The 5-HT1-receptor agonists(triptans)

The 5-HT₁-receptor agonists(triptans)

The 5-HT₁-receptor agonists, commonly known as the triptans, are the treatment of choice for moderate to severe migraine. They include:

·                 almotriptan

·                 eletriptan

·                 frovatriptan

·                 naratriptan

·                 rizatriptan

·                 sumatriptan

·                 zolmitriptan. (See Sound-alikes: Sumatriptan andzolmitriptan.)

Pharmacokinetics

When comparing the triptans, the key pharmacokinetic features are onset of action and duration of action. Rizatriptan, sumatrip-tan, and zolmitriptan have a half-life of approximately 2 hours; al-motriptan and eletriptan have a half-life of 3 to 4 hours; naratrip-tan has a half-life of about 6 hours; and frovatriptan has the longest half-life (25 hours) and the most delayed onset of action.

Triptan tablets

All of the triptans are available in an oral form. Rizatriptan and zolmitriptan are also available in rapid-dissolve tablets. Zolmitrip-tan and sumatriptan are available in intransal forms. Sumatriptan is also available as a subcutaneous injection. The injectable form of sumatriptan has the most rapid onset of action of all the trip-tans.

Pharmacodynamics

Triptans are serotonin 5-HT₁-receptor agonists, which constrict the cranial vessels, inhibit neuropeptide release, and reduce the neurogenic inflammatory process transmission along the trigemi-nal pathway. These actions may abort or provide symptomatic re-lief for migraines. Aside from relieving pain, triptans are also ef-fective in controlling the nausea and vomiting associated with mi-graines.

Pharmacotherapeutics

The choice of a triptan depends on patient preferences for dosage form (if nausea and vomiting are present), presence of recurrent migraines, and formulary restrictions. A patient experiencing nau-sea and vomiting may prefer injectable or intranasal sumatriptan. Recurrent migraines may respond to triptans with a longer half-life, such as frovatriptan and naratriptan. However, triptans with a longer half-life have a delayed onset of effect. Two newer triptans, almotriptan and eletriptan, have a rapid onset and an intermediate half-life.

Drug interactions

Triptans have many contraindications and aren’t for use in pa-tients with certain conditions. (See Triptans: Contraindicationsand cautions)

The safety of treating more than three migraine attacks in a 30-day period with triptans hasn’t been es-

tablished. (See Adverse reactions to 5-HT₁-receptor agonists [triptans].)In addition:

·                 Triptans shouldn’t be administered within 24 hours of another 5-HT₁-receptor agonist.

·                 Ergotamine-containing and ergot-type drugs (such as dihydroergotamine and methysergide) shouldn’t be given with-in 24 hours of a 5-HT₁-receptor agonist because prolonged vasospastic reac-tions may occur.

·                 Eletriptan shouldn’t be used within at least 72 hours of these potent CYP3A4 inhibitors: ketoconazole, itra-conazole, nefazodone, clarithromycin, ritonavir, nelfinavir, and any other drugs that have demonstrated potent CYP3A4 inhibition, as de-scribed in their labeling.

Wait two weeks

Almotriptan, rizatriptan, sumatriptan, and zolmitriptan should not be used with, or within 2 weeks of discontinuing, an MAOI.

Selective serotonin reuptake inhibitors (SSRIs), such as citalo-pram, fluoxetine, fluvoxamine, paroxetine, and sertraline, have, in rare cases, caused weakness, hyperreflexia, and incoordination when administered with a triptan. (This reaction has also been re-ported when the appetite suppressant sibutramine is used with a triptan.) Monitor the patient closely if concomitant treatment with a triptan and an SSRI is clinically warranted.

·                 The bioavailability of frovatriptan is 30% higher in patients tak-ing hormonal contraceptives.

·                 Propranolol increases the bioavailability of zolmitriptan, riza-triptan, frovatriptan, and eletriptan.