What’s Migraine? According to the International Headache Society, a migraine is a headache that lasts for 4–72 hours and presents with at least two of the following symptoms: 1. unilateral localisation, 2. moderate to severe pain intensity, 3. aggravation by movement, 4. and a pulsating throbbing feeling. The headache is also usually accompanied by nausea, vomiting, photo- and phonophobia. Treatment and prophylaxis: Prophylaxis: 1. Beta blockers 2. Calcium channel blockers 3. Antidepressants 4. anticonvulsants Acute episodes: • Non specific treatment 1. NSAIDs 2. ANTIEMETICS • Specific treatment 1. Triptans 2. dihydroergotamine CASE STUDY… I.J., a 36-year-old woman, presented to the neurologic clinic with a 2-month history of right- sided pulsatile head pain recurring on a weekly basis. The patient’s history indicated that her headaches usually occurred in the morning and were preceded by lightheadedness, hand numbness, and unformed flashes of light or a band of absent vision with a shimmering or glittering zigzag border (scintillating scotomas). About 30 minutes later a throbbing head- ache would occur. It was always unilateral and was commonly associated with nausea, vomiting, and photophobia. The pain usually lasted all day unless she was able to lie in a dark room and avoid any noise. The headache was partially relieved by two tablets of either aspirin (500 mg tablet) or ketoprofen (50 mg tablet), but recently she avoided these drugs because of epigastric pain. Both I.J.’s mother and grandmother were also affected by a similar type of headache. Past medical history was unremarkable, and I.J. denied any other medical problem. General physical and neurologic examinations were within normal limits. Current medications included only the analgesics for headache and a monophasic combination contraceptive (ethinyl estradiol 0.02 mg and norethindrone 1 mg). A diagnosis of migraine was made, and I.J. was given a prescription for ergotamine tartrate (2 mg sublingual) and metoclopramide (10 mg oral). She was instructed to take both medications at the first sign of headache attack and was asked to record the number, frequency, severity, and duration of her headaches so that an accurate assessment of her abortive therapy could be made at her next clinic visit. I.J. was also instructed on how to pre- determine her maximal tolerated dose of ergotamine so as to avoid its adverse effects. She was also instructed to avoid oral contraceptives and to use alternative birth control methods. At her follow-up clinic visit 1 month later, I.J. reported only moderate relief from her headaches with ergotamine, in spite of an evident increased use of the drug. She admitted the occasional use of an over-the-counter preparation (Anacin, an aspirin–caffeine combination) trying to relieve her headache. She also reported a persistent tingling sensation in her legs, and pain occurring in her calf on walking. Inspection of her diary suggests that ergotamine did not improve her headache with respect to any of the parameters noted. I.J.’s physical examination reveals cold lower extremities and decreased distal pulses. Ergotamine and metoclopramide were discontinued, and I.J. was given a prescription for acetaminophen (500 mg) and codeine (30 mg) combination. I.J. used the drug as directed for her next headache attacks. However, the headache continued to increase in intensity, and, 3 weeks later, the attacks were so frequent that she could no longer work. After vomiting twice during an attack I.J. was taken to the neurologic clinic by a friend. There she was treated with intramuscular sumatriptan. The dose was repeated 1 and 2 hours later, and the attack was abolished. I.J. was discharged from the clinic with the following postdischarge therapy: oral sumat- riptan at the first sign of the headache attack and oral propranolol for migraine prevention. At her follow-up clinic visit 2 months later, I.J. reported that sumatriptan was quite effective in aborting an impending attack. However, the frequency of these attacks was not decreased in spite of a 300 mg daily dose of propranolol. The neurologist decided to discontinue propranolol and to substitute it with valproic acid. I.J. was also instructed to carefully avoid pregnancy while taking this drug. QUESTIONS 1. I.J. was diagnosed with migraine. Which of the following is the prevalence of this disease for women in the United States? A. 1–2% B. 5–10% C. 15–20% D. 30–35% E. 40–45% Which of the following I.J.’s symptoms is practically diagnostic for her disease? 1. Throbbing pain 2. Nausea and vomiting 3. Photophobia 4. Scintillating scotomas 5. Lightheadedness 3. Which of the following pairs of patho- physiological actions most likely cause the pain of I.J.’s migraine attacks? A. Vasoconstriction–fibrosis B. Vasodilation–fibrosis C. Vasoconstriction–necrosis D. Vasodilation–necrosis E. Vasoconstriction–inflammation F. Vasodilation–inflammation 4. Which of the following cranial nerves seems primarily involved in the pathophysiology of I.J.’s migraine? A. CN I B. CN II C. CN III D. CN IV E. CN V F. CN XI G. CN XII 5. Taking into account I.J.’s medical his- tory, she was most likely at increased risk of which of the following neurologic disorders? 1. Chronic meningitis 2. Ischemicstroke 3. Epilepsy 4. Myasthenia gravis 5. Cerebellarataxia 6. Alzheimer disease 6. Both aspirin and ketoprofen were effective in decreasing I.J.’s headache. Which of the following molecular actions most likely mediates the analgesic effect of both drugs in the patient’s disorder? 1. Decreased synthesis of thromboxanes 2. Blockade of thromboxane receptors 3. Decreased synthesis of prostaglandins 4. Blockade of prostaglandin receptors 5. Decreased synthesis of leukotrienes 7. I.J. avoided aspirin and ketoprofen because of epigastric pain. Which of the following molecular actions most likely contributed to this adverse effect? 1. Increased prostaglandin activity 2. Increased ion-trapping activity 3. Inhibition of leukotriene synthesis 4. Activation of bradykinin synthesis 5. Increased nitric oxide activity . I.J. was started on a therapy with ergotamine tartrate. The activation of which of the following pairs of receptors most likely mediated the therapeutic effect of the drug in the patient’s disorder? 1. α-adrenoceptors–5-HT receptors 2. β-adrenoceptors–5-HT receptors 3. MuscarinicM3 receptors–α-adrenoceptors 4. Muscarinic M3 receptors–β-adrenoceptors 5. Muscarinic M3 receptors–5-HT receptors 6. α-adrenoceptors–β-adrenoceptors I.J. started a therapy with metoclo- pramide. The blockade of which of the following receptors most likely mediates the antiemetic action of this drug? 1. Dopamine D2-adrenoceptors 2. Muscarinic M1 receptors 3. Histamine H1 receptors 4. β-adrenoceptors 5. Nicotinic neuronal (Nn) acetylcholine receptors 10. At her follow-up clinic visit I.J. reported persistent tingling sensation in her legs and pain occurring in her calf on walking. Physical examination showed cold lower extremities and decreased distal pulses. Which of the following was most likely the primary cause of these symptoms and signs? 1. Excessive dosage of metoclopramide 2. Worsening of migraine disorder 3. Cluster headache superimposed to migraine 4. Excessive dosage of ergotamine 5. Excessive dosage of aspirin/caffeine combination 11. I.J. was given a prescription for an acetaminophen–codeine combination. Which of the following pairs of receptors/enzymes most likely mediates the analgesic effect of this combination? 1. κ-receptors–lipoxygenase 2. μ-receptors–cyclooxygenase 3. Glutamate receptors–phospholipase A 4. Muscarinic M3 receptors–lipoxygenase 5. Thromboxane receptors–cyclooxygenase 12. I.J.’s postdischarge therapy included sumatriptan. Activation of which of the following receptors most likely mediated the therapeutic effect of the drug in the patient’s disease? 1. α-adrenoceptors 2. β-adrenoceptors 3. Nn acetylcholine receptors 4. Muscarinic M3 receptors 5. 5-HT1D/1B receptors 6. 5-HT2 receptors 13. I.J.’s postdischarge therapy included propranolol, a drug approved by the U.S. Food and Drug Administration (FDA) for the prophylactic treatment of migraine. In addition to propranolol, which of the following groups of drugs are the only agents approved at present by FDA for migraine prevention? A. Timolol–valproate–topiramate B. Verapamil–ketorolac–lamotrigine C. Venlafaxine–lisinopril–valproate D. Gabapentin–naproxen–topiramate 14. Valproate was prescribed to I.J. The drug most likely acts through an enhancement of which of the following central neurotransmitter systems? A. Glutamatergic B. Cholinergic C. Noradrenergic D. Serotoninergic E. GABAergic F. Dopaminergic Case 2 For several years Sandra Baher, a young mother, has purchased combination analgesics for migraine with aura from your pharmacy every few months. She has suffered from migraine headaches since she was a child. Today she presents with a prescription for a combined oral contraceptive pill and asks if you have anything stronger for her migraine; the tablets do not seem to work like they used to and her migraine is more frequent. She is not taking any medicines on prescription. Sandra tells you that she now suffers from migraines two or three times a month, and they are making her life a misery. Nothing seems to trigger them, and the pain is not more severe than before. She has read about feverfew and wonders whether she should give it a try. 1-Should you dispense contraceptive pill for Mrs Sandra? Why? 2-What are the drugs used as first line to treat migraine? 3-How would you manage Mrs Sandra’s case? 4-what are the side effects of using feverfew? 5-Enumerate all the‘triptans’ you know? And what is their mechanism of action?are they given for acute attacks or prophylaxis? 6-What are CI to triptans? Any questions?
