How ergotamine works
Ergotamine is an active ingredient from the group of ergot alkaloids. After ingestion, it acts in the body in a variety of ways. Its effectiveness in migraine is mainly due to the fact that ergotamine has a similar structure to the body’s own messenger substance serotonin.
The active ingredient therefore also binds to the serotonin docking sites (5HT1 receptors) in the brain. As a result, the blood vessels in the brain constrict and the nerve cells release fewer pro-inflammatory messenger substances. Ergotamine therefore counteracts two mechanisms that are likely to cause a migraine attack.
In addition, ergotamine also binds to other docking sites. These include.
- Receptors on blood vessels (alpha-adrenoceptors): This causes ergotamine to have a vasoconstrictive effect on arteries and veins.
- Receptors on the uterus: ergotamine causes uterine muscles to contract, which can induce labor.
- Dopamine receptors in the central nervous system, such as in the vomiting center, causing ergotamine to cause nausea and vomiting.
Binding to these docking sites primarily explains the drug’s side effects.
How ergotamine, in turn, prevents cluster headaches is not precisely known.
Absorption, degradation and excretion
When is ergotamine used?
Ergotamine is approved for the treatment of migraine attacks, especially long ones, when other medications do not work sufficiently or are unsuitable.
In addition, doctors prescribe ergotamine to prevent cluster headaches for a limited time. Sufferers take the active ingredient until the effect of a more suitable preventive long-term therapy sets in. It is used particularly in patients who suffer from nocturnal cluster headache attacks. In addition, there is no direct approval for cluster headaches. Physicians therefore use the active ingredient “off-label” in these cases.
How ergotamine is taken
Patients take ergotamine as early as possible at the onset of a migraine attack. The active ingredient is available as a tablet that is sufficiently chewed before swallowing and left in the mouth for some time. If migraine attacks are accompanied by nausea or vomiting, it is recommended to dissolve the tablet in half a glass of water and then drink it.
The usual dose is one tablet of ergotamine (equivalent to two milligrams). If a migraine attack occurs again, sufferers can take another dose of ergotamine after four to six hours at the earliest. The maximum amount within a day is two tablets. The maximum amount in a week here is three tablets.
To prevent cluster headaches for a short time, sufferers take one tablet in the morning and one in the evening, for example. If patients suffer from attacks mainly at night, doctors usually advise them to swallow ergotamine shortly before going to bed.
By the way: Since ergotamine is not expressly approved for the prophylaxis of cluster headaches, there is no specific information on this in the package inserts of the corresponding preparations. Therefore, discuss the intake in detail with your doctor and take the tablets only as prescribed.
What are the side effects of ergotamine?
Ergotamine not only binds selectively to the serotonin docking sites (receptors), which contribute to the relief of migraine attacks. The active ingredient also activates other receptors and thus has some undesirable side effects.
Often these involve the gastrointestinal tract. Among other things, ergotamine excites the dopamine docking sites of the vomiting center: Sufferers feel nauseous and vomit. In addition, the active ingredient causes diarrhea in some people.
Ergotamine constricts blood vessels and can thus increase blood pressure and disrupt blood flow. If patients take ergotamine over a long period of time, they risk vascular occlusion due to the permanently disrupted blood flow.
Long-term use also makes the body more sensitive to pain, which can cause a continuous headache (drug-induced headache).
In isolated cases, ergotamine causes a circulatory disturbance of the heart muscle, which manifests itself with severe pain behind the breastbone (angina pectoris). Cardiac arrhythmias are also possible.
Seek immediate medical attention for sudden severe pain and a feeling of tightness in the chest, accompanied by shortness of breath, sweating and nausea.
When should ergotamine not be taken?
There are some circumstances when you should not take medicines containing ergotamine. These include:
- hypersensitivity to the active substance or to any of the other ingredients of the medicine
- known circulatory disorders of the brain or the large arteries of the arms and legs (peripheral arterial occlusive disease – pAVK)
- coronary artery disease (coronary artery disease)
- high blood pressure
- severe liver and kidney diseases
- a tumor of the adrenal medulla (pheochromocytoma)
- a thyrotoxic crisis (disease of the thyroid gland with excessive amounts of thyroid hormones in the blood)
- Pregnancy and lactation (ergotamine may induce labor).
Ergotamine tablets contain lactose. Patients suffering from galactose or lactose intolerance are better not to take Ergotamine Tablets.
In addition, ergotamine is not suitable for people taking the following medications:
- triptans and other ergotamine-containing medicines
- medicines for HIV (HIV protease inhibitors, e.g., ritonavir)
- Beta-blockers
- Macrolide antibiotics (e.g., azithromycin, erythromycin)
- Tetracycline antibiotics
These drug interactions may occur with ergotamine
Patients taking concomitant medications to treat cardiovascular disease (beta-blockers) may experience poorer blood flow to the major arteries in the arms and legs. Ergotamine, like some beta-blockers, has a vasoconstrictor effect, which is why this effect is increased when taken at the same time .
Ergotamine is broken down in the liver by an enzyme system (CYP3A4). If patients simultaneously use agents that inhibit this system (CYP inhibitors), this prevents the breakdown of ergotamine. Consequently, the concentration of the active substance in the blood is increased, the vasoconstrictive effect is enhanced, and circulatory disorders occur. These inhibitors include, for example, macrolide antibiotics, various drugs against fungal infections, and also grapefruit.
Ergotamine during pregnancy and breastfeeding
Ergotamine constricts blood vessels and can thus reduce or completely cut off the blood supply to the unborn child via the placenta.
By acting on alpha receptors, ergotamine also mediates a rhythmic contraction of the uterine muscles. As a result, the drug induces premature labor and increases the risk of miscarriage. Ergotamine should not be taken during pregnancy.
During breastfeeding, ergotamine reduces milk production. In some cases, it may not be produced at all. This is because ergotamine acts on the pituitary gland like dopamine, preventing the release of the hormone prolactin, which normally stimulates milk production in the mammary gland.
Ergotamine also passes into breast milk and causes diarrhea, vomiting, and cramping in the newborn. If breastfeeding women absolutely want to take ergotamine, they must wean before taking it, according to the manufacturer’s information.
As an alternative, the painkiller paracetamol is best for mild migraine attacks throughout pregnancy. For more severe pain or if acetaminophen does not work adequately, doctors prescribe triptans that have been well studied, such as sumatriptan, during pregnancy and breastfeeding. Ideally, mothers pause breastfeeding for twelve hours after taking them.
How to obtain medication with ergotamine
In Germany, ergotamine is available by prescription in any dosage and package size. It is therefore only available in pharmacies with a doctor’s prescription.
Medicines with the active ingredient ergotamine have not been on the market in Switzerland since 2014. In Austria, no medicines containing ergotamine are currently available either.
Since when is ergotamine known?
Ergot alkaloids such as ergotamine first became known in the Middle Ages due to the epidemic-like disease of ergot poisoning (ergotism). St. Anthony’s fire, as the disease was still called, occurred at irregular intervals and claimed about 40,000 victims in 943. The poisoning occurred after eating rye colonized with ergot fungus.
After research as a basic substance for pharmaceuticals, ergotamine was first produced purely from the ergot fungus by a biochemist from Switzerland in 1918. In the beginning, ergotamine was mainly used to treat postpartum hemorrhage and abortions. Later, it was considered the drug of choice for migraine attacks.
