Triptans is a family of tryptamine-based drugs used as a cure for failure in the treatment of migraines and cluster headaches. This class of drugs was first introduced in the 1990s. Although effective in treating individual headaches, they do not provide preventive care and are not considered medications. They are not effective for the treatment of tension type headaches, except in people who also have migraines. They may be effective in disabling tension-type headaches, which are present in the migraine spectrum. Triptans does not relieve other pain.
These class medications act as 5-HT serotonin receptor agonists 1B and 5-HT 1D in the blood vessels and nerve endings in the brain. The first clinically available triptan is sumatriptan, which has been marketed since 1991. Triptans have replaced ergotamine, an older class of drugs used to alleviate migraine and cluster headaches.
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Migrain
Triptans are used for the treatment of severe migraine attacks or those that do not respond to NSAIDs or over the counter drugs. Triptans is a midfield treatment that is suitable for many migraines with typical attacks. They may not work for atypical or extraordinarily severe migraine attacks, altering migraines, or migrainosus status (ongoing).
Triptans are very effective, reduce symptoms or thwart attacks within 30 to 90 minutes in 70-80% of patients.
Tests that measure the sensitivity of a person's skin during a migraine may indicate whether the individual will respond to treatment with triptans. Triptans are most effective in those without skin sensitivity; with skin sensitivity, it is best to take triptans within twenty minutes from the onset of headaches.
Oral rizatriptan and nasal zolmitriptan are the triptans most commonly used for migraines in children.
Cluster headache
Triptans is effective for the treatment of cluster headaches. This has been demonstrated for intranasal subcutaneous and subcutaneous sumatriptan, which was previously more effective according to Cochrane 2013 review. Tablets are not considered appropriate in this review.
Higher disease
One randomized controlled trial found that sumatriptan may be able to prevent altitude sickness.
Available form
All marketed triptans are available in oral form; some in the form of sublingual tablets. Sumatriptan and zolmitriptan are also available as nasal sprays. For sumatriptan, a number of other application forms are marketed: suppositories, subcutaneous injection, iontophoretic transdermal patches, using low voltage controlled by pre-programmed microchips to provide a single dose of sumatriptan through the skin in 30 minutes; combinations of drugs containing "breathing" sumatriptane powders allow users to blow the sumatriptan powder into their nostrils; as well as a needle-free injection system that works with air pressure.
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Contraindications
All triptans are contraindicated in patients with cardiovascular disease (coronary spasm, symptomatic coronary artery disease, after a heart attack or stroke, uncontrolled hypertension, Raynaud's disease, peripheral artery disease). Most triptans are also contraindicated during pregnancy and lactation and for patients younger than 18 years; but the sumatriptan and zolmitriptan nasal sprays are also approved for youth over 12. Despite expert opinions and contradictory evidence, the FDA and some other drug governance bodies have stated that monoamine oxidase inhibitors are contraindicated for sumatriptan, zolmitriptan and rizatriptan, and combinations with ergot alkaloids such as ergotamine for all substances.
At least two triptans (sumatriptan and rizatriptan) have been listed under drugs that can not be accepted by Canadian Blood Services as a potential risk for the recipient; therefore, donors are required not to take medication for the last 72 hours.
Adverse effects
Triptans has some side effects if used in appropriate doses and frequencies. The most common side effect is migraine relapse. A systematic review found that "10 mg rizatriptan was the only triptan with a greater recurrence rate than placebo".
There is a theoretical risk of coronary spasm in patients with established heart disease, and cardiac occurrence after taking triptans may be rare.
Interactions
Combinations of triptans with other serotonergic drugs such as ergot alkaloids, monoamine oxidase inhibitors, selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRI) or St. John's wort have been suspected to cause symptoms of serotonin syndrome (mental status change syndrome, autonomic instability, neuromuscular and gastrointestinal symptoms), whereas scientific studies show no potentially life-threatening serotonin syndrome in patients taking triptans and SSRIs or SNRIs at the same time, even though the FDA has officially stated otherwise.. Combining triptans with ergot alkaloids is contraindicated because of the danger of coronary spasm.
In a study from Harvard Medical School and the University of Florida College of Medicine involving 47,968 patients and published on February 26, 2018, the joint use of selective serotonin reuptake inhibitors or selective norepinephrine reuptake inhibitors for depression with triptans for migraines did not show an increased risk of serotonin syndrome.
Pharmacokinetic interactions (eg, mediated by CYP liver enzymes or transporter proteins) are different for each substance; for most triptans, they are light to none. Blood plasma levels of Eletriptan are increased by strong inhibitors CYP3A4, and levels of frovatriptan by CYP1A2 inhibitors such as fluvoxamine.
Pharmacology
Action mechanism
Their actions are associated with their agonist effects on 5-HT 1B and 5-HT 1D serotonin recipes in blood vessels (causing constriction) and nerve endings in the brain, and subsequent inhibition of release pro-inflammatory neuropeptides, including CGRP and substance P. Triptans are selective agents for 5-HT 1B and 5-HT 1D and have low or no affinity for receptor types 5-HT more.
5-HT receptors are classified into seven different families named 5-HT 1 to 5-HT 7 . All receptors are G protein receptors in pairs with seven transmembrane domains with one exception of 5-HT receptor 3 which is a gated ligand ion channel. There is a high homology in the amino acid sequence in each family. Each couple of families to the same second courier system. Subtype 5-HT 1 is 5-HT 1A , 5-HT 1B , 5-HT 1D , Recipes 5-HT 1E and 5-HT 1F . All 5-HT receptors 1D are combined with inhibition of adenylate cyclase. Recipes 5-HT 1B and 5-HT 1D are difficult to distinguish pharmacologically. After cloning two different genes for 5-HT 1B and 5-HT 1D recipes, a better insight into distribution and expression in different tissues was obtained, except in brain tissue where they overlap in some areas.
Most mammalian species, including humans, have a 5-HT 1D binding site that is widely distributed throughout the central nervous system. 5-HT 1D recipes are found in all areas of the brain but they differ in numbers in each area. An important initiator of headache is advised to be activation of the trigeminovascular afferent nerve that after activation releases neuropeptides such as CGRP, substance P and neurokinin A. Also they are thought to promote an important neurogenic inflammatory response for sensory sensory sensitization, as well as transmission and generation of headaches centered. 5-HT 1D has been found to be responsible for inhibition of neurogenic inflammation after administration with sumatriptan and other related compounds acting on a 5-HT pre-functional receptor 1D .
All triptans, such as the old drug dihydroergotamine, have an agonistic effect on the 5-HT 1D recipe. Comparison of sumatriptan and dihydroergotamine shows that dihydroergotamine has a high affinity and sumatriptan has a moderate affinity for 5-HT 1D . Triptan has at least three modes of action. These antimigrain mechanisms are:
- vasoconstriction of pain that results in intracranial extracebral vessels by a direct effect on smooth muscle of the blood vessels. Sumatriptan and rizatriptan have been shown to cause vasoconstriction in the middle meningeal arteries of humans.
- inhibition of vasoactive neuropeptide release by the terminal trigeminal innervating intracranial vessels and dura mater. The trigeminocervical complex has a 5-HT 1D receptor that binds dihydroergotamine and triptans in humans. Rizatriptan has been shown to block dural vasodilation and plasma protein extravasion by inhibiting the release of CGRP through activation of receptors at the trigeminal preganglionic nermor terminal. Sumatriptan has been shown to inhibit CGRP secretion that stimulates potassium from the culture-trigeminal neurons in a dose-dependent manner and may also inhibit the release of P.
- inhibition of nociceptive neurotransmitters in the trigeminocervical complexes in the brainstem and upper cervical spine. Rizatriptan has a central trigeminal antinociceptive activity.
Another possibility of triptans in the antimigrain effect is modulation of signal transduction pathways depending on nitric oxide, nitric oxide that scavenges in the brain, and the activity of cell metabolism depends on sodium.
Pharmacokinetics
Triptans have various pharmacokinetic properties. Bioavailability is between 14% and 70%, biological half-life (T 1/2 ) between 2 and 26 hours. Their good ability to cross the blood-brain barrier and a longer half-life of some triptans can result in lower frequency of migraine relapse.
Comparison
Zolmitriptan is different from other triptans because it is converted to an active N-desmethyl metabolite that has a higher affinity for 5-HT 1D and 5-HT 1B recipes; both substances have biological half-lives of 2 to 3 hours. In the study, the new triptan was largely compared to sumatriptan. They are better than sumatriptan for longer half-life in plasma and higher oral bioavailability, but have a higher potential for central nervous side effects.
Donitriptan and avitriptan never marketed.
History
The history of triptans begins with the proposed existence of unknown serotonin (5-hydroxytryptamine, 5-HT). In the late 1940s two groups of researchers, one in Italy and the other in the United States, identified a substance called serotonin in the US and enteramine in Italy. In the early 1950s it was confirmed that the two substances were the same. In the mid-1950s it was proposed that serotonin has a role as a neurotransmitter in the central nervous system (CNS) of animals. The investigation of the mechanism of action was not very successful because the experimental technique was lacking.
Then in 1960, research showed that vasoconstriction caused by 5-HT, noradrenaline and ergotamine can reduce migraine attacks. Patrick P.A. Humphrey, among others, at Glaxo began researching the 5-HT receptor to find a more direct 5-HT agonist with fewer side effects.
They continue to develop and work on the desired action on 5-HT by 5-HT 1 activation receptor for anti-migraine drugs. Further work leads to the development of sumatriptan, now known as the first 5-HT 1 agonist, selective for 5-HT recipes 1D/B and also 5-HT 1F receptors with little affinity. In 1991, sumatriptan became available in clinical use in the Netherlands and in the US in 1993. However, there is always a debate about its mechanism of action, and it remains unclear until now. Later, Mike Moskowitz proposed the theory of "neuronal extravasation," and this is the first clue that sumatriptan may have a direct neuronal effect in migraine attacks.
Sumatriptan becomes another prototype for triptans that has been developed to increase the selectivity for 5-HT receptors 1D/B .
Society and culture
Legal status
These drugs are only available on prescription (US, Canada and UK), but sumatriptan became freely available in the UK in June 2006. The brand name of OTC products in the UK is Immigrant Recovery. The patent on Imitrex STATDose ended in December 2006, and injectable sumatriptan became available as a generic formula in August 2008. Sumavel Dosepro is a US approved shipment of syringe injections approved by the FDA in July 2009. Sumatriptan becomes available as generic in the US at end of 2009. It used to be sold over-the-counter in Romania under the Immigrant brand; however, per August 2014 prescription is required. Zecuity, a sumatriptan transdermal patch, has been approved by the US FDA in January 2013. Sumatriptan nasal powder was approved by the FDA in January 2016 and available in the US in May 2016.
References
- Notes
- Source
- Tepper S. J.; Rapoport A. M. (1999). "The triptans - Summary". CNS Drugs . 12 (5): 403-417. doi: 10.2165/00023210-199912050-00007.
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