Low levels of the neurotransmitter serotonin, also known as 5-hydroxytryptamine (5-HT), are also believed to be involved.Calcitonin gene-related peptides (CGRPs) have been found to play a role in the pathogenesis of the pain associated with migraine, as levels of it become elevated during an attack. Diagnosis
The diagnosis of a migraine is based on signs and symptoms. Neuroimaging tests are not necessary to diagnose migraine, but may be used to find other causes of headaches in those whose examination and history do not confirm a migraine diagnosis. It is believed that a substantial number of people with the condition remain undiagnosed.The diagnosis of migraine without aura, according to the International Headache Society, can be made according to the following criteria, the "5, 4, 3, 2, 1 criteria":
Five or more attacks—for migraine with aura, two attacks are sufficient for diagnosis. Four hours to three days in duration
Two or more of the following:
Unilateral (affecting one side of the head)
Pulsating
Moderate or severe pain intensity
Worsened by or causing avoidance of routine physical activity
One or more of the following:
Nausea and/or vomiting
Sensitivity to both light (photophobia) and sound (phonophobia)If someone experiences two of the following: photophobia, nausea, or inability to work or study for a day, the diagnosis is more likely. In those with four out of five of the following: pulsating headache, duration of 4–72 hours, pain on one side of the head, nausea, or symptoms that interfere with the persons life, the probability that this is a migraine attack is 92%.
Contraindications
Prior to administration of the first dose, the corrected QT (QTc) must be determined. If the QTc is greater than 440 msec (or 500 msec in patients with ventricular conduction abnormalities), dofetilide is contraindicated. If heart rate is less than 60 bpm, the uncorrected QT interval should be used. After each subsequent dose of dofetilide, QTc should be determined and dosing should be adjusted. If at any time after the second dose of dofetilide the QTc is greater than 500 msec (550 msec in patients with ventricular conduction abnormalities), dofetilide should be discontinued. Adverse effects
Torsades de pointes is the most serious side effect of dofetilide therapy. The incidence of torsades de pointes is 0.3-10.5% and is dose-related, with increased incidence associated with higher doses. The majority of episodes of torsades de pointes have occurred within the first three days of initial dosing. Patients should be hospitalized and monitored for the first three days after starting dofetilide.The risk of inducing torsades de pointes can be decreased by taking precautions when initiating therapy, such as hospitalizing individuals for a minimum of three days for serial creatinine measurement, continuous telemetry monitoring and availability of cardiac resuscitation. Pharmacology
Mechanism of action
Dofetilide works by selectively blocking the rapid component of the delayed rectifier outward potassium current (IKr).This causes the refractory period of atrial tissue to increase, hence its effectiveness in the treatment of atrial fibrillation and atrial flutter. Dofetilide does not affect dV/dTmax (the slope of the upstroke of phase 0 depolarization), conduction velocity, or the resting membrane potential.