Migraine%20Lecture%202002

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Migraine Lecture2002

• Jin-Hyeun Huh
• Pharmacy Practice Leader
• TWH, UHN

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What are the patients current and / or likely
(potential) undesirable signs and symptoms?

• working 16-18 hours per day
• drinking 6-8 cups of coffee daily
• skipping meals and eating poorly.
• Minimal to no relief with aspirin, ibuprofen
  and even OTC acetaminophen with codeine over the
  last few months
• gave up taking these medications two days ago
• the attacks come on suddenly without warning
• a terrible throbbing on one side of her head.
• The headaches are often accompanied by severe
  nausea and commonly vomiting.
• some relief by taking frequent breaks and going
  to lie down with the lights off.
• E.T. has been having at least two headaches per
  week with one occurrence lasting over twelve
  hours resolving with sleep. She had her last
  headache three days ago

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Urgency

• Quality of Life issue
• Prognosis
• Stroke
• Higher risk with migraine with Aura Higher
  risk with hemiplegic migraine
• Epilepsy
• prolonged or chronic headache
• Psychological disorders ( depression, etc.)

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Migraine Disability Assessment Scale (MIDAS)
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Are the patients signs and symptoms caused by a
drug?If so, how is it related to drug therapy?

• Triggers
• Vasodilators
• rebound analgesic HA

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Medication Induced Headache

• Drugs implicated
• ASA , NSAIDS, Opiods, acetaminophen,triptans
• Clinical Presentation/Hallmarks
• daily HA , sometimes throbbing
• Frequent use of analgesics
• Treatment
• Remove offending agents
• Provide effective acute treatment
• Consider prophylaxis

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Are the patients signs and symptoms suggestive
of a disease process?

• Differential diagnosis

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  Are the patients signs and symptoms suggestive
of a disease process?

• hypoglycemia
• Hypertension emergency
• Ischemic stroke
• Subarachnoid hemorrhage
• meningitis
• head trauma

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Risk Factors Migraine

• Age
• Peak ages ? adolescence or in the 20s
• By age 50 ? Most migrainers report complete
  remission
• New onset ? unlikely after 40
• Sex
• Females ?70-75 overall are female
• Prior to puberty incidence is equal
• Family Hx
• 70 of patients have relatives with Headache
  history

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Triggers

• Stress
• Emotion
• Glare
• Hypoglycemia
• Altered Sleep Pattern
• Menses
• Exercise
• Alcohol
• Excess caffeine /withdrawal

• Foods containing
• MSG
• tyramine
• nitrates
• phenylethylamine
• aspartame
• Drugs
• Estrogen (eg. OC)
• Nitroglycerin
• Excess analgesic use or withdrawal

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History of HA what questions would you ask?
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History Profile of HA

• time from onset to peak
• usual time of onset (week , month, season, hour
  of day)
• frequency duration
• change over lifetime
• description pulsating, pressing, sharp
• location unilateral or bilateral or changing

• severity
• precipitating factors
• Aggravating factors
• factors that relieve the headache
• effectiveness of pharmacological or
  non-pharmacological treatments
• Aura

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Definition of Migraine

• Migraine
• recurring headache disorder manifesting in
  attacks lasting 4-72 hrs. Typical
  characteristics unilateral (sometimes bilateral)
  location, pulsating quality, mod or severe
  intensity, aggravation by routine physical
  intensity, and association with nausea, photo-
  and phono- phobia.

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Classification

• 2 major types
• Classic migraine with aura
• Common migraine without aura
• Other less common
• Hemiplegic
• Status Migrainosus
• Menstrual

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Diagnosis Migraine without Aura

• Number of attacks
• Associated symptoms

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Diagnosis Migraine without Aura

• 5 attacks each lasting 4- 72 hrs
• each attack to be accompanied by one of the
  following
• nausea or vomiting
• phonophobia
• photophobia
• 2 of the 4 pain characteristics
• unilateral location
• pulsating quality
• moderate to severe intensity
• aggravation by physical activity

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DiagnosisMigraine with aura

• Number of attacks
• Associated symptoms

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DiagnosisMigraine with aura

• At least 2 attacks
• Include any 3 of the following
• one or more fully reversible aura symptoms
• aura developing over more than 4 minutes
• aura lasting less than 60 minutes
• headache following aura with a free interval of
  less than 60 minutes

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Pathophysiology3 Systems

• Sympathetic
• NE
• Parasympathetic
• NO , VIP
• Trigeminal
• CRGP

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PathophysiologyTriggers
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Response to Vasoconstriction
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Treatment Strategies Goals

• Acute Treatment (Abortive)
• Prophylaxis

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Treatment Strategies Goals

• Acute Treatment
• decrease duration of attack
• Prophylaxis
• decrease severity, duration and frequency
• Based on severity frequency of migraine attacks

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Non-pharmacological methods

• Effective gt 50
• Diet, education re triggers,relaxation
• Moderately effective 30-50
• Stop smoking, exercise, riboflavin
• Ineffective lt30
• Avoiding tyramine, aspartame,chocolate
• Magnesium, feverfew

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Drug related problems

• MH is suffering from migraine and requires
  effective acute therapy .
• MH may be experiencing headache due to analgesic
  overuse and requires effective acute therapy.

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Treatment StrategiesAcute Treatment

• Analgesics Acetaminophen, NSAIDS
• Analgesics with barbiturates
• Analgesics with OPIODS
• ergotamine derivatives
• triptans or 5-HT1 agonists
• neuroleptics
• antiemetics
• Misc. (divalprolex, lidocaine, magnesium, NOSI,
  propofol)

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Treatment Factors influencing efficacy

• Severity of migraine
• Time to onset
• Efficacy
• Duration of effect/headache recurrence
• Side effects

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Acetaminophen

• Severity of migraine mild
• Time to onset 1-2 hrs
• Effiacy 1st line agent
• Duration of effect/ headache recurrence
• 2-3 hrs
• with increasing frequency of use ,
  effectiveness may decrease
• Side effects
• well tolerated
• liver problems gt 4g daily

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NSAIDS

• Severity of migraine mild
• Time to onset depends on agents 1-2 hrs
• Efficacy partial
• Duration of effect/ headache recurrence
• depends on agents
• with increasing frequency of use ,
  effectiveness may decrease
• Side Effects
• GI bleeding
• renal dysfunction

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Ergotamine derivatives

• Severity of migraine severe
• Time to onset IN, SC, PO, IV, IM
• 15 min -2 hrs
• Efficacy 50-70
• Duration of effect/ headache recurrence
• 4 hrs
• 2-3 hrs
• Side effects
• N V -incr BP
  -incr. MI, stroke

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1st generation 5-HT1 agonistSumatriptan

• Severity of migraine Severe
• Time to onset 10 min -60 min
• 
  IN/SC PO
• Efficacy 70- 80
• Duration of effect/ headache recurrence
• 2 hrs
• 40-50
• Side effects
• N V - chest tightness
• dizziness

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Sumatriptan (Imitrex)

• Dosage forms PO, IN, SC
• pharmacokinetic
• T ½ 2 hr
• Onset 10
  min 1hr
• Metabolism MAO
• Pharmacodynamic
• Efficacy at 2 hrs
• Pain free 22-32
  25-100mg
• Sustained effect 17-20 25-100mg

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Assessment of 2nd generation triptans

• Dosage forms bioavailability
• Pharmacokinetic
• T ½
• Onset
• Metabolism
• Pharmacodynamic
• Efficacy at 2 hrs

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Rizatriptan (Maxalt)

• Dosage forms
• pharmacokinetic
• T ½
• Onset
• Metabolism
• Pharmacodynamic
• Efficacy at 2 hrs
• Pain free
• Sustained effect

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Rizatriptan (Maxalt)

• Dosage forms Po tablets , wafers
• pharmacokinetic
• T ½ 2 hrs
• Onset (peak) 1 hr
• Metabolism MAO
• Pharmacodynamic
• Efficacy at 2 hrs
• Pain free 30-40 5-10 mg
• Sustained effect 19-25 5-10 mg

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Zolmitriptan (Zomig, -Rapimelt)

• Dosage forms
• pharmacokinetic
• T ½
• Onset
• Metabolism
• Pharmacodynamic
• Efficacy at 2 hrs
• Pain free
• Sustained effect

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Zolmitriptan (Zomig,
-Rapimelt)

• Dosage forms Po tablets ,
• pharmacokinetic
• T ½ 3 hrs
• Onset (peak) 4 hr
• Metabolism
  MAO/CYP450
• Pharmacodynamic
• Efficacy at 2 hrs
• Pain free 30-32 2.5-5 mg
• Sustained effect 20-22 2.5-5 mg

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Naratriptan (Amerge)

• Dosage forms ,
• pharmacokinetic
• T ½
• Onset (peak)
• Metabolism
• Pharmacodynamic
• Efficacy at 2 hrs
• Pain free
• Sustained effect

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Naratriptan (Amerge)

• Dosage forms Po tablets ,
• pharmacokinetic
• T ½ 5-6.3
  hrs
• Onset (peak) 2-3 hr
• Metabolism renal
  70
• 
  CYP450
• Pharmacodynamic
• Efficacy at 2 hrs
• Pain free 20 2.5 mg
• Sustained effect 15 2.5 mg

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Triptans comparison
N Engl J Med,Vol.346,N .4 January 24,2002
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Triptans comparison
N Engl J Med,Vol.346,N .4 January 24,2002
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Triptans comparison
N Engl J Med,Vol.346,N .4 January 24,2002
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Triptans comparison
N Engl J Med,Vol.346,N .4 January 24,2002
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Triptans Side Effects
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Common Reasons for Prophylactic Treatment failure

• Analgesic or ergot overuse
• Inadequate trial duration
• 8 weeks at effective doses
• Inadequate trial of non-pharmacological regimens
• DI interactions
• Inaccurate diagnosis

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Criteria for Migraine Prophylaxis

• 2-3 attacks/month
• duration of attack is greater than 48 hrs
• extreme severity
• inadequate relief / side effects with acute
  medication
• migraine attacks occur after a prolonged aura

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Treatment StrategiesProphylaxis

• Beta-blockers
• Antidepressants
• Calcium channel blockers
• Anti-convulsants
• Serotonin antagonists
• Natural products
• Newer treatments ( BOTOX)

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Prophylaxis

• Beta blockers
• dose/frequency
• efficacy
• side effects
• Calcium channel blockers
• dose/frequency
• efficacy
• side effects

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Prophylaxis

• Antidepressants (TCA)
• dose/frequency
• efficacy
• side effects
• valproate
• dose/frequency
• efficacy
• side effects

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Prophylaxis

• Natural products
• feverfew
• magnesium
• vitamin B
• Newer treatments
• Botox

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Outcomes

• Clinical Outcomes
• Improve quality of life
• Decrease frequency of migraine attacks
• Decrease severity of attacks
• Pharmacotherapeutic Outcomes

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Pharmacotherapeutic Endpoint
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Therapeutic Plan

• Acute treatment /Prophylaxis ?
• Acute therapy
• Which triptan ? Why ?
• Route of triptan ?
• Dose of triptan ?
• Time frame to assess efficacy
• Cafergot

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Therapeutic Plan

• Prophylaxis
• Which agent? Why ?
• BB propanolol, metoprolol,atenolol
• TCA amitriptyline
• Metoprolol prn

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Monitoring Plan

• Side effects of medication
• Oral contraceptives