Headaches Flashcards
1) distinguish between the three most common types of primary headache diagnoses based on pathophysiology, epidemiology, and clinical signs and symptoms 2) Identify potentially life threatening headaches based on clinical warning signs or symptoms 3) Compare and contrast the mechanism of action, pharmacokinetics and side effects of triptans (e.g., sumitriptan), ergot alkaloids (e.g., dihydroergotamine [DHE]) with respect to the treatment of migraine headache and 4) Describe the role of serot
Tension-type Headache Epidemiology
30-80% prevalence Episodic < 180/year Chronic > 180/year Onset < age 40 More common in women Increased prevalence with increased educational attainment
Tension Headache Pathophysiology
Muscle contraction
Greater occipital nerve compression
Exacerbated by emotional stress
Tension Headache Clinical Presentation
30 min – 1 week Pressing/tightening Mild to moderate intensity Bilateral Not aggravated by routine physical activity No nausea or vomiting! Phono or photophobia, but not both
Tension Headache Management
Often self-treated Analgesics (ibu, asa, apap) Acupuncture Biofeeback Relaxation technique Other modalities
Cluster Headache Epidemiology
Male:female 4:1
Mean onset age 27-31
Incidence 2.5/100,000/year
Prevalence ~ 1/1000
Cluster Headache Pathophysiology
Incompletely understood Hypothalamic activation of trigeminovascular autonomic system Genetics Positive FH in 7-11% R>L shunt/PFO? short duration: 15 min to 2 hrs
Cluster Headache Clinical Presentation
Severe, unilateral, orbital, supraorbital or temporal pain lasting 15-180 minutes
Circadian periodicity
Frequency: every other day to 8/day
Autonomic symptoms:
Lacrimation, nasal congestion, rhinorrhea, forehead sweating, miosis, ptosis, eyelid edema, conjunctival injection
Cluster Headache Management
Oxygen 6-10 L/min for 15 min Sumatriptan subQ/nasal Zolmitriptan nasal Prophylaxis of episodic clusters Verapamil, melatonin, prednisone, capsaicin oral takes too long to be absorbed
Migraine Headache Epidemiology
Female:male 3:1 Onset age < 40 Prevalence 18% women, 6% men Lifetime prevalence 20 – 25% >50% people with migraines miss > 2 days of work/month
Migraine Headache Pathophysiology
Uncertain Possible spreading cortical depression Possible neurotransmitter dysfunction NO or CGRP Possible dorsal pontine activation
Migraine Headache Clinical Presentation
Typical symptoms – intermittent, unilateral, throbbing, crescendo-decrescendo headache lasting hours to days, gradual onset, associated with nausea; + family history helpful
Aura +/-
Migraine Headache Genetics
Positive family history common
Familial hemiplegic migraine
1/5 have associated nystagmus or ataxia
CACNA1A gene (neuronal ca++ channel)
Migraine Headache medication hx
Avoid OCPs in migraine with aura
Avoid Sildenafil?
There is an increased risk of stroke in patients who have migraine with aura, this risk is increased with the use of estrogen containing oral contraceptives. In my practice, if a woman has migraine with aura, I will not prescribe estrogen-containing birth control methods and instead recommend IUDs or barrier methods.Obstet
Migraine Headache1st line Treatment for Attacks
Triptans DHE Perchlorperazine, metoclopramide Apap, ibu, naproxen Dexamethasone
Migraine Prevention
Prevent MOH
Refractory HA
Predictable HA
Hemiplegic or Basilar Migraine
While triptans and DHE are effective for relieving an acute attack, they are less helpful in preventing attacks. Frequent use of over-the-counter analgesics, triptans, and opioids significantly increases the risk for medication overuse headache. MOH is challenging to treat and can be debilitating for patients. In general, if a patient is treating acute migraine more than twice/month it is appropriate to consider use of preventive medications. Prevention is also appropriate for people who have headaches that are not responsive to abortive therapy and for people who have predictable headaches, as in women who get menstrual migraines. Preventive strategies are also appropriate for people who have hemiplegic or basilar migraine, for which triptans are not indicated.
Serotonin
Serotonin or 5-hydroxytryptaine is a centrally acting neurotransmitter with a number of significant peripheral actions as well. It regulates smooth muscle in the GI tract and cardiovascular systems and plays a role in platelet aggregation. There are at least 14 serotonin receptor subtypes that can serve as targets for medications and drugs.
5-HT Synthesis & Metabolism
Serotonin is synthesized from the essential amino acid tryptophan and stored in secretory granules in serotonergic neurons. Activation of those neurons releases serotonin through exocytosis. In the nervous system, the activation of released serotonin is terminated by reuptake into the axon terminal via a specific transporter. This same transporter is responsible for uptake of serotonin into platelets. Serotonin is primarily metabolized by monoamine oxidase and aldehyde dehydrogenase into 5- hydroxyindole acetic acid (5-HIAA). 5HIAA is actively transported out of the brain, by a process that is inhibited by probenecid. The role of MAO in metabolism of 5HT is the reason for the drug interactions between SSRIs and MAO inhibitors.
5-HT in CNS
Sleep-wake cycle regulation, aggression & impulsivity, cognition, sensory perception, motor activity, temperature regulation, nociception, mood, appetite, sexual behavior & hormone secretion.
5-HT in GI Tract
Produced & stored in enterochromaffin cells of gastric mucosa
Released in response to mechanical stretch, eg eating, and vagal stimulation
Metabolized by MOA in liver
Uptake by platelets
5-HT in CV System
Constriction of cerebral vasculature
Constriction of splanchnic, renal & pulmonary vasculature
Role of Serotonin in Migraine
[5-HT] vary in migraine attack
Increased 5-HT levels as trigger
5-HT1 agonists as treatment
While the complete pathophysiology of migraine headache is unknown, there is evidence that serotonin plays a key role. (Mehrotra et al, 2008). Plasma and platelet concentrations of serotonin vary with the different phases of a migraine attack and urinary concentrations of serotonin and its metabolites are elevated during migraine attacks. Medications that release serotonin can precipitate migraine attacks and serotonin receptor agonists are effective in management of acute migraine.
Triptans
Triptans are selective agonists of the 5-HT1b and 5-HT1d receptors and are effective for acute migraine treatment. Triptans help abort the attack, alleviate pain and decrease nausea and vomiting that is common in migraines. Because of our incomplete understanding of the exact cause of migraines, we are not sure exactly how triptans work to relieve symptoms. Triptan-mediated activation of the 1b and 1d serotonin receptors causes vasoconstriction of the cerebral vasculature and activation of the 1b and 1d receptors modulates neurotrasmitter release which may block release of proinflammatory neuropeptides.
Triptans Pharmacokinetics
Triptans are metabolized by MOA in the liver and excreted both as unchanged drug and active and inactive metabolites in the urine and feces. Most triptans have a relatively short half-life of about 1-3 hours, although the half-life of naratriptan approaches 6 hours and the half-life of frovatriptan is 26 hours. Frovatriptan seems to be less effective than other triptans for acute migraine attack to to longer time to peak plasma concentrations.
Triptan Contraindications
Triptans generally constrict vessels and can cause vasospasm. Because of this, they are contraindicated in patients with CAD, including Printzmetal’s angina, hemiplegic or basilar migraines, stroke and ischemic bowel disease.
Triptans can also cause increased blood pressure and are contraindicated in patients with uncontrolled blood pressure.
Triptans should not be used in people who have taken MAO-inhibitors in the past 2 weeks or in patients who have or will take ergots or other triptans within 24 hours. Because of hepatic metabolism, triptans are also contraindicated in people with hepatic impairment.
