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Neuropathology > Headache Pharmacotherapy > Flashcards

Headache Pharmacotherapy Flashcards

1
Q

Headache disorders

epidemiology

A

 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%

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2
Q

Common chars of primary headache disorders

Migraine/tension/cluster

Prevalence/frequency/severity

A

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

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3
Q

Common chars of primary headache disorders

Migraine/tension/cluster

Unilateral/duration/pain type/assoc sx

A 
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)
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4
Q

Chronic daily headache

A

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)

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5
Q

Mechanisms of headache

Vascular hypothesis

A

HA due to alteration in blood flow

HA due to compensatory vasodilation

Many effective drugs dont effect bld vessels

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6
Q

Mechanisms of headache

Neurovascular hypothesis

A

Implicates trigeminovascular system

complex interaction between trigeminal nerve and the cranial blood vessels

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7
Q

Mechanisms of headache pain

Trigeminovascular system

A

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

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8
Q

Principles of headache pharmacotherapy

Acute therapy

A

Used during individual attacks to treat the intensity of pain and its associated symptoms

Treat early in the attack!

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9
Q

Headache pharmacotherapy

Prophylactic therapy

A

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)

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10
Q

Migraine therapy

Tx

A 
1st line:
Triptans
NSAIDs or acetaminophen may be helpful in mild cases
Alternatives:
Ergot alkaloids
Antiemetics in combination
Opioid analgesics
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11
Q

Migraine therapy

prophylaxis

A 
Prophylaxis
1st line:
β-blockers or topiramate
Alternatives:
Anti-depressants
Verapamil
Valproic acid
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12
Q

Tension-type therapy

Tx

A 
Treatment
1st line:
NSAIDs or acetaminophen 
Alternatives:
Butalbital + caffeine
Opioid analgesics
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13
Q

Tension-type therapy

prophylaxis

A

Prophylaxis
1st line:
Amitryptiline

Alternatives:
- migraine prophylaxis

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14
Q

Cluster type therapy

Tx

A 
Treatment
1st line:
oxygen
Alternatives:
Triptans
Ergot alkaloids
Steroids
Topical anesthetics
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15
Q

Cluster type therapy

prophylaxis

A

Prophylaxis
1st line:
Prednisone or verapamil or lithium

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16
Q

Menstrual migraine

chars

A

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

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17
Q

Menstrual migraine

tx

A

Standard therapy

“mini” prophylaxis- NSAIDS or triptans just prior to menses

Extended estrogen or low-dose estrogen

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18
Q

Pregnancy risk for headache medications

Simple analgesics

Risk factor/comments

A

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

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19
Q

Pregnancy risk for headache medications

NSAIDS

Risk factor/comments

A

Med
Risk Factor
Comments

NSAIDs
B/D
NSAIDs risk factor D if used in 3rd trimester or near delivery

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20
Q

Pregnancy risk for headache medications

Opioid analgesics

Risk factor/comments

A

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

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21
Q

Pregnancy risk for headache medications

Serotonin Agonists

Risk factor/comments

A

Med
Risk Factor
Comments

Serotonin agonists:

Ergot Alkaloids
Triptans

X
C

All ergot derivatives are contraindicated

22
Q

Pregnancy risk for headache medications

Antiemetics

Risk factor/comments

A

Med
Risk Factor
Comments

Antiemetics:
Metoclopramide
Prochlorperazine

B
C

None

23
Q

Medication misuse headache

Gen chars

A

Perpetuation of head pain in headache sufferers

Due to irresistible urge of pts to overuse drugs

24
Q

Medication misuse headache

Clinical features

A

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

25
Q

Agents used for acute tx

list
Ergot alkaloids

A 

 Ergotamine tartarate (Egomar®)
 Ergotamine + caffeine (Cafergot®, Wigrane®) 
 Available in PO, SL, PR forms
 DHE 45® (Dihydroergotamine IV) 
 Migranal® nasal spray (DHE + caffeine)
26
Q

Ergot alkaloids

chars

A

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)

27
Q

Ergot alkaloids

Adverse events

A

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)

28
Q

Ergot Alkaloids

contraindications

A 
Peripheral vascular disease
hepatic impairment
renal impairment
coronary artery disease
pregnancy
concomitant triptan use
29
Q

Triptans

MOA/clinical use

A

Active selectively at 5HT-1B and 1D subtypes unlike ergots (less nausea)

Are effective in both migraine as well as cluster headache

30
Q

Sumatriptan

Adverse effects

A 
Typically well tolerated 
Most severe adverse events are coronary vasospasm, MI, arrhythmias, stroke 
“Triptan” symptoms 
chest tightness, tingling, numbness 
neurologic- drowsiness, lethargy
31
Q

See if you need to know the chars of the various triptans

A

Pg. 427

32
Q

Triptans

Contraindications

A

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

33
Q

Headache therapies

Agents used for acute tx

acetaminophen

A

Safest of all treatments

Used in combination therapies (Midrin®)

Major concern is rebound in combinations

34
Q

Headache therapies

Agents used for acute tx

NSAIDs/ASA

A

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

35
Q

Headache therapies

Agents used for acute tx

Caffeine

A

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

36
Q

“Caffeinism”

A

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

37
Q

Headache therapies

Agents used for acute tx

Isometheptene combination

A

Midrin (isometheptene + dichloralphenazone + acetaminophen)

Isometheptene resembles epinephrine

Dichloralphenazone is a sedative

Side effects are numbness/dizziness

38
Q

Headache therapies

Agents used for acute tx

Dopamine antagonists

A

Metoclopramide - drug of choice for nausea in migraine

often given in combination to increase gut motility

Prochlorperazine
Chlorpromazine

39
Q

Headache therapies

Agents used for acute tx

Opioid analgesics

A

IV MSO4, butorphanol, codeine combinations

Role in migraine controversial

have few effects on fundamental pathogenesis

habituation/ rebound headaches

40
Q

Headache therapies

Agents used for acute prophylaxis

list

A 
TCA
Beta-blockers
Verapamil
Valproic acid
Topiramate
Lithium
Botulinum toxin
41
Q

Headache therapies

Agents used for acute prophylaxis

TCA

A

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

42
Q

Headache therapies

Agents used for acute prophylaxis

Beta blockers

A

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

43
Q

Headache therapies

Agents used for acute prophylaxis

verapamil

A

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

44
Q

Headache therapies

Agents used for acute prophylaxis

Valproic acid

A

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

45
Q

Headache therapies

Agents used for acute prophylaxis

Topirimate

A

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

46
Q

Headache therapies

Agents used for acute prophylaxis

Lithium

A

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

47
Q

Headache therapies

Agents used for acute prophylaxis

Botulinum toxin

A

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

48
Q

Headache pharmacotherapy

DDI

ergots

A

ergots with P450 3A4 inhibitors

ergots with macrolide antibiotics

49
Q

Headache pharmacotherapy

DDI

Triptans

A

Tripatans with MAO-I (phenylzene)
triptans metabolized by MAO, increase effect

Triptans with ergots
May cause extreme vasoconstriction

50
Q

Headache pharmacotherapy

DDI

MAO-I

A

MAO-I and isometheptene
excessive release of catecholamine

MAO-I and antidepressants

Neuropathology (29 decks)

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