Ergotamine Derivative | DrugBank Online

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Name

Ergotamine Derivative

Accession Number

DBCAT003327

Description

Not Available

Drugs

Drug	Drug Description
Dihydroergotamine	An ergot alkaloid used in the acute treatment of migraine headache and cluster headache.
Ergotamine	An alpha-1 selective adrenergic agonist vasoconstrictor used to treat migraines with or without aura and cluster headaches.
Dihydroergotoxine	Not Annotated

Drugs & Drug Targets

Drug	Target	Type
Dihydroergotamine	5-hydroxytryptamine receptor 1D	target
Dihydroergotamine	5-hydroxytryptamine receptor 1B	target
Dihydroergotamine	Cytochrome P450 3A4	enzyme
Dihydroergotamine	Alpha-2A adrenergic receptor	target
Dihydroergotamine	5-hydroxytryptamine receptor 2B	target
Dihydroergotamine	P-glycoprotein 1	transporter
Dihydroergotamine	5-hydroxytryptamine receptor 1A	target
Dihydroergotamine	5-hydroxytryptamine receptor 1E	target
Dihydroergotamine	5-hydroxytryptamine receptor 2A	target
Dihydroergotamine	5-hydroxytryptamine receptor 2C	target
Dihydroergotamine	Alpha-1 adrenergic receptors	target
Dihydroergotamine	Alpha-2 adrenergic receptors	target
Dihydroergotamine	Dopamine D2 receptor	target
Dihydroergotamine	Dopamine D3 receptor	target
Dihydroergotamine	Dopamine D4 receptor	target
Dihydroergotamine	5-hydroxytryptamine receptor 1F	target
Dihydroergotamine	5-hydroxytryptamine receptor 4	target
Dihydroergotamine	Beta-3 adrenergic receptor	target
Ergotamine	Alpha-1A adrenergic receptor	target
Ergotamine	5-hydroxytryptamine receptor 1D	target
Ergotamine	5-hydroxytryptamine receptor 1B	target
Ergotamine	5-hydroxytryptamine receptor 2A	target
Ergotamine	Alpha-2A adrenergic receptor	target
Ergotamine	Dopamine D2 receptor	target
Ergotamine	Cytochrome P450 3A4	enzyme
Ergotamine	Alpha-1B adrenergic receptor	target
Ergotamine	Alpha-1D adrenergic receptor	target
Ergotamine	P-glycoprotein 1	transporter
Ergotamine	D(1) dopamine receptor	target
Ergotamine	5-hydroxytryptamine receptor 1A	target
Ergotamine	5-hydroxytryptamine receptor 1F	target
Ergotamine	5-hydroxytryptamine receptor 2C	target
Ergotamine	5-hydroxytryptamine receptor 2B	target
Ergotamine	Alpha-2C adrenergic receptor	target

Ergot Alkaloids of Rye and its Derivatives; Salts Thereof (Excl.

Ergometrine, Ergotamine, Lysergic Acid and Salts Thereof): Commercial exchange, international purchases and sales, market and specialization

About

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The states with the most international purchases in 2022 were Ciudad de México (US$110k).

The main commercial origins of Ergot Alkaloids of Rye and its Derivatives; Salts Thereof (Excl. Ergometrine, Ergotamine, Lysergic Acid and Salts Thereof) in 2022 were Czech Republic (US$33.5k), India (US$30k), Italy (US$29k), Germany (US$16.6k), and France (US$1k).

In the global context, the main exporting countries of Ergot Alkaloids of Rye and its Derivatives; Salts Thereof (Excl. Ergometrine, Ergotamine, Lysergic Acid and Salts Thereof) in 2020 were Czech Republic (US$44.7M), Italy (US$27.1M), and India (US$3.71M). In the same year, the main importing countries of Ergot Alkaloids of Rye and its Derivatives; Salts Thereof (Excl. Ergometrine, Ergotamine, Lysergic Acid and Salts Thereof) were China (US$20. 3M), Japan (US$10.6M), and Romania (US$6.9M).

Trade Balance of Mexico

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Net Trade Balance

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Year20222021202020192018201720162015201420132012201120102009200820072006

The visualizations show the net balance of Ergot Alkaloids of Rye and its Derivatives; Salts Thereof (Excl. Ergometrine, Ergotamine, Lysergic Acid and Salts Thereof) at the level of states and countries. Colors more similar to blue, indicate that the territory presented a higher level of international sales. Colors more similar to red, indicate that the territory presented a higher level of international purchases.

Net International Trade

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June, 2020: US$5.74M, International Purchases

In June 2020, international sales of Ergot Alkaloids of Rye and its Derivatives; Salts Thereof (Excl. Ergometrine, Ergotamine, Lysergic Acid and Salts Thereof) were US$0, while international purchases reached US$5. 74M. The above results in a trade balance of -US$5.74M.

Exchange by Territory

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International Purchases

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Year20222021202020192018201720162015201420132012201120102009200820072006

In 2022, the states with the highest international in Ergot Alkaloids of Rye and its Derivatives; Salts Thereof (Excl. Ergometrine, Ergotamine, Lysergic Acid and Salts Thereof) were Ciudad de México (US$110k).

The countries with the most international sales to Mexico in 2022 were Czech Republic (US$33.5k), India (US$30k), Italy (US$29k), Germany (US$16.6k), and France (US$1k).

Specialization

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Specialization by State

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The RCA-Complexity  diagram compares the Revelead Comparative Advantages of states in Ergot Alkaloids of Rye and its Derivatives; Salts Thereof (Excl. Ergometrine, Ergotamine, Lysergic Acid and Salts Thereof)  and the Economic Complexity Index of each state.

RCA values ​​greater than 1 indicate that the state has comparative advantages in Ergot Alkaloids of Rye and its Derivatives; Salts Thereof (Excl. Ergometrine, Ergotamine, Lysergic Acid and Salts Thereof). On the other hand, high levels of complexity (ECI) are associated with higher levels of income, potential for economic growth, lower income inequality and lower emissions.

Global Market

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Origins and Trade Destinations

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20202019201820172016201520142013

The visualizations show the global market for Ergot Alkaloids of Rye and its Derivatives; Salts Thereof (Excl. Ergometrine, Ergotamine, Lysergic Acid and Salts Thereof). In both charts, Mexico stands out in order to identify its participation in the export and import market.

In 2020, the main exporting countries of Ergot Alkaloids of Rye and its Derivatives; Salts Thereof (Excl. Ergometrine, Ergotamine, Lysergic Acid and Salts Thereof) were Czech Republic (US$44.7M), Italy (US$27.1M), and India (US$3.71M). In the same year, the main importing countries for Ergot Alkaloids of Rye and its Derivatives; Salts Thereof (Excl. Ergometrine, Ergotamine, Lysergic Acid and Salts Thereof) were China (US$20.3M), Japan (US$10.6M), and Romania (US$6.9M).

How we are treated for migraine: ergot, acupuncture and everything else

Medicine from other types of headaches it will help better from it – ergotamine and triptans or non-specific painkillers, what kind of aura many patients begin to feel before an attack of this type of headache, and how a poisonous fungus that once pushed peasants to riots turned out to be a medicine, read in the section “How they treat us” from Indicator.Ru.

According to the World Health Organization, regular headaches are one of the most common disorders of the nervous system. They are caused by various factors and can be symptoms of various diseases – from glaucoma to a brain tumor. One of the most mysterious varieties of headache – migraine – has a primary origin. This means that it is “independent” and does not apply to the symptoms of other problems: a sharp change in blood or intracranial pressure, trauma, tumors or stroke.

The billion people who, according to 2010 data published in The Lancet, faced this problem, are having a hard time. If you are among the 15% of the world’s population who are familiar with these sufferings firsthand (and some of them interfere with work so much that they have to apply for disability), then this article is for you.

Aura of a (un)healthy person

Migraine differs from the other two types of primary headache (tension headache and cluster headache) in that it manifests itself in severe, painful attacks, most often occurring in one hemisphere (itself French word migraine came from the ancient Greek ἡμικρανία – “half of the head”). The pain can last from two hours to three days, along with it may come nausea, increased sensitivity to smells, light and sounds. With physical activity, the pain is exacerbated.

Seizures recur from once a year to twice a week. The onset of migraines often coincides with puberty, and its greatest peak occurs at a mature age – 35-45 years. Women suffer from migraines about twice as often as men.

Often migraine does not come on immediately, it may be preceded by a prodromal phase and an aura phase (although there are varieties of migraine without them). During the prodromal phase, a person feels unusual mood changes (sudden, unexplained euphoria or depression), unexplained cravings for certain foods, increased sensitivity to smells or noises. The migraine aura is not at all the aura that some people go to fortune tellers with questions about. This medical term refers to a temporary neurological disorder associated with the senses. Most often, an aura is a visual effect in which a person sees objects flickering, blurry, or “foggy”. The field of vision may narrow, sometimes dots and lines appear before the eyes.

Aura includes other auditory, olfactory, and tactile hallucinations and symptoms that precede migraine (eg, tingling, dizziness, numbness, or numbness).

After that comes the period of pain itself, which we have already described above. Its end can also be accompanied by its own set of symptoms: fatigue, weakness, mood changes, impaired ability to think.

Genes, wine riot of microbes

Predisposition to migraine is determined by the hereditary characteristics of the brain. A study on twins published in The Journal of Headache and Pain comparing the influence of genetic and environmental factors shows that the probability of getting this disease by inheritance is from 31 to 51%. This is influenced by dozens of genes, and the circle of “suspects” and “accomplices” is constantly expanding due to new discoveries.

You can learn how to understand medicines on your own in the author’s online course “How we are treated” by the editor of Indicator. Ru Ekaterina Mishchenko: https://clck.ru/Pnmtk

To establish how migraine develops at the physiological level, scientists are still too fails. It is believed that this is a neurovascular disease, but further opinions differ: some scientists in their articles and reviews attach more importance to the vessels (see the article in the journal Current Opinion in Neurology on this subject), others – to the nervous tissue (more on this in the journal article Brain), others consider the importance of these reasons to be approximately the same. If the causes of migraine lie in the nerve cells themselves, it may be a lack of serotonin or the activation of neurons responsible for pain, and if in the vessels, then their narrowing (and a concomitant decrease in blood supply to the brain) or uneven expansion can cause a migraine.

Migraines with aura are also characterized by the so-called spreading depression of the cortex, in which the activity of neurons first rises in waves and then falls. Understanding this process can also be key to understanding the causes of migraine itself.

Migraine attacks are known to be triggered by various external causes, from stress or loud noise to certain foods such as chocolate and red wine. This may be due to the connection of certain characteristics of the microflora and migraine, but this theory is also not comprehensive and shows only one side of the issue.

Holes in the skull and the mushroom crusade

When you have a headache, you don’t want to understand the details of this process, but to understand how to reduce unpleasant sensations (and, if possible, avoid them in the future). Doctors began to look for relief from migraines many centuries ago. The first descriptions of this type of headaches were made by the ancient Egyptians 1500 BC. Ancient people believed that the head hurts because of evil spirits locked in the skull, so they performed craniotomy on patients. Even the prominent 17th-century anatomist William Harvey recommended this method. Although such treatment more often freed sufferers not only from headaches, but from all worldly hardships and torments at once (many died due to infection).

Medicine has been losing in the fight against migraines for centuries, rushing from strange remedies and dubious potions to recommendations for more rest and proper nutrition. Everything changed in 1868, when a cure was invented from ergot (Claviceps purpurea) , a fungus that parasitizes on the ears of cereals. At first glance, this use was more than unexpected: fungus-infected ears became poisonous, and large “epidemics” of ergot provoked crop failures, contributing to popular uprisings and the Crusades in “pre-potato” Europe completely relying on rye and wheat. To combat poisoning with alkaloids (a kind of toxins containing nitrogen, most often of plant origin), ergot – “Anton’s fire” – even founded the Order of St. Anthony. However, at 19In 18, it was from this ill-fated fungus that a substance was isolated that was called ergotamine – from the English name for ergot, ergot .

In structure, ergotamine is similar to several neurotransmitters (substances for “communication” of neurons with each other): serotonin, dopamine, adrenaline. Ergotamine binds to their receptors as an agonist, “competing” with neurotransmitters for the receptor, so it affects the body in a complex way, and one of the main factors of its influence is vasoconstriction. It simultaneously constricts intracranial vessels and reduces the conductivity of the trigeminal nerve – all due to binding to serotonin receptors. This makes ergotamine dangerous for people with heart problems, especially diseases of the coronary artery that feeds it, according to a review in the journal Brain.

Although ergotamine has been in use for a long time, a search of the PubMed database of medical articles reveals only two articles on randomized, double-blind, controlled trials of this substance. One of them focuses mainly on another migraine drug, sumatriptan, which is compared to a number of other drugs, including ergotamine. However, it is difficult to isolate the results for ergotamine from the data presented, since only sumatriptan is listed separately, while data for other drugs are averaged.

Double-blind, randomized, placebo-controlled method is a method of clinical drug research in which the subjects are not privy to important details of the study being conducted. “Double-blind” means that neither the subjects nor the experimenters know who is being treated with what, “randomized” means that the distribution into groups is random, and placebo is used to show that the effect of the drug is not based on autosuggestion and that this medicine helps better than a tablet without active substance. This method prevents subjective distortion of the results. Sometimes the control group is given another drug with already proven efficacy, rather than a placebo, to show that the drug not only treats better than nothing, but also outperforms analogues.

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The second study compares the efficacy, tolerability and safety of a mixture of ergotamine with caffeine and eletriptan. A placebo is also used as a control. Here, ergotamine was significantly better than placebo, but lost to eletriptan.

Such a small number of works devoted to ergotamine can be explained by the fact that it entered clinical practice before the approval of evidence-based medicine standards. Despite this, it is approved by the US Food and Drug Administration (FDA), and on the European Medicines Agency (EMA) website you can find that it is approved in many countries. EU. She knows about ergotamine and WHO, and she considers it, if not the most effective, but rather cheap means. However, WHO experts removed it from the list of essential drugs in 2005, as more effective drugs appeared.

Triptans & Company

The already mentioned sumatriptan and eletriptan belong to the triptans, another group of drugs specifically prescribed for migraine. They appeared much later, in the 90s. Triptans bind to the 5-HT _1B and 5-HT _1D serotonin receptors (one of the routes of action of ergotamine). These receptors in the vessels cause them to constrict. Unlike ergotamine, which the liver tries to degrade and degrade as much as possible (resulting in a bioavailability of about 5%), triptans, according to a 2002 review, are very diverse in this characteristic, and their bioavailability ranges from 14 to 70 %.

The most studied triptans are zolmitriptan and sumatriptan. Zolmitriptan is the subject of a Cochrane review that collected data from 25 studies with a total of more than 20,000 patients. Although zolmitriptan has several forms of administration (nasal spray, lozenges, and regular tablets), most of the work has been on conventional tablets.

The Cochrane Library is a database of the Cochrane Collaboration, an international non-profit organization involved in the development of World Health Organization guidelines. The name of the organization comes from the name of its founder, the 20th-century Scottish medical scientist Archibald Cochrane, who championed the need for evidence-based medicine and the conduct of competent clinical trials and wrote the book Efficiency and Efficiency: Random Reflections on Public Health. Medical scientists and pharmacists consider the Cochrane Database one of the most authoritative sources of such information: the publications included in it have been selected according to the standards of evidence-based medicine and report the results of randomized, double-blind, placebo-controlled clinical trials.

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After reviewing these data, the authors of the review concluded that the quality of studies can be considered good, and the risk of subjective misrepresentation is low. A single dose of zolmitriptan reduced migraine pain in adults in two hours, with both 2.5 mg and 5 mg doses being as effective as sumatriptan at a dosage of 50 mg. In 14% of patients, the migraine went away and did not return for at least 24 hours, as did the wide range of symptoms that accompanied it. In 61%, pain improved from moderate or severe to mild (whereas in the placebo group, this only happened to 29% of participants). The nasal spray began to act faster (within 1 hour), but the results of its use are comparable to those of tablets.

Six Cochrane Reviews have been devoted to sumatriptan, four of which consider different modes of administration (from tablets to rectal) separately. One review (later than these four) includes all applications at once. The studies he reviewed included 50,000 people. The subcutaneous route of administration of this drug turned out to be the fastest and most effective, but it is also one of the most expensive and inconvenient and is associated with the highest risk of side effects. The smallest working dosage in tablets – 50 mg – helped to completely get rid of pain in 28% of the subjects, while the placebo worked only in 11% of cases.

The sixth review concerns the combination of sumatriptan with the non-steroidal anti-inflammatory drug (NSAID) naproxen. The review considers 12 research papers with a total of more than 9300 participants. The combination helped 6% more patients than sumatriptan and 14% more than naproxen.

Painkillers and antipyretics

Since we started talking about naproxen (by the way, one of the five components of Pentalgin we have already considered), it is worth mentioning other painkillers, antipyretics and NSAIDs.

Ibuprofen (often sold under the brand name Nurofen) has been the subject of several Cochrane reviews. In one of them, it proves its action against migraine in adults. Its effectiveness in children is supported by only two small articles, according to the authors of another review. Other migraine medications for children and adults are also discussed there. So, paracetamol does not help children get rid of pain, but triptans can be a solution, although not all of them are allowed for children.

A single dose of paracetamol, according to another Cochrane review, may help adults and is associated with a low risk of side effects. Another review (in the American Family Physician) on headache medication found paracetamol to be safe for pregnant women with migraines. According to this review, up to the third trimester of pregnancy, the use of paracetamol does not harm the development of the fetus, as does the use of “conventional” NSAIDs (paracetamol itself is not a classic NSAID).

In another Cochrane review, popular and cheap aspirin showed similar efficacy to sumatriptan. This conclusion was drawn from 13 randomized, double-blind, placebo-controlled trials involving 4222 patients. Adding metoclopramide (an antiemetic) to both paracetamol and aspirin reduces nausea and other gastrointestinal symptoms associated with migraine.

Diclofenac also has its own Cochrane review of anti-migraine activity (although it is better known to us as a gel for joint pain, it is actually available in tablets). In 1,356 patients and 2,711 migraine attacks, diclofenac was superior to placebo with one or, failing that, two doses of the drug.

Indicator.Ru recommends: use painkillers, triptans if they don’t help

to the doctor. Sometimes you really manage to find your own method: sleep helps someone, a hot shower helps someone, rest in silence and twilight helps someone. Nevertheless, it is far from every day that you can quit your business and run to sleep, and in themselves such measures may not be very effective. For example (according to the same “Atlas”), the “correct” acupuncture (acupuncture) can slightly reduce the frequency of headache attacks, but no more than placing the same needles in random places.

Ergotamine and triptans are more specific migraine medications than conventional pain and fever medications. At the same time, ergotamine and its derivative with similar properties – dihydroergotamine – will be cheaper, but less effective means.

Both triptans, in particular sumatriptan, and ergotamine are available by prescription, and both groups of these drugs are contraindicated in people with diseases of the cardiovascular system. Therefore, first of all, you can resort to the help of painkillers and non-steroidal anti-inflammatory drugs of general action, and only then, if they do not help, try to switch to one of these categories. Among the most popular painkillers and NSAIDs proven effective against migraine are aspirin, naproxen, diclofenac and ibuprofen. Paracetamol helps adults, it can be used until the third trimester of pregnancy, but it will not bring relief to children with migraine.

You might object that painkillers do not treat the cause of the disease, but only improve the condition. Here you will have to upset you: since the causes of migraine are vague and confusing (it’s not for nothing that we devoted so much text to them), doctors have not yet learned how to treat and prevent it with high efficiency. There are some advances in experimental methods. For example, in November 2017, scientists announced successful phase III trials for monoclonal antibody drugs, fremanezumab and erenumab, at 955 patients. The drugs act on the calcitonin gene-related peptide (CGRP), which is released from nerve cells and provokes inflammation and vasodilation. This mechanism also plays an important role in the development of a migraine attack, therefore, with the help of injections of these drugs, it was possible to reduce the number of days during which patients suffered from migraine by 2.5 times. Finally, just recently it became known that erenumab received FDA approval and is now entering the market under the trade name Aimovig.

There are not yet approaches available to every patient, so even more specific triptans still do not cure migraine, but stop the attack. And in terms of the percentage of patients who felt relief after a single dose, they did not go very far from aspirin and other NSAIDs. All of them are effective about half the time, although no one says that this is the same half.

When choosing any of these types of treatment, remember that each type has its own contraindications. Triptans and ergotamine are not suitable for people with cardiovascular disease, and NSAIDs and paracetamol should not be taken continuously, as NSAIDs can increase the risk of heart attack, and long-term use of paracetamol harms the liver. In addition, due to the too frequent use of these drugs, so-called medication overuse headache Often it comes from opioid analgesics, which are also not very effective against migraine by themselves and are not used as often (which is why we did not mention them in this review).

If nothing helps (and it’s definitely a migraine), your doctor may suggest some medical (or even surgical) preventive measures for you. However, their list is very wide, and the action has not been proven for all of these methods, so this is more of a topic for a separate article.

Our advice cannot be compared to a doctor’s prescription. Before you start taking this or that drug, be sure to consult a specialist.

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Author: Ekaterina Mishchenko

Tags #How we are treated

Consequences of abuse of painkillers

Pain medications (non-steroidal anti-inflammatory drugs – NSAIDs, ergotamine derivatives, analgesics) are the most popular and widely used over-the-counter drugs.

Pain medications (non-steroidal anti-inflammatory drugs – NSAIDs, ergotamine derivatives, analgesics) are the most popular and widely used OTC drugs. At the same time, headaches (cephalgia) are very often the cause of their use. Most often it is the so-called tension headache and migraine.

The possibility of buying a drug without a doctor’s prescription in Ukraine leads to the fact that many people decide on their own which drug, at what dose and with what frequency to take. And therein lies the danger, since for each drug there are certain contraindications and restrictions for use.

First, the uncontrolled use of analgesics and NSAIDs often leads to the development of various side effects, including changes in blood composition, gastrointestinal bleeding, erosions and ulcers in the digestive tract.

And secondly, irrational (too frequent or exceeding the recommended dosage) use of painkillers for cephalalgia, including migraine, often causes the so-called drug-induced or abuse headache. Most often, such a headache occurs in chronic migraine as a result of chronic abuse of drugs for the treatment of attacks of cephalalgia. The development of overuse headache is indicated by the use of painkillers more than 2-3 times a week (10 times a month) for 3 or more months. At the same time, the severity of headache attacks and the frequency of their occurrence can progress against the background of excessive drug intake.

Interestingly, analgesic-associated headache occurs only in patients with primary headache (80% of overbusy headache patients are migraine patients) and never develops as a result of taking the same drugs, but according to different indications (for example, osteoarthritis).

Theoretically, too frequent use of any migraine medications, including analgesics, NSAIDs, ergotamine derivatives, opioids, triptans, can lead to the development of “abuses”. However, since the fact of abuse (i.e., excessive frequency of use) of the drug is of greatest importance here, this problem most often occurs when taking NSAIDs and analgesics, given their greater availability and less effectiveness in moderate and severe forms of migraine. As for the mechanisms of development of abusus cephalgia, it is assumed that it is based on changes in the parts of the brain responsible for conducting pain impulses that arise as a result of regular use of headache medications.

Diagnosis of overuse headache is not difficult – it is enough to analyze the entries in the headache diary of a patient who has addressed a doctor with complaints of progression of migraine or other primary headache, in which the time of onset of headache attacks and the number of pain medications taken for at least 3 months.

The superimposition of drug-induced headache on migraine symptoms significantly worsens the patient’s condition and requires proper treatment, the effectiveness of which depends on the patience and discipline of the patient. First of all, the doctor studies the treatment regimen, finds and cancels the “guilty” drug. Usually the complete withdrawal of such pain medication is sufficient intervention, however, in severe cases, inpatient treatment with antidepressants and detoxification therapy may be required. At the second stage, a correction of the migraine treatment regimen is carried out in order to effectively prevent attacks and most sparing pain relief in the event of the development of cephalalgia. Treatment regimens with alternating periods of frequent use of the drug and relatively long periods without treatment are preferred, since the regular use of painkillers is a major risk factor for the development of abuse headaches. A necessary condition for the effective treatment of “abuses” is the refusal to take the analgesic that caused the development of abuses headache, since any therapy will be much less effective if the patient continues to use such a drug on a regular basis.

Prevention of the development of drug-induced headaches in people with migraine and other primary cephalalgias consists in refusing self-medication and strictly following the doctor’s recommendations. In particular, it is of great importance to abandon the uncontrolled increase in the doses and frequency of taking NSAIDs and analgesics, in case of their ineffectiveness, in favor of switching to triptans.