Triptan
Encyclopedia
Triptans are a family of tryptamine
-based drugs
used as abortive medication
in the treatment of migraine
s and cluster headache
s. They were first introduced in the 1990s. While effective at treating individual headaches, they do not provide preventative treatment and are not considered a cure
.
Triptans include sumatriptan
(marketed as Imitrex in the USA), rizatriptan
(Maxalt), naratriptan
(Amerge, Naramig), zolmitriptan
(Zomig), eletriptan
(Relpax), almotriptan
(Axert, Almogran), frovatriptan
(Frova, Migard, Frovamig), and avitriptan
(BMS-180,048).
5-HT1B and 5-HT1D receptors in cranial blood vessel
s (causing their constriction
) and subsequent inhibition of pro-inflammatory neuropeptide
release. Evidence is accumulating that these drugs are effective because they act on serotonin receptors in nerve endings as well as the blood vessels. This leads to a decrease in the release of several peptide
s, including CGRP and substance P
.
became available over-the-counter in the UK in June, 2006. The brand name of the OTC product in the UK is Imigran Recovery. The patent on Imitrex STATDose expired in December 2006, and injectable sumatriptan became available in generic formula in August 2008. Sumavel Dosepro is a needle free delivery of injectable sumatriptan that was approved in the US by the FDA in July 2009. Sumatriptan became available as a generic in the US in late 2009. Sumatriptan is over-the-counter in Romania, under the Imigran brand. Sumatriptan is also available as a nasal spray
, and Phase III clinical trials with a iontophoretic patch (Zelrix) are under way .
and related selective serotonin receptor agonist
s are excellent for severe migraines or those that do not respond to NSAIDs or other over-the-counter
drugs. Triptans are a mid-line treatment suitable for many migraineurs with typical migraines. They may not work for atypical or unusually severe migraines, transformed migraines, or status (continuous) migraines.
Triptans are highly effective, reducing the symptoms or aborting the attack within 30 to 90 minutes in 70-80% of patients. Many patients have a recurrent migraine later in the day, and only one such recurrence in a day can be treated with a second dose of a triptan.
Triptan therapy has been shown to result in a reduction in lost productivity. Sumatriptan has been shown to result in an average of 0.5 fewer missed workdays during the first three months of therapy and 0.7 fewer missed workdays within the first six months, as well as a reduction in the number of days spent working while symptomatic.
The average reduction in lost productivity has been estimated at $1,249, at a cost of $25 per day of disability avoided. The annual net savings in reduced health care costs and lost productivity, over the increased cost of triptan therapy, has been estimated at between $114 and $540 per patient; thus the use of these pharmaceuticals represents a cost savings as well as an improvement in the patients' quality of life.
Assessment of efficacy may be contaminated by how the triptan is encapsulated in order to mask active treatment.
A test measuring a person's skin
sensitivity during a migraine may indicate whether the individual will respond to treatment with triptans. Triptans are most effective in those with no skin sensitivity; with skin sensitivity, it is best to take triptans within twenty minutes of the headache's onset.
found that sumatriptan may be able to prevent altitude sickness
.
found that "rizatriptan 10 mg was the only triptan with a recurrence rate greater than that of placebo".
There is a theoretical risk of coronary spasm in patients with established heart disease, and cardiac events after taking triptans may rarely occur.
There is the potential for life-threatening serotonin syndrome
(a syndrome of changes in mental status, autonomic instability, neuromuscular abnormalities, and gastrointestinal symptoms) in patients taking triptans and selective serotonin reuptake inhibitors (SSRIs) or selective serotonin/norepinephrine reuptake inhibitors (SNRIs) at the same time.
At least two types of triptans (sumatriptan
and rizatriptan
) have been listed under the unacceptable medication by the Canadian Blood Services
, as a potential risk to the recipient; hence, donors are required not to have taken the medication for the last 72 hours.
Tryptamine
Tryptamine is a monoamine alkaloid found in plants, fungi, and animals. It is based around the indole ring structure, and is chemically related to the amino acid tryptophan, from which its name is derived...
-based drugs
Medication
A pharmaceutical drug, also referred to as medicine, medication or medicament, can be loosely defined as any chemical substance intended for use in the medical diagnosis, cure, treatment, or prevention of disease.- Classification :...
used as abortive medication
Abortive medication
Abortive medication is used to interrupt an attack or episode of severe headache.-See also:* Prophylaxis* Cluster Headache* Migraine...
in the treatment of migraine
Migraine
Migraine is a chronic neurological disorder characterized by moderate to severe headaches, and nausea...
s and cluster headache
Cluster headache
Cluster headache, nicknamed "suicide headache", is a neurological disease that involves, as its most prominent feature, an immense degree of pain in the head. Cluster headaches occur periodically: spontaneous remissions interrupt active periods of pain. The cause of the disease is currently unknown...
s. They were first introduced in the 1990s. While effective at treating individual headaches, they do not provide preventative treatment and are not considered a cure
Cure
A cure is a completely effective treatment for a disease.The Cure is an English rock band.Cure, or similar, may also refer to:-Film and television:* The Cure , a short film starring Charlie Chaplin...
.
Triptans include sumatriptan
Sumatriptan
Sumatriptan is a triptan sulfa drug containing a sulfonamide group. It is used for the treatment of migraine headaches. Sumatriptan is produced and marketed by various drug manufacturers with many different trade names such as Sumatriptan, Imitrex, Imigran, Imigran recovery.-Approval and...
(marketed as Imitrex in the USA), rizatriptan
Rizatriptan
Rizatriptan is a 5-HT1 agonist triptan drug developed by Merck & Co. for the treatment of migraine headaches. It is available in strengths of 5 and 10 mg as tablets and orally disintegrating tablets ....
(Maxalt), naratriptan
Naratriptan
Naratriptan is a triptan drug marketed by GlaxoSmithKline and is used for the treatment of migraine headaches. Naratriptan is available in 2.5 mg tablets. It is a selective 5-HT1 receptor subtype agonist...
(Amerge, Naramig), zolmitriptan
Zolmitriptan
Zolmitriptan is a selective serotonin receptor agonist of the 1B and 1D subtypes. It is a triptan, used in the acute treatment of migraine attacks with or without aura and cluster headaches....
(Zomig), eletriptan
Eletriptan
Eletriptan is a second generation triptan drug marketed and manufactured by Pfizer Inc for the treatment of migraine headaches. It is sold in the US under the brand name Relpax.-Approval and availability:...
(Relpax), almotriptan
Almotriptan
Almotriptan ,...
(Axert, Almogran), frovatriptan
Frovatriptan
Frovatriptan is a triptan drug developed by Vernalis for the treatment of migraine headaches and for short term prevention of menstrual migraine. The product is licensed to Endo Pharmaceuticals in North America and Menarini in Europe.-Pharmacology:Frovatriptan inhibits excessive dilation of...
(Frova, Migard, Frovamig), and avitriptan
Avitriptan
Avitriptan is an anti-migraine drug of the triptan class. It acts as a 5-HT1B and 5-HT1D receptor agonist. It has yet to be marketed....
(BMS-180,048).
Mechanism of action
Their action is attributed to their binding to serotoninSerotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...
5-HT1B and 5-HT1D receptors in cranial blood vessel
Blood vessel
The blood vessels are the part of the circulatory system that transports blood throughout the body. There are three major types of blood vessels: the arteries, which carry the blood away from the heart; the capillaries, which enable the actual exchange of water and chemicals between the blood and...
s (causing their constriction
Vasoconstriction
Vasoconstriction is the narrowing of the blood vessels resulting from contraction of the muscular wall of the vessels, particularly the large arteries, small arterioles and veins. The process is the opposite of vasodilation, the widening of blood vessels. The process is particularly important in...
) and subsequent inhibition of pro-inflammatory neuropeptide
Neuropeptide
Neuropeptides are small protein-like molecules used by neurons to communicate with each other. They are neuronal signaling molecules, influence the activity of the brain in specific ways and are thus involved in particular brain functions, like analgesia, reward, food intake, learning and...
release. Evidence is accumulating that these drugs are effective because they act on serotonin receptors in nerve endings as well as the blood vessels. This leads to a decrease in the release of several peptide
Peptide
Peptides are short polymers of amino acid monomers linked by peptide bonds. They are distinguished from proteins on the basis of size, typically containing less than 50 monomer units. The shortest peptides are dipeptides, consisting of two amino acids joined by a single peptide bond...
s, including CGRP and substance P
Substance P
In the field of neuroscience, substance P is a neuropeptide: an undecapeptide that functions as a neurotransmitter and as a neuromodulator. It belongs to the tachykinin neuropeptide family. Substance P and its closely related neuropeptide neurokinin A are produced from a polyprotein precursor...
.
Discovery and development
Availability
These drugs have been available only by prescription (US, Canada and UK), but sumatriptanSumatriptan
Sumatriptan is a triptan sulfa drug containing a sulfonamide group. It is used for the treatment of migraine headaches. Sumatriptan is produced and marketed by various drug manufacturers with many different trade names such as Sumatriptan, Imitrex, Imigran, Imigran recovery.-Approval and...
became available over-the-counter in the UK in June, 2006. The brand name of the OTC product in the UK is Imigran Recovery. The patent on Imitrex STATDose expired in December 2006, and injectable sumatriptan became available in generic formula in August 2008. Sumavel Dosepro is a needle free delivery of injectable sumatriptan that was approved in the US by the FDA in July 2009. Sumatriptan became available as a generic in the US in late 2009. Sumatriptan is over-the-counter in Romania, under the Imigran brand. Sumatriptan is also available as a nasal spray
Nasal spray
Nasal sprays come in a variety of forms. Medicated such as Astelin, Afrin and Nasonex and natural such as Sinusoothe and Sterimar. Although delivery methods vary, most nasal sprays function by instilling a fine mist into the nostril by action of a hand-operated pump mechanism.-Antihistamine nasal...
, and Phase III clinical trials with a iontophoretic patch (Zelrix) are under way .
Migraines
SumatriptanSumatriptan
Sumatriptan is a triptan sulfa drug containing a sulfonamide group. It is used for the treatment of migraine headaches. Sumatriptan is produced and marketed by various drug manufacturers with many different trade names such as Sumatriptan, Imitrex, Imigran, Imigran recovery.-Approval and...
and related selective serotonin receptor agonist
Serotonin receptor agonist
A serotonin receptor agonist is a compound that activates serotonin receptors, mimicking the effect of the neurotransmitter serotonin. There are various serotonin receptors and ligands.-5-HT1A receptor:...
s are excellent for severe migraines or those that do not respond to NSAIDs or other over-the-counter
Over-the-counter drug
Over-the-counter drugs are medicines that may be sold directly to a consumer without a prescription from a healthcare professional, as compared to prescription drugs, which may be sold only to consumers possessing a valid prescription...
drugs. Triptans are a mid-line treatment suitable for many migraineurs with typical migraines. They may not work for atypical or unusually severe migraines, transformed migraines, or status (continuous) migraines.
Triptans are highly effective, reducing the symptoms or aborting the attack within 30 to 90 minutes in 70-80% of patients. Many patients have a recurrent migraine later in the day, and only one such recurrence in a day can be treated with a second dose of a triptan.
Triptan therapy has been shown to result in a reduction in lost productivity. Sumatriptan has been shown to result in an average of 0.5 fewer missed workdays during the first three months of therapy and 0.7 fewer missed workdays within the first six months, as well as a reduction in the number of days spent working while symptomatic.
The average reduction in lost productivity has been estimated at $1,249, at a cost of $25 per day of disability avoided. The annual net savings in reduced health care costs and lost productivity, over the increased cost of triptan therapy, has been estimated at between $114 and $540 per patient; thus the use of these pharmaceuticals represents a cost savings as well as an improvement in the patients' quality of life.
Assessment of efficacy may be contaminated by how the triptan is encapsulated in order to mask active treatment.
A test measuring a person's skin
Skin
-Dermis:The dermis is the layer of skin beneath the epidermis that consists of connective tissue and cushions the body from stress and strain. The dermis is tightly connected to the epidermis by a basement membrane. It also harbors many Mechanoreceptors that provide the sense of touch and heat...
sensitivity during a migraine may indicate whether the individual will respond to treatment with triptans. Triptans are most effective in those with no skin sensitivity; with skin sensitivity, it is best to take triptans within twenty minutes of the headache's onset.
Altitude sickness
A single randomized controlled trialRandomized controlled trial
A randomized controlled trial is a type of scientific experiment - a form of clinical trial - most commonly used in testing the safety and efficacy or effectiveness of healthcare services or health technologies A randomized controlled trial (RCT) is a type of scientific experiment - a form of...
found that sumatriptan may be able to prevent altitude sickness
Altitude sickness
Altitude sickness—also known as acute mountain sickness , altitude illness, hypobaropathy, or soroche—is a pathological effect of high altitude on humans, caused by acute exposure to low partial pressure of oxygen at high altitude...
.
Adverse effects
Triptans have few side effects if used in correct dosage and frequency. The most common adverse effect is recurrence of migraine. A systematic reviewSystematic review
A systematic review is a literature review focused on a research question that tries to identify, appraise, select and synthesize all high quality research evidence relevant to that question. Systematic reviews of high-quality randomized controlled trials are crucial to evidence-based medicine...
found that "rizatriptan 10 mg was the only triptan with a recurrence rate greater than that of placebo".
There is a theoretical risk of coronary spasm in patients with established heart disease, and cardiac events after taking triptans may rarely occur.
There is the potential for life-threatening serotonin syndrome
Serotonin syndrome
Serotonin syndrome is a potentially life-threatening adverse drug reaction that may occur following therapeutic drug use, inadvertent interactions between drugs, overdose of particular drugs, or the recreational use of certain drugs...
(a syndrome of changes in mental status, autonomic instability, neuromuscular abnormalities, and gastrointestinal symptoms) in patients taking triptans and selective serotonin reuptake inhibitors (SSRIs) or selective serotonin/norepinephrine reuptake inhibitors (SNRIs) at the same time.
At least two types of triptans (sumatriptan
Sumatriptan
Sumatriptan is a triptan sulfa drug containing a sulfonamide group. It is used for the treatment of migraine headaches. Sumatriptan is produced and marketed by various drug manufacturers with many different trade names such as Sumatriptan, Imitrex, Imigran, Imigran recovery.-Approval and...
and rizatriptan
Rizatriptan
Rizatriptan is a 5-HT1 agonist triptan drug developed by Merck & Co. for the treatment of migraine headaches. It is available in strengths of 5 and 10 mg as tablets and orally disintegrating tablets ....
) have been listed under the unacceptable medication by the Canadian Blood Services
Canadian Blood Services
Canadian Blood Services is a national, not-for-profit charitable organization that manages the blood supply in all provinces and territories of Canada, outside of Quebec, and oversees the OneMatch Stem Cell and Marrow Network . A separate organization, Héma-Québec, operates in the province of Quebec...
, as a potential risk to the recipient; hence, donors are required not to have taken the medication for the last 72 hours.