Download Dear Parents of A Smith, Your child currently has a final 9

Drugs for Headache Disorders
I. Classification of Headache
A. Primary headache disorders
a. Cluster- No aura, are recurring (can use tryptans)
b. Migraine- associated with nausea, vomiting, diarrhea, and vertigo
c. Tension- episodic; may be stress related, can be exacerbated by
fatigue, noise, or glare
i. Most common type of recurring headache
B. Secondary headache disorders- management focuses on underlying disorder
a. Arise from other disorders
i. Hemorrhage
ii. Infection
iii. Neuropathy
iv. Stroke
v. Tumor
II. Pathogenesis of Migraine Headaches
A. Neurovascular dysfunction
a. Imbalance of excitatory and inhibitory neurotransmitter activity in
CNS
i. Serotonin is the primary neurotransmitter for migraine
ii. Norepinephrine and dopamine can also be considered
iii. Trigeminal nerve is anatomical epicenter
b. The imbalance may be triggered by
i. Hormones- estrogen, hormone replacement therapy,
menstruation, ovulation, and oral contraceptives
ii. Stress
iii. Lack of sleep
iv. Food
1. Alcohol(red wine)
2. Aspartame
3. Coffee
4. Nuts
5. Chocolate
6. MSG
7. Nitrites/nitrates
8. Pickled meats
v. Drugs
1. Danazol (Danocrine)
a. Anti-gonadotropic drug- used form
endometriosis, fibrolytic breast disease,
angioedema
2. Oral contraceptives
3. H2 blockers
vi. Sensorial
1. Bright or flickering lights
2. Odors
B. Phases of migraine attack
a. First phase
i. Characterized by cerebral vasoconstriction and ischemia
ii. Release of 5-HT from CNS neurons and circulating platelets
contribute to this phase
1. Use anti-platelet drugs and serotonin antagonists
b. Second phase (longer than first phase)
i. Cerebral vasodilation and pain
1. Trigeminal neurovascular system has central role
2. Neurons in trigeminal complex release peptides,
including substance P and Calcitonin gene-related
peptide (CGRP)
3. Peptides trigger vasodilation and inflammation of dural
vessels- stimulates nociceptive fibers of trigeminal
nerve- pain
c. AURA of migraine headaches- result of vasoconstriction and ischemia
i. Occur in 15% of patients- lasts 15-20 minutes
ii. May be visual or sensory
iii. Migraine without aura- aka common headache- may be
accompanied by photophobia, nausea and vomiting
III. General approach to treatment of migraines
A. Goals of long term migraine treatment (prophylaxis)
a. Reduce frequency, severity, and disability of migraine
b. Reduce reliance on poorly tolerated medications
c. Improve quality of life (QOL)
d. Avoid increased headache medication use
e. Educate patients to manage their disease
f. Select medication based on side-effect profile and patient’s underlying
disease states Medication should be used for at least 2-3 months to
assess efficacy
B. Goals of acute/abortive migraine treatment
a. Treat migraine attacks rapidly and consistently without recurrence
b. Restore the patients ability to function
c. Minimize the use of backup and rescue medications
d. Optimize self-care for overall management
e. Be cost effective in overall management
f. Cause minimal or no adverse effects
IV. Drugs for Migraine Headaches
A. Prophylactic drugs
a. Anticonvulsants
b. Antidepressants
c. NSAIDS
d. Beta blockers and calcium channel blockers
e. 5-HT2 receptor blockers
i. Serotonin receptors are widely distributed in CNS, smooth
muscles, and platelets to mediate platelet aggregation
ii. 5-HT2 blockers prevent vasoconstriction
B. Abortive (symptomatic drugs)- reverse vasodilative phase and
pain/inflammation
a. Dihydroergotamine and ergotamine
b. 5-HT 1d/1b receptor agonist (triptans)
i. Predominant 5-HT receptor in CNS, presynaptic autoreceptor
to prevent release of 5-HT
ii. Mediates cerebral vasoconstriction
c. Miscellaneous- NSAIDS, corticosteroids, narcotic analgesics
V. Prophylactic drugs to prevent migraine
A. Anticonvulsants
a. Onset 2-3 weeks
b. ADRs- weight gain, sedation, and tremor
c. Examples
i. Divalproex Na (Depakote, Depakote ER) - most common
epileptic drug used for migraine
ii. Topiramate (Topamax) - just FDA approved
C. Antidepressants
a. Onset of efficacy is 3-4 weeks
b. MOA for prevention of migraine no fully understood- may stabilize
seroternergic neurotransmission by anatagonizing down regulation of
5-HT2 receptors
c. Examples
i. Selective serotonin reuptake inhibitors (SSRI) (Prozac and
others)
1. More efficacious with migraines associated with
depression- increases serotonin levels
2. May increase phase 1 effects
3. ADR- anxiety, GI effects, Sexual dysfunction
ii. Tricyclic antidepressants (TCA)
1. ADRs- drowsiness, tremor and anticholinergic side
effects
2. Amitriptyline (Elavil)- most common drug in this class
iii. Monoamine oxidase inhibitors (MAO inhibitors)
1. ADRs- hypertensive crisis with tyramine containing
foods, sympathomimetic amine drugs
D. NSAIDS
a. MOA- inhibit thromboxane synthesis and platelet aggregation- reduce
release of serotonin
b. Can also be used for the treatment of migraines
c. Examples
i. Aspirin, naproxen, ibuprofen, diclofenac
ii. ADRs- GI effects, bleeding, Na and H2O retention, antagonize
antihypertensive effects
E. Beta Blockers
a. Must be without ISA (intrinsic sympathomimetic activity) activity
(timolol, Propanolol)
b. MOA- may block beta 2 mediated vasodilation and reduce platelet
aggregation (uncertain)
F. Calcium channel blockers
a. Less effective than other prophylactic migraine drugs
b. Verapimil primarily used
G. 5-HT2 receptor antagonists
a. Methysergide (Sansert) (X)- ergot alkaloid
i. MOA- blocks 5-HT2 receptor- prevents vasoconstrictive phase
of migraine
ii. Associated with several potentially life threatening ADRsretroperitoneal, pleural and cardiac valve fibrosis
iii. Rarely used, limit to 6 months of use, monitor serum creatinine
and chest x-ray
H. Miscellaneous agents
a. Feverfew- herbal preparation. Contraindicated in pregnancy
i. Inhibit prostaglandin and leukotriene migration
b. Magnesium
c. Riboflavin
VI. Abortive drugs to treat migraines
A. Dihydroergotamine (DHE) and ergotamine- both pregnancy category X
a. Used for migraine and cluster headaches
b. Ergot alkaloids- derived from fungus that grows on rye
c. MOA- activate serotonin 5-HT1d/1b receptors in trigeminal
neurovascular system- produces vasoconstriction- reverses
vasodilation and reduces throbbing. Also inhibits release of peptides
that cause vasodilation, inflammation, and pain. Also prevents
activation of trigeminal nerves involved in migraine
d. Contraindicated in CAD, PVD, uncontrolled HTN, and in patients
using MAO inhibitors
e. Must follow strict dosing guidelines and maximum dosing
recommendations
f. ADRs- N,V,D muscle cramps,. More serious- severe cerebral
vasoconstriction, ischemia, rebound vasodilation and headache
g. Ergotamine
i. PO, SC, PR
ii. Combined with caffeine (Cafergot)
1. Increases absorption
h. DHE
i. Intranasal, INJ
ii. INJ often combined with Metoclopramide to prevent N/V
B. 5-HT 1d/1b receptor agonists (triptans) (C)
a. Structural analogs of 5-HT
b. MOA- similar to ergotamine and DHE
c. Sumatriptan (Imitrex) (SC, PO, nasal_
i. Newer version has rapid release and is used to compete with
newer triptans
d. Newer triptans- Zolmitriptan (Zomig), Rizatriptan (Maxalt)
i. More lipophilic with increased bioavailability
ii. May be more effective than Imitrex with less recurrence of
headaches
iii. Examples
1. Almotriptan (Axert)
2. Eletriptan (Replax)
3. Frovatriptan (Frova)
4. Naratriptan (Amerge)
5. Rizatriptan (Maxalt)
6. Zolmitriptan (Zomig)
e. Contraindicated in CAD, PVD, uncontrolled HTN, and in patients
using MAO inhibitors
f. All have specific dosing recommendations with maximum doses
g. ADRs- chest tightness, weakness, dizziness, paresthesias, nausea
i. More serious- coronary vasospasm
h. Use injections during morning migraines, vomiting, or unable to take
PO
C. Miscellaneous agents
a. Non-narcotic analgesics: First line for abortive treatment
i. Acetaminophen and aspirin; also combine with caffeine in
OTC products like Excedrin
ii. NSAIDS
1. Ketorlac IM (Toradol)
a. Very effective
b. Limit use < 5 days due to ADRs (GI bleeding,
renal effects)
iii. Narcotic analgesics
1. Opiods effective to relieve pain. Less commonly used.
2. Pregnancy C/D
3. Good for acute migraine when sedation will not put
patient at risk
4. Examples
a. Butorphanol nasal spray (Stadol NS)
b. Hydrocodone/ APAP (Vicodin)
5. Barbituate hypnotics
a. Pregnancy Category D
b. Avoid due to overuse and misuse. Max daily
dose = 6 doses per day
c. Examples
i. Butalbital/APAP/Caffeine (Fioricet)
ii. Butalbital/ASA/Caffeine (Fiorinal) C2
6. Steroids
a. Good for status migrainosus
b. Most common is dexamethasone IM
7. Isometheptene
a. Works like sympathomimetic to treat migraine
b. Available as combo product with APAP and
mild sedative dichlorphenazone (Midrin)
c. Good for mild-moderate headaches
VII. Treatment of tension and cluster headaches
A. Tension headaches
a. Prophylaxis: TCA antidepressants
b. Abortive: NSAIDS
B. Cluster headaches- similar to migraine treatment
a. Prophylaxis: CCBs, ergots, steroids
b. Abortive: triptans, ergots, oxygen