About one-third of migraine patients using sumatriptan, especially those with long attacks of 2—3 days, will consistently experience headache recurrence in each successfully treated attack, while patients with shorter attacks experience headache recurrence only rarely Visser et al. A major point of discussion, even among the authors of the present review, is whether headache recurrence rates differ between drugs, and whether any differences have clinical implications.
The general perception is that, when effective, ergotamine carries a lower risk of headache recurrence than the triptans. However, the questions arise as to whether this impression is correct, whether such a comparison can actually be made and whether this also implies that patients who experience headache recurrence on triptans will not do so on ergotamine.
The initial response, since a patient has to respond first in order to be at risk for headache recurrence, and the use of analgesics for early treatment of recurring headache must be taken into account. It is important to bear in mind that headache recurrence is assessed in a non-randomized population responders to treatment , and therefore an imbalance in the baseline clinical characteristics cannot be excluded. As a result, simple comparison of headache recurrence may be misleading.
Instead of reporting response and recurrence rates separately, overall efficacy might be better ascertained with a composite measure which includes all the factors mentioned above. Ideally, one would like to know how many patients require only one dose of medication to treat a migraine attack effectively.
Ergotamine has a low degree of receptor selectivity which increases the risk of experiencing a drug-induced side-effect see above. Ergotamine often causes nausea and vomiting in a migraine sufferer and these are major clinical disadvantages given the high prevalence of these symptoms during the migraine attack. Nausea is most probably caused by a direct effect on CNS emetic centres. Weakness in the legs has been reported, and occasionally severe muscle pains have occurred in the extremities following ergotamine use.
Numbness and tingling of the fingers and toes are other reminders of the ergotism that this alkaloid may cause. Localized oedema and itching may occur in an occasional hypersensitive patient. Most of these effects are not alarming and ordinarily do not necessitate interruption of ergotamine therapy. In doses used in the treatment of migraine, the rectal administration of ergotamine produces little change in blood pressure but does cause a slowly progressing increase in peripheral arterial constriction that persists for up to 24 h Bulow et al.
Ergotamine usually induces bradycardia even when the blood pressure is not increased Hoffman and Lefkowitz, This is due predominantly to increased vagal activity, but a reduction in sympathetic tone by a central as well as peripheral presynaptic action and direct myocardial depression may also be involved Saxena and Cairo-Rawlins, ; Hoffman and Lefkowitz, Ergotamine can produce coronary vasoconstriction, often with associated ischaemic changes and anginal pain in patients with coronary artery disease Galer et al.
In contrast to triptans, the contractile effect of ergotamine in the human isolated coronary artery is long-lasting and persists even after repeated washings Fig.
Similarly, administration of ergotamine 0. Ergotamine doses that produce peripheral vasoconstriction can also damage the capillary endothelium. The mechanism of this toxic action is not clearly understood. Vascular stasis, thrombosis and gangrene are prominent features of ergot poisoning. The propensity of ergotamine to cause gangrene appears to parallel its vasoconstrictor activity Peroutka, Ergotamine increases the motor activity of the uterus.
After small doses, contractions are increased in force or frequency, or both, but are followed by a normal degree of relaxation. As the dose is increased, contractions become more forceful and prolonged, resting tonus is markedly increased, and sustained contracture can result Graves, Ergotamine is contraindicated in women who are or may become pregnant, since the drugs may cause foetal harm. Ergotamine is also contraindicated in patients with peripheral vascular disease, coronary heart disease, uncontrolled hypertension, stroke, impaired hepatic or renal function, and sepsis.
Based on the theoretical additive pharmacological effects of the drugs, ergotamine should not be taken within 6 h of the use of triptans, and similarly triptans should not be administered within 24 h of ergotamine. It also is recommended that ergotamine should not be used in complicated migraine Peroutka, , migraine with prolonged aura, basal migraine or familial hemiplegic migraine. It seems likely that any medication used for the treatment of migraine attacks can be misused by being taken daily or almost daily Diener and Tfelt-Hansen, ; Kaube et al.
The problem with ergotamine overuse with rebound headache was recognized by Graham in the late s Wolfson and Graham, and further clarified by Peters and Horton Peters and Horton, and Friedman and colleagues Friedman et al. Why some patients are more prone to develop abuse and daily headache than others is unclear. Genetic and psychological factors seem to be involved.
Analgesic abuse as a major cause of chronic daily headache was recognized in the s Mathew et al. Migraine patients taking ergotamine daily suffer from several kinds of headaches Diener and Tfelt-Hansen, : i a constant, diffuse, dull headache; ii a frequent throbbing headache in the early morning, sometimes combined with nausea, which disappears within 1 h after the intake of ergotamine and is probably a minor withdrawal headache; iii migraine attacks; and iv a withdrawal headache resembling a severe and prolonged migraine attack with gradual return over weeks to the underlying headache pattern if ergotamine is stopped.
In addition, the patients often have constant nausea, acrocyanosis and intermittent claudication due to ergotamine toxicity von Storch, Some authors Mathew et al. When patients are abusing ergotamine, they fear the withdrawal headache and keep on taking ergotamine.
The withdrawal headache is often so severe that the ergotamine abusers have to be hospitalized in the withdrawal phase. Spontaneous improvement is common after the medication is discontinued Diener and Tfelt-Hansen, When ergotamine is discontinued, the prophylactic medications that previously have been largely without benefit become more effective. The prevention of ergotamine abuse is achieved primarily by restricting the frequency of intake to once per week, as a general rule.
Furthermore, patients should be carefully instructed to use ergotamine only for migraine attacks and not for tension-type headaches. Despite the lack of consistent evidence for the efficacy of ergotamine, we as clinicians are left to place the drug in a therapeutic context. Should ergotamine ever be used and if so, when? The writers take the view that there remains a place for ergotamine in modern clinical practice but only when used carefully. The recommendations for ergotamine use are a distillation of the views of the authors as they emerged during consideration of the data in this review and reflect our clinical practice.
Ergotamine remains useful in certain patients, such as those with prolonged attacks or in whom headache recurrence is a substantial issue. It no doubt has cost advantages, but in the use of medicines there is a need to balance cost with clinical outcome.
When ergotamine is ineffective, a repeated dosing within half an hour is sometimes recommended, but we do not support this recommendation. This is partly for the reason that one simply cannot expect onset of efficacy within this short time frame, and thus this approach increases the risk for drug-induced side-effects.
Table 3 summarizes a prudent use of ergotamine. Ultimately, physicians will decide to whom ergotamine will be given. Clearly those patients taking ergotamine who have a satisfactory response, as judged by the patient, and who have infrequent headache and no medical contraindication can usefully continue to use ergotamine.
Those patients, as with all migraine sufferers, need medical review from time to time to ensure there are no issues of concern arising that would necessitate a change of medication, such as increased headache frequency.
Migraine is not unlike hypertension in terms of the attitude to follow-up that we must adopt. The real question is what to do with a patient who has failed to improve with analgesics and NSAIDs non-steroidal anti-inflammatory drugs , with prokinetics.
In the first instance, should they be advanced to triptans immediately or channelled through ergotamine first? This question assumes a stepped care model, where each patient is moved systematically through each level of care; this assumption is now being tested in clinical trials Lipton et al. Putting aside financial considerations, moving patients straight to triptans and by-passing ergotamine would be ideal practice as we consider it highly likely that most patients who take ergotamine will be more satisfied with triptans and end up taking them eventually.
Receptor profile of ergotamine compared with dihydroergotamine and sumatriptan. Double-blind randomized trials with pure oral ergotamine Erg or an ergotamine compound with caffeine ErgC in the treatment of migraine attacks. Persistent contractile response by ergots, but not triptans, on human isolated coronary arteries. All drugs were administered once at a concentration twice their EC General practitioner clinical trials: treatment of migraine.
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Privacy Notice and Terms of Use. ChEBI Ontology. Automatic Xrefs. ChEBI Name. A peptide ergot alkaloid that is dihydroergotamine in which a double bond replaces the single bond between positions 9 and Colin Batchelor. Supplier Information. Find compounds which contain this structure Find compounds which resemble this structure Take structure to the Advanced Search. Read full article at Wikipedia. Average Mass.
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