Triptans Pharmacology!

Triptans Pharmacology

Triptans are medicines used in the treatment of migraine and cluster headaches. They are not used to prevent either of these conditions, nor are they considered a cure. However, they do provide significant symptomatic treatment. Below, we review triptans pharmacology in terms of indications, mechanism, side effects, and drug interactions.

Triptans have been around since the 1990s, largely replacing ergotamine drugs in the relief of patients with cluster headaches or migraine.

Sumatriptan, the first FDA approved triptan, was made available to the public in 1993. It was long believed that activity at serotonin receptors led to reduced incidence of migraine attacks, but it was not precisely known why. Triptans filled the gap and became an instant success.

Examples of widely prescribed triptans:

• Sumatriptan
• Eletriptan
• Zolmitriptan
• Almotriptan
• Rizatriptan

Though triptans are used to treat cluster headaches and migraines, they are not used to treat other types of headache. For example – they are not used to treat tension headaches. Note that triptans are not prophylactic agents and do not prevent migraines and cluster headaches.

Instead, triptans are abortive agents – meaning that they help to hasten the end of an ongoing event.

Mechanism of Action

As we alluded to earlier, researchers long knew that a connection existed between migraine and its relief via activity at serotonergic receptors. This research commenced in the 1940s, but it was only in the 1990s that triptans became widely used.

Specifically, triptans work as agonists at 5-HT_1B and 5-HT_1D receptors. They have activity at other receptor sites, but it’s through their activity at these two receptor sites that primarily accounts for their therapeutic impact.

Agonism at 5-HT_1B / 5-HT_1D receptors causes vasoconstriction of blood vessels surrounding the brain.

However, triptans also have two other modes of effect:

• Inhibition of neuropeptide release from nerve terminals. Implicated neuropeptides include Substance P and CGRP, or calcitonin gene-related peptide.
• Inhibition of nociceptive neurotransmission. This refers to “pain transmission”, which is inhibited at sites such as the brainstem.

These are the three primary ways in which triptans exert their therapeutic impact.

Side Effects

Side effects with triptans include:

• Paresthesias
• Nausea
• Chest pain
• Sweating
• Muscle pain
• Weakness
• Dry mouth

Though triptans are linked to these effects, it’s worth emphasizing that triptans are very well-tolerated drugs.

More rarely, triptans are linked to cardiovascular events, not least because triptans are linked to the risk of high blood pressure.

Sumatriptan overdose is linked to sulfhemoglobinemia – an effect which causes blood to change from red to green. However, once sumatriptan is discontinued from use, the change reverses within a matter of weeks. The condition arises due to the presence of a sulfur group within the hemoglobin molecule.

Clinical Pharmacology

When we think about the clinical pharmacology of triptans, we need to talk about the following factors:

• That triptans are classified as pregnancy category C in the United States, meaning “risk is not ruled out”. Triptans should be avoided.
• That triptans increase the risk of serotonin syndrome, particularly when taken with SSRIs, SNRIs, MAO inhibitors and St. John’s wort. However, recent research casts doubt on the established risk.
• That due to their hypertensive effects, triptans are contraindicated in patients with established cardiovascular disease.
• That later triptans have longer half-lives and greater oral bioavailability compared to older agents, such as the founding triptan, sumatriptan.

That concludes our rapid revision of triptans pharmacology. They remain a widely prescribed, and highly effective, drug class. Check back to our PharmaFactz blog soon for even more exclusive content to help you master the science of medicines!