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- palpitation,( >  1% )    hypertension, migraine, peripheral vascular disorder,tachycardia, (0.1% to 1% ) angina pectoris, arrhythmias, artial fibrillation, AV block, bradycardia, cerebrovascular disorders,hypotension, syncope, thrombophlebitis, vasospasm, ventricular arrhythmias (< 1% )

CNS- hypertonia, hypesthesia, vertigo, ( >  1% )  abnormal dreams, agitation, anxiety, apathy, confusion,depression, emotional liability, euphoria, hyperkinesia, incordination, insomnia, nervousness,speech disorders, stupor, thinking abnormal, tremor,( 0.1% to 1% )  abnormal gait, amnesia, dementia, hallucinations,maniac reaction, pscychotic disorder, sleep disorder, twitching.(< 1% )

Dermatologic- sweating , ( >  1% )   pruritus, rash, skin disorder,( 0.1% to 1% )  alopecia, dry skin,eczema, exfoliative dermatitis, maculopapalar rash, skin  discoloration, skin hypertrophy, urticaria (< 1% )

Endocrine- goiter, thyroid adenoma, thyroiditis (< 1% )

GI- anorexia, constipation, diarrhea, eructation, esophagitis, flatulence, gastritis, GI order, glossitis,increased salivation, liver function tests abnormal, ,( 0.1% to 1% )  gingivitis, increased appetite, rectal disorder,tongue disorder, tongue edema, tooth disorder (< 1% )

GU- impotence, polyuria, urinary frequency, urinary tract disorder, ( 0.1% to 1% )  breast pain, kidney  pain, leukorrhea, menorrhagia, menstrual disorder, vaginitis (< 1% )


Hematologic/lymphatic-  anemia, cyanosis, leukopenia, lymphadepathy, monocytosis,
purpura (< 1% )

Metabolic- CPK  increased, edema, peripheral edema, thirst, ( 0.1% to 1% )  alkaline phosphate  increased ,bilirubinemia, hyperglycemia, weight gain, weight loss.(< 1% )

Musculoskeletal - arthalgia, arthiritis, bone pain, myalgia, myasthesnia, ( 0.1% to 1% ), bone neoplasm, joint  disorder, myopathy, tenosynovitis (< 1% )

Respiratory - pharynigitis,( >  1% )  asthma, dyspnea, respiratory disorder, respiratory tract infection,rhinitis, voice alteration, yawn , ( 0.1% to 1% )  bronchitis, choking sensation, cough  increased (< 1% )

Special senses- abnormal vision, conjuntivitis, ear pain, eye pain, lacrimation disorder,
photophobia, taste pervertion, tinnitus, ( 0.1% to 1% ) abnormality of accomodation, dry eyes,ear disorder, eye haemorrhage, otis media, paronia (< 1% )

Miscellaneous- back pain, chills pain, face edema, malaise,( 0.1% to 1% )   accidental injury, allergic  reaction, fever, flu syndrome, hernia, rheumatoid arthiritis, shock  (< 1% )

 

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 cardiacrhythm, 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 . 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.

Phtosensitivity-
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.    

 

Dosage-

Initial dose- singledose  of 20 and 40mg were effective for acute atacks of migraine.
If after the initial dose headache improves butthen returns, a repeat dose may be  beneficial.
if a second dose is required at least 2 hours after initial dose.

Maximum dose- 40m as a single dose; 80mg total daily dose.

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 pain, tightness, pressure or heaviness in the chest , throat, neck or jaw occurs when using these agents, instruct patients to discuss it with a physician before using more.
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, advice 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.

Instruct patiens not to remove the blister from the outer pouch until just prior to dosing
zolmitriptan or rizatriptan orally -disintegrating tablets.

Instruct patients to peel blister packs open with  dry hands and to place orally-disintegrating
tablets on the tongue,where it will dissolve and be swalllowed with the saliva.

Inform phenylketonuric patients that riztriptan and zolmitriptan orally-disintegrating tablets
contain phenylalamine ( a component of aspartame )  

Each 5mg rizatriptan orally -disintegrating tablet contains 1.05mg phenylalamine  and
each 10mg orally-disintegrating tablet contains 2.1mg phenylalamine.
Each 2.5 mg zolmitriptan orally-disintegrating tablet contains 2.81 mg phenylalamine

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  

 

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-

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.  


Eletriptan - the effects of severe effects of hepatic impairment on eletriptan metabolism have not  been evaluated. Subjectswith mild or modrate hepatic impairment demonstrated an increase in AUC (34% ) and half life . Cmax was increased by 18%.
Elderly- there is stastically significant increase in electriptan half life  ( from approx 4.4        to 5.7 hrs ) between elderly 65 to 93  years of age and younger adults subjects ( 18 to 45 years of age )

Food has significant effect on oral 5-HT1 agonists bioavailability, but delays sumatriptans Tmax by approximately 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 been established.

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