Agents for Migraine include-

Almotriptan, Eletriptan, Frovatriptan, Naratriptan, Rizatriptan, Sumatriptan, Zolmitriptan

Refer -Sumatriptan

Serious coronary vasospasm ,

Transient mycardial ischemia, ventricullar fibrillation/ tachycardia, and MI have been associated with 5-HT1 agonists.

Oral - these agents have been well tolerated.

Across all doses most adverse reactions have been mild and transcient and did not lead to long lasting effects.

Injectable preparation used IV because of potential to cause coronary vasospasm,

Patients with ischemic heart disease ( angina pectoris )

History of MI , strokes, ischemic attacks TIAs or documented silent ischemia

Prinzmetal variant angina or significant underlying cardiovascular disease

Concurrent use of ( use within 24 hours of ) ergot containing prepn or ergot type medications such as dihydroergotamine or methysergide

Concurrent monoamine oxidase inhibitors MAOI therapy ( or within 2 weeks of discontinuing an MAOI ( except eletriptan )

Naratriptan and sumitriptan - cerbrovascular or peripheral vascular syndromes, severe impairment, ( child Pugh grade C)

Severe renal impairment (Ccr less than 15mL/min ( naratriotan only) Frovatriotan and eletriptan - peripheral vascular disease Eletriptan - severe hepatic impairment

Warnings/precautions-

Risk of myocardial ischemia or MI and other adverse cardiac events- because of the potential of these compounds to cause coronary vasospasm, do not give these agents to patients with documented ischemic or vasopastic coronary artery disease

It is strongly recommended that that 5-HT1 agonists not be given to patients in whom unrecognized coronary artery disease CAD is predicted by the presence of risk factors eg. hypertension, hyperchloesrolemia, smoking, obesity, diabetes, strong family history of CAD, female with surgical or physilogical menopause or male older than 40 years of age) unless a cardiovascular evaluation provides satisfactory clinical evidence that the patient is reasonably free of coronary artery and ischemic myocardial disease or significant underlying cardiovascular disease

Zolmitriptan- there is a report of at least 1 patient experiencing coronary vasospasm without the history of cardiac disease and with documented history of absence of CAD.

Patients with symptomatic Wolff- Parkinson -White syndrome or arrhthmias associated with cardiac accessory conduction pathway disorders should not receive zolmitriptan

Cardiac events and fatalities associated with 5-HT1 agonists- serious adverse cardiac events including acute MI , life threatening disturbances of cardiac rhythm, and death have been reported within few hours following admin. of 5- HT1 agonists.

Considering the use of 5 - HT1 agonists in patients with migraine , the incidence of these events is extremely low.

 It should be noted that patients with migraine may be at increased risk of certain cerebrovacular events eg. stroke, hemorrhage, TIA Other vasospasm related events- 5-HT1c agonists may cause vasospatic reactions other than coronary artery vasospasm .

Renal function impairment- Use rizatriptan and sumitriptan with caution in dialysis patients becausec of decrease in clearance

Hepatic function impairment- Administer with caution to patients with diseases that may alter the absorption,metabolism, or excretion of drugs.

Phtosensitivity- Photosenitization may occur. Caution patients to take protective measures

Use during pregnancy only if the potential benefits justifies the potential risk to the fetus

Lactation- Sumatriptan and eletriptan are excreted in human breast milk. Lactating rats dosed with zolmitriptan had milk levels equivalent to maternal plasma levels at 1 hour and 4 times higher than plasma levels at 4 hours Naratriptan -related material is excreted in milk of rats.

Rizatriptan is extensively excreted in rat milk at a level 5-fold or greater than matenal plasms levels Frovatriptan and its metabolites are excreted in the milk of lactating rats with maximum concentration being 4 fold than seen in blood.

Excercise caution when administering to a nursing woman

Children- safety and efficacy have not beenestablished.

Elderly- Pharmacokinetics disposition of 5-HT1 agonists in the elderly is similar to that seen in younger adults.

Indication-

Migraine

Dosage

Usual dosage- single tablet taken orally with fluids. if headache recurs after initial relief a second tablet may be taken providing that there is an interval of at least 2 hours between doses between doses.

Safety of treating an average of more than 4 migraine attacks in a 30 day period has not been established Maximum dose 3 tablets (3x 2,5mg /day)

Injection- sumitriptan-

Instruct patients who are advised to self administer sumatriptan in medically unsupervised situations, on the proper use of the product prior to doing so for the first time, including loading the auto-injector and discarding empty syringes

For adults the usual dose is a single injection given just below the skin.

Administer as soon as migraine symptoms appear, but it may given at any time during the attack. A second injection can be given if symptoms of migraine return.

Do not use more than 2 injections/24 hours and allow at least 1 hour between each dose.

The patient may experience pain or redness at the site of injection, but this usually lasts less than 1 hour.

Intranasal- for adults, Usual dose is a single nasal spray into 1 nostril. If headache returns, a second nasal spray may be given 2 hours after the first spray

. For any attack where the patient has no response to the first nasal spray, do not use a second nasal spray without consulting a physician

Do not administer more than 40mg sumatriptan or more than 10mg zolmitriptan nasal spray in any 24 hour period.

Oral- Take a single dose with fluids as soon as symptoms of migraine appear.

A second dose may be taken if symptoms return, but no sooner than 2 hours ( sumatriptan, zolmitriptan, eletriptan ) or 4 hours ( naratriptan, ) following the first dose.

For a given attack if there is no response to the first dose do not take a second dose without first consulting a physician.

Do not take more than 200mg sumatriptan, more than 5mg naratriptan, more than 10mg zolmitriptan or more than 80mg eletriptan in any 24 hours period.

Tell a physician if the patient has risk factors for heart disease (eg. high blood pressure, high cholesterol, obesity, diabetes, smoking, strong family history of heart disease or stroke, a male over 40 years of age postmenopausal women )

These agents are intended to relieve migraine but not to prevent or reduce the number of attacks.

Use only to treat an actual migraine attack or cluster headache ( sumatriptan inj only )

Instruct patients not to use these agents if they are pregnant, think that they might be pregnant, are trying to become pregnant, or not taking adequate contraception , unless they have discussed this with their physician

If the chest pain is severe or does not go away, instruct patients to immediately call a physician If sudden or severe abdominal pain occurs following naratriptan or sumatriptan admin.,

Instruct patient to immediately call a physician If shortness of breath, wheezing ,heart throbbing, swelling of eye lids, face or lips, skin rash, skin lumps, or hives occur,

Aadvice patients to immediately tell a physician . Instruct patients not to take additional dose unless directed by the physician.

If feelings of tingling, heat, flushing ( redness of face lasting for a short time) heaviness, pressure, drowsiness, dizziness, tiredness, or sickness develop, instruct patients to tell a physician

Migraine or treatment with Rizatriptan may cause somnolence in some patients. Dizziness also has been reported.

Evalute ability to perform complex tasks during migraine and after administration of Rizatriptan.

 Photosensitization ( photoallergy or photoxicity ) may occur. Therefore, caution patients to take protective measures (ie. sunscreens, protective clothing ) against exposure to sunlight or ultraviolet light until tolerance is determined

Pharmacology-

Sumatriptan, naratriptan, zolmitriptan, rizatriptan, frovatriptan, eletriptan and almotriptan are selective 5-hydroxytryptamine1 (5-HT1 or serotonin ) receptor agonists

Pharmacokinetics-

Renal function impairment-- Frovatriptan - because less than 10% of frovatriptan  practically impaired patients is excreted in urine after an oral dose, it is unlikely that the exposure of frovatriptan will be affected by renal impairment.

The pharmacokinetics frovatriptan following a single oral dose of 2.5mg was not different in patients with renal impairment 5males and 6 females ) Ccr 16 to 73mL/min ) vs subjects with normal renal function.

Hepatic function impairment-  liver plays an important role in presystemic clearance of 5-HT1 agonists. Accodingly the bioavailability may be markedly increased in patientsdwith liver disease.

Food has significant effect on oral 5-HT1 agonists bioavailability, but delays sumatriptans Tmax by aaproximately 30 minutes and rizatriptans time to reach peak concentration by 1 hour.

AUC and Cmax of eletriptan are increased approximately 20% to 30% following oral admin. of a high fat meal.

Pregnancy-

There are no adequate and well controlled studies in pregnant women Use during pregnancy only if the potential benefits justifies the potential risk to the fetus

Lactation-

Excercise caution when administering to a nursing woman Children- safety and efficacy have not beenestablished.

Elderly-

Pharmacokinetics disposition of 5-HT agonists in the elderly is similar to that seen in younger adults.