Principles of pharmacology in n eurology Presented by:Dr mehran Homam Neurologist & Neurophysiologist Department of neurology Mashhad azad university

Topics 1-Headache 2-Parkinson 3-Multiple Sclerosis 4-Dementia 5-Epilepsy (from Solomon S, Lipton RB. Headache 1991;31(6):384-7.)

1-Headache

Headache A Common Health Problem Headache has troubled humankind from the dawn of civilization Evidence of trepanation, an early form of neurosurgery, was found on skulls from 7000 BC Migraine symptoms,have been described for over 1,000 years

Primary Headaches Benign, recurrent NOT associated with underlying pathology The headache is the disease (from Solomon S, Lipton RB. Headache 1991;31(6):384-7.)

Primary Headaches Migraine (with or without aura) Tension-type headache (episodic or chronic) Cluster headache (from Solomon S, Lipton RB. Headache 1991;31(6):384-7.)

Primary Headache Migraine Tension Cluster

QUESTIONS 1-SEVERITY 2-QUALITY 3-DURATION 4-ASSOCIATED SYMPTOMS & SIGNS 5-PEAK ONSET 6-FREQUENCY 7-AGGREVATING AND RELIEVING 8-LOCATION

Migraine Headaches

Hildegard von Bingen Famous people suffering from migraine Sigmund Freud Ludwig van Beethoven Madame de Pompadour

What is Migraine? Repeated attacks of throbbing headache – Moderately or severely painful – Frequent or infrequent – Last a few hours to a couple of days Often only one side of the head hurts Often experience loss of appetite, nausea, and vomiting;photophobia;phonophobia Periodic familial World Federation of Neurology

1 Migraine originates deep within the brain 2 Electrical impulses spread to other regions of the brain. 3 Changes in nerve cell activity and blood flow may result in visual disturbance, numbness or tingling, and dizziness. 4 Chemicals in the brain cause blood vessel dilation and inflammation of the surrounding tissue 5 The inflammation irritates the trigeminal nerve, resulting in severe or throbbing pain How Migraine Works

Migraine Major Forms: Migraine without aura (common) 70% Migraine with aura (classical) 25% Migraine variants and complicated migraine 5%

How Migraine Stacks Up Against Other Common Diseases From the Centers for Disease Control and Prevention, the US Census Bureau, and the Arthritis Foundation. 1% 5% 6% 7% 12% Rheumatoid arthritis AsthmaDiabetesOsteoarthritisMigraine Affected patientss:

Women Men Age (years) Percentage Stewart WF, Lipton RB, et al. JAMA. 1992;267(1): Migraine Prevalence

The Stages of a Migraine Attack

1.2% 18.4% 47.2% 33.2% Mild Moderately severe Severe Extremely severe Most Patients’ Headaches Are Severe or Extremely Severe National Headache Foundation. American Migraine Study II: Migraine in the United States: Burden of Illness and Patterns of Treatment

52% 39% 9% Need bed rest Can work with some difficulty Can work as normal Migraine Takes Quality Time Out From Your Life National Headache Foundation. American Migraine Study II: Migraine in the United States: Burden of Illness and Patterns of Treatment

Unnecessary Suffering More than half of people with migraine suffer for at least a year before they are diagnosed with migraine 38% suffer for 3 or more years National Headache Foundation. American Migraine Study II: Migraine in the United States: Burden of Illness and Patterns of Treatment

What You Might Experience During an Attack Nausea Vomiting Diarrhea Sweating Cold hands Sensitivity to light Sensitivity to sound Scalp tenderness Pale color Pulsing temple Pressure pain

Triggers and Risk Factors Migraine headaches are often triggered by specific things

Triggers: Changes in Daily Cycles

Triggers: Environment or Diet

Triggers: Mental

Protective Factors Regular sleep Regular meals Regular exercise Biofeedback Healthy lifestyle

Treatment Acute:1-nsaids 2-Ergo 3-Triptans 4-Corton Prophylactic

DHE Dihydroergotamine – Nasal Spray (Migranal ® ) – Injectable (D.H.E. ) - Supp - Tab

Your Symptoms May Affect The Choice of Medication Medication TypeProCon Oral (tablets)Easy to takeWon’t work if you are vomiting Nasal sprayGood for patient with nausea/vomiting, easy to use Fewer choices InjectionWorks fastHarder to use

1-Ergotamines Ergotamine Ergotamine C Mechanism:Ergots 2-advantages:The most effective 3-Contraindications:Htn-Pregnancy-IHD-Raynoud disease 4-Disadventages:Ergotism/limitation of Dosage/age 5-Dosage :6 mg in attack 10mg each week Drug reactions:

2-triptans Triptans need to be taken as soon as you recognize an attack – Most patients wait too long – No need to suffer Triptans work best in the first couple of hours of an attack Mechanism:serotonin agonist Dihydroergotamine works at any time during an attack Available :sumatriptan 50 mg also sc 8mg Dosage; Advantage:faster Effect / Sc injection Disadventage:Relapse/Cost

3-(NSAID)Medicines to Stop a Migraine Attack Mechanism:anti inflammatory Adventages: Very effective.tension headache Disadventages:Side effects medications – use with care and tell your doctor – NSAIDs (eg, ibuprofen, naproxen,indometacin) – Aspirin, acetaminophen, caffeine combination (avoid using more often than twice a week, especially if using several agents or if you drink a lot of coffee, tea, or caffeinated soda)

Options for Preventive Treatment Divalproex sodium/sodium valproate (anticonvulsant) Propranolol (beta-blocker) Timolol (beta-blocker) Methysergide (serotonin antagonist) Other anticonvulsants Other beta-blockers Antidepressants NSAIDs (eg, aspirin) These are medicines you take every day to prevent headaches

Some Medications May Cause Migraine to Become Chronic May cause chronic headaches: Opiates Combination analgesics Caffeine Barbiturate-containing medications Ergotamine tartrate, isometheptene Triptans Others Not clearly associated with chronic headaches: Acetaminophen Aspirin Dihydroergotamine Others

Self Treatment Efforts: What You Can Do For Your Migraines Rest Biofeedback Ice/heat Massage Exercise Avoid triggers Seek treatment early Keep a headache diary Take medications as directed by your doctor Many options are available for migraine relief – ask your doctor what’s right for you

Cluster Headache  Duration  15 to 180 minutes untreated  Pain characteristics  Severe unilateral orbital, supraorbital, or temporal pain  Associated symptoms (at least 1)  Conjunctival injection, Lacrimation  Nasal congestion, Rhinorrhea  Forehead and facial swelling  Miosis  Eyelid Edema  Frequency:  between 1 every other day to 8/day

Treatment of Cluster Headache Acute treatment: – 100% Oxygen via face mask at 8liters/min given in a seated position – SL ergotamine at onset of HA and repeated once if needed – Triptans shown effective in two RCTs – Intranasal administration of a local anesthetic (4% lidocaine) may be helpful

Treatment of Cluster Headache Preventive Treatment – Verapamil 80 mg qid – Lithium mg per day – Prednisone 40 mg per day in divided doses, tapered over 3 weeks – Ergotamine 2 mg 2 hrs before bedtime to prevent nocturnal attacks – Divalproex sodium mg per day

Tension Headache  Duration  30 min to 7 days  Pain characteristics (at least 2)  Pressing/tightening quality  Mild to moderate severity  Bilateral location  No aggravation by routine physical activity  Associate symptoms (Must have both)  No vomiting  No more than one of: nausea, photophobia, phonophobia  H&P and diagnostic tests do not suggest underlying organic disease

Secondary Headache Sudden, progressive Associated with pathology May require immediate action

Patient 45 years old with HTN and migraine once monthly 1-tab;Ergotamine c twice daily 2-tab;valproate Na each night 3-tab:advil; when pain qid