User:Slalop/Antimigraine drug

Antimigraine drugs are medications intended to reduce the effects or intensity of migraine headache. They include drugs for the treatment of acute migraine symptoms as well as drugs for the prevention of migraine attacks. Treatment of migraines requires an individualistic approach, as people respond differently to anti-migraine medications. Several medications may need to be tried in order to find the best therapy for a specific person. More than one medication may be needed to adequately treat the migraine. Efficacy of past treatments, any medical conditions the patient may have, other medications, and severity should be taken into account when selecting an anti-migraine agent.

Treatment of Acute Symptoms

With acute migraine attacks, attack severity is a major factor to consider when selecting an anti-migraine agent. Past response to other anti-migraines should also be considered. When patients have tried many anti-migraine drugs to no success, education of treatment options available is important to prevent the patient from being discouraged and not seeking help. Anti-migraine medications work best when taken as soon as possible.Different formulations are also available depending on the patient and how their migraine presents. Patients with migraines that present very quickly may benefit from an injectable anti-migraine agent. Patients prone to nauseaand vomiting may benefit from a nasal administration. Patients without significant nausea or vomiting may try tablet, capsule or orally disintegrating tablet.Though they take longer to work, most patients prefer oral formulations due to their ease of use.

Triptans

Triptans are serotonin (5-HT) receptor agonists with relative specificity for the 5-HT1B and 5-HT1D receptors. Common examples include sumatriptan, zolmitriptan, and rizatriptan. Triptans work by causing cranial vasoconstriction, peripheral trigeminal inhibition, and inhibition of transmission through second order neurons of the trigeminocervical complex. This vasoconstriction helps relieve migraine symptoms. Many patients respond well to triptans, and they have fewer side effects than older ergot derivatives,which used to be one of the only options available for migraines. The pharmacology of triptans is selective, and they have reliable and consistent pharmacokinetics, making dosing more reliable.² They are have a good safety profile, though they are contraindicated in cardiovascular disease due to their vasoconstrictive effects.Serotonin syndrome was a potential concern as a side-effect, though studies show that the risk is very rare, even while using selective serotonin reuptake inhibitors (SSRIs).Studies have been conducted comparing the efficacy of various triptans to one another, commonly with sumatriptan as the comparator. Most show very little difference between the triptans. Some studies do show a modest benefit with rizatriptan, showing it provides faster relief than other triptans. More studies are needed to compare all triptans, and more evidence is needed to definitively suggest one triptan over another. Most existing studies are small, with limited power to find differences between the triptans.

Non-Steroidal Anti Inflammatory Drugs (NSAIDs)

Non-steroidal anti-inflammatory drugs, or NSAIDs, are commonly used in migraines, and especially considered a first line treatment before the introduction of triptans. They are considered “non-specific” agents for migraines. NSAIDs work through cyclooxygenase (COX) enzyme inhibition. This in turn prevents the conversion of arachidonic acid into E2 prostaglandins, prostacyclins and thromboxanes, which are associated with pain and inflammation. COX enzymes can be categorized into COX-1 and COX-2 categories, with COX-1 being prevalent throughout the body and having more physiological effects in both body regulation and protection.COX-2 is primarily activated by inflammation and pro-inflammatory cytokines. Depending on their specificity for COX-2, NSAIDs can be categorized as non-specific, such asibuprofen and naproxen,and COX-2 specific inhibitors such as celecoxib.COX-1 inhibition is responsible for most of the side effects associated with NSAIDs, as it acts on various systems throughout the body. As side effects increase with duration of NSAID use, considerations for more COX-2 specific NSAIDs are made for those using NSAIDs long-term.

Studies show that NSAIDs are similar to triptans in efficacy, but clinical practice suggests triptans are more efficacious in treating migraines than “non-specific” agents like NSAIDs in many patients. NSAIDs do have the advantage of being less expensive than triptans. NSAIDs may be combined with triptans for greater odds of migraine relief. NSAIDs also have the benefit of not being connected to rebound headaches or an increased risk of causing migraines to become chronic, unlike other treatment options such as acetaminophen. However, NSAIDS do come with potential side-effects and contraindications. As they can irritate the stomach lining and gastrointestinal tract, those with peptic ulcer disease, gastroesophageal reflux disease (GERD), irritable bowel syndrome, or other GI disorders should avoid using NSAIDs. Common side effects include heartburn, diarrhea, and edema.Due to this, NSAIDs may potentiate hypertension and kidney or liver damage, with this being more likely in daily users.

Ergot Derivatives

There are 2 common types of ergot derivatives used in migraines, the ergot alkaloids ergotamine and dihydroergotamine mesylate.Ergotamine has been used since 1926 as an acute migraine treatment.Both ergotamine and dihydroergotamine mesylate have similar mechanisms of action. They interact with a variety of receptors, such as serotonin (5-HT), dopamine, and noradrenaline receptors.  The action on serotonin 5-HT1D receptors especially results in vasoconstriction of meningealblood receptors. Dihydroergotamine mesylate was a created as a newer type of ergot compared to ergotamine, marketed as having less side-effects.⁵ It acts more specifically on 5-hydroxytryptamine 5-HT1B and 5-HT1D serotonergic receptors. While there are currently more varied and potentially safer options for acute migraine relief, most clinicians feel they still have a role to play in migraine treatment, especially in those already stabilized on ergot derivatives or have exhausted other options. Common side effects include nausea and vomiting, especially in intravenous (IV) and intramuscular (IM) routes of administration. The older, less receptor-specific ergotamine has more potential for side effects than dihydroergotamine mesylate.Other potential side effects include leg weakness, numbness, and tingling of the extremities. Due to the vasoconstriction caused by ergots, especially ergotamine, there is potential for arterial constriction, vasoconstriction, and the constriction of peripheral blood vessels. This can cause an increase in blood pressure and long-lasting cardiovascular effects. Interestingly, it is the findings of ergot derivatives’ effect on serotonin receptors that led to the invention of the more 5-HT1B and 5-HT1D specific triptans. Ergots are available in various formulations, such as oral, IV, IM, and intranasal.

Prevention

While a good portion of migraine sufferers (approximately 38%) are in need of preventive therapy, few (3%–13%) currently use it. Prevention of acute migraine attacks is highly important in improving quality of life. Preventative therapy can reduce migraine frequency, severity, and progression. Preventative therapy may be considered for those who have four or more headaches a month, eight or more headache days a month, debilitating headaches, and medication overuse headaches.  Classes of medications that have been studied for use in migraine prevention include: angiotensin receptor blockers (ARBs), angiotensin converting enzyme (ACE) inhibitors, antiepileptic drugs such as valproate, gabapentin, and lamotrigine, antidepressants such as fluoxetine and venlafaxine, beta blockers such as metoprolol and propranolol, calcium channel blockers, and the triptans. Antiepileptics and beta-blockers especially, along with antidepressants and triptans demonstrated the most efficacy for migraine prevention, while clomipramine and lamotrigine were showed to be ineffective. Research combined with patient-specific factors are required to make a more definitive choice in preventative therapy.  Non-pharmacological measures are also highly important in preventing migraines. Identifying and avoiding migraine triggers can help with migraine prevention. Common migraine triggers include additives, alcohol, artificial sweeteners, caffeine (overconsumption or acute withdrawal from regular use), delayed/missed meals, exercise, foods. and odors. Other measures such as relaxation training, thermal and electromyographic biofeedback and cognitive behavioral therapy may be considered as treatment options for the prevention of migraine. These measures may be combined with preventive drug therapy to achieve additional clinical improvement for migraine relief.