Agents for Migraine include- Almotriptan, Eletriptan, Frovatriptan, Naratriptan, Rizatriptan, Sumatriptan, Zolmitriptan

Refer -Sumatriptan

Migraine

Agents for Migraine include- Almotriptan, Eletriptan, Frovatriptan, Naratriptan, Rizatriptan, Sumatriptan, Zolmitriptan

Refer -Sumatriptan

Serious coronary vasospasm , transient mycardial ischemia, ventricullar fibrillation/ tachycardia, amd 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 aand did not lead to long lasting effects.

Cardiovascular- arrhythmias, hypertension, syncope, bradycardia, extrasystoless, postural hypertension , QT prolongation, tachycardia, thrombophlebitis,

CNS- agitation, anxiety, depression, emotional lability, hyperesthesia, insomnia, amnesia, apathy, ataxia, cerbral ischemia, dystonia, euphoria, hallucinations, irritability

Dermatologic- pruritus, rash, urticaria

GI - esophagitis, gastroenteritis, increased appetite, liver function abnormalites, thirst, tongue edema, anorexia, constipation, gastritis, pancreatitis, ulcer.

GU- cystitis, hematuria, polyuria, urinary frequency/urgency, dysmenorrhoea, miscarriage Hematologic- ecchymosis, cyanosis, eosinophillia, leukopenia, thrombocytopenia

Metabolic- edema, alkaline phosphatase increased, hyperglycemia Musculoskeletal - back pain, leg cramps, tenosynovitis, arthiitis, tetany, twitching

Respiratory- bronchitis, bronchospasm, epistaxis, hicough, laryngitis, yawn, apnea, voice alteration

Special senses- dry eye, ear pain, eye pain, hyperacusis, parosmia, tinnitus, diplopia,lacrimation

Miscellaneous- allergic reaction, chills, facial edema, fever, malaise, photosentivity

Injectable preparation used IV because of potential to cause coronary vasospasm, patients wit 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 containg 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. Cerbrovascular events and fatalities with 5-HT1 agonists- cerebral hemorrhage , subarachnoid hemorrhage , stroke, and other cerebrovascular events have been reported in patients treated with 5-Ht1 agonists and some have resulted in fatalites. 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 . Peripheral vascular ischemiand colonic ischemia with abdominal pain and bloody diarrhea have been reported with 5-HT1 agonists.

Increase in blood pressure- significant increase in blood pressure including hypertensive crisis have been reported on rare occassions in patients with a history of with or without hypertension trreated with 5HT1 agonists. 5-HT1 agonists are contraindicated in patients with uncontrolled hypertension. 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.

Phtoosensitivity- Photosenrization 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.

Migraine

Dosage-

Patients should be started on 2.5mg or lower. A dose lower than 2.5mg can be acheived by manuaaly breaking a scored tablet in half.

If headache returns, the dosemay be repeated after 2 hours not to exceed 10mg within 24 hours.

Controlled trials have not adequately established the effectiveness of a second dose if the initial dose is ineffective.

Agents for Migraine include- Almotriptan, Eletriptan, Frovatriptan, Naratriptan, Rizatriptan, Sumatriptan, Zolmitriptan

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

Pharmacokinetics

RENAL FUNCTION IMPAIRMENT

Zolmitriptan -Clearance of zolmitriptan was reduced by 25% in patients with severe renal impairment ( Ccr approx 5 to 25mL/min. No significant change was observed in those with moderate renal impairment 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.

Zolmitriptan - in severely hepatically impaired patients, the mean Cmx and Tmax and AUC of zolmitriptan were increased 1.5, 2 and 3 fold respy. Seven of 27 patients experienced 20 to 80mmHg elevations in systolic or diastolic blood pressure after 10mg dose. Administer zolmitriptan with caution in patients with liver disease, generally using doses less than 2.5mg

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.