
Acute therapy
Used during individual attacks to treat the intensity of pain and its associated symptoms
Treat early in the attack!
Headache pharmacotherapy
Prophylactic therapy
Indicated when patients have either frequent headaches or despite infrequent headaches the devastating nature makes prevention worthwhile
Attacks of headache occur at a frequency greater than 2 per week (except cluster)
Migraine therapy
Tx
1st line: Triptans NSAIDs or acetaminophen may be helpful in mild cases Alternatives: Ergot alkaloids Antiemetics in combination Opioid analgesics
Migraine therapy
prophylaxis
Prophylaxis 1st line: β-blockers or topiramate Alternatives: Anti-depressants Verapamil Valproic acid
Tension-type therapy
Tx
Treatment 1st line: NSAIDs or acetaminophen Alternatives: Butalbital + caffeine Opioid analgesics
Tension-type therapy
prophylaxis
Prophylaxis
1st line:
Amitryptiline
Alternatives:
- migraine prophylaxis
Cluster type therapy
Tx
Treatment 1st line: oxygen Alternatives: Triptans Ergot alkaloids Steroids Topical anesthetics
Cluster type therapy
prophylaxis
Prophylaxis
1st line:
Prednisone or verapamil or lithium
Menstrual migraine
chars
Migraine occurring before or during menses
Affects 26-60% of women with migraine
Occurs frequently during period in life where estrogen levels may be rapidly changing
Occurs less when estrogen is more constant
Mechanism is unknown
Serotonergic systems suppressed during late luteal phase
Menstrual migraine
tx
Standard therapy
“mini” prophylaxis- NSAIDS or triptans just prior to menses
Extended estrogen or low-dose estrogen
Pregnancy risk for headache medications
Simple analgesics
Risk factor/comments
Med:
Simple analgesics:
Acetaminophen
Aspirin
Caffeine
Risk Factor:
Acetaminophen B
Aspirin C/D
Caffeine B
Comments: Aspirin risk factor D in full dose in 3rd trimester
Pregnancy risk for headache medications
NSAIDS
Risk factor/comments
Med
Risk Factor
Comments
NSAIDs
B/D
NSAIDs risk factor D if used in 3rd trimester or near delivery
Pregnancy risk for headache medications
Opioid analgesics
Risk factor/comments
Med
Risk Factor
Comments
Opioid analgesics
C/D
Opioid analgesics are risk factor D if used in high doses or for prolonged periods near delivery
Pregnancy risk for headache medications
Serotonin Agonists
Risk factor/comments
Med
Risk Factor
Comments
Serotonin agonists:
Ergot Alkaloids
Triptans
X
C
All ergot derivatives are contraindicated
Pregnancy risk for headache medications
Antiemetics
Risk factor/comments
Med
Risk Factor
Comments
Antiemetics:
Metoclopramide
Prochlorperazine
B
C
None
Medication misuse headache
Gen chars
Perpetuation of head pain in headache sufferers
Due to irresistible urge of pts to overuse drugs
Medication misuse headache
Clinical features
Headaches occur nearly daily
headaches are refractory to treatment
pts use relief medications very frequently and in excessive quantities (more than 2-3 times/ week)
spontaneous improvement occurs when discontinuing the medications
Prolonged use of analgesics may suppress natural opioids causing heightened pain sensitivity
Most common offenders are OTC analgesics
Treatment is removal of the agent
Agents used for acute tx
list
Ergot alkaloids
Ergotamine tartarate (Egomar®) Ergotamine + caffeine (Cafergot®, Wigrane®) Available in PO, SL, PR forms DHE 45® (Dihydroergotamine IV) Migranal® nasal spray (DHE + caffeine)
Ergot alkaloids
chars
Structurally related to amines (DA, EPI,NE) and can cause potent vasoconstriction
MOA is by vasoconstriction of cranial arteries or by stimulating 5HT- 1 receptors (NON-SELECTIVE)
Ergot alkaloids
Adverse events
Peripheral vasoconstriction is most serious adverse event
Numbness/tingling in extremities
Muscle pain
Gangrene
Nausea/vomiting occur in up to 10% of pts
Use lowest dose possible
Use with metoclopramide (antiemetic)
Ergot Alkaloids
contraindications
Peripheral vascular disease hepatic impairment renal impairment coronary artery disease pregnancy concomitant triptan use
Triptans
MOA/clinical use
Active selectively at 5HT-1B and 1D subtypes unlike ergots (less nausea)
Are effective in both migraine as well as cluster headache
Sumatriptan
Adverse effects
Typically well tolerated Most severe adverse events are coronary vasospasm, MI, arrhythmias, stroke “Triptan” symptoms chest tightness, tingling, numbness neurologic- drowsiness, lethargy
See if you need to know the chars of the various triptans
Pg. 427
Triptans
Contraindications
PVD
uncontrolled HTN
coronary artery disease or significant cardiovascular disease
concomitant MAO-A inhibitor within 2 weeks
Except Almotriptan
concomitant ergot use within 24hrs
significant hepatic disease
Headache therapies
Agents used for acute tx
acetaminophen
Safest of all treatments
Used in combination therapies (Midrin®)
Major concern is rebound in combinations
Headache therapies
Agents used for acute tx
NSAIDs/ASA
Wide margin of safety
Mech of action due to inhibition of prostaglandins as well as possible central mechanisms
Commonly used in combinations
GI bleeding and rebound are major concerns
Headache therapies
Agents used for acute tx
Caffeine
Wide margin of safety
Mech of action probably due to vasoconstriction properties
Used in combinations (Excedrin®)
Side effects related to stimulant properties
elevated mood, insomnia, palpitations, diuresis
Major concern is rebound in combinations
“Caffeinism”
Average caffeine intake 220-240mg/day
Withdrawal syndrome characterized by yawning, decreased concentration and headache
Headache occurs 18-24hrs after withdrawal
Most effective therapy is reintroduction. May try taper of 5oz every week
Headache therapies
Agents used for acute tx
Isometheptene combination
Midrin (isometheptene + dichloralphenazone + acetaminophen)
Isometheptene resembles epinephrine
Dichloralphenazone is a sedative
Side effects are numbness/dizziness
Headache therapies
Agents used for acute tx
Dopamine antagonists
Metoclopramide - drug of choice for nausea in migraine
often given in combination to increase gut motility
Prochlorperazine
Chlorpromazine
Headache therapies
Agents used for acute tx
Opioid analgesics
IV MSO4, butorphanol, codeine combinations
Role in migraine controversial
have few effects on fundamental pathogenesis
habituation/ rebound headaches
Headache therapies
Agents used for acute prophylaxis
list
TCA Beta-blockers Verapamil Valproic acid Topiramate Lithium Botulinum toxin
Headache therapies
Agents used for acute prophylaxis
TCA
Tricyclics like amitryptyline (Elavil®) are drugs of choice for tension- type prophylaxis and are also effective in migraine prophylaxis
Most common side effects are ANTICHOLINERGIC in nature
Do not use in pregnant women, glaucoma, urinary retention, with MAO-I
Headache therapies
Agents used for acute prophylaxis
Beta blockers
Generally, treatment of choice for prevention of migraines
Propranalol, atenolol, metoprolol effective
MOA unknown; may raise migraine threshold
Side effects include fatigue, hypotension, bradycardia. Caution in asthma, diabetes
Headache therapies
Agents used for acute prophylaxis
verapamil
CA channel blocker of choice for prevention of both cluster and migraine headaches
Affects may take 3-8wks (limiting factor)
Side effects include hypotension, edema, constipation
Headache therapies
Agents used for acute prophylaxis
Valproic acid
o MOA unknown, but has been effective in both migraine and cluster headache
o Numerous side effects (n/v, weight gain, hepatotoxicity)
o Consider for pts unresponsive to other agents or with a history of bipolar or seizure disorder
Headache therapies
Agents used for acute prophylaxis
Topirimate
FDA approved for migraine prophylaxis o Effective at 100-200mg/day
Several patients dropped out of studies due to adverse events. Cognitive (confusion, slowed speech,memory). Weight loss
Headache therapies
Agents used for acute prophylaxis
Lithium
O Treatment of choice for prophylaxis of chronic cluster headache
O Benefits take 1-2 weeks Enhances serotenergic neurotransmission
O Can also precipitate a headache as well as lethargy and abdominal discomfort
O Avoid in pregnancy, renal disease
Headache therapies
Agents used for acute prophylaxis
Botulinum toxin
O Mechanism of action unknown. May reduce release of pain mediators (substance P, glutamate) O Administered by several intradermal injections q2-3 months
O Early controlled studies found no benefit for several types of headaches
O More recent PREEMPT trials showed reduction in headache frequency when compared to placebo in patients with chronic migraine
o Most common side effects were neck pain and muscle weakness
o Botox appears to have some efficacy, however questions regarding long term safety and conflicting evidence remain
Headache pharmacotherapy
DDI
ergots
ergots with P450 3A4 inhibitors
ergots with macrolide antibiotics
Headache pharmacotherapy
DDI
Triptans
Tripatans with MAO-I (phenylzene)
triptans metabolized by MAO, increase effect
Triptans with ergots
May cause extreme vasoconstriction
Headache pharmacotherapy
DDI
MAO-I
MAO-I and isometheptene
excessive release of catecholamine
MAO-I and antidepressants
