1. Treatment of migraine headache

2. Introduction Migraine is a severe type of unilateral periodic headache characterized by: 1.Prodorme 2.Aura: mild headache, nausea and some visual disturbances 3.Severe headache: associated with highly pulsating temporal vessels due to dilatation of the cerebral vessels. This stage may be accompanied by vomiting. 4.Headache relief 5.Postdorme

3. Pathogenesis of migraine Serotonin appears to be involved in cause. – Decreased levels = excessive vasodilation in cranial arteries = headache. – By stimulating serotonin receptors, vasoconstriction will occur thereby alleviating the migraine.

4. Management A. Initial Treatment – Identifying and eliminating triggers e.g. red wine, caffeine, certain foods, bright lights – If attacks are still frequent, drug therapy may be indicated B. Pharmacological therapy: B. Abortive Therapy – Treats acute migraine attacks – Taken after headache occurs, at first sign of a headache C. Prophylactic Therapy – Attempts to prevent or reduce recurrence

5. Pharmacological Treatment of Migraine A. Abortive therapy These drugs are most effective when administered at the onset of migraine. If the patient developed headache he will not benefit from vasoconstrictor drugs. It will be effective if it is given at the onset of the aura. Pretreatment with antiemetics e.g. metoclopramide 15 to 30 minutes before administering oral acute migraine therapy to prevent nausea and vomiting and to enhance absorption of oral medications. Or use of non oral treatments (rectal suppositories, nasal spray, injections)

6. Drugs for Acute migraine headache 1. Analgesics and Nonsteroidal Antiinflammatory Drugs: Simple analgesics and nonsteroidal anti-inflammatory drugs (NSAIDs) are effective as first-line treatment for mild to moderate migraine attacks.E.g. Aspirin, ibuprofen, naproxen Combination of acetaminophen + aspirin + caffeine are effective

7. 2-Ergot Alkaloids and Derivatives: E.g. ergotamine and dihydroergotamine Ergot alkaloids are nonselective 5HT 1 receptor agonists that constrict intracranial blood vessels. Adverse effects: – Nausea and vomiting are common a – Abdominal pain – Weakness, Fatigue, Paresthesias – Muscle pain – Diarrhea – Chest tightness. – Symptoms of severe peripheral ischemia (ergotism) include cold, numb, painful extremities, and claudication.

8. Drug interaction: – Ergotamine derivatives and triptans should not be used within24 hours of each other. Contraindications: – Renal and hepatic failure; – Coronary, cerebral, or peripheral vascular disease; – Uncontrolled hypertension; – Pregnancy and lactation.

9. 3-Serotonin Receptor Agonists (Triptans): Examples: Sumatriptan, rizatriptan Pharmacokinetics – All triptans (except sumatriptan) have high oral bioavailability and long half-lives. Therapeutic uses: – Used for patients with moderate to severe migraine or when other medications are ineffective. Mechanism of action: – They are selective agonists of the 5HT 1B and 5HT 1D receptors which causes vasoconstriction.

10. Side effects – Paresthesias, fatigue, dizziness, – Chest tightness – Pain in the chest, neck, or throat. Contraindications include: – Ischemic heart disease, – Uncontrolled hypertension, – Cerebrovascular disease.

11. 4-Opioids: Opioids derivatives (e.g., tramadol, butorphanol) provide effective relief of severe infrequent headaches in whom conventional therapies are contraindicated or after failure to respond to conventional therapies. Adverse effects: – Dizziness, – Nausea, vomiting, drowsiness, – Dependence and addiction.

12. B. Prophylaxis of Migraine Prophylactic therapies are administered to reduce the frequency, severity, and duration of attacks. Many drugs are used e.g. Calcium channel blockers, estrogen,NASAIDs,SSRIs,Tricyclic antidepressants

13. 1.β- Adrenergic blockers – E.G. Propranolol, timolol 2.Antidepressants – E.G.: amitriptyline, imipramine,. – Causes downregulation of central 5HT2 and adrenergic receptors. 3.Selective serotonin reuptake inhibitors : – They are less effective than TCAs for migraine prophylaxis. 4.Anticonvulsants – E.G. Valproic acid, Topiramate

14. 5. Methysergide Methysergide is a semisynthetic ergot alkaloid It is a potent 5HT 2 receptor antagonist. Its use is limited because it causes serious adverse effects (retroperitoneal, endocardial, and pulmonary fibrosis) after prolong treatment It is reserved for patients with refractory headaches. 4-week, medication-free period is recommended after each 6-month treatment period. Monitoring for fibrotic complications. 6- Calcium Channel Blockers: – E.g. Verapamil

15. Drugs used in Alzheimer's disease The aim of therapy is to either improving cholinergic transmission within the CNS or preventing the excitatory actions of NMDA glutamate receptors in selected brain areas.

16. 1. Cholinesterase inhibitors Donepezil, Rivastigmine, Tacrine They are more selective for ChE enzyme in the CNS They provide a modest reduction in the rate of loss of cognitive functions. Side effects: – Nausea, vomiting, anorexia, and muscle cramps. – Tacrine is associated with hepatotoxicity.

17. 2. NMDA receptor antagonist Memantine It is a derivative of amantadine It prevents rate of memory loss in both vascular- associated and Alzheimer dementia. Side effects are rare: confusion, agitation, restlessness.

18. 3. Recent drugs A. β & γ-secretase inhibitors: β & γ-secretase converts amyloid precursor protein to amyloid beta which is found in amyloid plaques in Alzheimer's disease Inhibition of these enzymes reduces deposition of amyloid. B. Ibuprofen and indomethacin These NSAIDs reduce formation of Aβ42 (amyloid beta) by inhibition of γ-secretase enzyme which is unrelated to their COX inhibition. Aspirin doesn't produce this effect (but found to be beneficial in Alzheimer disease). C. Copper and zinc chelating agents: Removal of these metals promotes dissolution of amyloid plaques in brain tissue.

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