Pharmacotherapy of Migraine - AJ. pptx.

This ppt contains brief explanation about migraine, phases of migraine, classification, triggers, pathophysiology of migraine. Management of migraine - Pharmacological and Nonpharmacological. Prophylaxis of migraine. Recent advances in Migraine treatment

1. Pharmacotherapy of Migraine Presenter: Dr. Anie Jacob (JR-2) Moderator: Dr. Shoebul Haque (SR) Peer support – Dr. Vishal Tiwari (JR-2) Department of Pharmacology and Therapeutics King George’s Medical University, Lucknow, U.P, India e-mail : [email protected]

2. Contents Introduction Pathophysiology Pharmacotherapy Summary References

3. Introduction Primary headache Second most common cause of headache, Female > Male E pisodic headache associated with certain features: nausea, vomiting, phonophobia, photophobia Characteristics of headache: unilateral, throbbing, aggravated by movement, lasting 4-72 hours

4. Phases A migraine attack has three phases P remonitory (prodrome) Headache phase and Postdrome About 20–25% of migraine patients have a fourth ; aura phase

5. Two major types M igraine without aura : common migraine M igraine with aura : classical migraine neurological symptoms, visual aura - most common , sensory symptoms O thers: Chronic migraine, Hemiplegic migraine etc. Classification

6. Pathophysiology Pulsatile dilatation of large cranial vessels Vascular theory & Neurogenic theory Neurogenic dysfunction: primary role Cortical spreading depression, Trigeminal Nerve activation, Neurovascular dysfunction, Serotonin& Dopamine imbalance

7. Management Assess the extent of a patient’s disease and disability Migraine Disability Assessment Score (MIDAS) Nonpharmacological and Pharmacological management

8. Nonpharmacologic management Patient education Identify the triggers Avoid precipitating factors Regulated lifestyle: healthy diet, regular exercise, regular sleep patterns, avoidance of excess caffeine and alcohol, stress management

9. Pharmacotherapy Individualized Severity, frequency of attacks and response of individual patients to drugs used earlier determine the choice Based on the severity- Mild, Moderate and Severe

10. DRUG THERAPY OF MIGRAINE SEVERITY DRUG THERAPY MILD Simple analgesics/ NSAIDS or their combinations / ± antiemetics MODERATE NSAIDS combinations/ a triptan/ergot alkaloids/ +antiemetic SEVERE A triptan/ ergot alkaloids/ +antiemetic + prophylaxis • Propranolol/other blockers • Amitriptyline/other tricyclic antidepressants • Flunarizine/other calcium channel blockers • Valproate/topiramate

11. Drug therapy of migraine S imple analgesics P aracetamol (0.5- 1 g) Aspirin (300-600 mg ) T aken at the first indication of an attack Repeated 4-6 hourly abort and suppress most mild attacks

12. Nonsteroidal antiinflammatory drugs (NSAIDs) Ibuprofen (400- 800 mg) Q8H Naproxen (500 mg followed by 250 mg) Q8H Diclofenac (50 mg) Q8H Mephenamic acid (500 mg) Q8H either alone or combined with paracetamol/codeine/diazepam or another sedative/diphenhydramine or another antihistaminic/caffeine

13. Antiemetics Metoclopramide (10 mg oral/ i.m. ) Relieves nausea, vomiting and gastric stasis Domperidone ( 1 0- 20 mg oral) P rochlorperazine (10-25 mg oral/ i . m .) Diphenhydramine or promethazine

14. Specific antimigraine drugs Ergot Alkaloids Non selective 5-HT receptor agonists MOA- Ergotamine acts by constricting the dilated cranial vessels R educe neurogenic inflammation and leakage of plasma in duramater , mediated through 5HT 1B/1D partial agonism

15. Ergotamine Most effective ergot alkaloid Given early in attack Oral/sublingual route is preferred Parenteral administration- rapid in action, more hazardous Adverse effects – Nausea, vomiting, coronary vasospasm, rebound headache

16. Dihydroergotamine (DHE) P arenteral administration Ergot alkaloids have no prophylactic value and rarely used now except for considerations of cost or when triptans fail Caffeine 100 mg taken with ergotamine E nhances its absorption and adds to the cranial vasoconstricting action

17. 5HT 1B/1D Receptor Agonists Triptans Constrict dilated cranial blood vessels and arteriovenous shunts Decrease vasoactive peptide release by acting on 5-HT 1B/1D receptors on presynaptic nerve endings Decreased pain signal transmission Should be given before the prodrome phase

18. Triptans I nhibiting the release of inflammatory peptides from the nerve endings in the perivascular space, they decrease inflammation P referred drugs for acute attack of migraine All triptans are administered orally Sumatriptan can also be administered by s.c. and nasal routes Riza triptan- more potent, higher oral bioavailability

19. Triptans Adverse Effects- Paraesthesia , tightness in the chest, flushing and dizziness and coronary vasospasm Contraindications- Pregnancy, patients with ischaemic heart disease, and those with peripheral vascular disease, hypertension and risk factor for coronary artery disease

20. Prophylaxis of migraine Reduce the frequency and/or severity of attacks Recommended for moderate-to-severe migraine 2- 3 or more attacks occur per month/ when attacks are disabling despite treatment/ patients with contraindications for triptans/ergotamine Prophylactic regimen- 6 months, d iscontinue after 6 months to check whether its continuation is required

21. β - Adrenergic blockers Propranolol R educes frequency and severity of attacks S tarting dose- 40 mg BD, increased upto 160 mg BD if required. The mechanism of action due to β adrenergic blockade Others- nonselective (timolol) and β 1 selective (metoprolol, atenolol )

22. Tricyclic antidepressants A mitriptyline (25-50 mg HS) r educes migraine attacks The antimigraine effect is independent of antidepressant property Better s uited for patients who concurrently suffer from depression Calcium channel blockers Flunarizine- C erebro - selective Ca2+ channel blocker Verapamil

23. Anticonvulsants T opiramate starting dose -25 mg OD and gradually increase to 50 mg OD or BD V alproic acid ( 400 -1200 mg/day) G abapentin (300- 1200 mg/day) I ndication- refractory to other drugs or when propranolol is contraindicated

24. CGRP antagonist Erenumab F ully human monoclonal antibody R educe number of attacks I njected s.c. once a month in patients with severe migraine US-FDA approved

25. Recent Advances CGRP receptor antagonists: Gepants 5-HT1F receptor agonists : D itans Onabotulinum toxin A: Chronic Migraine Neuromodulation: Single-pulse transcranial magnetic stimulation, external trigeminal nerve stimulators

26. CGRP receptor antagonist - Gepants Rimegepant Inhibits pain transmission, reduces neurogenic inflammation Lacks vasoconstrictor property Orally dissolving tablet Hypersensitivity reactions

27. 5-HT 1F Receptor agonists- Ditans Lasmiditan Highly selective, oral No vascular effects used in patients with cardiovascular and cerebrovascular disease. Major side effect is dizziness and somnolence Patients are advised not to drive for 8 hours after treatment

28. Summary Migraine: neurovascular phenomenon, characterised by unilateral throbbing headache Two major types: classical and common migraine, pathophysiology: neurogenic and vascular theory- neurovascular dysfunction Pharmacotherapy: i ndividualized, based on s everity, frequency of attacks, response of individual patients to drugs used earlier determine the choice Major pharmacologic classes: NSAIDS; 5-HT 1B/1D receptor agonist- triptans; CGRP receptor antagonists- gepants ; 5-HT1F receptor agonist- ditans

29. References Nichols C., Amara S, and David R. 5-Hydroxytryptamine (Serotonin) and Dopamine. Goodman & Gilman's The Pharmacological Basis of Therapeutics. 14th ed. New York: McGraw Hill; 2023. Chapter-15. p. 292-294 Tripathi KD. 5-Hydroxytryptamine, its Antagonists and Drug Therapy of Migraine. Essentials of Medical Pharmacology. 9th ed. New Delhi: Jaypee Medical Publishers; 2023. p.185-196 . Goadsby P.J. Migraine and other primary headache disorders. Harrison’s Principles of Internal Medicine. McGraw Hill LLC. 2022 , Chapter-430, p 3357-3362

30. THANK YOU!