{"id":642,"date":"2020-02-17T20:40:05","date_gmt":"2020-02-17T15:10:05","guid":{"rendered":"https:\/\/medicineplexus.com\/?p=642"},"modified":"2020-02-17T20:40:05","modified_gmt":"2020-02-17T15:10:05","slug":"drug-therapy-of-migraine","status":"publish","type":"post","link":"https:\/\/medicineplexus.com\/drug-therapy-of-migraine\/","title":{"rendered":"Drug Therapy Of Migraine"},"content":{"rendered":"\n<p><strong>Drug Therapy Of Migraine<\/strong><\/p>\n\n\n\n<ul><li>characterized by pulsating headache, usually restricted to one side, which comes in attacks lasting 4-48 hours and is often associated with nausea, vomiting, sensitivity to light and sound. flashes of light, vertigo, loose motions and other symptoms.<\/li><li>Two major types <em>are-<\/em><ul><li><em>migraine with aura <\/em>(classical migraine) \u00e0 headache is preceded by visual or other neurological symptoms, and<\/li><\/ul><ul><li><em>migraine without aura <\/em>(common migraine).<\/li><\/ul><\/li><\/ul>\n\n\n\n<p>Pulsatile dilatation of certain large cranial vessels is the immediate cause of pain.<\/p>\n\n\n\n<p><strong>Pathogenic mechanisms<\/strong><\/p>\n\n\n\n<p><strong><em>Vascular theory<\/em><\/strong><em><\/em><\/p>\n\n\n\n<p>initial vasoconstriction or shunting of blood through carotid arterio-venous anastomoses produces cerebral ischemia and starts the attack.<\/p>\n\n\n\n<p><strong><em>Neurogenic theory<\/em><\/strong><em><\/em><\/p>\n\n\n\n<p>spreading <strong>depression of cortical electrical activity<\/strong> followed by vascular phenomena.<\/p>\n\n\n\n<p>Some triggering event \u00e0 produce <strong>neurogenic inflammation of the affected blood vessel wall<\/strong> \u00e0 and release of mediators like 5-HT, neurokinin, substance P, calcitonin gene related peptide (CGRP), nitric oxide, etc.<\/p>\n\n\n\n<ul><li>Migraine involves the <strong>trigeminal nerve distribution to intracranial arteries<\/strong><\/li><li>These nerves release peptide neurotransmitters \u00e0 especially <strong>calcitonin gene related peptide<\/strong>\u00e0 extremely powerful v<strong>asodilato<\/strong>r \u00e0 also, increases glutamate activation of <strong>AMPA receptors<\/strong><\/li><li><strong>TRPV1 receptors <\/strong>play an important role in \u00e0 <strong>modulating trigeminal sensory processing<\/strong> and this have been proposed as <strong>potential targe<\/strong>ts for migraine treatment.<\/li><li>Substance P and Neurokinnin A may also be involved.<\/li><li>Vasodilatation results in extravasation of plasma and plasma proteins into the perivascular space leading to edema<\/li><li>The mechanical stretch then caused by the perivascular edema is the cause of activation of pain nerve endings in the duramater.<\/li><\/ul>\n\n\n\n<p><strong>The International Classification of Headache Disorders, 3rd edition (ICHD-3)<\/strong> specifies diagnostic criteria for migraine<\/p>\n\n\n\n<figure class=\"wp-block-table\"><table><tbody><tr><td><strong>Migraine without aura<\/strong><\/td><\/tr><tr><td>A. At least five attacks fulfilling criteria B through D<\/td><\/tr><tr><td>B. Headache attacks lasting 4 to 72 hours (untreated or unsuccessfully treated)<\/td><\/tr><tr><td>C. Headache has at least two of the following characteristics:<\/td><\/tr><tr><td>Unilateral location<\/td><\/tr><tr><td>Pulsating quality<\/td><\/tr><tr><td>Moderate or severe pain intensity<\/td><\/tr><tr><td>Aggravation by or causing avoidance of routine physical activity (eg, walking or climbing stairs)<\/td><\/tr><tr><td>D. During headache at least one of the following:<\/td><\/tr><tr><td>Nausea, vomiting, or both<\/td><\/tr><tr><td>Photophobia and phonophobia<\/td><\/tr><tr><td>E. Not better accounted for by another ICHD-3 diagnosis<\/td><\/tr><\/tbody><\/table><\/figure>\n\n\n\n<figure class=\"wp-block-image size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"317\" height=\"298\" src=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-240.png?w=317\" alt=\"\" class=\"wp-image-676\" srcset=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-240.png 317w, https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-240-300x282.png 300w\" sizes=\"(max-width: 317px) 100vw, 317px\" \/><\/figure>\n\n\n\n<p><strong>Mild migraine<\/strong><\/p>\n\n\n\n<p>fewer than one attack per month of throbbing but tolerable headache lasting upto 8 hours which does not incapacitate the individual<\/p>\n\n\n\n<ul><li><strong><em>Simple analgesics<\/em><\/strong><em><\/em><ul><li>paracetamol (0.5-1 g) or<\/li><\/ul><ul><li>aspirin (300-600 mg) and repeated 4-6 hourly abort and suppress most mild attacks<\/li><\/ul><\/li><\/ul>\n\n\n\n<p><strong>(ii) <em>Nonsteroidal anti-inflammatory drugs (NSAIDs)<\/em><\/strong><em> and their combinations<\/em><\/p>\n\n\n\n<ul><li>ibuprofen (400- 800 mg 8 hourly),<\/li><li>naproxen (500 mg followed by 250 mg 8 hourly),<\/li><li>diclofenac (50 mg 8 hourly),<\/li><li>mephenamic acid (500 mg 8 hourly),<\/li><li>indomethacin (50 mg 6- 8 hourly) either alone or combined with paracetamol\/codeine\/ diazepam or another sedative\/diphenhydramine or another antihistaminic\/caffeine<\/li><\/ul>\n\n\n\n<ul><li>Dispersible or effervescent formulations \u00e0 should be preferred , because gastric stasis attending migraine attack may hamper absorption from the regular tablet.<\/li><\/ul>\n\n\n\n<ul><li>Analgesics are more effective in migraine without aura,<\/li><li>taken only till the attack passes off. Excessive use of analgesic may itself cause headache.<\/li><li>Long term treatment on a regular schedule to ward off migraine attacks is not advised.<\/li><\/ul>\n\n\n\n<ul><li><strong>Antiemetics<\/strong><\/li><li>Gastric stasis occurs during migraine which delays absorption of oral drugs.<\/li><li>Metoclopramide (10 mg oral\/ i.m.) is frequently used.<\/li><li>relieves nausea, vomiting and gastric stasis<\/li><li>Domperidone ( I 0- 20 mg oral) and prochlorperazine ( I 0-25 mg oral\/ i.m.) are also effective.<\/li><li>Diphenhydramine or promethazine exert sedative as well as antiemetic action.<\/li><\/ul>\n\n\n\n<p><strong>Moderate migraine<\/strong><\/p>\n\n\n\n<p>throbbing headache is more intense, lasts for 6-24 hours, nausea\/ vomiting and other features are more prominent and the patient is functionally impaired. One or more attacks occur per month.<\/p>\n\n\n\n<p>Simple analgesics are usually not effective,<\/p>\n\n\n\n<p>stronger NSAlDs or their combinations mentioned above are beneficial in many cases.<\/p>\n\n\n\n<p>The remaining are treated with a specific antimigraine drug, i.e. a triptan or an ergot preparation.<\/p>\n\n\n\n<p>Antiemetics are almost regularly needed.<\/p>\n\n\n\n<p><strong>Prophylactic therapy is advised only when attacks are more frequent than 2- 3 per month.<\/strong><\/p>\n\n\n\n<p><strong>Severe migraine<\/strong><\/p>\n\n\n\n<p>patients suffer 2- 3 or more attacks per month of severe throbbing headache lasting 12-48 hours, often accompanied by vertigo, vomiting and other symptoms; the subject is grossly incapacitated during the attack.<\/p>\n\n\n\n<p>Analgesics\/NSAIDs and their combinations \u00e0 usually do not afford adequate relief-<\/p>\n\n\n\n<p>Specific antimigraine drugs have to be prescribed along with antiemetics.<\/p>\n\n\n\n<p>Combination of a longer acting analgesic like naproxen with a triptan may be more suitable for patients who have prolonged migraine attacks and suffer recurrences when treated with a triptan alone.<\/p>\n\n\n\n<p>Prophylactic regimens lasting 6 months or more are recommended.<\/p>\n\n\n\n<p><strong>SPECIFIC ANTIMIGRAINE DRUGS<\/strong><\/p>\n\n\n\n<p><strong>Ergotamine<\/strong><\/p>\n\n\n\n<ul><li>most effective ergot alkaloid for migraine.<\/li><li>Given early in attack, lower doses generally suffice, and relief is often dramatic.<\/li><li>Oral\/ sublingual route is preferred, 1 mg is given at half hour intervals till relief is obtained or a total of 6 mg is given.<\/li><li>Parenteral administration, though rapid in action is more hazardous.<\/li><\/ul>\n\n\n\n<ul><li>acts by constricting the dilated cranial vessels and\/or by specific constriction of carotid A-V shunt channels<\/li><li>reduce neurogenic inflammation and leakage of plasma in duramater that occurs due to retrograde stimulation of perivascular afferent nerves \u00e0 mediated via \u00e0 partial agonism at 5-HT 1B\/1D receptors in and around cranial vessels.<\/li><\/ul>\n\n\n\n<p><strong>Dihydroergotamine (DHE)<\/strong><\/p>\n\n\n\n<ul><li>nearly as effective as ergotamine and<\/li><li>preferred for parenteral administration because injected DHE is less hazardous.<\/li><\/ul>\n\n\n\n<p><strong><em>Current status<\/em><\/strong><em><\/em><\/p>\n\n\n\n<ul><li>rarely used now, except for considerations of cost or when triptans fail<\/li><li>Because of erratic oral absorption, frequent side effects, especially nausea, vomiting, muscle cramps and availability of triptans<\/li><li>no prophylactic value \u00e0 regular use is not justified<\/li><\/ul>\n\n\n\n<p><strong><em>Caffeine <\/em><\/strong><strong>100 mg<\/strong> taken with ergotamine enhances its absorption from oral and rectal routes and adds to the cranial vasoconstricting action.<\/p>\n\n\n\n<p><strong>Selective <\/strong><strong>5-HT 1B\/1D<\/strong> <strong>agonists (Triptans)<\/strong><\/p>\n\n\n\n<ul><li>selectively activate 5-HT 1B\/1D receptors, and are called <em>&#8216;trip<\/em>tans&#8217;<\/li><li>Currently \u00e0 first line drugs for patients who fail to respond to analgesics.<\/li><li>Ergot alkaloids are now required only in few cases.<\/li><\/ul>\n\n\n\n<p>Because these drugs have been designed to act on the same subtype of5-HT receptor, pharmacodynamic differences among them are minor, but there are significant pharmacokinetic differences.<\/p>\n\n\n\n<figure class=\"wp-block-image size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"610\" height=\"187\" src=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-241.png?w=610\" alt=\"\" class=\"wp-image-677\" srcset=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-241.png 610w, https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-241-300x92.png 300w\" sizes=\"(max-width: 610px) 100vw, 610px\" \/><\/figure>\n\n\n\n<ul><li>All others triptans have higher oral bioavailability than the prototype drug sumatriptan.<\/li><li>Fewer headache recurrences in an attack are reported with naratriptan and frovatriptan due to their longer t\u00bd, but they may be slower in affording initial pain relief<\/li><li><strong>The use of sumatriptan (or other triptans) should be restricted to treatment of acute attacks of moderate to severe migraine not responding to analgesics or their combinations.<\/strong><\/li><\/ul>\n\n\n\n<p><strong>Sumatriptan<\/strong><\/p>\n\n\n\n<ul><li>first selective <strong>5-HT 1B\/1D <\/strong>receptor agonist; activates other subtypes of 5-HT1 receptors only at very high concentrations<\/li><li>only triptan available for <strong>nasal and parenteral administration<\/strong> as well<\/li><li>Administered at the onset of an attack of migraine, sumatriptan is as effective and better tolerated than ergotamine.<\/li><li>About 3\/4 patients obtain complete\/significant relief within 2-3 hours.<\/li><li>However, recurrence of headache within 24 hr has been noted in 20-40% patients, probably due to short t\u00bd of sumatriptan.<\/li><li>A distinct advantage \u00e0 <strong>tends to suppress nausea and vomiting of migraine, while ergotamine accentuates these symptoms.<\/strong><\/li><\/ul>\n\n\n\n<p><strong>MOA<\/strong> \u00e0 <strong>5-HT 1B\/1D<\/strong> receptor mediated constriction of dilated cranial blood vessels, especially the arterio-venous shunts in the carotid artery, which express 5-HT10110 receptors.<\/p>\n\n\n\n<p>Dilatation of these shunt vessels during migraine attack is believed to divert blood flow away from brain parenchyma.<\/p>\n\n\n\n<p><strong>5-HT 1B\/1D<\/strong> receptors are presynaptic autoreceptors \u00e0 sumatriptan can reduce 5-HT release at these<\/p>\n\n\n\n<p>blood vessels.<\/p>\n\n\n\n<p>in addition \u00e0 may inhibit inflammatory neuropeptide release around the affected vessels as well as extravasation<\/p>\n\n\n\n<p>of plasma proteins across dural vessels.<\/p>\n\n\n\n<p>suppress neurogenic inflammation of cranial vessels.<\/p>\n\n\n\n<p><em>Pharmacokinetics:<\/em><\/p>\n\n\n\n<p>Sumatriptan is absorbed rapidly and completely after s.c. injection.<\/p>\n\n\n\n<p>Oral bioavailability averages only 15%.<\/p>\n\n\n\n<p>Absorption is faster after intranasal spray, but bioavailability remains almost the same.<\/p>\n\n\n\n<p><strong><em>Side effects<\/em><\/strong><em> <\/em>of sumatriptan are usually mild.<\/p>\n\n\n\n<ul><li>Tightness in head and chest, feeling of heat and other paresthesias in limbs, dizziness, weakness are short lasting, but dose related side effects.<\/li><li>These are more common after s.c. injection, which is painful.<\/li><li>Slight rise in BP occurs, but has little clinical relevance, because sumatriptan is not a drug for regular use.<\/li><li>Bradycardia, coronary vasospasm and risk of myocardial infarct ion are the serious, but infrequent adverse effects.<\/li><li>Seizures and hypersensitivity reactions are rare.<\/li><\/ul>\n\n\n\n<p><strong><em>Contraindications:<\/em><\/strong><em><\/em><\/p>\n\n\n\n<ul><li>lschaemic heart disease, hypertension, epilepsy, hepatic or renal impairment and pregnancy are the contraindications.<\/li><li>Patients should be cautioned not to drive.<\/li><li>Sumatriptan and ergotamine should not be administered within 24 hours of each other.<\/li><\/ul>\n\n\n\n<p><strong><em>Dose:<\/em><\/strong><em> <\/em>50- 100 mg oral al the onset or migraine attack, may be repeated once within 24 hours if required.<\/p>\n\n\n\n<p>6 mg s.c. may be given to patients who cannot take the drug orally or in whom the pain develops very rapidly.<\/p>\n\n\n\n<p>25 mg nasal spray can be used<\/p>\n\n\n\n<p>combination of sumatriptan (a migraine-specific triptan) and naproxen (an anti-inflammatory pain reliever) in a single tablet for the acute treatment of migraine.<\/p>\n\n\n\n<p><strong>FDA Approved:<\/strong>&nbsp;Yes (First approved April 15, 2008)<strong>May 15, 2015&nbsp;&nbsp;&nbsp; FDA Approves Treximet (sumatriptan and naproxen sodium) for Migraine in Pediatric<\/strong><\/p>\n\n\n\n<p><strong>Rizatriptan:<\/strong><\/p>\n\n\n\n<p>more potent, has higher oral bioavailability with slightly faster onset of action.<\/p>\n\n\n\n<p><em>Dose: <\/em>5-1 0 mg<\/p>\n\n\n\n<p><em>Naratriptan. Zolmitriptan, Almotriptan, Frovatriptan <\/em>and <em>Eletriptan <\/em>are other triptans used in some countries.<\/p>\n\n\n\n<p><strong>PROPHYLAXIS OF MIGRAINE<\/strong><\/p>\n\n\n\n<ul><li>moderate-to-severe migraine when 2- 3 or more attacks occur per month, or<\/li><li>when attacks are disabling despite treatment, or<\/li><li>in patients with contraindications for triptans\/ergotamine.<\/li><\/ul>\n\n\n\n<p>Diverse classes of drugs are used, but none is effective in all cases, and none abolishes the attacks totally.<\/p>\n\n\n\n<p><strong>Discontinue prophylaxis every 6 months <\/strong>to check whether its continuation is needed or not. It is important<\/p>\n\n\n\n<p>to avoid the precipitating factor(s).<\/p>\n\n\n\n<ul><li><strong><em>beta-Adrenergic blockers<\/em><\/strong> \u00e0 Propranolol<\/li><li>most commonly used drug.<\/li><li>reduces frequency as welI as severity of attacks in upto 70% patients.<\/li><li>Effect is generally seen in 4 weeks and is sustained during prolonged therapy.<\/li><li>starting dose \u00e0 40 mg BD, which may be increased upto 160 mg BD if required.<\/li><\/ul>\n\n\n\n<p>MOA\u00e0 is not clear<\/p>\n\n\n\n<ul><li>Other nonselective (timolol} and beta1 selective (metoprolol, atenolol) agents are also effective, but pindolol and others having intrinsic sympathomimetic action are not useful.<\/li><\/ul>\n\n\n\n<ul><li><strong><em>Tricyclic antidepressants<\/em><\/strong><strong>\u00e0<\/strong> <strong><em>amitriptyline <\/em>(25-50 mg at bed time)<\/strong><ul><li>has been most extensively tried, reduce migraine attacks.<\/li><\/ul><ul><li>effective in many patients but produces more side effects than propranolol.<\/li><\/ul><ul><li>Whether its 5-HT (and other monoamine) uptake blocking property is causally related to the prophylactic effect is not known.<\/li><\/ul><ul><li>The antimigraine effect is independent of antidepressant property<\/li><\/ul><ul><li>This class of drugs are better suited for patients who concurrently suffer from depression.<\/li><\/ul><\/li><\/ul>\n\n\n\n<p><strong>(iii) <em>Calcium channel blockers<\/em><\/strong><strong><em>\u00e0<\/em><\/strong><strong><em> <\/em><\/strong><strong>Verapamil<\/strong><\/p>\n\n\n\n<ul><li>reduce migraine attacks \u00e0 inferior to propranolol.<\/li><\/ul>\n\n\n\n<p><strong><em>Flunarizine<\/em><\/strong><em> <\/em>\u00e0 relatively weak Ca2+ channel blocker that inhibits Na+ channels as well.<\/p>\n\n\n\n<ul><li>Claimed as effective as propranolol, but convincing proof is lacking.<\/li><li>cerebro-selective Ca2+ channel blocker, which may benefit migraine by reducing intracellular Ca2+ overload due to brain hypoxia and other causes.<\/li><li>Side effects \u00e0 sedation, constipation, dry mouth, hypotension, flushing. weight gain.<\/li><\/ul>\n\n\n\n<p><strong>(iv) <em>Anticonvulsants<\/em><\/strong><strong><em>\u00e0<\/em><\/strong><strong><em> Valproic acid <\/em><\/strong><strong>( 400-1200 mg\/day) and <em>gabapentin <\/em>(300- 1200 mg\/day)<\/strong><\/p>\n\n\n\n<ul><li>have some prophylactic effect in migraine.<\/li><li>newer drug <strong><em>topiramate<\/em><\/strong>has recently been approved for migraine prophylaxis.<\/li><li>50% reduction in the number of attacks in half of the patients was noted in 2 randomized trials.<\/li><li>topiramate 25 mg OD and gradually increase to 50 mg OD or BD.<\/li><li>Efficacy of anticonvulsants in migraine is lower than that of beta blockers.<\/li><li><strong>indicated in patients refractory to other drugs or when propranolol is contraindicated.<\/strong><\/li><\/ul>\n\n\n\n<p><strong>(v) <em>CGRP antagonist<\/em> &#8211; Erenumab<\/strong><\/p>\n\n\n\n<ul><li>fully human monoclonal antibody &#8211; blocks calcitonin gene-related peptide (CGRP) receptor<\/li><li>recently found to reduce number of migraine attacks when injected s.c. once a month in patients with severe migraine<\/li><li>approved by US-FDA.<\/li><\/ul>\n\n\n\n<p><strong>(vi) <em>5-HT antagonists<\/em><\/strong><em> <\/em><em>\u00e0<\/em><em> <\/em>methysergide and cyproheptadine<\/p>\n\n\n\n<p>less impressive than beta blockers\u00e0 not used now for migraine.<\/p>\n\n\n\n<p><strong>Selection of drug for prophylaxis:<\/strong><\/p>\n\n\n\n<ul><li>For patients with <strong>hypertension<\/strong> who are nonsmokers and <strong>\u226460 years of age<\/strong>, reasonable options \u00e0<strong>metoprolol, propranolol, or timolol<\/strong> in the absence of contraindications to beta blockers.<\/li><\/ul>\n\n\n\n<ul><li>For patients <strong>with hypertension<\/strong> who are smokers or <strong>are &gt;60 years of age<\/strong>, options include verapamil or flunarizine.<\/li><\/ul>\n\n\n\n<p>using beta blockers as initial therapy for migraine prevention in these patients \u00e0 may be associated with a higher rate of stroke and other cardiovascular events<\/p>\n\n\n\n<p>\u25cfFor patients with depression or mood disorder\u00e0 include amitriptyline or venlafaxine.<\/p>\n\n\n\n<p>\u25cfFor patients with epilepsy, \u00e0 valproate or topiramate.<\/p>\n\n\n\n<p>\u25cfFor patients with insomnia \u00e0amitriptyline is a reasonable option.<\/p>\n\n\n\n<p>\u25cfFor patients with obesity \u00e0 topiramate is a reasonable option.<\/p>\n\n\n\n<p>\u25cfFor patients with Raynaud phenomenon\u00e0 verapamil or flunarizine.<\/p>\n\n\n\n<h2 class=\"wp-block-heading\"><strong>Recent advances in migraine<\/strong><\/h2>\n\n\n\n<ol type=\"A\"><li><strong>CGRP antagonists (Telcagepant and olcagepant)<\/strong><\/li><li>The calcitonin gene-related peptide (CGRP) is a therapeutic target in migraine because of its hypothesized role in mediating trigeminovascular pain transmission and the vasodilatory component of neurogenic inflammation.<\/li><\/ol>\n\n\n\n<ul><li>development of telcagepant was stopped \u00e0 hepatotoxicity, and<\/li><li>development of olcegepant was halted \u00e0 poor oral bioavailability<\/li><\/ul>\n\n\n\n<p><strong>Erenumab (2018)<\/strong><\/p>\n\n\n\n<p>human monoclonal antibody that binds to and inhibits the CGRP receptor \u2013 <strong>for prophylaxis<\/strong><\/p>\n\n\n\n<p><strong>Fremanezumab \u2014 (<\/strong>September 2018<strong>)<\/strong><\/p>\n\n\n\n<p>human monoclonal antibody that binds to both isoforms of the CGRP ligand, appears to be modestly effective for prevention of episodic migraine.<\/p>\n\n\n\n<p><strong>Galcanezumab<\/strong>&nbsp;\u00e0 a human monoclonal antibody that binds to the CGRP ligand<\/p>\n\n\n\n<ol type=\"A\"><li>May 15, 2015 \u00e0FDA Approves Treximet (<strong>sumatriptan and naproxen sodium) for Migraine in Pediatric Patients<\/strong><\/li><\/ol>\n\n\n\n<ul><li><strong>5HT1F agonist: Lasmiditan (<\/strong>completed two Phase III randomized<strong>)<\/strong><\/li><li>MOA: inhibits trigeminal nucleus Fos activation and decreases neuronal activation and neuronal firing.<\/li><li>No direct vasoconstrictor activity of self.<\/li><li>lasmiditan had a relatively high rate of serious adverse events, particularly at higher doses; the most common were dizziness, fatigue, vertigo, paresthesia, and somnolence<\/li><\/ul>\n\n\n\n<ul><li><strong>Gap junction inhibitor \u2013 Tonabersat (not approved)<\/strong><\/li><\/ul>\n\n\n\n<p>selectively binding and blocking glial cell gap junction activity and thus interfering with excitation of nearby trigeminal neurons and propagation of cortical depolarization<\/p>\n\n\n\n<p>There was a lack of evidence to support use of tonabersat for migraine prophylaxis<\/p>\n\n\n\n<ul><li><strong>Vanilloid TRPV1 receptor antagonists &#8211; SB-705498<\/strong><\/li><\/ul>\n\n\n\n<p><strong>TRPV1 receptors <\/strong>play an important role in \u00e0 <strong>modulating trigeminal sensory processing<\/strong> and this have been proposed as <strong>potential targe<\/strong>ts for migraine treatment.<\/p>\n\n\n\n<p>prevent and reverse central sensitization<\/p>\n\n\n\n<ul><li><strong>Glutamate receptor antagonists: Tezampanel<\/strong><\/li><li>Glutamate is excitatory NT. There are 3 types of ionotropic glutamate receptors. Glutamate plays a role in migraine pathophysiology. (decreases central sensitization and CSD)<\/li><\/ul>\n\n\n\n<ul><li><strong>nNOS inhibitors and 5HT1B\/1D agonist:<\/strong> triptans increase expression of nNOS, hence this combination is being tested<\/li><li><strong>PG EP4 receptor antagonist:<\/strong> might not be more effective than NSAIDS<\/li><li><strong>Transcranial magnetic stimulation and transcranial direct stimulation<\/strong><\/li><\/ul>\n\n\n\n<ol type=\"1\"><li><strong>New delivery systems<\/strong><\/li><li>Sumatriptan rectal route: bypass nausea<\/li><li><strong>Sumatriptan intranasal route:<\/strong> but absorbed by gut: Bypass nausea<\/li><\/ol>\n\n\n\n<p>Tosymra (sumatriptan nasal spray) \u00e0Approved January 2019<\/p>\n\n\n\n<p><strong>Specific Treatments: <\/strong>acute migraine in adults<\/p>\n\n\n\n<p>The efficacy of Tosymra was based on the relative bioavailability of Tosymra nasal spray compared to sumatriptan subcutaneous injection (4 mg) in healthy adults<\/p>\n\n\n\n<ul><li>Ultrafine sumatriptan for pulmonary delivery<\/li><li><strong>Transdermal sumatriptan:<\/strong> bypass nausea<ul><li>\uf0a7&nbsp;&nbsp;&nbsp;&nbsp; January 2013, FDA approved: acute medication sumatriptan delivery by new mechanism (transdermal patch)<\/li><\/ul><ul><li>\uf0a7&nbsp;&nbsp;&nbsp;&nbsp; ADR: Painful sensation at the patch application site<\/li><\/ul><\/li><\/ul>\n\n\n\n<ul><li>Intranasal DHE<\/li><\/ul>\n\n\n\n<ul><li>FDC<\/li><li>85 mg of sumatriptan with 500 mg of naproxen approved by FDA<\/li><li>Triptan with caffeine and triptan with PCM are being tested<\/li><\/ul>\n\n\n\n<ul><li>Recent advances for migraine prophylaxis<\/li><li><strong>Onabotulinum toxin A (2010)<\/strong><\/li><li>MOA: synaptobrevin, syntaxin, SNAP-25. The light chain of toxin inhibits SNAP-25<\/li><li><strong>Drugs in development:<\/strong> Ethosuximide, Lacosamide, iNOS inhibitor, Ramelteon.<\/li><\/ul>\n\n\n\n<p><strong>Cerena<\/strong><strong><\/strong><\/p>\n\n\n\n<ul><li>13 December 2013: <strong>FDA allowed marketing of first device to relieve migraine headache pain (Cerena)<\/strong><\/li><\/ul>\n\n\n\n<ul><li>Device delivers Pulse transcranial magnetic stimulation at the onset of headache or aura<\/li><li><img loading=\"lazy\" decoding=\"async\" width=\"131\" height=\"171\" src=\"\">Disrupts cortical spreading depression<\/li><\/ul>\n\n\n\n<p><strong>Cefaly<\/strong><\/p>\n\n\n\n<ul><li><strong>11 March 2014<\/strong>: USFDA approved device for preventing migraine.<\/li><li>Transcutaneous Electrical Nerve Stimulator to Treat Headache<\/li><\/ul>\n\n\n\n<ul><li><strong>Warnings: <\/strong>Indicated for use by adults and should only be used for 20 minutes\/day<\/li><li><strong>ADR<\/strong>: Tingling or massaging sensation where electrode applied.<\/li><\/ul>\n\n\n\n<figure class=\"wp-block-image size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"130\" height=\"171\" src=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2020\/02\/image-242.png?w=130\" alt=\"\" class=\"wp-image-678\" \/><\/figure>\n","protected":false},"excerpt":{"rendered":"<p>Drug Therapy Of Migraine characterized by pulsating headache, usually restricted to one side, which comes in attacks lasting 4-48 hours and is often associated with nausea, vomiting, sensitivity to light and sound. flashes of light, vertigo, loose motions and other symptoms. Two major types are- migraine with aura (classical migraine) \u00e0 headache is preceded by[&#8230;]\n","protected":false},"author":3,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_seopress_robots_primary_cat":"","_seopress_titles_title":"","_seopress_titles_desc":"","_seopress_robots_index":"","footnotes":""},"categories":[3],"tags":[],"_links":{"self":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/posts\/642"}],"collection":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/comments?post=642"}],"version-history":[{"count":0,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/posts\/642\/revisions"}],"wp:attachment":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/media?parent=642"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/categories?post=642"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/tags?post=642"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}