Transcript Migraine
Drugs used in Migraine Dr.B.V.Venkataraman Professor in Pharmacology Faculti Perubatan, Shah Alam, Malaysia- 40450 [email protected] Ph:603-5544-2849/0163630196 What is a migraine? A migraine is a throbbing, intense headache in one half of the head. Affect people of all ages. Associated with anorexia, nausea and vomiting Dilatation of cranial blood vessels causes the pain. Migraine Triggers Food Changes in wake-sleep pattern Hormonal changes (e.g.menopause) Drugs Physical exertion Stress Sensory stimuli Environmental changes Hunger Psychological factors Phases of Acute Migraine PRODROME AURA HEADACHE POSTDROME PRODROME Vague premonitory symptoms that begin from 12 to 36 hours before the aura and headache Symptoms include Yawning Excitation Depression Lethargy Craving or distaste for various foods Duration – 15 to 20 min AURA (absent in some people) Aura is a warning or signal before onset of headache Symptoms Flashing of lights Zigzag lines Difficulty in focussing Duration : 15-30 min HEADACHE Headache is generally unilateral and is associated with symptoms like: Anorexia Nausea Vomiting Photophobia (fear of light) Phonophobia (fear of sound) Tinnitus Duration is 4-72 hrs POSTDROME (RESOLUTION PHASE) Following headache, patient complains of Fatigue Depression Severe exhaustion Some patients feel unusually fresh Duration: Few hours or up to 2 days MIGRAINE – CLASSIFICATION According to Headache Classification Committee of the International Headache Society, Migraine has been classified as: Migraine without aura (common migraine) Migraine with aura (classic migraine) Complicated migraine MIGRAINE: CLINICAL FEATURES Migraine Without Aura Migraine With Aura No aura or Prodrome Aura or prodrome is present Unilateral throbbing headache Unilateral throbbing headache may be accompanied by and later becomes nausea and vomiting generalised During headache, patient complains of phonophobia and photophobia Patient complains of visual disturbances and may have mood variations MIGRAINE - PATHOPHYSIOLOGY VASCULAR THEORY Intracerebral blood vessel vasoconstriction – aura Intracranial/Extracranial blood vessel vasodilation – headache Vascular Theory MIGRAINE - PATHOPHYSIOLOGY Serotonin Theory Decreased serotonin levels linked to migraine Specific serotonin receptors found in blood vessels of brain Present Understanding Neurovascular process, in which neural events result in activation of blood vessels, which in turn results in pain and further nerve activation Arterial Activation Release of Neurotransmitter Worsening of Pain calcitonin gene-related peptide /Nitric oxide MIGRAINE MANAGEMENT Non-pharmacological treatment Identification of triggers Meditation Relaxation training Psychotherapy Pharmacotherapy non-specific Abortive therapy specific Preventive therapy MIGRAINE: ABORTIVE THERAPY Non-specific treatment Drug Dose Route Aspirin 500-650 mg Oral Paracetamol 500 mg-4 g Oral Ibuprofen 200- 300 mg Oral Diclofenac 50-100 mg Oral/IM Naproxen 500-750 mg Oral NSAIDs Relieve mild migraines Inhibition of PG Chronic use leads to ulcers, gastrointestinal bleeding and rebound headaches. ABORTIVE THERAPY FOR MIGRAINE Specific treatment Drug Dose Route Ergot alkaloids Ergotamine 1-2 mg/d; max-6 g/d Dihydroergotamine 0.75-1 mg Oral SC 5-HT receptor agonists Sumatriptan 25-300 mg 6 mg Orally SC nasal Rizatriptan 10 mg Orally ERGOTS Ergotamine alkaloid from the fungus, claviceps purpurae Non-selective 5HT agonist & alpha blocker Constriction of cranial arteries Caffeine added to increase the absorption from GIT Nausea, vomiting, diarrhoea – common side effect Dihydroergotamine – more effective with lesser side effect – also available as nasal drops TRIPTANS Severe attack Relieve pain, nausea, phonophobia, photophobia that are associated with attack 5-HT1B (blood vessels) and 5-HT1D (trigeminal) receptors agonist Sumatriptan: nasal, sc preparation avoid Gastric irritation rizatriptan, naratriptan, zolmitriptan, almotriptan, frovatriptan, eletriptan Side effects: nausea, dizziness, muscle weakness. Coronary vasoconstriction, heart attack and rarely stroke ANTI-NAUSEANT DRUGS FOR MIGRAINE TREATMENT Drug Dose (mg)/d Route Domperidone 10-80 mg Oral Metoclopramide 5-10 mg Oral/IV Promethazine 50-125 mg Oral/IM Chlorpromazine 10-25 mg Oral/IV Anti-nausea medications Attacks usually accompanied by nausea, vomiting Medication for these symptoms appropriate combined with other medication WHY THE NEED FOR PROPHYLAXIS ? Abortive drugs should not be used more than 2-3 times a week Long-term prophylaxis improves quality of life by reducing frequency and severity of attacks 80% of migraineurs may require prophylaxis PREVENTIVE THERAPY FOR MIGRAINE Drugs 1. Betablockers – Propranolol 2. Calcium Channel Blockers – Flunarizine – Verapamil 3. 40-320 10-20 120-480 TCAs – Amitriptyline 4. Dose (mg/d) 10-20 SSRIs – Fluoxetine 20-60 PROPRANOLOL – MECHANISMS OF ACTION Mechanisms proposed Vasoconstriction Anxiolytic action Decrease sympathetic activity CALCIUM CHANNEL BLOCKERS Flunarizine, Verapamil Vasodilatation due to calcium channel blocking Common side effects: constipation and postural hypotension. ANTI DEPRESSANTS Tricyclic antidepressants: effective Amitriptyline, nortriptyline, protriptyline: commonly used All types of headache including migraine Patient need not have depression PREVENTIVE THERAPY FOR MIGRAINE (CONTD.) Drugs 5. Anti-convulsant – Sodium valproate 6. Anti-histaminic – Cyproheptadine Dose (mg/d) 600-1200 4-8 ANTI SEIZURE DRUGS Drugs with dual property (anti-seizure and bipolar depression): useful 5HT Antagonist Cyproheptadine: antihistaminic, Calcium antagonist Methysergide: rarely used because of risk of retroperitoneal fibrosis and renal failure. Anti-hypertensive Clonidine: Alpha-2 agonist Botulinum toxin type A Used in wrinkles