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Migraine pharma

UVa med pharmacology block 2

QuestionAnswer
Sumatriptan Triptan - serotonergic 5-HT1b/d/f agonist - 1b/1d vasoconstict mening vessels, decr inflamm meds from trigem afferent, 1F decr trans btw trigem affs - tx acute migraine/cluster headaches CI: CAD, angina, SSRI/MAOI, ergots
Zomitriptan/Naratriptan/Rizatriptan Triptan - serotonergic 5-HT1b/d/f agonist - 1b/1d vasoconstict mening vessels, decr inflamm meds from trigem afferent, 1F decr trans btw trigem affs - tx acute migraine/cluster headaches incr duration/efficacy than sumatriptan
Ergotamine Ergot alkaloid - partial 5-HT1B/1D, DA, adrenergic agonist - rescue therapy abort migraine attack, cluster headache fx: periph vasoconstrict, cap endothel damage->thrombosis/gangreme, incr uterine contraction, emesis CI: preg, HTN, CAD, renal/hep disease
Dihydroergotamine Ergot alkaloid - partial 5-HT1B/1D, DA, adrenergic agonist - acute tx severe migraine T1/2 long 9hrs, milder fx than ergotamine
Butalbital barbituate/sedative - used in combination analgesics +NSAID+caffeine - tx acute migraine FX: barbiturate dependence
Amitriptyline/Nortryptyline TCA migraine prophylaxis mech unknown - use at low dose 2nd line prophylaxis side fx: anti-cholnergic sedation, incr weight
Propanolol/Timolol beta blocker 1st line migraine prophylaxis fx req 1mth - sidefx: decr HDL, semnolence, depression
Valproate Anticonvulsant migraine prophylaxis - decr ion channel fx (Na/Ca)
Methysergide semi-synthetic ergot deriv 3rd line migraine prophylaxis - non-spec 5-HT receptor antag, incr efficacy @ 5-HT2 receptor Fx: retroperitoneal fibrosis reqs 1-2 mth drug holiday every 6mths CI: PVD, HTN, angina, beta blocker use
How are ergot alkaloids used in migraine treatment? For rescue therapy. Can help "abort" a migraine attack if taken early.
What is a clinically important side-effect of Sumatriptan? Coronary circulation may be adversely affected, due to coronary vasospasm.
How are TCA's used in migraine therapy? Prophylaxis, 2nd line to Beta antagonists.
What are the features of a "Moderate" migraine? Moderate/Severe headaches, some impairment of functioning. Nausea common.
How much does Sumatriptan cost? $20/pill, and treatment may require 2 pills.
What Serotonin agonists are used in the acute treatment of migraine attacks? Drug Class: Triptans. Prototype: Sumatriptan, which is structurally related to 5-HT.
What are the features of a "Severe" migraine? More than 3 severe headaches a month. Significant functional impairment. Marked nausea/vomiting.
What drugs are used to help nausea/vomiting in migraines (other than serotonergics)? Antiemetics: Metoclopramide. Sometimes combination analgesics that contain muscarinic blockers can alleviate nausea.
Why are ergot alkaloids contraindicated in patients with peripheral vascular disease/hypertension/ischemic HD/renal/hepatic disease? They cause peripheral vasoconstriction via alpha-1 adrenergic receptors. Remember, WHY-ee.. not what... Why-ee?
Why are the ergo alkaloids contraindicated during pregnancy? They cause uterine contraction (and thus possibly premature labor).
What are the features of a "Mild" migraine? Throbbing headaches, but no major impairment of functioning.
Why should mixing barbuturates + caffeine to help migraine symptoms be used sparingly? Barbiturate dependence can occur. Thus, use them only when Triptans are contraindicated due to CAD, or because of their very low cost.
Why is Methysergide the last line of treatment for migraine prophylaxis? It can infrequently cause inflammatory fibrosis of the lung, heart, or peritoneum. To minimize this, a "drug holiday" for 1-2 months every 6 months is recommended.
What stage of migraines would necessitate prophylactic treatment? Severe, but only give for 6 months at a time and then re-assess.
What are the 3 stages of migraine treatment? Trigger avoidance Abortive treatment Prophylaxis
What is the anti-convulsant of choice in migraine therapy? Valproate
What is the most likely cause of migraine headaches? Abnormal activation of Trigeminal sensory nerve endings, located within meninges and vasculature. Nociceptive fibers may be activated by stretch (from dilation and increased flow of vessels, edema in walls), or by inflammatory mediators (autocoids).
What is the mechanism of the drug Methysergide, and how is it used in migraine therapy? It is a non-specific 5-HT receptor antagonist. May also have alpha-1 agonist activity. It is used for prophylaxis, and is the 3rd line treatment.
How are Beta-adrenergic antagonists used in Migraine therapy? Propanolol and Timolol are approved for prophylaxis of migraines, and benefit 60-80% of patients. Unknown mechanism.
What drugs are used for mild migraine pain? NSAIDs or Acetominophen. Addition of Codeine can boost efficacy.
Why would a Serotonergic agonist be helpful in treating Migraine pain? VSM from meningeal vessels are contracted by serotonin (this could help reverse dilation/edema causing stretch on nociceptors). receptors on Cranial sensory afferents reduce release of inflammatory peptides, reduce activation of nociceptive fibers
What is a 2nd line therapy to Triptans for Migraine attacks? Ergo Alkaloids: Ergotamine and Dihydroergotamine. They are not selective for serotonin receptors (also affect dopaminergic and adrenergic), although their clinical effect on migraines probably comes from the serotonergic effect.
What are the major drug interactions with Sumatriptan? SSRI's and MAOI's are contraindicated.
What kind of pharmacological effects does Sumatriptan have on migraine attacks? Relieves headache, nausea, vomiting, pain, photo/phono-phobia.
Created by: sam.mrosenfeld
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